https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/06/STS_PODCAST.mp3Welcome back to the SO Files! Shout out to our listeners for suggesting we dive into the world of soft tissue sarcomas. Soft Tissue Sarcomas are a very diverse group of cancers so today we focus on the two most common groupings – extremity vs retroperitoneal. We also bring Dr. Brian Van Tine on to focus on current trends in the field. Dr. Van Tine is an Associate Professor in the Division of Medical Oncology at Washington University who specializes in the treatment of soft tissue and bone sarcomas. [Brian Van Tine, MD,PhD]We also plug our Surg Onc Files Questionnaire which we designed to get to know you all a little better. It takes less than a minute to fill out so be sure to click the link and give us some feedback!Survey Monkey LinkIntroduction and Sarcoma Overview: 0-25:50Interview with Dr. Van Tine: 25:50-Outline: Extremity Soft Tissue Sarcoma Retroperitoneal Soft Tissue Sarcoma Interview with Dr. Brian Van Tine As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions, and remember to fill out our survey!!NCCN Practice Guidelines SarcomaReferences1. ANNOUNCE Trial (Eli Lilly Link); (ClinicalTrials.gov link)Randomized, double-blind, Phase 3 study of olaratumab (anti-PDGFRA) in combination with doxorubicine, followed by olaratumab monotherapy; vs doxorubicin plus placebo followed by placebo, in patients with advanced or metastatic STS. Two primary endpoints were OS in the ITT population and in the Leimyosarcoma sub-population. There was no difference in survival between the study arms for either population. Findings were presented at ASCO 2019, and have not yet been published in a journal. Takeaway: No survival benefit gained by adding olaratumab to doxorubicin for locally advanced/metastatic STS.2. SARC021 (Lancet link) (CT.gov link)International, open-label, randomised, phase 3, multicenter trial. Included 81 sites in 13 countries. Patients randomly assigned to either doxorubicin alone or doxorubicin plus evofosfamide. 640 patients enrolled, primary endpoint was overall survival, not reached (18.4 months in combo group vs 19.0 months in DOX alone). Takeaway: No survival benefit gained by adding evofosfomide to doxorubicine for locally advanced or metastatic STS.3. The Angiosarcoma ProjectNationwide clinical genomics study that allows patients diagnosed with angiosarcoma to send in their normal and tumor specimens. This in turn helps create a large tissue-bank which fuels large-scale sequencing efforts. Enrollment is ongoing. P.S. For those of you who like a good, old fashioned diagram, here’s one from Cameron’s Current Surgical Therapy that we found to be useful and easy to follow, enjoy!Current Surgical Therapy 12th Ed, Cameron et al. 2017

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/06/STS_PODCAST.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/06/STS_PODCAST.mp3</a>Welcome back to the SO Files! Shout out to our listeners for suggesting we dive into the world of soft tissue sarcomas. Soft Tissue Sarcomas are a very diverse group of cancers so today we focus on the two most common groupings – extremity vs retroperitoneal. We also bring Dr. Brian Van Tine on to focus on current trends in the field. Dr. Van Tine is an Associate Professor in the Division of Medical Oncology at Washington University who specializes in the treatment of soft tissue and bone sarcomas. [<a href="https://oncology.wustl.edu/people/faculty/Van_Tine/Van_Tine_Bio.html" rel="nofollow" target="_blank">Brian Van Tine, MD,PhD</a>]We also plug our Surg Onc Files Questionnaire which we designed to get to know you all a little better. It takes less than a minute to fill out so be sure to click the link and give us some feedback!<a href="https://www.surveymonkey.com/r/FMBC3F9" rel="nofollow" target="_blank">Survey Monkey Link</a>Introduction and Sarcoma Overview: 0-25:50Interview with Dr. Van Tine: 25:50-Outline:<ul> <li>Extremity Soft Tissue Sarcoma</li> <li>Retroperitoneal Soft Tissue Sarcoma</li> <li>Interview with Dr. Brian Van Tine</li> </ul>As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions, and remember to fill out our survey!!<a href="https://www.nccn.org/professionals/physician_gls/default.aspx" rel="nofollow" target="_blank">NCCN Practice Guidelines Sarcoma</a>References1. <a href="https://investor.lilly.com/node/40206/pdf" rel="noopener noreferrer nofollow" target="_blank">ANNOUNCE Trial (Eli Lilly Link); </a><a href="https://clinicaltrials.gov/ct2/show/NCT02451943" rel="noopener noreferrer nofollow" target="_blank">(ClinicalTrials.gov link)</a>Randomized, double-blind, Phase 3 study of olaratumab (anti-PDGFRA) in combination with doxorubicine, followed by olaratumab monotherapy; vs doxorubicin plus placebo followed by placebo, in patients with advanced or metastatic STS. Two primary endpoints were OS in the ITT population and in the Leimyosarcoma sub-population. There was no difference in survival between the study arms for either population. Findings were presented at ASCO 2019, and have not yet been published in a journal. Takeaway: No survival benefit gained by adding olaratumab to doxorubicin for locally advanced/metastatic STS.2. SARC021 (<a href="https://www.sciencedirect.com/science/article/pii/S1470204517303819?via%3Dihub" rel="nofollow" target="_blank">Lancet link</a>) (<a href="https://clinicaltrials.gov/ct2/show/NCT01440088" rel="noopener noreferrer nofollow" target="_blank">CT.gov link</a>)International, open-label, randomised, phase 3, multicenter trial. Included 81 sites in 13 countries. Patients randomly assigned to either doxorubicin alone or doxorubicin plus evofosfamide. 640 patients enrolled, primary endpoint was overall survival, not reached (18.4 months in combo group vs 19.0 months in DOX alone). Takeaway: No survival benefit gained by adding evofosfomide to doxorubicine for locally advanced or metastatic STS.3. <a href="https://ascproject.org/" rel="nofollow" target="_blank">The Angiosarcoma Project</a>Nationwide clinical genomics study that allows patients diagnosed with angiosarcoma to send in their normal and tumor specimens. This in turn helps create a large tissue-bank which fuels large-scale sequencing efforts. Enrollment is ongoing. P.S. For those of you who like a good, old fashioned diagram, here’s one from Cameron’s Current Surgical Therapy that we found to be useful and easy to follow, enjoy!Current Surgical Therapy 12th Ed, Cameron et al. 2017

Soft Tissue Sarcoma 101

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/Absite-Part-2-2019.mp3 Welcome back to the SO Files! Here you’ll find the part two of our ABSITE-themed surgical oncology tour de force. On this 2nd part of our review we cover GI, HPB and GU cancers, as well as Melanoma. Our goal is to hit the high points on the major cancer topics throughout the body with the hopes of getting you an extra few points this weekend. Best wishes from the SurgOnc Files, good luck and happy studying! Outline:  Gynecology (Vaginal, Ovarian, Endometrial, Cervical) Stomach Liver HPB Urology (Renal/Bladder/Prostate) Adrenal Small Intestine Colorectal Melanoma/Sarcoma  As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions and good luck this weekend! https://www.nccn.org/professionals/physician_gls/default.aspx

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/Absite-Part-2-2019.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/Absite-Part-2-2019.mp3</a> Welcome back to the SO Files! Here you’ll find the part two of our ABSITE-themed surgical oncology tour de force. On this 2nd part of our review we cover GI, HPB and GU cancers, as well as Melanoma. Our goal is to hit the high points on the major cancer topics throughout the body with the hopes of getting you an extra few points this weekend. Best wishes from the SurgOnc Files, good luck and happy studying! Outline: <ul> <li>Gynecology (Vaginal, Ovarian, Endometrial, Cervical)</li> <li>Stomach</li> <li>Liver</li> <li>HPB</li> <li>Urology (Renal/Bladder/Prostate)</li> <li>Adrenal</li> <li>Small Intestine</li> <li>Colorectal</li> <li>Melanoma/Sarcoma</li> </ul> As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions and good luck this weekend! <a href="https://www.nccn.org/professionals/physician_gls/default.aspx" rel="nofollow" target="_blank">https://www.nccn.org/professionals/physician_gls/default.aspx</a>

SurgOnc ABSITE Review: Part 2- GI, HPB, GU and Melanoma

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/ABSITE_HeadtoDiaphragm.mp3 Welcome back to the SO Files! With the ABSITE right around the corner we thought we’d go for a marathon session and build up our stamina for test day – here we present a head to toe review of all things surgical oncology that you might be asked this weekend. Although initially intended to be released en bloc, I think you’ll understand why we broke this bad boy up. So sit back and enjoy a brief review (~ 30 minutes) of high yield surgical oncology – and be sure to come back for part 2! Outline:  Neurosurgery HEENT (including salivary gland and thyroid disease) Thoracic/Cardiac (including esophageal and lung cancers) Mediastinum Breast  As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions and good luck this weekend! https://www.nccn.org/professionals/physician_gls/default.aspx

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/ABSITE_HeadtoDiaphragm.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2019/01/ABSITE_HeadtoDiaphragm.mp3</a> Welcome back to the SO Files! With the ABSITE right around the corner we thought we’d go for a marathon session and build up our stamina for test day – here we present a head to toe review of all things surgical oncology that you might be asked this weekend. Although initially intended to be released en bloc, I think you’ll understand why we broke this bad boy up. So sit back and enjoy a brief review (~ 30 minutes) of high yield surgical oncology – and be sure to come back for part 2! Outline: <ul> <li>Neurosurgery</li> <li>HEENT (including salivary gland and thyroid disease)</li> <li>Thoracic/Cardiac (including esophageal and lung cancers)</li> <li>Mediastinum</li> <li>Breast</li> </ul> As much as possible, our goal was to stay high yield and not get too bogged down in the details. Please refer to the NCCN guidelines for any additional information or questions and good luck this weekend! <a href="https://www.nccn.org/professionals/physician_gls/default.aspx" rel="nofollow" target="_blank">https://www.nccn.org/professionals/physician_gls/default.aspx</a>

SurgOnc ABSITE Review: Part 1- Head, Neck and Chest

Mark Faries

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/11/Mel_Faries_FINAL.mp3 Welcome back to the SO Files! On today’s show we focus on melanoma and welcome Dr. Mark Faries onto the podcast. We discuss his role in the MSLT-I and MSLT-II trials as well as how their results have influenced the most recent editions of the NCCN and AJCC clinical practice guidelines. Before jumping into our interview with Dr. Faries, we take some time to introduce the basic staging principles for melanoma and the highlights of the MSLT-I and MSLT-II trials. Dr. Faries is the head of the division of surgical oncology and co-director of the melanoma program at the Angeles Clinic and Research Institute, as well as a Professor of Surgery and Surgical Director of Experimental Therapeutics at Cedars Sinai Medical Center. He is a member of the AJCC Melanoma Staging Committee and the American Society of Clinical Oncology / Society of Surgical Oncology Melanoma guidelines panel. He has also published numerous chapters and articles on melanoma research and therapy, and was the lead investigator on the recently published, and practice changing, MSLT-II trial. 0-12:00 – Brad and Alston give overview of melanoma workup and 8th edition AJCC staging. Brief intro to MSLTI and MSLTII. 12:00- Interview with Dr. Faries Background: AJCC 8th Edition (2018) Melanoma Staging An updated, evidence based overview of melanoma staging. NCCN Clinical Practice Guidelines (v3.2018) Clinical practice guidelines for the treatment of melanoma from the national comprehensive cancer network, version 3.2018.  Relevant Reading: 1. MSLT-I Trial;  MSLT-I Trial – 10 year followup Sentinel-Node Biopsy or Nodal Observation in Melanoma; Morton et al. NEJM, Sept 2006 Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma; Morton et al. NEJM Feb 2014 Patients (n = 2001) with primary cutaneous melanoma were randomly assigned to either wide excision (WE) and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred [observation group], or to wide excision (WE) and sentinel-node biopsy (SLNBx) with immediate lymphadenectomy if nodal micrometastases were detected on biopsy [biopsy group]. No difference in 10-yr melanoma-specific survival seen in overall treatment group. But significantly improved disease-free survival rates were seen in biopsy group compared to observation group among patients with intermediate-thickness melanoma, defined as 1.2 to 3.5mm depth, 71% vs 64%, p=0.01; as well as thick melanoma, defined as &gt; 3.5mm – 50% vs 40%, p=0.03. In addition, among patients with nodal mets and intermediate thickness melanoma, 10 year melanoma specific survival was 62.1% for those who got upfront SLN biopsy followed by dissection, versus 41.5% in the observation group (HR 0.56, p=0.006). Takeaway – Biopsy-based staging of intermediate or thick primary melanomas provides important prognostic information. In addition SLN biopsy followed by lymphadenectomy appears to increase melanoma specific survival for patients who have involved lymph nodes and intermediate thickness disease. 2. MSLT-II Trial Completion Dissection of Observation for Sentinel-Node Metastasis in Melanoma; Faries et al, NEJM, June 2017. After MSLT-I, SLNBx was associated with increased melanoma-specific survival among patients with node-positive, intermediate-thickness melanomas (1.2 to 3.5mm). This trial set out to determine the value of completion lymph-node dissection at the time of surgery. Randomly assigned patients (n = 1934) with sentinel-node metastases to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Mean 3-yr melanoma-specific survival was similar between groups (86% in both) at a median follow-up of 43 months. However, rate of disease-free survival was higher in the dissection group (68% vs 63%, p=0.05)) which was primarily attributed to better regional nodal disease control at 3 years (92% vs 77%, p&lt;0.001) Takeaway – Immediate completion LN dissection increased the rate of regional disease control and provided prognostic information, but didn’t increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. 

