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.
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. [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!
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!!
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.
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.
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
SurgOnc ABSITE Review: Part 2- GI, HPB, GU and Melanoma
Jan 22, 2019
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!
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!
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!
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.
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 > 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.
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<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.
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!
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 > chemo alone for gastric cancer
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.
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.
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.
Oncotype DX Score, TailorX Trial, and the Role of Oncotype DX Score in Breast Cancer Management
Aug 09, 2018
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.
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 >50 y/o.
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
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.
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.
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.
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: >1 liver metastasis, node positive primary, <12 months between primary colorectal tumor and liver met, >5cm liver tumor, preop CEA >200.
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.
Controversies in Differentiated Thyroid Cancer with Dr. Julie Ann Sosa
Mar 31, 2018
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!
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.
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.
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.
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.
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.
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.
Management of Barrett’s Esophagus and Associated Lesions
Mar 16, 2018
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.
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.
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.
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
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 >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.
Systemic Options for Pancreatic Adenocarcinoma
Feb 17, 2018
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?
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%).
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.
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).
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).
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!!
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.
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.
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.
Gastric Cancer Review- Resident geared, ABSITE friendly
Jan 07, 2018
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.
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.
Minimally Invasive HPB and Oncologic Surgery
Dec 19, 2017
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.
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.
The Future of Surgical Lymph Node Management
Nov 27, 2017
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!
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.
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.
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).
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 <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.
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.
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).
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.
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.
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 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.
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.
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 <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.
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<0.0001).
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 >1.7% are candidates for chemoprevention.
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.
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 recently published (September 2017) and well written review article in the NEJM , highlighting several forms of radiation oncology and the mechanisms behind them.
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%.
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.
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!
Lynch Syndrome- Modern management and outcomes
Nov 06, 2017
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.
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)
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.
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.
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.
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.
On this episode of the SO files, Brad and Linda cover the recently published trials on adjuvant options for melanoma, including the COMBI-AD trial and the CHECKMATE-238 trial. As a very special guest, they’ll be interviewing Dr. Robert Andtbacka, Associate Professor of Surgery at the University of Utah, co-author of the recently published MSLT II trial, panel member of the NCCN guidelines on Melanoma, and lead investigator in the use of viral oncolytic therapy “T-VEC”. Given these new results, how will our approach to completion lymph node dissection and adjuvant therapy change in patients with advanced melanoma?
Segments
Melanoma Staging and Treatment 1:46
Overview of checkpoint blockade/BRAF/MEK targeted therapies 11:58
Overview of papers: CHECKMATE 238/COMBI-AD trials 17:30
Interview with Dr. Andtbacka 23:59
HIGH YIELD: Dr. Andtbacka summarizes how he will synthesize MSLTII/new adjuvant options into his practice for advanced melanoma 51:05
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.
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.
Recently published paper that established 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).
Major papers establishing efficacy of checkpoint blockade (PD-1/ CTLA-4) in metastatic melanoma
F. Stephen Hodi, M.D., Steven J. O’Day, M.D., David F. McDermott, M.D., Robert W. Weber, M.D., Jeffrey A. Sosman, M.D., John B. Haanen, M.D., Rene Gonzalez, M.D., Caroline Robert, M.D., Ph.D., Dirk Schadendorf, M.D., Jessica C. Hassel, M.D., Wallace Akerley, M.D., Alfons J.M. van den Eertwegh, M.D., Ph.D., Jose Lutzky, M.D., Paul Lorigan, M.D., Julia M. Vaubel, M.D., Gerald P. Linette, M.D., Ph.D., David Hogg, M.D., Christian H. Ottensmeier, M.D., Ph.D., Celeste Lebbé, M.D., Christian Peschel, M.D., Ian Quirt, M.D., Joseph I. Clark, M.D., Jedd D. Wolchok, M.D., Ph.D., Jeffrey S. Weber, M.D., Ph.D., Jason Tian, Ph.D., Michael J. Yellin, M.D., Geoffrey M. Nichol, M.B., Ch.B., Axel Hoos, M.D., Ph.D., and Walter J. Urba, M.D., Ph.D.
Caroline Robert, M.D., Ph.D., Luc Thomas, M.D., Ph.D., Igor Bondarenko, M.D., Ph.D., Steven O’Day, M.D., Jeffrey Weber, M.D., Ph.D., Claus Garbe, M.D., Celeste Lebbe, M.D., Ph.D., Jean-François Baurain, M.D., Ph.D., Alessandro Testori, M.D., Jean-Jacques Grob, M.D., Neville Davidson, M.D., Jon Richards, M.D., Ph.D., Michele Maio, M.D., Ph.D., Axel Hauschild, M.D., Wilson H. Miller, Jr., M.D., Ph.D., Pere Gascon, M.D., Ph.D., Michal Lotem, M.D., Kaan Harmankaya, M.D., Ramy Ibrahim, M.D., Stephen Francis, M.Sc., Tai-Tsang Chen, Ph.D., Rachel Humphrey, M.D., Axel Hoos, M.D., Ph.D., and Jedd D. Wolchok, M.D., Ph.D.
Two landmark Phase III Trials published in 2010 and 2011, respectively, that established survival benefit for patients with advanced melanoma treated with CTLA-4 blockade (ipilimumab).
Julie R. Brahmer, M.D., Scott S. Tykodi, M.D., Ph.D., Laura Q.M. Chow, M.D., Wen-Jen Hwu, M.D., Ph.D., Suzanne L. Topalian, M.D., Patrick Hwu, M.D., Charles G. Drake, M.D., Ph.D., Luis H. Camacho, M.D., M.P.H., John Kauh, M.D., Kunle Odunsi, M.D., Ph.D., Henry C. Pitot, M.D., Omid Hamid, M.D., Shailender Bhatia, M.D., Renato Martins, M.D., M.P.H., Keith Eaton, M.D., Ph.D., Shuming Chen, Ph.D., Theresa M. Salay, M.S., Suresh Alaparthy, Ph.D., Joseph F. Grosso, Ph.D