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/11/Mel_Faries_FINAL.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/11/Mel_Faries_FINAL.mp3</a> Welcome back to the SO Files! On today’s show we focus on melanoma and welcome Dr. Mark Faries onto the podcast. We discuss his role in the MSLT-I and MSLT-II trials as well as how their results have influenced the most recent editions of the NCCN and AJCC clinical practice guidelines. Before jumping into our interview with Dr. Faries, we take some time to introduce the basic staging principles for melanoma and the highlights of the MSLT-I and MSLT-II trials. Dr. Faries is the head of the division of surgical oncology and co-director of the melanoma program at the Angeles Clinic and Research Institute, as well as a Professor of Surgery and Surgical Director of Experimental Therapeutics at Cedars Sinai Medical Center. He is a member of the AJCC Melanoma Staging Committee and the American Society of Clinical Oncology / Society of Surgical Oncology Melanoma guidelines panel. He has also published numerous chapters and articles on melanoma research and therapy, and was the lead investigator on the recently published, and practice changing, MSLT-II trial. 0-12:00 – Brad and Alston give overview of melanoma workup and 8th edition AJCC staging. Brief intro to MSLTI and MSLTII. 12:00- Interview with Dr. Faries Background: <a href="https://link.springer.com/content/pdf/10.1245/s10434-018-6513-7.pdf" rel="noopener nofollow" target="_blank">AJCC 8th Edition (2018) Melanoma Staging</a> An updated, evidence based overview of melanoma staging. <a href="https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf" rel="noopener nofollow" target="_blank">NCCN Clinical Practice Guidelines (v3.2018)</a> Clinical practice guidelines for the treatment of melanoma from the national comprehensive cancer network, version 3.2018.  Relevant Reading: 1. <a href="https://www.nejm.org/doi/10.1056/NEJMoa060992?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov" rel="nofollow" target="_blank">MSLT-I Trial;  </a><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1310460" rel="nofollow" target="_blank">MSLT-I Trial – 10 year followup</a> Sentinel-Node Biopsy or Nodal Observation in Melanoma; Morton et al. NEJM, Sept 2006 Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma; Morton et al. NEJM Feb 2014 Patients (n = 2001) with primary cutaneous melanoma were randomly assigned to either wide excision (WE) and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred [observation group], or to wide excision (WE) and sentinel-node biopsy (SLNBx) with immediate lymphadenectomy if nodal micrometastases were detected on biopsy [biopsy group]. No difference in 10-yr melanoma-specific survival seen in overall treatment group. But significantly improved disease-free survival rates were seen in biopsy group compared to observation group among patients with intermediate-thickness melanoma, defined as 1.2 to 3.5mm depth, 71% vs 64%, p=0.01; as well as thick melanoma, defined as &gt; 3.5mm – 50% vs 40%, p=0.03. In addition, among patients with nodal mets and intermediate thickness melanoma, 10 year melanoma specific survival was 62.1% for those who got upfront SLN biopsy followed by dissection, versus 41.5% in the observation group (HR 0.56, p=0.006). Takeaway – Biopsy-based staging of intermediate or thick primary melanomas provides important prognostic information. In addition SLN biopsy followed by lymphadenectomy appears to increase melanoma specific survival for patients who have involved lymph nodes and intermediate thickness disease. 2. <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1613210" rel="nofollow" target="_blank">MSLT-II Trial</a> Completion Dissection of Observation for Sentinel-Node Metastasis in Melanoma; Faries et al, NEJM, June 2017. After MSLT-I, SLNBx was associated with increased melanoma-specific survival among patients with node-positive, intermediate-thickness melanomas (1.2 to 3.5mm). This trial set out to determine the value of completion lymph-node dissection at the time of surgery. Randomly assigned patients (n = 1934) with sentinel-node metastases to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Mean 3-yr melanoma-specific survival was similar between groups (86% in both) at a median follow-up of 43 months. However, rate of disease-free survival was higher in the dissection group (68% vs 63%, p=0.05)) which was primarily attributed to better regional nodal disease control at 3 years (92% vs 77%, p&lt;0.001) Takeaway – Immediate completion LN dissection increased the rate of regional disease control and provided prognostic information, but didn’t increase melanoma-specific survival among patients with melanoma and sentinel-node metastases.

Melanoma Lymph Nodes with Dr. Mark Faries

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/10/gastric_TCGA_COMPILED_EDITS.mp3 Welcome back to the SO Files! We’re happy to present part 2 of our gastric cancer series. Here we briefly review the historical gastric cancer classifications (Lauren and WHO) and then explain how this has drastically changed over the past 5-10 years with the advent of next-generation sequencing capabilities. We go in depth to evaluate how this applies to the budding surgical oncologist, and what discoveries may lie on the horizon. We also welcome back Dr. Ryan Fields, MD, FACS who is an Associate Professor in the Department of Surgery at Washington University in St. Louis and was recently appointed co-leader of the Solid Tumor Therapeutics Program (STTP) at Siteman Cancer Center.  Dr. Fields talks about the outcomes of several recent trials and how they are helping us to treat gastric cancer patients in the clinic today. As always, all references from the podcast are linked below, enjoy! Background: NCCN Guidelines – Gastric Cancer  An updated, evidence based overview of gastric cancer management. Workup, and    surgical/ medical treatment algorithms discussed. Relevant Reading: 1. Comprehensive molecular characterization of gastric adenocarcinoma The Cancer Genome Atlas, Nature 2014 Comprehensive molecular evaluation of 295 primary gastric adenocarcinoma specimens reveals four distinct subtypes of gastric cancer: Epstein – Barr virus (EBV) positive (~10% of tumors), microsatellite unstable tumors (MSI-Hi, ~20% of tumors), genomically stable tumors (~20% of tumors), and chromosome instability tumors (~50% of tumors).  2. ToGA (Trastuzumab for Gastric Cancer) Trial Bang et al. The Lancet 2010 International (122 centers in 24 countries), phase 3, RCT comparing chemotherapy versus chemotherapy PLUS trastuzumab in patients with gastric cancer that over-expresses HER2 protein. 594 patients, primary endpoint was overall survival. Median overall survival was 13.8 months in the chemo PLUS trastuzumab group, compared to 11.1 months in the chemo alone group. Takeaway – Chemo + Trastuzumab &gt; chemo alone for gastric cancer 3. Adjuvant Options for Advanced Melanoma Melanoma episode with Dr. Andtbacka where we discussed the role of PD-1/PDL1-2 in cancer. 4. PD-1 and Mismatch Repair Deficiency Trial Le et al., NEJM 2015 Treated 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency with Pembrolizumab (anti-PD 1 immune checkpoint inhibitor). Coprimary end points were immune-related objective response rate and 20-week immune-related progression-free survival rate. Mismatch repair-deficient colorectal carcinomas had 40% and 78% objective response rate and progression free survival respectively. Compared to mismatch repair-proficient tumors, which saw 0% and 11% immune-related objective response rate and immune-related progression-free survival rates respectively. Patients with mismatch repair-deficient noncolorectal cancers had responses similar to those of patients with mismatch repair -deficient colorectal cancer.  Takeaway – MMR status can predict clinical benefit of immune checkpoint blockade with pembrolizumab.  5. KEYNOTE – 059 Trial  Fuchs et al., JAMA Oncology 2018 International, Phase 2 trial designed to evaluate safety and efficacy of pembrolizumab in patients with previously treated advanced Gastric and GE junction cancer. 259 patients, 16 countries were treated with IV pembrolizumab until disease progression. Primary end points were objective response rate (ORR) and safety. Demonstrated promising activity for all patients (11.6%) which was more prominent in PD-L1+ tumors (15.5% ORR) compared to PD-L1- tumors (6.4%).  Takeaway – Pembrolizumab demonstrated objective response for all-comers with progressive (failed 2 or more previous chemo regimens) advanced gastric cancer, with especially pronounced response in PD-L1+ tumors. 6. PD-1 Inhibition in Metastatic Gastric Cancer Trial Kim et al., Nature Medicine 2018 Phase 2 trial that performed molecular characterization of tissues and circulating tumor DNA (ctDNA) from 61 patients with metastatic gastric cancer (mGC); tried to identify determinants of response to salvage pembrolizumab therapy. Saw very high overall response rates in patients with EBV+ tumors (100%) and MSI-high tumors (85.7%). Overall response rate was also higher in patients with PD-L1+ tumors compared to PD-L1 negative tumors, 50% vs 0% respectively Takeaway – EBV positivity, MSI-high status, and PD-L1 positivity in gastric cancer all predict likely response to pembrolizumab.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/10/gastric_TCGA_COMPILED_EDITS.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/10/gastric_TCGA_COMPILED_EDITS.mp3</a> Welcome back to the SO Files! We’re happy to present part 2 of our gastric cancer series. Here we briefly review the historical gastric cancer classifications (Lauren and WHO) and then explain how this has drastically changed over the past 5-10 years with the advent of next-generation sequencing capabilities. We go in depth to evaluate how this applies to the budding surgical oncologist, and what discoveries may lie on the horizon. We also welcome back Dr. Ryan Fields, MD, FACS who is an Associate Professor in the Department of Surgery at Washington University in St. Louis and was recently appointed co-leader of the Solid Tumor Therapeutics Program (STTP) at Siteman Cancer Center.  Dr. Fields talks about the outcomes of several recent trials and how they are helping us to treat gastric cancer patients in the clinic today. As always, all references from the podcast are linked below, enjoy! Background: <a href="https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf" rel="noopener nofollow" target="_blank">NCCN Guidelines – Gastric Cancer </a> An updated, evidence based overview of gastric cancer management. Workup, and    surgical/ medical treatment algorithms discussed. Relevant Reading: 1. <a href="https://www.nature.com/articles/nature13480" rel="noopener nofollow" target="_blank">Comprehensive molecular characterization of gastric adenocarcinoma</a> The Cancer Genome Atlas, Nature 2014 Comprehensive molecular evaluation of 295 primary gastric adenocarcinoma specimens reveals four distinct subtypes of gastric cancer: Epstein – Barr virus (EBV) positive (~10% of tumors), microsatellite unstable tumors (MSI-Hi, ~20% of tumors), genomically stable tumors (~20% of tumors), and chromosome instability tumors (~50% of tumors).  2. <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61121-X/fulltext" rel="noopener nofollow" target="_blank">ToGA (Trastuzumab for Gastric Cancer) Trial</a> Bang et al. The Lancet 2010 International (122 centers in 24 countries), phase 3, RCT comparing chemotherapy versus chemotherapy PLUS trastuzumab in patients with gastric cancer that over-expresses HER2 protein. 594 patients, primary endpoint was overall survival. Median overall survival was 13.8 months in the chemo PLUS trastuzumab group, compared to 11.1 months in the chemo alone group. Takeaway – Chemo + Trastuzumab &gt; chemo alone for gastric cancer 3. <a href="https://surgoncfiles.com/2017/10/30/adjuvant-melanoma/" rel="noopener nofollow" target="_blank">Adjuvant Options for Advanced Melanoma</a> Melanoma episode with Dr. Andtbacka where we discussed the role of PD-1/PDL1-2 in cancer. 4. <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1500596" rel="nofollow" target="_blank">PD-1 and Mismatch Repair Deficiency Trial</a> Le et al., NEJM 2015 Treated 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency with Pembrolizumab (anti-PD 1 immune checkpoint inhibitor). Coprimary end points were immune-related objective response rate and 20-week immune-related progression-free survival rate. Mismatch repair-deficient colorectal carcinomas had 40% and 78% objective response rate and progression free survival respectively. Compared to mismatch repair-proficient tumors, which saw 0% and 11% immune-related objective response rate and immune-related progression-free survival rates respectively. Patients with mismatch repair-deficient noncolorectal cancers had responses similar to those of patients with mismatch repair -deficient colorectal cancer. Takeaway – MMR status can predict clinical benefit of immune checkpoint blockade with pembrolizumab.  5. <a href="https://jamanetwork.com/journals/jamaoncology/fullarticle/2675013" rel="noopener nofollow" target="_blank">KEYNOTE – 059 Trial </a> Fuchs et al., JAMA Oncology 2018 International, Phase 2 trial designed to evaluate safety and efficacy of pembrolizumab in patients with previously treated advanced Gastric and GE junction cancer. 259 patients, 16 countries were treated with IV pembrolizumab until disease progression. Primary end points were objective response rate (ORR) and safety. Demonstrated promising activity for all patients (11.6%) which was more prominent in PD-L1+ tumors (15.5% ORR) compared to PD-L1- tumors (6.4%).  Takeaway – Pembrolizumab demonstrated objective response for all-comers with progressive (failed 2 or more previous chemo regimens) advanced gastric cancer, with especially pronounced response in PD-L1+ tumors. 6. <a href="https://www.nature.com/articles/s41591-018-0101-z" rel="noopener nofollow" target="_blank">PD-1 Inhibition in Metastatic Gastric Cancer Trial</a> Kim et al., Nature Medicine 2018 Phase 2 trial that performed molecular characterization of tissues and circulating tumor DNA (ctDNA) from 61 patients with metastatic gastric cancer (mGC); tried to identify determinants of response to salvage pembrolizumab therapy. Saw very high overall response rates in patients with EBV+ tumors (100%) and MSI-high tumors (85.7%). Overall response rate was also higher in patients with PD-L1+ tumors compared to PD-L1 negative tumors, 50% vs 0% respectively Takeaway – EBV positivity, MSI-high status, and PD-L1 positivity in gastric cancer all predict likely response to pembrolizumab.

Gastric Cancer Deep Dive

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/08/TailorX_Episode_original-edits.mp3 On this episode of SO Files, Alston, Brad and Linda take a closer look at the recently published TAILORx Clinical Trial Published in NEJM by Sparano and colleagues. The study expands the existing clinical application of the Oncotype DX score. If that score sounds familiar its because it has been quickly making its way into clinical practice over the past few years (see our last episode on the new AJCC guidelines!). We explain the origin of the score, how it has been incorporated into clinical practice thus far, and how this trial addresses a large gap in the existing literature. Relevant Reading: TAILORx Trial Sparano et. al., NEJM 2018 A randomized controlled trial, designed to assess the utility of the Oncotype DX Score in predicting the need for chemotherapy, in addition to anti endocrine therapy, for hormone receptor +, Her2 -, node negative breast cancer. Bottom Line: Patients with an intermediate Oncotype DX Score of 11-25 can forgo chemotherapy, especially those patients &gt;50 y/o. NSABP B14 Study Fisher et al. NEJM 1989 Overview of study layout in 1980’s – establishes adjuvant tamoxifen &gt; no adjuvant therapy in ER+/Node negative patients. NSABP B20 Study Fisher et al. JNCI 1997 Overview of study layout in 1990’s – establishes chemo + endocrine for ER+/Node negative patients = decreased recurrence.  Oncotype Dx Study Paik et al. NEJM 2004 First description of OncotypeDx use and correlation with outcomes. Patients can now be stratified into low, intermediate, high risk of recurrence. Oncotype DX applied study Paik et al. J Clin Onc 2006 Same group shows that the score can be used to predict benefit from chemotherapy in individual patients. ASCO 2007 Update  Harris et al. JCO 2007 ASCO first updates their guidelines to recommend use of gene assays in clinical care.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/08/TailorX_Episode_original-edits.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/08/TailorX_Episode_original-edits.mp3</a> On this episode of SO Files, Alston, Brad and Linda take a closer look at the recently published TAILORx Clinical Trial Published in NEJM by Sparano and colleagues. The study expands the existing clinical application of the Oncotype DX score. If that score sounds familiar its because it has been quickly making its way into clinical practice over the past few years (see our last episode on the new AJCC guidelines!). We explain the origin of the score, how it has been incorporated into clinical practice thus far, and how this trial addresses a large gap in the existing literature. Relevant Reading: <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1804710" rel="noopener nofollow" target="_blank">TAILORx Trial</a> Sparano et. al., NEJM 2018 A randomized controlled trial, designed to assess the utility of the Oncotype DX Score in predicting the need for chemotherapy, in addition to anti endocrine therapy, for hormone receptor +, Her2 -, node negative breast cancer. Bottom Line: Patients with an intermediate Oncotype DX Score of 11-25 can forgo chemotherapy, especially those patients &gt;50 y/o. <a href="http://www.nsabp.pitt.edu/B-14.asp" rel="noopener nofollow" target="_blank">NSABP B14 Study</a> Fisher et al. NEJM 1989 Overview of study layout in 1980’s – establishes adjuvant tamoxifen &gt; no adjuvant therapy in ER+/Node negative patients. <a href="http://www.nsabp.pitt.edu/B-20.asp" rel="noopener nofollow" target="_blank">NSABP B20 Study</a> Fisher et al. JNCI 1997 Overview of study layout in 1990’s – establishes chemo + endocrine for ER+/Node negative patients = decreased recurrence.  <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa041588" rel="noopener nofollow" target="_blank">Oncotype Dx Study</a> Paik et al. NEJM 2004 First description of OncotypeDx use and correlation with outcomes. Patients can now be stratified into low, intermediate, high risk of recurrence. <a href="https://www.ncbi.nlm.nih.gov/pubmed/16720680" rel="noopener nofollow" target="_blank">Oncotype DX applied study</a> Paik et al. J Clin Onc 2006 Same group shows that the score can be used to predict benefit from chemotherapy in individual patients. <a href="https://pdfs.semanticscholar.org/ae93/0cb0420190992d2f360c836c2a7b6fd830e4.pdf" rel="noopener nofollow" target="_blank">ASCO 2007 Update </a> Harris et al. JCO 2007 ASCO first updates their guidelines to recommend use of gene assays in clinical care.

Oncotype DX Score, TailorX Trial, and the Role of Oncotype DX Score in Breast Cancer Management

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/07/Breast-Staging-Compiled-1-1.mp3 On this episode of SO Files, Brad and Linda cover the updated staging guidelines for breast cancer that have been in practice (theoretically) since Jan 1, 2018. The possibilities for stage groups now cover a full six pages in the AJCC manual and you can hear Brad and Linda read through each one right here…. just kidding. We will however cover the major changes, the reasoning behind them, and talk about how they are fitting into practice with podcast favorite Dr. Cyr. BONUS: listen to Brad, Alston and Linda survive a tornado during the live taping of this show! Show Breakdown: 0-14 minutes: Background information with Brad, Linda and Alston 14 minutes- end: Brad and Linda interview Dr. Cyr Relevant Reading: NCCN Guidelines Updated NCCN breast cancer guidelines, which includes the new AJCC 8th edition staging system. AJCC 8th Edition Staging Chapter Gabriel N. Hortobagyi, James L. Connolly, Carl J. D’Orsi, Stephen B. Edge, Elizabeth A. Mittendorf, Hope S. Rugo, Lawrence J. Solin, Donald L. Weaver, David J. Winchester, and Armando Giuliano Detailed chapter outlining the new AJCC staging system.  Oncotype DX Score Background Background info on Oncotype DX Score from the company, Genomic Health, with links to relevant articles.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/07/Breast-Staging-Compiled-1-1.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/07/Breast-Staging-Compiled-1-1.mp3</a> On this episode of SO Files, Brad and Linda cover the updated staging guidelines for breast cancer that have been in practice (theoretically) since Jan 1, 2018. The possibilities for stage groups now cover a full six pages in the AJCC manual and you can hear Brad and Linda read through each one right here…. just kidding. We will however cover the major changes, the reasoning behind them, and talk about how they are fitting into practice with podcast favorite Dr. Cyr. BONUS: listen to Brad, Alston and Linda survive a tornado during the live taping of this show! Show Breakdown: 0-14 minutes: Background information with Brad, Linda and Alston 14 minutes- end: Brad and Linda interview Dr. Cyr Relevant Reading: <a href="https://www.nccn.org/professionals/physician_gls/default.aspx" rel="nofollow" target="_blank">NCCN Guidelines</a> Updated NCCN breast cancer guidelines, which includes the new AJCC 8th edition staging system. <a href="https://cancerstaging.org/references-tools/deskreferences/Documents/AJCC%20Breast%20Cancer%20Staging%20System.pdf" rel="nofollow" target="_blank">AJCC 8th Edition Staging Chapter</a> Gabriel N. Hortobagyi, James L. Connolly, Carl J. D’Orsi, Stephen B. Edge, Elizabeth A. Mittendorf, Hope S. Rugo, Lawrence J. Solin, Donald L. Weaver, David J. Winchester, and Armando Giuliano Detailed chapter outlining the new AJCC staging system.  <a href="http://www.oncotypeiq.com/en-US/breast-cancer/healthcare-professionals/oncotype-dx-breast-recurrence-score/about-the-test" rel="nofollow" target="_blank">Oncotype DX Score Background</a> Background info on Oncotype DX Score from the company, Genomic Health, with links to relevant articles.

AJCC 8 Breast Staging Updates with Dr. Cyr

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/04/CRLM-BK-Compiled.mp3 Today we will be discussing the modern management of colorectal liver metastases. For today’s episode, we are excited to be welcoming on Dr. Yuman Fong, Sangiacomo Family Chair in Surgical Oncology and Surgical chair at City of Hope Cancer Center in California. Dr. Fong previously held the Murray F. Brennan Chair of Surgery at Memorial Sloan Kettering Cancer center, and is an international expert in both liver and pancreatic surgery. Background Reading: NCCN Guidelines: Colon Cancer NCCN guidelines for colon cancer, which includes the management strategy for patients with liver metastases. Sabiston Textbook of Surgery, Twentieth Edition Overview of the surgical management of the liver and hepatic neoplasms, including metastatic colorectal cancer. Articles Discussed: Patient selection for the surgical treatment of resectable colorectal liver metastases. Araujo RL, Riechelmann RP, Fong Y 2017 review article in The Journal of Surgical Oncology, outlining the surgical and medical management of colorectal liver metastases. Figure depicting the utilization of the colorectal liver metastasis clinical risk score in order to guide chemotherapy and surgical strategy. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH Classic article depicting a clinical risk score that predicts survival in patients with resected colorectal liver metastasis. 5 preoperative factors, with each factor contributing to 1 point on the score, with more points = worse prognosis. At time of initial publication in 1998: 5 pts led to 14% 5 year survival vs. 60% for someone with 0 points. The 5 factors are: &gt;1 liver metastasis, node positive primary, &lt;12 months between primary colorectal tumor and liver met, &gt;5cm liver tumor, preop CEA &gt;200.  Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution. House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP, Brennan MF, Blumgart LH, Jarnagin WR, D’Angelica MI Data from Memorial Sloan Kettering that compared survival after resection for colorectal liver metastases for patients during 2 different eras: 1985-1998, and 1999-2004. Many of the patients in the more modern era were offered therapy with oxaliplatin or irinotecan, which likely led to the improved survival in these patients. Recurrence free survival in both generations were similar, suggesting that chemotherapy regimens and possibly patient selection differences led to differences in overall survival. 

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/04/CRLM-BK-Compiled.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/04/CRLM-BK-Compiled.mp3</a> Today we will be discussing the modern management of colorectal liver metastases. For today’s episode, we are excited to be welcoming on Dr. Yuman Fong, Sangiacomo Family Chair in Surgical Oncology and Surgical chair at City of Hope Cancer Center in California. Dr. Fong previously held the Murray F. Brennan Chair of Surgery at Memorial Sloan Kettering Cancer center, and is an international expert in both liver and pancreatic surgery. Background Reading: <a href="https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf" rel="nofollow" target="_blank">NCCN Guidelines: Colon Cancer</a> NCCN guidelines for colon cancer, which includes the management strategy for patients with liver metastases. <a href="https://www.elsevier.com/books/sabiston-textbook-of-surgery/townsend/978-0-323-29987-9" rel="nofollow" target="_blank">Sabiston Textbook of Surgery, Twentieth Edition</a> Overview of the surgical management of the liver and hepatic neoplasms, including metastatic colorectal cancer. Articles Discussed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/27778357" rel="nofollow" target="_blank">Patient selection for the surgical treatment of resectable colorectal liver metastases.</a> Araujo RL, Riechelmann RP, Fong Y 2017 review article in The Journal of Surgical Oncology, outlining the surgical and medical management of colorectal liver metastases. Figure depicting the utilization of the colorectal liver metastasis clinical risk score in order to guide chemotherapy and surgical strategy. <a href="https://www-ncbi-nlm-nih-gov.beckerproxy.wustl.edu/pubmed/27778357" rel="nofollow" target="_blank">Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.</a> Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH Classic article depicting a clinical risk score that predicts survival in patients with resected colorectal liver metastasis. 5 preoperative factors, with each factor contributing to 1 point on the score, with more points = worse prognosis. At time of initial publication in 1998: 5 pts led to 14% 5 year survival vs. 60% for someone with 0 points. The 5 factors are: &gt;1 liver metastasis, node positive primary, &lt;12 months between primary colorectal tumor and liver met, &gt;5cm liver tumor, preop CEA &gt;200.  <a href="https://www.ncbi.nlm.nih.gov/pubmed/10493478" rel="nofollow" target="_blank">Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution.</a> House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP, Brennan MF, Blumgart LH, Jarnagin WR, D’Angelica MI Data from Memorial Sloan Kettering that compared survival after resection for colorectal liver metastases for patients during 2 different eras: 1985-1998, and 1999-2004. Many of the patients in the more modern era were offered therapy with oxaliplatin or irinotecan, which likely led to the improved survival in these patients. Recurrence free survival in both generations were similar, suggesting that chemotherapy regimens and possibly patient selection differences led to differences in overall survival.

Modern Management of Colorectal Liver Metastases

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/DTC-Compiled-Final-.mp3 We were so lucky to catch up with Dr. Julie Ann Sosa, who is the new Chair of Surgery at UCSF starting April 1st, 2018, and also world renowned endocrine surgeon on the newly updated staging guidelines for differentiated thyroid cancer and some common controversies in management in the US. We also chat about mentorship and her advice to learners at all stages! Check it out! Background Reading: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer Bryan R. Haugen, Erik K. Alexander, Keith C. Bible, Gerard M. Doherty, Susan J. Mandel, Yuri E. Nikiforov, Furio Pacini, Gregory W. Randolph, Anna M. Sawka, Martin Schlumberger, Kathryn G. Schuff, Steven I. Sherman, Julie Ann Sosa, David L. Steward, R. Michael Tuttle, and Leonard Wartofsky American Thyroid Association guidelines for both differentiated thyroid cancer and thyroid nodules. Differentiated thyroid cancer= papillary thyroid cancer, follicular thyroid cancer or Hurthle cell cancer. Differentiated and Anaplastic Thyroid Carcinoma: Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual Nancy D. Perrier, James D. Brierley, and R. Michael Tuttle Overview of the changes made from the 7th to 8th editions of the AJCC staging system for thyroid cancer. One major change is that cut point age for staging is now 55 years of age, rather than 45.  NCCN Guidelines for Thyroid Carcinoma Updated guidelines from the NCCN outlining the management strategy for patients diagnosed with thyroid cancer. Papers we discussed: Controversies in the Management of Low-Risk Differentiated Thyroid Cancer Megan R. Haymart, Nazanene H. Esfandiari, Michael T. Stang, and Julia Ann Sosa Great overview and discussion of the controversies in the management of low-risk differentiated thyroid cancer. Controversies discussed include: surgical management, radioactive iodine ablation therapy, thyroid hormone supplementation, and long-term surveillance. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A. 2003 article in Thyroid that demonstrated in a Japanese population with 10mm or less papillary thyroid micro carcinoma, active surveillance appears to be safe. In this observation trial patients with papillary micro carcinoma either elected to undergo thyroidectomy or active surveillance. Over 5 years of surveillance 27.5% of patients had an increased size of the lesion. 1.2% of patients developed lymph node disease. In total 35% of patients in the observation group went on to have surgery either due to progression or preference. No patients in the observation group had a thyroid cancer related death. Extent of surgery affects survival for papillary thyroid cancer. Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS, Sturgeon C. Annals of Surgery article from 2007, that utilized NCDB data to demonstrate that total thyroidectomy leads to improved survival over thyroid lobectomy for patients 1cm+ papillary thyroid carcinoma. Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients. Adam MA, Pura J, Gu L, Dinan MA, Tyler DS, Reed SD, Scheri R, Roman SA, Sosa JA. Annals of Surgery article from 2014, that used NCDB data from 1998-2006 to look at outcomes after lobectomy or total thyroidectomy for papillary thyroid cancer 1cm+. The authors found equivalent survival for total thyroidectomy and thyroid lobectomy groups, unlike the Bilimoria study from 2007. Of note, the NCDB began more accurately tracking comorbidities in 2003, and it is likely that the addition of this data allowed for more accurate modeling–and thus the change in study outcome.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/DTC-Compiled-Final-.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/DTC-Compiled-Final-.mp3</a> We were so lucky to catch up with Dr. Julie Ann Sosa, who is the new Chair of Surgery at UCSF starting April 1st, 2018, and also world renowned endocrine surgeon on the newly updated staging guidelines for differentiated thyroid cancer and some common controversies in management in the US. We also chat about mentorship and her advice to learners at all stages! Check it out! <h3>Background Reading:</h3> <a href="https://www.liebertpub.com/doi/pdf/10.1089/thy.2015.0020" rel="noopener nofollow" target="_blank">2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer</a> Bryan R. Haugen, Erik K. Alexander, Keith C. Bible, Gerard M. Doherty, Susan J. Mandel, Yuri E. Nikiforov, Furio Pacini, Gregory W. Randolph, Anna M. Sawka, Martin Schlumberger, Kathryn G. Schuff, Steven I. Sherman, Julie Ann Sosa, David L. Steward, R. Michael Tuttle, and Leonard Wartofsky American Thyroid Association guidelines for both differentiated thyroid cancer and thyroid nodules. Differentiated thyroid cancer= papillary thyroid cancer, follicular thyroid cancer or Hurthle cell cancer. <a href="https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21439" rel="noopener nofollow" target="_blank">Differentiated and Anaplastic Thyroid Carcinoma: Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual</a> Nancy D. Perrier, James D. Brierley, and R. Michael Tuttle Overview of the changes made from the 7th to 8th editions of the AJCC staging system for thyroid cancer. One major change is that cut point age for staging is now 55 years of age, rather than 45.  <a href="https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf" rel="nofollow" target="_blank">NCCN Guidelines for Thyroid Carcinoma</a> Updated guidelines from the NCCN outlining the management strategy for patients diagnosed with thyroid cancer. <h3>Papers we discussed:</h3> <a href="http://Controversies in the Management of Low-Risk Differentiated Thyroid Cancer." rel="noopener nofollow" target="_blank">Controversies in the Management of Low-Risk Differentiated Thyroid Cancer</a> Megan R. Haymart, Nazanene H. Esfandiari, Michael T. Stang, and Julia Ann Sosa Great overview and discussion of the controversies in the management of low-risk differentiated thyroid cancer. Controversies discussed include: surgical management, radioactive iodine ablation therapy, thyroid hormone supplementation, and long-term surveillance. <a href="https://www.ncbi.nlm.nih.gov/pubmed/12804106" rel="nofollow" target="_blank">An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid.</a> Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A. 2003 article in Thyroid that demonstrated in a Japanese population with 10mm or less papillary thyroid micro carcinoma, active surveillance appears to be safe. In this observation trial patients with papillary micro carcinoma either elected to undergo thyroidectomy or active surveillance. Over 5 years of surveillance 27.5% of patients had an increased size of the lesion. 1.2% of patients developed lymph node disease. In total 35% of patients in the observation group went on to have surgery either due to progression or preference. No patients in the observation group had a thyroid cancer related death. <a href="https://www.ncbi.nlm.nih.gov/pubmed/17717441" rel="nofollow" target="_blank">Extent of surgery affects survival for papillary thyroid cancer.</a> Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS, Sturgeon C. Annals of Surgery article from 2007, that utilized NCDB data to demonstrate that total thyroidectomy leads to improved survival over thyroid lobectomy for patients 1cm+ papillary thyroid carcinoma. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25203876" rel="nofollow" target="_blank">Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients.</a> Adam MA, Pura J, Gu L, Dinan MA, Tyler DS, Reed SD, Scheri R, Roman SA, Sosa JA. Annals of Surgery article from 2014, that used NCDB data from 1998-2006 to look at outcomes after lobectomy or total thyroidectomy for papillary thyroid cancer 1cm+. The authors found equivalent survival for total thyroidectomy and thyroid lobectomy groups, unlike the Bilimoria study from 2007. Of note, the NCDB began more accurately tracking comorbidities in 2003, and it is likely that the addition of this data allowed for more accurate modeling–and thus the change in study outcome.

Controversies in Differentiated Thyroid Cancer with Dr. Julie Ann Sosa

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/Esophagus-Compiled.mp3 This week we discuss Barrett’s esophagus, and management of associated dysplastic and neoplastic lesions. We are excited to welcome on esteemed guest Dr. John Hunter, former chair of surgery at and now the CEO of OHSU Health Systems and also the Kenneth A.J. Mackenzie Professor of Surgery, who will help guide us through the conversation about treatment options for both Barrett’s esophagus and early esophageal cancer. High Yield Reviews/ Practice Guidelines: NCCN Clinical Practice Guidelines: Esophageal and Esophagogastric Junction Cancers High yield resource to explore the management of esophageal cancers, including those early T stage lesions. Advances in the Diagnosis and Treatment of Barrett’s Esophagus and Early Esophageal Cancer; Summary of the Kelly and Carlos Pellegrini SSAT/SAGES Luncheon Symposium. Gould JC, Wendling MR, Oeschlager BK, Mittal SK, Komanduri S, Perry KA, Cleary S, Galandiuk S, Scott DJ, Fisichella PM, Shaheen NJ, Haisley KR11, Hunter JG. Great updated 2017 review outlining the management of Barrett’s and early esophageal adenocarcinoma. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus Nicholas J Shaheen MD, MPH, FACG, Gary W Falk MD, MS, FACG, Prasad G Iyer MD, MSc, FACG, Lauren B Gerson MD, MSc, FACG Guidelines from the American College of Gastroenterology, outlining diagnosis and management strategy for Barrett’s–written in 2015. Primary Literature Discussed in the Episode: Durability of radiofrequency ablation in Barrett’s esophagus with dysplasia. Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, Sharma VK, Eisen GM, Fennerty MB, Hunter JG, Bronner MP, Goldblum JR, Bennett AE, Mashimo H, Rothstein RI, Gordon SR, Edmundowicz SA, Madanick RD, Peery AF, Muthusamy VR, Chang KJ, Kimmey MB, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Dumot JA, Falk GW, Galanko JA, Jobe BA, Hawes RH, Hoffman BJ, Sharma P, Chak A, Lightdale CJ. The AIM Dysplasia Trial, published in Gastroenterology in 2011, which helped to validate the efficacy of ablation for barrett’s + dysplasia. 90%+ of patients in both the low grade dysplasia and high grade dysplasia group had complete eradication of dysplasia and metaplasia. Progression of disease, defined as low grade dysplasia turning into high grade dysplasia or invasive cancer or high grade dysplasia turning into invasive cancer occurred  in 1.37% chance per patient, per year in patients that had RFA. In the SHAM cohort (over the first year, prior to SHAM group cross over into the RFA group), annual progression rate was 16.3%. So a marked difference. Late Recurrence of Barrett’s Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial. Cotton CC, Wolf WA, Overholt BF, Li N, Lightdale CJ, Wolfsen HC, Pasricha S, Wang KK, Shaheen NJ; AIM Dysplasia Trial Group.   5 year follow up data from the AIM trial, published in Gastroenterology in 2017. They showed, that of the 92% of patients that had metaplasia completely eradicated, about a third had recurrence of barretts or dysplasia, with 17% having recurrence of dyplasia. Importantly, about 70% of these recurrences occured within 1 year follow up, and incidence of recurrence after 1 year went down during every subsequent follow up year, with no recurrences occuring in any patient during the 5th and final follow up year.   Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, Fullarton G, Di Pietro M, Ravi N, Visser M, Offerhaus GJ, Seldenrijk CA, Meijer SL, ten Kate FJ, Tijssen JG, Bergman JJ. Published in JAMA 2013. They assigned patients with low grade dysplasia in the setting of Barretts to either ablation or surveillance. There was a reduced risked of progression to high grade dysplasia and cancer for RFA ablation of the barretts and dysplasia versus surveillance alone. Progression to high grade dysplasia or invasive cancer occured in 1.5% of patients in the ablation group vs 26.5% in the control group. Ablation reduced risk of progression to invasive cancer by 7.4% with a number needed to treat of 13.6. After ablation, 12% of patients suffered from a postop stricture, requiring a median of 1 dilation Important Literature Not Directly Discussed: Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett’s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. van Vilsteren FG, Pouw RE, Seewald S, Alvarez Herrero L, Sondermeijer CM, Visser M, Ten Kate FJ, Yu Kim Teng KC, Soehendra N, Rösch T, Weusten BL, Bergman JJ.   2011 paper in Gut, out of the Netherlands. They assigned patients with high grade dysplasia, in situ cancer or T1a cancer to either endoscopic resection of the dyplastic lesion and then ablation of Barretts in 6-8 weeks, or endoscopic resection of the lesion with a portion of the Barretts, and then stepwise resection of the rest of the Barretts over a max 4 more EGD sessions. They found that for both groups &gt;90% had complete response of neoplasia and metaplasia at a median follow up of 2 years. Importantly, in the local endoscopic resection and RFA group 14% of patients developed postop stenosis, versus nearly 90% of patients in the stepwise endoscopic resection group. 

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/Esophagus-Compiled.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/03/Esophagus-Compiled.mp3</a> This week we discuss Barrett’s esophagus, and management of associated dysplastic and neoplastic lesions. We are excited to welcome on esteemed guest Dr. John Hunter, former chair of surgery at and now the CEO of OHSU Health Systems and also the Kenneth A.J. Mackenzie Professor of Surgery, who will help guide us through the conversation about treatment options for both Barrett’s esophagus and early esophageal cancer. High Yield Reviews/ Practice Guidelines: <a href="https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf" rel="nofollow" target="_blank">NCCN Clinical Practice Guidelines: Esophageal and Esophagogastric Junction Cancers</a> High yield resource to explore the management of esophageal cancers, including those early T stage lesions. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28243981" rel="nofollow" target="_blank">Advances in the Diagnosis and Treatment of Barrett’s Esophagus and Early Esophageal Cancer; Summary of the Kelly and Carlos Pellegrini SSAT/SAGES Luncheon Symposium.</a> Gould JC, Wendling MR, Oeschlager BK, Mittal SK, Komanduri S, Perry KA, Cleary S, Galandiuk S, Scott DJ, Fisichella PM, Shaheen NJ, Haisley KR11, Hunter JG. Great updated 2017 review outlining the management of Barrett’s and early esophageal adenocarcinoma. <a href="https://www.nature.com/articles/ajg2015322" rel="nofollow" target="_blank">ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus</a> Nicholas J Shaheen MD, MPH, FACG, Gary W Falk MD, MS, FACG, Prasad G Iyer MD, MSc, FACG, Lauren B Gerson MD, MSc, FACG Guidelines from the American College of Gastroenterology, outlining diagnosis and management strategy for Barrett’s–written in 2015. Primary Literature Discussed in the Episode: <a href="https://www.ncbi.nlm.nih.gov/pubmed/21679712" rel="nofollow" target="_blank">Durability of radiofrequency ablation in Barrett’s esophagus with dysplasia.</a> Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, Sharma VK, Eisen GM, Fennerty MB, Hunter JG, Bronner MP, Goldblum JR, Bennett AE, Mashimo H, Rothstein RI, Gordon SR, Edmundowicz SA, Madanick RD, Peery AF, Muthusamy VR, Chang KJ, Kimmey MB, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Dumot JA, Falk GW, Galanko JA, Jobe BA, Hawes RH, Hoffman BJ, Sharma P, Chak A, Lightdale CJ. The AIM Dysplasia Trial, published in Gastroenterology in 2011, which helped to validate the efficacy of ablation for barrett’s + dysplasia. 90%+ of patients in both the low grade dysplasia and high grade dysplasia group had complete eradication of dysplasia and metaplasia. Progression of disease, defined as low grade dysplasia turning into high grade dysplasia or invasive cancer or high grade dysplasia turning into invasive cancer occurred  in 1.37% chance per patient, per year in patients that had RFA. In the SHAM cohort (over the first year, prior to SHAM group cross over into the RFA group), annual progression rate was 16.3%. So a marked difference. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28579538" rel="nofollow" target="_blank">Late Recurrence of Barrett’s Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial.</a> Cotton CC, Wolf WA, Overholt BF, Li N, Lightdale CJ, Wolfsen HC, Pasricha S, Wang KK, Shaheen NJ; AIM Dysplasia Trial Group. 5 year follow up data from the AIM trial, published in Gastroenterology in 2017. They showed, that of the 92% of patients that had metaplasia completely eradicated, about a third had recurrence of barretts or dysplasia, with 17% having recurrence of dyplasia. Importantly, about 70% of these recurrences occured within 1 year follow up, and incidence of recurrence after 1 year went down during every subsequent follow up year, with no recurrences occuring in any patient during the 5th and final follow up year. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24668102" rel="nofollow" target="_blank">Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial.</a> Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, Fullarton G, Di Pietro M, Ravi N, Visser M, Offerhaus GJ, Seldenrijk CA, Meijer SL, ten Kate FJ, Tijssen JG, Bergman JJ. Published in JAMA 2013. They assigned patients with low grade dysplasia in the setting of Barretts to either ablation or surveillance. There was a reduced risked of progression to high grade dysplasia and cancer for RFA ablation of the barretts and dysplasia versus surveillance alone. Progression to high grade dysplasia or invasive cancer occured in 1.5% of patients in the ablation group vs 26.5% in the control group. Ablation reduced risk of progression to invasive cancer by 7.4% with a number needed to treat of 13.6. After ablation, 12% of patients suffered from a postop stricture, requiring a median of 1 dilation Important Literature Not Directly Discussed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/21209124" rel="nofollow" target="_blank">Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett’s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.</a> van Vilsteren FG, Pouw RE, Seewald S, Alvarez Herrero L, Sondermeijer CM, Visser M, Ten Kate FJ, Yu Kim Teng KC, Soehendra N, Rösch T, Weusten BL, Bergman JJ. 2011 paper in Gut, out of the Netherlands. They assigned patients with high grade dysplasia, in situ cancer or T1a cancer to either endoscopic resection of the dyplastic lesion and then ablation of Barretts in 6-8 weeks, or endoscopic resection of the lesion with a portion of the Barretts, and then stepwise resection of the rest of the Barretts over a max 4 more EGD sessions. They found that for both groups &gt;90% had complete response of neoplasia and metaplasia at a median follow up of 2 years. Importantly, in the local endoscopic resection and RFA group 14% of patients developed postop stenosis, versus nearly 90% of patients in the stepwise endoscopic resection group.

Management of Barrett’s Esophagus and Associated Lesions

Welcome to the Surg Onc Files! We are Washington University general surgery residents with an interest in surgical oncology. This is us trying to digest the latest research and trends in surg onc and often enlisting a lot of help to get us all the way there. Our goal is to cover surgical oncology from head to toe, discuss interesting topics in surgical oncology, and for each topic including where we are now, how got here, and what the future holds.

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/02/Pancreas-Adjuvant-Compiled.mp3 On this episode of the SO files, we interview Dr. Andrea Wang-Gillam MD/PhD, associate professor in the division of oncology at Wash U School of medicine and clinical director of the GI oncology, about systemic options for treating pancreatic adenocarcinoma. As much as we all love a good Whipple, this really is a systemic disease, and unlike other cancers 100% of patients regardless of stage will need some form of systemic treatment. Good thing we have great options to choose from! …Right? Resources NCCN guidelines RCTs in the metastatic setting  Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine NEJM 2013 Daniel D. Von Hoff, M.D., Thomas Ervin, M.D., Francis P. Arena, M.D., E. Gabriela Chiorean, M.D., Jeffrey Infante, M.D., Malcolm Moore, M.D., Thomas Seay, M.D., Sergei A. Tjulandin, M.D., Wen Wee Ma, M.D., Mansoor N. Saleh, M.D., Marion Harris, M.D., Michele Reni, M.D., Scot Dowden, M.D., Daniel Laheru, M.D., Nathan Bahary, M.D., Ramesh K. Ramanathan, M.D., Josep Tabernero, M.D., Manuel Hidalgo, M.D., Ph.D., David Goldstein, M.D., Eric Van Cutsem, M.D., Xinyu Wei, Ph.D., Jose Iglesias, M.D., and Markus F. Renschler, M.D. Take away: nab-Paclitaxel (Abraxane) added to gemcitabine improved survival when compared to gemcitabine alone (median OS 8.5 pos vs 6.7 mos, ORR 23% vs 7%).  FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer NEJM 2011 Thierry Conroy, M.D., Françoise Desseigne, M.D., Marc Ychou, M.D., Ph.D., Olivier Bouché, M.D., Ph.D., Rosine Guimbaud, M.D., Ph.D., Yves Bécouarn, M.D., Antoine Adenis, M.D., Ph.D., Jean-Luc Raoul, M.D., Ph.D., Sophie Gourgou-Bourgade, M.Sc., Christelle de la Fouchardière, M.D., Jaafar Bennouna, M.D., Ph.D., Jean-Baptiste Bachet, M.D., Faiza Khemissa-Akouz, M.D., Denis Péré-Vergé, M.D., Catherine Delbaldo, M.D., Eric Assenat, M.D., Ph.D., Bruno Chauffert, M.D., Ph.D., Pierre Michel, M.D., Ph.D., Christine Montoto-Grillot, M.Chem., and Michel Ducreux, M.D., Ph.D. for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) is a much more effective regimen than gemcitabine alone (median OS 11.1 mos vs 6.8 mos; ORR 32% vs 9%), but is a more toxic regimen with higher rate of adverse events.   RCTS in the Adjuvant Setting  Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013. Helmut Oettle, MD, PhD; Peter Neuhaus, MD, PhD; Andreas Hochhaus, MD, PhD; Jörg Thomas Hartmann, MD, PhD; Klaus Gellert, MD, PhD; Karsten Ridwelski, MD, PhD; Marco Niedergethmann, MD, PhD; Carl Zülke, MD, PhD; Jörg Fahlke, MD, PhD; Michael B. Arning, MD, PhD; Marianne Sinn, MD; Axel Hinke, PhD; Hanno Riess, MD, PhD Take away: 6 months of gemcitabine treatment after complete resection was better for OS than no treatment (13.4 mos vs 6.7 mos).  Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet 2017 Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Take away: Combination gemcitabine and capecitabine (Xeloda) did better than gemcitabine alone in patients with completely resected disease (OS 28 mos v 25.5 pos).   New and exciting things coming down the pipeline… 1. Targeting desmoplastic reaction HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. JCO 2018 Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE. Take away: The addition of PEGPH20 (pegvorhyaluronidase alfa) to gem/abraxane improved PFS and OS compared to gem/abraxane alone in patients with untreated metastatic disease, especially in patients with hyaluron high tumors. Phase III study ongoing!! 2. Targeting cancer stem cells  A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer Ongoing phase Ib dose escalation study of BBI608 (Napabucasin), STAT3/cancer stem cell inhibitor, in combination with other standard chemotherapy regimens (gem/abraxane, FOLFIRINOX, FOLFIRI). Accrual slated to complete June 2018.  3. Targeting innate immunity  Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Onc. 2016 Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, Fowler KJ, Lockhart AC, Suresh R, Tan BR, Lim KH, Fields RC, Strasberg SM, Hawkins WG, DeNardo DG, Goedegebuure SP, Linehan DC. Blockade of CCR2, as a means to suppress tumor infiltration of immunosuppressive tumor associated macrophages, in combination with FOLFIRINOX chemotherapy for borderline resectable or locally advanced PDAC resulted in a 49% objective tumor response rate. Phase 1b Study of CCX872-B in Patients With Pancreatic Adenocarcinoma CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. In preliminary data presented at ASCO, CX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Estimated study completion date December 2018. 

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/02/Pancreas-Adjuvant-Compiled.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2018/02/Pancreas-Adjuvant-Compiled.mp3</a> On this episode of the SO files, we interview Dr. Andrea Wang-Gillam MD/PhD, associate professor in the division of oncology at Wash U School of medicine and clinical director of the GI oncology, about systemic options for treating pancreatic adenocarcinoma. As much as we all love a good Whipple, this really is a systemic disease, and unlike other cancers 100% of patients regardless of stage will need some form of systemic treatment. Good thing we have great options to choose from! …Right? <h2>Resources</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/pancreatic_blocks.pdf" rel="nofollow" target="_blank">NCCN guidelines</a> <h3>RCTs in the metastatic setting </h3> <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1304369" rel="nofollow" target="_blank">Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine</a> NEJM 2013 Daniel D. Von Hoff, M.D., Thomas Ervin, M.D., Francis P. Arena, M.D., E. Gabriela Chiorean, M.D., Jeffrey Infante, M.D., Malcolm Moore, M.D., Thomas Seay, M.D., Sergei A. Tjulandin, M.D., Wen Wee Ma, M.D., Mansoor N. Saleh, M.D., Marion Harris, M.D., Michele Reni, M.D., Scot Dowden, M.D., Daniel Laheru, M.D., Nathan Bahary, M.D., Ramesh K. Ramanathan, M.D., Josep Tabernero, M.D., Manuel Hidalgo, M.D., Ph.D., David Goldstein, M.D., Eric Van Cutsem, M.D., Xinyu Wei, Ph.D., Jose Iglesias, M.D., and Markus F. Renschler, M.D. Take away: nab-Paclitaxel (Abraxane) added to gemcitabine improved survival when compared to gemcitabine alone (median OS 8.5 pos vs 6.7 mos, ORR 23% vs 7%).  <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1011923" rel="nofollow" target="_blank">FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer</a> NEJM 2011 Thierry Conroy, M.D., Françoise Desseigne, M.D., Marc Ychou, M.D., Ph.D., Olivier Bouché, M.D., Ph.D., Rosine Guimbaud, M.D., Ph.D., Yves Bécouarn, M.D., Antoine Adenis, M.D., Ph.D., Jean-Luc Raoul, M.D., Ph.D., Sophie Gourgou-Bourgade, <a href="http://M.Sc" rel="nofollow" target="_blank">M.Sc</a>., Christelle de la Fouchardière, M.D., Jaafar Bennouna, M.D., Ph.D., Jean-Baptiste Bachet, M.D., Faiza Khemissa-Akouz, M.D., Denis Péré-Vergé, M.D., Catherine Delbaldo, M.D., Eric Assenat, M.D., Ph.D., Bruno Chauffert, M.D., Ph.D., Pierre Michel, M.D., Ph.D., Christine Montoto-Grillot, M.Chem., and Michel Ducreux, M.D., Ph.D. for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) is a much more effective regimen than gemcitabine alone (median OS 11.1 mos vs 6.8 mos; ORR 32% vs 9%), but is a more toxic regimen with higher rate of adverse events.  <h4></h4> <h3>RCTS in the Adjuvant Setting </h3> <a href="https://jamanetwork.com/journals/jama/fullarticle/1750131" rel="nofollow" target="_blank">Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.</a> JAMA 2013. Helmut Oettle, MD, PhD; Peter Neuhaus, MD, PhD; Andreas Hochhaus, MD, PhD; Jörg Thomas Hartmann, MD, PhD; Klaus Gellert, MD, PhD; Karsten Ridwelski, MD, PhD; Marco Niedergethmann, MD, PhD; Carl Zülke, MD, PhD; Jörg Fahlke, MD, PhD; Michael B. Arning, MD, PhD; Marianne Sinn, MD; Axel Hinke, PhD; Hanno Riess, MD, PhD Take away: 6 months of gemcitabine treatment after complete resection was better for OS than no treatment (13.4 mos vs 6.7 mos).  <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32409-6/fulltext" rel="nofollow" target="_blank">Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.</a> Lancet 2017 Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Take away: Combination gemcitabine and capecitabine (Xeloda) did better than gemcitabine alone in patients with completely resected disease (OS 28 mos v 25.5 pos).  <h4></h4> <h3>New and exciting things coming down the pipeline…</h3> <h4>1. Targeting desmoplastic reaction</h4> <a href="http://ascopubs.org/doi/abs/10.1200/JCO.2017.74.9564?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%3dpubmed#affiliationsContainer" rel="nofollow" target="_blank">HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma.</a> JCO 2018 Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE. Take away: The addition of PEGPH20 (pegvorhyaluronidase alfa) to gem/abraxane improved PFS and OS compared to gem/abraxane alone in patients with untreated metastatic disease, especially in patients with hyaluron high tumors. Phase III study ongoing!! 2. Targeting cancer stem cells  <a href="https://clinicaltrials.gov/ct2/show/NCT02231723" rel="nofollow" target="_blank">A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer</a> Ongoing phase Ib dose escalation study of BBI608 (Napabucasin), STAT3/cancer stem cell inhibitor, in combination with other standard chemotherapy regimens (gem/abraxane, FOLFIRINOX, FOLFIRI). Accrual slated to complete June 2018.  3. Targeting innate immunity  <a href="https://www.ncbi.nlm.nih.gov/pubmed/27055731" rel="nofollow" target="_blank">Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial.</a> Lancet Onc. 2016 Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, Fowler KJ, Lockhart AC, Suresh R, Tan BR, Lim KH, Fields RC, Strasberg SM, Hawkins WG, DeNardo DG, Goedegebuure SP, Linehan DC. Blockade of CCR2, as a means to suppress tumor infiltration of immunosuppressive tumor associated macrophages, in combination with FOLFIRINOX chemotherapy for borderline resectable or locally advanced PDAC resulted in a 49% objective tumor response rate. <a href="https://clinicaltrials.gov/show/NCT02345408" rel="nofollow" target="_blank">Phase 1b Study of CCX872-B in Patients With Pancreatic Adenocarcinoma</a> CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. In preliminary data presented at ASCO, CX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Estimated study completion date December 2018.

Systemic Options for Pancreatic Adenocarcinoma

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/Gastric-ABSITE-review-.mp3 Happy new years from SO Files! Ring in 2018 with an algorithm based review of gastric cancer management! We released this all out of order so excuse our Thanksgiving banter but the great news is that bad jokes never go out of style, so enjoy some useful review while adhering to your gym goals for at least the first week of January.  Resources NCCN Guidelines – Gastric Cancer  An updated, evidence based overview of gastric cancer management. Workup, and surgical/ medical treatment algorithms discussed. 7th Edition of the AJCC Cancer Staging Manual: Stomach Updated AJCC staging information for gastric cancer. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. 15 year follow-up data from the Dutch D1D2 trial for gastric cancer. D2 lymphadenectomy resulted in a 29% overall survival for the D2 group vs. 21% for the D1 group (p=0.34). Gastric cancer related death was higher in the D1 group than the D2 group (48% vs. 37%, respectively, p=0.01).  In this trial a D2 gastrectomy included a splenectomy as standard protocol.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/Gastric-ABSITE-review-.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/Gastric-ABSITE-review-.mp3</a> Happy new years from SO Files! Ring in 2018 with an algorithm based review of gastric cancer management! We released this all out of order so excuse our Thanksgiving banter but the great news is that bad jokes never go out of style, so enjoy some useful review while adhering to your gym goals for at least the first week of January. <h2>Resources</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf" rel="noopener nofollow" target="_blank">NCCN Guidelines – Gastric Cancer </a> An updated, evidence based overview of gastric cancer management. Workup, and surgical/ medical treatment algorithms discussed. <a href="https://link.springer.com/article/10.1245/s10434-010-1362-z" rel="noopener nofollow" target="_blank">7th Edition of the AJCC Cancer Staging Manual: Stomach</a> Updated AJCC staging information for gastric cancer. <a href="https://www.ncbi.nlm.nih.gov/pubmed/20409751" rel="nofollow" target="_blank">Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial.</a> Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. 15 year follow-up data from the Dutch D1D2 trial for gastric cancer. D2 lymphadenectomy resulted in a 29% overall survival for the D2 group vs. 21% for the D1 group (p=0.34). Gastric cancer related death was higher in the D1 group than the D2 group (48% vs. 37%, respectively, p=0.01).  In this trial a D2 gastrectomy included a splenectomy as standard protocol.

Gastric Cancer Review- Resident geared, ABSITE friendly

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/MIS_POD_DRHAMMILL__FINAL_EDITS.mp3 On this episode of the SO Files, Brad and Linda discuss minimally invasive hepatobiliary surgical oncology, focusing specifically on MIS pancreatic and liver surgery. The SO Files welcome special guest, Dr. Chet Hammill, Associate Professor of Surgery in the Hepatobiliary and GI Surgical Section at Wash U, Barnes Jewish Hospital. Papers Discussed Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-Matched Study From a National Cohort of Patients.Nassour I, Wang SC, Christie A, Augustine MM, Porembka MR, Yopp AC, Choti MA, Mansour JC, Xie XJ, Polanco PM, Minter RM.A propensity matched analysis of MIS vs. open pancreaticoduodenectomy, using the pancreas-targeted ACS NSQIP database. Minimally invasive whipples had a similar morbidity/mortality to open whipples. A decreased length of stay in the MIS group was partially offset by an increased readmission rate, and SSI was only decreased when removing those MIS whipples without conversion to open or open assist. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial. Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, Kazaryan AM, Kristiansen R, Fagerland MW, Hausken J, Tønnessen TI, Abildgaard A, Barkhatov L, Yaqub S, Røsok BI, Bjørnbeth BA, Andersen MH, Flatmark K, Aas E, Edwin B; Oslo-CoMet study group. A randomized controlled trial of lap vs open surgery for colorectal liver mets that could be resected with a parenchyma sparing resection. Lap liver resection had equivalent R0 rate to open, was cost effective, and had fewer postoperative complications.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/MIS_POD_DRHAMMILL__FINAL_EDITS.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/12/MIS_POD_DRHAMMILL__FINAL_EDITS.mp3</a> On this episode of the SO Files, Brad and Linda discuss minimally invasive hepatobiliary surgical oncology, focusing specifically on MIS pancreatic and liver surgery. The SO Files welcome special guest, Dr. Chet Hammill, Associate Professor of Surgery in the Hepatobiliary and GI Surgical Section at Wash U, Barnes Jewish Hospital. <h2>Papers Discussed</h2> <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Minimally+Invasive+Versus+Open+Pancreaticoduodenectomy%3A+A+Propensity-Matched+Study+From+a+National+Cohort+of+Patients" rel="nofollow" target="_blank">Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-Matched Study From a National Cohort of Patients.</a> Nassour I, Wang SC, Christie A, Augustine MM, Porembka MR, Yopp AC, Choti MA, Mansour JC, Xie XJ, Polanco PM, Minter RM. A propensity matched analysis of MIS vs. open pancreaticoduodenectomy, using the pancreas-targeted ACS NSQIP database. Minimally invasive whipples had a similar morbidity/mortality to open whipples. A decreased length of stay in the MIS group was partially offset by an increased readmission rate, and SSI was only decreased when removing those MIS whipples without conversion to open or open assist. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28657937" rel="nofollow" target="_blank">Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial.</a> Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, Kazaryan AM, Kristiansen R, Fagerland MW, Hausken J, Tønnessen TI, Abildgaard A, Barkhatov L, Yaqub S, Røsok BI, Bjørnbeth BA, Andersen MH, Flatmark K, Aas E, Edwin B; Oslo-CoMet study group. A randomized controlled trial of lap vs open surgery for colorectal liver mets that could be resected with a parenchyma sparing resection. Lap liver resection had equivalent R0 rate to open, was cost effective, and had fewer postoperative complications.

Minimally Invasive HPB and Oncologic Surgery

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/LN-Mets-Hawkins-11-22.mp3 On this episode of the SO Files, Brad and Linda discuss the current state and future of surgical lymph node management. The SO Files welcome special guest, Dr. William Hawkins, Neidorff Family and Robert C. Packman Professor of Surgery and Chief, Section of Hepatobiliary-Pancreatic and Gastrointestinal Surgery at the Washington University School of Medicine/ Siteman Cancer Center. We hope you enjoy this interesting discussion! Background Reading Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome. Yeo CJ, Cameron JL, Sohn TA, Coleman J, Sauter PK, Hruban RH, Pitt HA, Lillemoe KD. Randomized single center trial out of Johns Hopkins, with 114 patients accrued from 1996-97. Bottom line: radical pancreaticoduodenectomy (+distal gastrectomy/ RP lymphandenectomy) can be done with similar morbidity/mortality to traditional Whipple.  Extended pancreatic resections and lymphadenectomy: An appraisal of the current evidence. Shailesh V Shrikhande and Savio G Barreto. Review article outlining recent data on extended pancreatic resections for pancreatic cancer. The overall conclusion from multiple trials shows that extended resection can be done safely and is technically feasible, but there is a lack of data supporting improved overall survival in patients undergoing more radical resection. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. 15 year follow-up data from the Dutch D1D2 trial for gastric cancer. D2 lymphadenectomy resulted in a 29% overall survival for the D2 group vs. 21% for the D1 group (p=0.34). Gastric cancer related death was higher in the D1 group than the D2 group (48% vs. 37%, respectively, p=0.01).    Papers we Discuss/ Mention Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. A practice changing article that established that for patients with clinical T1-2 N0 breast cancer with &lt;3 SLN metastases found on SLN biopsy, there is no benefit of completion axillary lymph node dissection over no further surgical treatment of the axilla. This is high yield for the ABSITE, and a good thing to know for any medical student scrubbing in on a breast cancer operation during their surgical rotation. Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma. Donald L. Morton, M.D., John F. Thompson, M.D., Alistair J. Cochran, M.D., Nicola Mozzillo, M.D., Omgo E. Nieweg, M.D., Ph.D., Daniel F. Roses, M.D., Harold J. Hoekstra, M.D., Ph.D., Constantine P. Karakousis, M.D., Ph.D., Christopher A. Puleo, P.A.-C., Brendon J. Coventry, B.M., B.S., Ph.D., Mohammed Kashani-Sabet, M.D., B. Mark Smithers, M.B., B.S., Eberhard Paul, M.D., William G. Kraybill, M.D., J. Gregory McKinnon, M.D., He-Jing Wang, M.D., Robert Elashoff, Ph.D., and Mark B. Faries, M.D., for the MSLT Group Phase III MSLT1 trial which definitively established the utility of SLN biopsy for intermediate thickness melanomas. Improved recurrence free and melanoma specific survival for patients with SLN metastases identified. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, Jahkola T, Bowles TL, Testori A, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, Wouters MWJM, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Rossi CR, Neves RI, Trocha SD, Wright F, Byrd DR, Matter M, Hsueh E, MacKenzie-Ross A, Johnson DB, Terheyden P, Berger AC, Huston TL, Wayne JD, Smithers BM, Neuman HB, Schneebaum S, Gershenwald JE, Ariyan CE, Desai DC, Jacobs L, McMasters KM, Gesierich A, Hersey P, Bines SD, Kane JM, Barth RJ, McKinnon G, Farma JM, Schultz E, Vidal-Sicart S, Hoefer RA, Lewis JM, Scheri R, Kelley MC, Nieweg OE, Noyes RD, Hoon DSB, Wang HJ1, Elashoff DA, Elashoff RM. MSLTII Trial: Among patients with intermediate thickness melanoma (1.2-3.5mm) and a positive SLN biopsy there is equivalent melanoma specific survival at 3 years in the immediate completion lymphadenectomy group and the observation group (DSS 86% in both groups at 3 yrs).  Origins of lymphatic and distant metastases in human colorectal cancer. Naxerova K, Reiter JG, Brachtel E, Lennerz JK, van de Wetering M, Rowan A, Cai T, Clevers H, Swanton C, Nowak MA, Elledge SJ, Jain RK. For a highly selected group of colorectal cancer patients, the primary tumor, lymph node met(s), and distant met(s) were characterized via hypermutable DNA regions to create phylogenetic trees. In ~2/3rds of cases distant mets came from a different sub-clone than the sub-clone found in the lymph node met–suggesting they arose separately from the primary colorectal tumor.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/LN-Mets-Hawkins-11-22.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/LN-Mets-Hawkins-11-22.mp3</a> On this episode of the SO Files, Brad and Linda discuss the current state and future of surgical lymph node management. The SO Files welcome special guest, Dr. William Hawkins, Neidorff Family and Robert C. Packman Professor of Surgery and Chief, Section of Hepatobiliary-Pancreatic and Gastrointestinal Surgery at the Washington University School of Medicine/ Siteman Cancer Center. We hope you enjoy this interesting discussion! <h2>Background Reading</h2> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420805/pdf/19990500s00003p613.pdf" rel="nofollow" target="_blank">Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome.</a> Yeo CJ, Cameron JL, Sohn TA, Coleman J, Sauter PK, Hruban RH, Pitt HA, Lillemoe KD. Randomized single center trial out of Johns Hopkins, with 114 patients accrued from 1996-97. Bottom line: radical pancreaticoduodenectomy (+distal gastrectomy/ RP lymphandenectomy) can be done with similar morbidity/mortality to traditional Whipple.  <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999214/" rel="nofollow" target="_blank">Extended pancreatic resections and lymphadenectomy: An appraisal of the current evidence.</a> Shailesh V Shrikhande and Savio G Barreto. Review article outlining recent data on extended pancreatic resections for pancreatic cancer. The overall conclusion from multiple trials shows that extended resection can be done safely and is technically feasible, but there is a lack of data supporting improved overall survival in patients undergoing more radical resection. <a href="https://www.ncbi.nlm.nih.gov/pubmed/20409751" rel="nofollow" target="_blank">Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial.</a> Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. 15 year follow-up data from the Dutch D1D2 trial for gastric cancer. D2 lymphadenectomy resulted in a 29% overall survival for the D2 group vs. 21% for the D1 group (p=0.34). Gastric cancer related death was higher in the D1 group than the D2 group (48% vs. 37%, respectively, p=0.01).   <h2> Papers we Discuss/ Mention</h2> <a href="https://jamanetwork.com/journals/jama/fullarticle/645514" rel="nofollow" target="_blank">Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.</a> Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. A practice changing article that established that for patients with clinical T1-2 N0 breast cancer with &lt;3 SLN metastases found on SLN biopsy, there is no benefit of completion axillary lymph node dissection over no further surgical treatment of the axilla. This is high yield for the ABSITE, and a good thing to know for any medical student scrubbing in on a breast cancer operation during their surgical rotation. <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1310460#t=article" rel="nofollow" target="_blank">Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma.</a> Donald L. Morton, M.D., John F. Thompson, M.D., Alistair J. Cochran, M.D., Nicola Mozzillo, M.D., Omgo E. Nieweg, M.D., Ph.D., Daniel F. Roses, M.D., Harold J. Hoekstra, M.D., Ph.D., Constantine P. Karakousis, M.D., Ph.D., Christopher A. Puleo, P.A.-C., Brendon J. Coventry, B.M., B.S., Ph.D., Mohammed Kashani-Sabet, M.D., B. Mark Smithers, M.B., B.S., Eberhard Paul, M.D., William G. Kraybill, M.D., J. Gregory McKinnon, M.D., He-Jing Wang, M.D., Robert Elashoff, Ph.D., and Mark B. Faries, M.D., for the MSLT Group Phase III MSLT1 trial which definitively established the utility of SLN biopsy for intermediate thickness melanomas. Improved recurrence free and melanoma specific survival for patients with SLN metastases identified. <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1613210" rel="nofollow" target="_blank">Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.</a> Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, Jahkola T, Bowles TL, Testori A, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, Wouters MWJM, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Rossi CR, Neves RI, Trocha SD, Wright F, Byrd DR, Matter M, Hsueh E, MacKenzie-Ross A, Johnson DB, Terheyden P, Berger AC, Huston TL, Wayne JD, Smithers BM, Neuman HB, Schneebaum S, Gershenwald JE, Ariyan CE, Desai DC, Jacobs L, McMasters KM, Gesierich A, Hersey P, Bines SD, Kane JM, Barth RJ, McKinnon G, Farma JM, Schultz E, Vidal-Sicart S, Hoefer RA, Lewis JM, Scheri R, Kelley MC, Nieweg OE, Noyes RD, Hoon DSB, Wang HJ1, Elashoff DA, Elashoff RM. MSLTII Trial: Among patients with intermediate thickness melanoma (1.2-3.5mm) and a positive SLN biopsy there is equivalent melanoma specific survival at 3 years in the immediate completion lymphadenectomy group and the observation group (DSS 86% in both groups at 3 yrs).  <a href="https://www.ncbi.nlm.nih.gov/pubmed/28684519" rel="nofollow" target="_blank">Origins of lymphatic and distant metastases in human colorectal cancer.</a> Naxerova K, Reiter JG, Brachtel E, Lennerz JK, van de Wetering M, Rowan A, Cai T, Clevers H, Swanton C, Nowak MA, Elledge SJ, Jain RK. For a highly selected group of colorectal cancer patients, the primary tumor, lymph node met(s), and distant met(s) were characterized via hypermutable DNA regions to create phylogenetic trees. In ~2/3rds of cases distant mets came from a different sub-clone than the sub-clone found in the lymph node met–suggesting they arose separately from the primary colorectal tumor.

The Future of Surgical Lymph Node Management

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/ABSITE-Review-Cyr-Interview-LXJ-Edit-11-19.mp3 On this episode of the SO files, Brad and Linda welcome Assistant Professor of Surgery at Washington University in St. Louis/ Siteman Cancer Center, and co-author of the NCCN Clinical Practice Guidelines for Breast Cancer, Dr. Amy Cyr . We will take you through both benign, pre-malignant, and malignant breast oncology, with a focus on ABSITE relevant information. Background Reading NCCN Clinical Practice Guidelines in Breast Cancer, Revised Nov. 2017 A high-yield, recently updated review of the standard of care guidelines for non-invasive and invasive breast cancer. Includes updated AJCC 7th edition TNM staging tables. Sabistons Textbook of Surgery, Chapter 34: Disease of the Breast Kelly K Hunt and Elizabeth A Mittendorf. Great review of breast pathology, with an overview of all facets of breast cancer–with tables and text highlighting key practice changing articles. Papers/Resources we Mention in the Episode NCCN Clinical Practice Guidelines in Breast Cancer, Revised Nov. 2017 A high-yield, recently updated review of the standard of care guidelines for non-invasive and invasive breast cancer. Includes updated AJCC 7th edition TNM staging tables. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society Kevin C. Oeffinger, Elizabeth T. H. Fontham, Ruth Etzioni, Abbe Herzig, James S. Michaelson, Ya-Chen Tina Shih, Louise C. Walter, Timothy R. Church, Christopher R. Flowers, Samuel J. LaMonte, Andrew M. D. Wolf, Carol DeSantis, Joannie Lortet-Tieulent, Kimberly Andrews, Deana Manassaram-Baptiste, Debbie Saslow, Robert A. Smith, Otis W. Brawley, Richard Wender. ACS updated recommendations for breast cancer screening for average risk women. Recommendations: Annual screening from 45-54, 55+ biennial screening or have the opportunity to continue annual screening. Screening should continue as long as the women has good overall health, and a life expectancy of 10+ years. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. A practice changing article that established that for patients with clinical T1-2 N0 breast cancer with &lt;3 SLN metastases found on SLN biopsy, there is no benefit of completion axillary lymph node dissection over no further surgical treatment of the axilla. This is high yield for the ABSITE, and a good thing to know for any medical student scrubbing in on a breast cancer operation during their surgical rotation. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. AMAROS Phase III Trial: For patients with clinical T1-2 N0 breast cancer and 1 or more positive SLNs identified during surgery, axillary radiotherapy results in statistically equivalent axillary recurrence at 5 years vs. completion axillary lymph node dissection (1.19% and 0.43%, respectively, at 5 years). No significant differences in disease free or overall survival. Of note, at 5 years significantly more patients in the completion axillary lymph node dissection group had ipsilateral arm lymphedema than the axillary radiotherapy group (23% vs. 11%, respectively, p&lt;0.0001). Gail Model to Predict Breast Cancer Risk. A commonly used model to predict future breast cancer risk for patients with no history of invasive breast cancer, DCIS or LCIS. Patients with a 5 year risk of &gt;1.7% are candidates for chemoprevention.

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/ABSITE-Review-Cyr-Interview-LXJ-Edit-11-19.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/ABSITE-Review-Cyr-Interview-LXJ-Edit-11-19.mp3</a> On this episode of the SO files, Brad and Linda welcome Assistant Professor of Surgery at Washington University in St. Louis/ Siteman Cancer Center, and co-author of the NCCN Clinical Practice Guidelines for Breast Cancer, Dr. Amy Cyr . We will take you through both benign, pre-malignant, and malignant breast oncology, with a focus on ABSITE relevant information. <h2>Background Reading</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf" rel="nofollow" target="_blank">NCCN Clinical Practice Guidelines in Breast Cancer, Revised Nov. 2017</a> A high-yield, recently updated review of the standard of care guidelines for non-invasive and invasive breast cancer. Includes updated AJCC 7th edition TNM staging tables. <a href="https://www.elsevier.com/books/sabiston-textbook-of-surgery/townsend/978-0-323-29987-9" rel="nofollow" target="_blank">Sabistons Textbook of Surgery, Chapter 34: Disease of the Breast</a> Kelly K Hunt and Elizabeth A Mittendorf. Great review of breast pathology, with an overview of all facets of breast cancer–with tables and text highlighting key practice changing articles. <h2>Papers/Resources we Mention in the Episode</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf" rel="nofollow" target="_blank">NCCN Clinical Practice Guidelines in Breast Cancer, Revised Nov. 2017</a> A high-yield, recently updated review of the standard of care guidelines for non-invasive and invasive breast cancer. Includes updated AJCC 7th edition TNM staging tables. <a href="https://jamanetwork.com/journals/jama/fullarticle/2463262" rel="nofollow" target="_blank">Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society</a> Kevin C. Oeffinger, Elizabeth T. H. Fontham, Ruth Etzioni, Abbe Herzig, James S. Michaelson, Ya-Chen Tina Shih, Louise C. Walter, Timothy R. Church, Christopher R. Flowers, Samuel J. LaMonte, Andrew M. D. Wolf, Carol DeSantis, Joannie Lortet-Tieulent, Kimberly Andrews, Deana Manassaram-Baptiste, Debbie Saslow, Robert A. Smith, Otis W. Brawley, Richard Wender. ACS updated recommendations for breast cancer screening for average risk women. Recommendations: Annual screening from 45-54, 55+ biennial screening or have the opportunity to continue annual screening. Screening should continue as long as the women has good overall health, and a life expectancy of 10+ years. <a href="https://jamanetwork.com/journals/jama/fullarticle/645514" rel="nofollow" target="_blank">Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.</a> Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. A practice changing article that established that for patients with clinical T1-2 N0 breast cancer with &lt;3 SLN metastases found on SLN biopsy, there is no benefit of completion axillary lymph node dissection over no further surgical treatment of the axilla. This is high yield for the ABSITE, and a good thing to know for any medical student scrubbing in on a breast cancer operation during their surgical rotation. <a href="http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(14)70460-7.pdf" rel="nofollow" target="_blank">Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.</a> Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. AMAROS Phase III Trial: For patients with clinical T1-2 N0 breast cancer and 1 or more positive SLNs identified during surgery, axillary radiotherapy results in statistically equivalent axillary recurrence at 5 years vs. completion axillary lymph node dissection (1.19% and 0.43%, respectively, at 5 years). No significant differences in disease free or overall survival. Of note, at 5 years significantly more patients in the completion axillary lymph node dissection group had ipsilateral arm lymphedema than the axillary radiotherapy group (23% vs. 11%, respectively, p&lt;0.0001). <a href="https://www.mdcalc.com/gail-model-breast-cancer-risk" rel="nofollow" target="_blank">Gail Model to Predict Breast Cancer Risk.</a> A commonly used model to predict future breast cancer risk for patients with no history of invasive breast cancer, DCIS or LCIS. Patients with a 5 year risk of &gt;1.7% are candidates for chemoprevention.

ABSITE Breast Oncology Review

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/XRT-Intro-Oct24-2017.mp3 On this episode of the SO files, Brad and Linda dive into the basics of radiation oncology, with the goal to give a basis of understanding for different radiation therapy regimens. The episode begins with an overview of what is radiation oncology and what are the major types of radiation oncology we should know about. For this episode, the SO files are excited to welcome on repeat guest Dr. Parag Parikh, Associate Professor of Radiation Oncology, and chief of GI radiation oncology at Washington University in St. Louis School of Medicine. Segments Interview with Dr. Parikh: 13:00 Background Reading Textbook of Complex General Surgical Oncology: Chapter 11, Radiation Oncology: Concepts and Techniques Geraldine Jacobson, Alexander Chi, Dongxu Wang, Phillip Devlin, Ivan Buzorovic, Antonio Damato, Desmond O’Farrell, Alexandra J. Stewart A recently published textbook covering all aspects of surgical oncology, with this specific chapter focusing on radiation oncology basics. The chapter runs through the various forms of radiation therapy, explaining both the utility and limitations of each technique. Recent Developments in Radiotherapy Deborah E. Citrin A recently published (September 2017) and well written review article in the NEJM , highlighting several forms of radiation oncology and the mechanisms behind them. Stereotactic body radiation therapy for inoperable early stage lung cancer Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Phase 2 RTOG 0236 trial of stereotactic body radiotherapy for cT1-2N0M0 medically inoperable NSCLC patients. Only 59 patients enrolled, with 55 evaluable, and median follow up 34.4 months. Estimated 3 year local control was 97.6%.  Lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer Rosen JE, Salazar MC, Wang Z, Yu JB, Decker RH, Kim AW, Detterbeck FC, Boffa DJ. Rosen and colleagues looked at the national cancer database for healthy patients that were surgical candidates with cT1-2N0 lung cancer. They found that patients undergoing lobectomy did better than those receiving stereotactic radiotherapy. They went on to propensity score match lobectomy and stereotactic body radiation therapy patients, with lobectomy conferring a 59% 5 year survival vs 29% for stereotactic radiotherapy. Sorafenib Tosylate With or Without Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer Ongoing phase III RCT comparing sorafenib + stereotactic body radiotherapy versus sorafenib alone for patients with hepatocellular carcinoma who are not suitable for surgery, transplant or radiofrequency ablation. This episode was produced by Brad Krasnick and Linda Jin. You can email us at surgoncfiles@gmail.com. Thanks for listening!

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/XRT-Intro-Oct24-2017.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/11/XRT-Intro-Oct24-2017.mp3</a> On this episode of the SO files, Brad and Linda dive into the basics of radiation oncology, with the goal to give a basis of understanding for different radiation therapy regimens. The episode begins with an overview of what is radiation oncology and what are the major types of radiation oncology we should know about. For this episode, the SO files are excited to welcome on repeat guest Dr. Parag Parikh, Associate Professor of Radiation Oncology, and chief of GI radiation oncology at Washington University in St. Louis School of Medicine. <h2>Segments</h2> Interview with Dr. Parikh: 13:00 <h2>Background Reading</h2> <a href="https://accesssurgery.mhmedical.com/content.aspx?bookid=2209§ionid=168937258" rel="nofollow" target="_blank">Textbook of Complex General Surgical Oncology: Chapter 11, Radiation Oncology: Concepts and Techniques</a> Geraldine Jacobson, Alexander Chi, Dongxu Wang, Phillip Devlin, Ivan Buzorovic, Antonio Damato, Desmond O’Farrell, Alexandra J. Stewart A recently published textbook covering all aspects of surgical oncology, with this specific chapter focusing on radiation oncology basics. The chapter runs through the various forms of radiation therapy, explaining both the utility and limitations of each technique. <a href="http://www.nejm.org/doi/full/10.1056/NEJMra1608986" rel="nofollow" target="_blank">Recent Developments in Radiotherapy</a> Deborah E. Citrin A recently published (September 2017) and well written review article in the NEJM , highlighting several forms of radiation oncology and the mechanisms behind them. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Stereotactic+Body+Radiation+Therapy+for+Inoperable+Early+Stage+Lung+Cancer+JAMA" rel="nofollow" target="_blank">Stereotactic body radiation therapy for inoperable early stage lung cancer</a> Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Phase 2 RTOG 0236 trial of stereotactic body radiotherapy for cT1-2N0M0 medically inoperable NSCLC patients. Only 59 patients enrolled, with 55 evaluable, and median follow up 34.4 months. Estimated 3 year local control was 97.6%.  <a href="https://www.ncbi.nlm.nih.gov/pubmed/27131846" rel="nofollow" target="_blank">Lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer</a> Rosen JE, Salazar MC, Wang Z, Yu JB, Decker RH, Kim AW, Detterbeck FC, Boffa DJ. Rosen and colleagues looked at the national cancer database for healthy patients that were surgical candidates with cT1-2N0 lung cancer. They found that patients undergoing lobectomy did better than those receiving stereotactic radiotherapy. They went on to propensity score match lobectomy and stereotactic body radiation therapy patients, with lobectomy conferring a 59% 5 year survival vs 29% for stereotactic radiotherapy. <a href="https://clinicaltrials.gov/ct2/show/NCT01730937" rel="nofollow" target="_blank">Sorafenib Tosylate With or Without Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer</a> Ongoing phase III RCT comparing sorafenib + stereotactic body radiotherapy versus sorafenib alone for patients with hepatocellular carcinoma who are not suitable for surgery, transplant or radiofrequency ablation. This episode was produced by Brad Krasnick and Linda Jin. You can email us at surgoncfiles@gmail.com. Thanks for listening!<code></code>

Radiation Oncology for Dummies

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/09/Lynch-Compiled-9-29-Mixed-1-1.mp3  On this episode of the SO files, Brad and Linda cover the genetic basis of Lynch syndrome, who should get screened, when patients should get surveillance, and go over two recent papers covering surgical options for colon cancer in Lynch as well as long term outcomes after resection. Then, we discuss current management with Dr. Paul Wise, Professor of Surgery and Director of the Washington University Inherited Colorectal Cancer and Polyposis Registry. Background reading  Identification of Lynch syndrome among patients with colorectal cancer. Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Castells A; EPICOLON Consortium. Paper that established universal MMR testing of colorectal tumors, with subsequent germline analysis of positive results has greatest sensitivity for identification of Lynch Syndrome (100% sensitivity, 93% specificity) Hereditary Colorectal Cancer Syndromes. Katerina Wells and Paul Wise. Updated overview of the many hereditary syndromes in colorectal cancer. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal Updated clinical practice guidelines for patients with polyposis and non-polyposis syndromes, including Lynch Syndrome. Clinical Practice Guidelines for the Surgical Treatment of Patients With Lynch Syndrome Daniel O. Herzig, M.D., W. Donald Buie, M.D., Martin R. Weiser, M.D. Y. Nancy You, M.D., Janice F. Rafferty, M.D., Daniel Feingold, M.D.  and Scott R. Steele, M.D.  Short update on best practices for surgical treatment of Lynch Syndrome, from the American Society of Colon and Rectal Surgeons. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, Baron JA, Giles GG, Leggett BA, Winship I, Lipton L, Young GP, Young JP, Lodge CJ, Southey MC, Newcomb PA, Le Marchand L, Haile RW, Lindor NM, Gallinger S, Hopper JL, Jenkins MA. Showed that more extensive colonic resection for colorectal cancer in setting of Lynch Syndrome decreased likelihood of subsequent colorectal cancer. Risk of metachronous colorectal cancer reduced by 31% for every 10 cm of bowel removed at initial cancer operation. Papers we discussed Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome Laura Renkonen-Sinisalo, M.D., Ph.D., Toni T. Seppälä, M.D., Ph.D., Heikki J. Järvinen, M.D., Ph.D., Jukka-Pekka Mecklin, M.D., Ph.D. Based on Finnish registry data, the authors show that patients who underwent subtotal colectomy instead of segmental resection had a decreased risk of subsequent colon cancer and repeat operation. However these differences did not translate to a difference in overall or disease specific survival.  Incidence of and survival after subsequent cancer in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database  Pål Møller, Toni Seppälä, Inge Bernstein, Elke Holinski-Feder, Paola Sala, D Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf Sijmons, Jacqueline Jeffries, Hans Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H de Vos tot Nederveen Cappel, James Hill, Juul Wijnen, Mark Jenkins, Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Ian M Frayling, John-Paul Plazzer, Kirsi Pylvanainen, Maurizio Genuardi,32 Jukka-Pekka Mecklin, Gabriela Möslein,34 Julian R Sampson,16 Gabriel Capella,14 in collaboration with The Mallorca Group (http://mallorca-group.org) Registry data on LS patients with primary operations between 1984 and 2010, retrospective cohort study. Data on subsequent cancer risk, types of cancers by mutation type. Lynch Syndrome Risk Calculator: lscarisk.org  This episode was produced by Linda Jin and Brad Krasnick. You can email us at surgoncfiles@gmail.com

<a href="https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/09/Lynch-Compiled-9-29-Mixed-1-1.mp3" rel="nofollow" target="_blank">https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/09/Lynch-Compiled-9-29-Mixed-1-1.mp3</a> On this episode of the SO files, Brad and Linda cover the genetic basis of Lynch syndrome, who should get screened, when patients should get surveillance, and go over two recent papers covering surgical options for colon cancer in Lynch as well as long term outcomes after resection. Then, we discuss current management with Dr. Paul Wise, Professor of Surgery and Director of the Washington University Inherited Colorectal Cancer and Polyposis Registry. <h2>Background reading </h2> <a href="http://jamanetwork.com/journals/jama/fullarticle/1383232" rel="noopener nofollow" target="_blank">Identification of Lynch syndrome among patients with colorectal cancer.</a> Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Castells A; EPICOLON Consortium. Paper that established universal MMR testing of colorectal tumors, with subsequent germline analysis of positive results has greatest sensitivity for identification of Lynch Syndrome (100% sensitivity, 93% specificity) <a href="http://www.sciencedirect.com/science/article/pii/S0039610917300099?via%3Dihub" rel="noopener nofollow" target="_blank">Hereditary Colorectal Cancer Syndromes.</a> Katerina Wells and Paul Wise. Updated overview of the many hereditary syndromes in colorectal cancer. <a href="https://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf" rel="noopener nofollow" target="_blank">NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal</a> Updated clinical practice guidelines for patients with polyposis and non-polyposis syndromes, including Lynch Syndrome. <a href="https://www.fascrs.org/sites/default/files/downloads/publication/cpg_for_the_surgical_treatment_of_patients_with_lynch_syndrome_feb_2017_dcr_issue.pdf" rel="noopener nofollow" target="_blank">Clinical Practice Guidelines for the Surgical Treatment of Patients With Lynch Syndrome</a> Daniel O. Herzig, M.D., W. Donald Buie, M.D., Martin R. Weiser, M.D. Y. Nancy You, M.D., Janice F. Rafferty, M.D., Daniel Feingold, M.D.  and Scott R. Steele, M.D. Short update on best practices for surgical treatment of Lynch Syndrome, from the American Society of Colon and Rectal Surgeons. <a href="http://gut.bmj.com/content/60/7/950.long" rel="noopener nofollow" target="_blank">Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery.</a> Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, Baron JA, Giles GG, Leggett BA, Winship I, Lipton L, Young GP, Young JP, Lodge CJ, Southey MC, Newcomb PA, Le Marchand L, Haile RW, Lindor NM, Gallinger S, Hopper JL, Jenkins MA. Showed that more extensive colonic resection for colorectal cancer in setting of Lynch Syndrome decreased likelihood of subsequent colorectal cancer. Risk of metachronous colorectal cancer reduced by 31% for every 10 cm of bowel removed at initial cancer operation. <h2>Papers we discussed</h2> <a href="https://www.ncbi.nlm.nih.gov/pubmed/28682964" rel="noopener nofollow" target="_blank">Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome</a> Laura Renkonen-Sinisalo, M.D., Ph.D., Toni T. Seppälä, M.D., Ph.D., Heikki J. Järvinen, M.D., Ph.D., Jukka-Pekka Mecklin, M.D., Ph.D. Based on Finnish registry data, the authors show that patients who underwent subtotal colectomy instead of segmental resection had a decreased risk of subsequent colon cancer and repeat operation. However these differences did not translate to a difference in overall or disease specific survival. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=incidence+and+survival+after+subsequent+cancer+in+carriers+of+pathogenic+mar+variants" rel="nofollow" target="_blank">Incidence of and survival after subsequent cancer in carriers of pathogenic MMR variants with </a><a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=incidence+and+survival+after+subsequent+cancer+in+carriers+of+pathogenic+mar+variants" rel="noopener nofollow" target="_blank">previous cancer: a report from the prospective Lynch syndrome database </a> Pål Møller, Toni Seppälä, Inge Bernstein, Elke Holinski-Feder, Paola Sala, D Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf Sijmons, Jacqueline Jeffries, Hans Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H de Vos tot Nederveen Cappel, James Hill, Juul Wijnen, Mark Jenkins, Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Ian M Frayling, John-Paul Plazzer, Kirsi Pylvanainen, Maurizio Genuardi,32 Jukka-Pekka Mecklin, Gabriela Möslein,34 Julian R Sampson,16 Gabriel Capella,14 in collaboration with The Mallorca Group (<a href="http://mallorca-group.org" rel="noopener nofollow" target="_blank">http://mallorca-group.org</a>) Registry data on LS patients with primary operations between 1984 and 2010, retrospective cohort study. Data on subsequent cancer risk, types of cancers by mutation type. Lynch Syndrome Risk Calculator: <a href="http://lscarisk.org" rel="noopener nofollow" target="_blank">lscarisk.org </a> This episode was produced by Linda Jin and Brad Krasnick. You can email us at surgoncfiles@gmail.com

Lynch Syndrome- Modern management and outcomes

Adjuvant Options for Advanced Melanoma

http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-2-Compiled-10-28-2.mp3  Today we resume our discussion of neoadjuvant therapy for rectal cancer. In this episode we welcome on special guests, Dr. Matt Silviera, Assistant Professor of Surgery in the Section of Colon and Rectal Surgery and Dr. Parag Parikh, Associate Professor of Radiation Oncology, both at Washington University in St. Louis School of Medicine. Segments SC with delay option (Stockholm III Trial) 1:28 Trimodal therapy: SC with consolidation chemotherapy then surgery (Polish II Trial/RAPIDO Trial) 6:18 Interview with radiation oncologist Dr. Parag Parikh 15:08 Interview with colorectal surgeon Dr. Matt Silviera 29:02 Literature Discussed NCCN Guidelines for Rectal Cancer Updated guidelines highlighting the management strategy for rectal cancer. Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. Myerson RJ, Tan B, Hunt S, Olsen J, Birnbaum E, Fleshman J, Gao F, Hall L, Kodner I, Lockhart AC, Mutch M, Naughton M, Picus J, Rigden C, Safar B, Sorscher S, Suresh R, Wang-Gillam A, Parikh P. Prospective phase II trial, where patients with cT3-4 rectal cancer were given 5 cycles of radiotherapy, followed by FOLFOX x 4 cycles, and then surgery. At 30 months local control was 95%, and 39% of patients had final path of ypT0N0. Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution. Roy A, Mahasittiwat P, Weiner AA, Hunt SR, Mutch MG, Birnbaum EH, Kodner IJ, Read TE, Fleshman JW, Olsen JR, Myerson RJ, Parikh PJ. SC therapy with immediate surgery, the Washington University experience: SC preoperative radiation in a US experience is a safe and effective option for treatment of US rectal cancer patients. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer(Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallböök O, Syk I, Glimelius B, Martling A. Stockholm III Trial: Lancet Oncology 2017, RCT with three arms: SC with immediate surgery (within 1 week), SC with delay to surgery (4-8 weeks), or LC (25 doses of 2Gy/fraction) with delay to surgery. Conclusion: SC with delay gave similar oncologic results as both other arms, but with less treatment time than LC and less operative complications compared with SC no delay. Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Polish 2 Trial: Patients with cT3/T4 rectal cancer were randomized to me-adjuvant SC + FOLFOX4 vs LC  with concomitant chemotherapy. At 3 years DFS was 53% in the SC + consolidation chemo group vs. 52% in LC group (p=0.85), while OS was 73% vs. 65% respectively (p=0.046). No difference in terms of local recurrence or distant mets between groups. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. MERCURY Study Group. The specificity for prediction of a clear circumferential resection margin by MRI for patients with rectal cancer was shown to be 92%. Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Taylor FG, Quirke P, Heald RJ, Moran B, Blomqvist L, Swift I, Sebag-Montefiore DJ, Tekkis P, Brown G; MERCURY study group. Demonstrated that patients with stage I-III disease with predicted clear circumferential resection margins on preop MRI (deemed “good prognosis”) had a local recurrence rate at 5 years of 3% with surgery alone. Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study. Battersby NJ, How P, Moran B, Stelzner S, West NP, Branagan G, Strassburg J, Quirke P, Tekkis P, Pedersen BG, Gudgeon M, Heald B, Brown G; MERCURY II Study Group. Mercury II Study: Enrolled patients with rectal cancer at 6cm or lower, and showed that in patients with a predicted clear MRI low rectal surgical plane who went to surgery without preop therapy had a low 1.6% + circumferential resection margin rate. In addition, patients who underwent preop radiotherapy for MRI imaging demonstrating an involved low rectal surgical resection plane, were accurately restaged with an MRI→with a clear margin on imaging predicting a clear circumfrential resection margin on final path (no patients with  clear imaging after upfront treatment had a positive circumferential resection margin on surgical path). Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial. Nilsson PJ, van Etten B, Hospers GA, Påhlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B. Rapido Trial study protocol: Patient with rectal cancer are staged with preop MRI: patients are included if they have cT4 disease, N2 nodes, involved mesolectal fascia, extramural vascular invasion or nodes outside the circumferential resection margin. They are then randomized to standard LC radiation therapy + Capecitabine or SC radiation + 6 cycles of FOLFOX. The primary endpoint is DFS at 3 years, with the hypothesis being that DFS will be improved in the SC + FOLFOX neoadjuvant group. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. OPRA Phase II Trial Study Protocol: Patients with stage II/III rectal cancer are randomized to 2 different protocols of total neoadjuvant treatment, and are then restaged. Patients with residual disease undergo surgical resection and those with complete response are treated non-operatively and followed (Q3mo x 2 years, and Q6mo after this). The trial is designed to test the hypothesis that patients treated with total neoadjuvant therapy followed by surgery (non-complete responders) or non operative management (complete responders) will have improved 3 year disease free survival when compared to historical controls treated with preop chemoradiation, followed by surgery, and then adjuvant chemotherapy. PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery Prospect Trial: Ongoing US trial, where patients with T2N1, T3N0, or T3N1 rectal cancer 5-12cm from the anal verge are randomized to A) either standard of care chemoradiation, followed by surgery, and adjuvant FOLFOX or B) neoadjuvant FOLFOX, with restaging–&gt; and patients with a 20%+ response go right to surgery followed by adjuvant chemotherapy, and non responders to FOLFOX get radiation followed by surgery and then adjuvant chemo. Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. Qian Shi, Alberto F. Sobrero, Anthony Frank Shields, Takayuki Yoshino, James Paul, Julien Taieb, Ioannis Sougklakos, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Franck Bonnetain, Toshiaki Watanabe, Ioannis Boukovinas, Lindsay A. Renfro, Axel Grothey, Donna Niedzwiecki, Valter Torri, Thierry Andre, Daniel J. Sargent, Timothy Iveson. Recently completed IDEA Study: For patients with stage III colorectal cancer, 3 months of adjuvant XELOX was non-inferior to 6 months of standard adjuvant therapy, with 3 year DFS nearly the same in both groups (both ~75%).

<a href="http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-2-Compiled-10-28-2.mp3" rel="nofollow" target="_blank">http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-2-Compiled-10-28-2.mp3</a> Today we resume our discussion of neoadjuvant therapy for rectal cancer. In this episode we welcome on special guests, Dr. Matt Silviera, Assistant Professor of Surgery in the Section of Colon and Rectal Surgery and Dr. Parag Parikh, Associate Professor of Radiation Oncology, both at Washington University in St. Louis School of Medicine. <h2>Segments</h2> SC with delay option (Stockholm III Trial) 1:28 Trimodal therapy: SC with consolidation chemotherapy then surgery (Polish II Trial/RAPIDO Trial) 6:18 Interview with radiation oncologist Dr. Parag Parikh 15:08 Interview with colorectal surgeon Dr. Matt Silviera 29:02 <h2>Literature Discussed</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf" rel="nofollow" target="_blank">NCCN Guidelines for Rectal Cancer</a> Updated guidelines highlighting the management strategy for rectal cancer. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24606849" rel="nofollow" target="_blank">Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.</a> Myerson RJ, Tan B, Hunt S, Olsen J, Birnbaum E, Fleshman J, Gao F, Hall L, Kodner I, Lockhart AC, Mutch M, Naughton M, Picus J, Rigden C, Safar B, Sorscher S, Suresh R, Wang-Gillam A, Parikh P. Prospective phase II trial, where patients with cT3-4 rectal cancer were given 5 cycles of radiotherapy, followed by FOLFOX x 4 cycles, and then surgery. At 30 months local control was 95%, and 39% of patients had final path of ypT0N0. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Roy+A%2C+Mahasittiwat+P%2C+Weiner+AA%2C+Hunt+SR%2C+Mutch+MG%2C+Birnbaum+EH%2C+Kodner+IJ%2C+Read+TE%2C+Fleshman+JW%2C+Olsen+JR%2C+Myerson+RJ%2C+Parikh+PJ." rel="nofollow" target="_blank">Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution.</a> Roy A, Mahasittiwat P, Weiner AA, Hunt SR, Mutch MG, Birnbaum EH, Kodner IJ, Read TE, Fleshman JW, Olsen JR, Myerson RJ, Parikh PJ. SC therapy with immediate surgery, the Washington University experience: SC preoperative radiation in a US experience is a safe and effective option for treatment of US rectal cancer patients. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28190762" rel="nofollow" target="_blank">Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer(Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial.</a> Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallböök O, Syk I, Glimelius B, Martling A. Stockholm III Trial: Lancet Oncology 2017, RCT with three arms: SC with immediate surgery (within 1 week), SC with delay to surgery (4-8 weeks), or LC (25 doses of 2Gy/fraction) with delay to surgery. Conclusion: SC with delay gave similar oncologic results as both other arms, but with less treatment time than LC and less operative complications compared with SC no delay. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26884592" rel="nofollow" target="_blank">Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.</a> Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Polish 2 Trial: Patients with cT3/T4 rectal cancer were randomized to me-adjuvant SC + FOLFOX4 vs LC  with concomitant chemotherapy. At 3 years DFS was 53% in the SC + consolidation chemo group vs. 52% in LC group (p=0.85), while OS was 73% vs. 65% respectively (p=0.046). No difference in terms of local recurrence or distant mets between groups. <a href="https://www.ncbi.nlm.nih.gov/pubmed/16984925" rel="nofollow" target="_blank">Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study.</a> MERCURY Study Group. The specificity for prediction of a clear circumferential resection margin by MRI for patients with rectal cancer was shown to be 92%. <a href="https://www.ncbi.nlm.nih.gov/pubmed/21475011" rel="nofollow" target="_blank">Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study.</a> Taylor FG, Quirke P, Heald RJ, Moran B, Blomqvist L, Swift I, Sebag-Montefiore DJ, Tekkis P, Brown G; MERCURY study group. Demonstrated that patients with stage I-III disease with predicted clear circumferential resection margins on preop MRI (deemed “good prognosis”) had a local recurrence rate at 5 years of 3% with surgery alone. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=prospective+validation+of+a+low+rectal+cancer+magnetic" rel="nofollow" target="_blank">Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.</a> Battersby NJ, How P, Moran B, Stelzner S, West NP, Branagan G, Strassburg J, Quirke P, Tekkis P, Pedersen BG, Gudgeon M, Heald B, Brown G; MERCURY II Study Group. Mercury II Study: Enrolled patients with rectal cancer at 6cm or lower, and showed that in patients with a predicted clear MRI low rectal surgical plane who went to surgery without preop therapy had a low 1.6% + circumferential resection margin rate. In addition, patients who underwent preop radiotherapy for MRI imaging demonstrating an involved low rectal surgical resection plane, were accurately restaged with an MRI→with a clear margin on imaging predicting a clear circumfrential resection margin on final path (no patients with  clear imaging after upfront treatment had a positive circumferential resection margin on surgical path). <a href="https://www.ncbi.nlm.nih.gov/pubmed/23742033" rel="nofollow" target="_blank">Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial.</a> Nilsson PJ, van Etten B, Hospers GA, Påhlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B. Rapido Trial study protocol: Patient with rectal cancer are staged with preop MRI: patients are included if they have cT4 disease, N2 nodes, involved mesolectal fascia, extramural vascular invasion or nodes outside the circumferential resection margin. They are then randomized to standard LC radiation therapy + Capecitabine or SC radiation + 6 cycles of FOLFOX. The primary endpoint is DFS at 3 years, with the hypothesis being that DFS will be improved in the SC + FOLFOX neoadjuvant group. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26497495" rel="nofollow" target="_blank">Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.</a> Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. OPRA Phase II Trial Study Protocol: Patients with stage II/III rectal cancer are randomized to 2 different protocols of total neoadjuvant treatment, and are then restaged. Patients with residual disease undergo surgical resection and those with complete response are treated non-operatively and followed (Q3mo x 2 years, and Q6mo after this). The trial is designed to test the hypothesis that patients treated with total neoadjuvant therapy followed by surgery (non-complete responders) or non operative management (complete responders) will have improved 3 year disease free survival when compared to historical controls treated with preop chemoradiation, followed by surgery, and then adjuvant chemotherapy. <a href="http://PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery" rel="nofollow" target="_blank">PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery</a> Prospect Trial: Ongoing US trial, where patients with T2N1, T3N0, or T3N1 rectal cancer 5-12cm from the anal verge are randomized to A) either standard of care chemoradiation, followed by surgery, and adjuvant FOLFOX or B) neoadjuvant FOLFOX, with restaging–&gt; and patients with a 20%+ response go right to surgery followed by adjuvant chemotherapy, and non responders to FOLFOX get radiation followed by surgery and then adjuvant chemo. <a href="https://meetinglibrary.asco.org/record/147028/abstract" rel="nofollow" target="_blank">Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration.</a> Qian Shi, Alberto F. Sobrero, Anthony Frank Shields, Takayuki Yoshino, James Paul, Julien Taieb, Ioannis Sougklakos, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Franck Bonnetain, Toshiaki Watanabe, Ioannis Boukovinas, Lindsay A. Renfro, Axel Grothey, Donna Niedzwiecki, Valter Torri, Thierry Andre, Daniel J. Sargent, Timothy Iveson. Recently completed IDEA Study: For patients with stage III colorectal cancer, 3 months of adjuvant XELOX was non-inferior to 6 months of standard adjuvant therapy, with 3 year DFS nearly the same in both groups (both ~75%).

Short course versus Long course radiation for preoperative treatment of rectal cancer Part 2

http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-1-Compiled-10-25.mp3  Listen to the part 1 of the 2 part inaugural episode of the Surg Onc Files, where Linda and Brad dive into the morass of trials regarding the optimal preoperative radiation regimen for rectal cancer. Spoiler alert: it’s complicated! But hopefully less confusing after the episode. For part 1 of this episode gives an overview of the workup/ management for rectal cancer. Segments Rectal cancer workup/staging/basic treatment options 2:48 Preop therapy is better (Dutch Trial/German Trial) 10:43 Short course v Long course seems equivalent (Polish Trial/TROG01.04 Trial) 15:38 ……… Literature Discussed/ Background Reading NCCN Guidelines for Rectal Cancer Updated guidelines highlighting management strategy for rectal cancer. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Dutch Trial: NEJM 2001, RCT comparing preoperative SC radiation with surgery alone in all resectable rectal cancer patients. Conclusion: Preop SC radiation is beneficial for decreasing local recurrence when compared to surgery alone, but the benefit is really for T3/T4 or node positive patients. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Trial: JCO 2005, RCT comparing SC preop radiation with surgery alone, also all T stages. Conclusion: SC radiation conferred both a benefit in terms of local recurrence AND overall survival–thus far the only trial to do so. Preoperative versus postoperative chemoradiotherapy for rectal cancer. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. German Trial: NEJM 2004, RCT comparing preoperative LC chemoradiation with POSToperative LC chemoradiation in rectal cancer for T3/T4 or N+ disease. Conclusion: Preoperative LC had lower local recurrence rates compared to postop LC (6% v 13%) and also had lower toxicity and higher rates of therapy completion. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Polish Trial: BJS 2006, RCT comparing preoperative SC radiation vs preoperative LC chemoradiation. Conclusion: No difference in OS, DSS or local recurrence at four years. Also no difference in severe toxicities. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans–Tasman Radiation Oncology Group trial 01.04. Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. TransTasman Trial (TROG 01.04): 2012 JCO, RCT comparing preoperative SC radiation with LC chemoradiation in T3 rectal cancer patients. Conclusion: At three years f/u, no difference in local recurrence, OS, DFS, distant recurrence or late toxicity. Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). Ansari N, Solomon MJ, Fisher RJ, Mackay J, Burmeister B, Ackland S, Heriot A, Joseph D, McLachlan SA, McClure B, Ngan SY. Operative complications and acute adverse events from TROG 01.04 data. Conclusion: Long course patients had significantly higher rate of acute AE, while POCs were similar between arms, slightly (but not significantly) higher leak rate with SC (7% v 3.5%). This episode was produced by Linda Jin and Brad Krasnick. You can email use at surgoncfiles@gmail.com

<a href="http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-1-Compiled-10-25.mp3" rel="nofollow" target="_blank">http://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/Rectal-Cancer-Preop-Therapy-Part-1-Compiled-10-25.mp3</a> Listen to the part 1 of the 2 part inaugural episode of the Surg Onc Files, where Linda and Brad dive into the morass of trials regarding the optimal preoperative radiation regimen for rectal cancer. Spoiler alert: it’s complicated! But hopefully less confusing after the episode. For part 1 of this episode gives an overview of the workup/ management for rectal cancer. <h2>Segments</h2> Rectal cancer workup/staging/basic treatment options 2:48 Preop therapy is better (Dutch Trial/German Trial) 10:43 Short course v Long course seems equivalent (Polish Trial/TROG01.04 Trial) 15:38 ……… <h2>Literature Discussed/ Background Reading</h2> <a href="https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf" rel="nofollow" target="_blank">NCCN Guidelines for Rectal Cancer</a> Updated guidelines highlighting management strategy for rectal cancer. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=dutch+rectal+cancer+trial+nejm+2001" rel="nofollow" target="_blank">Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.</a> Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Dutch Trial: NEJM 2001, RCT comparing preoperative SC radiation with surgery alone in all resectable rectal cancer patients. Conclusion: Preop SC radiation is beneficial for decreasing local recurrence when compared to surgery alone, but the benefit is really for T3/T4 or node positive patients. <a href="https://www.ncbi.nlm.nih.gov/pubmed/16110023" rel="nofollow" target="_blank">Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.</a> Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Trial: JCO 2005, RCT comparing SC preop radiation with surgery alone, also all T stages. Conclusion: SC radiation conferred both a benefit in terms of local recurrence AND overall survival–thus far the only trial to do so. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=german+trial+nejm+2004" rel="nofollow" target="_blank">Preoperative versus postoperative chemoradiotherapy for rectal cancer.</a> Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. German Trial: NEJM 2004, RCT comparing preoperative LC chemoradiation with POSToperative LC chemoradiation in rectal cancer for T3/T4 or N+ disease. Conclusion: Preoperative LC had lower local recurrence rates compared to postop LC (6% v 13%) and also had lower toxicity and higher rates of therapy completion. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=bujko+2006+rectal+british+journal+of+surgery" rel="nofollow" target="_blank">Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.</a> Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Polish Trial: BJS 2006, RCT comparing preoperative SC radiation vs preoperative LC chemoradiation. Conclusion: No difference in OS, DSS or local recurrence at four years. Also no difference in severe toxicities. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23008301" rel="nofollow" target="_blank">Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans–Tasman Radiation Oncology Group trial 01.04.</a> Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. TransTasman Trial (TROG 01.04): 2012 JCO, RCT comparing preoperative SC radiation with LC chemoradiation in T3 rectal cancer patients. Conclusion: At three years f/u, no difference in local recurrence, OS, DFS, distant recurrence or late toxicity. <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=trog+01.04" rel="nofollow" target="_blank">Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04).</a> Ansari N, Solomon MJ, Fisher RJ, Mackay J, Burmeister B, Ackland S, Heriot A, Joseph D, McLachlan SA, McClure B, Ngan SY. Operative complications and acute adverse events from TROG 01.04 data. Conclusion: Long course patients had significantly higher rate of acute AE, while POCs were similar between arms, slightly (but not significantly) higher leak rate with SC (7% v 3.5%). This episode was produced by Linda Jin and Brad Krasnick. You can email use at surgoncfiles@gmail.com

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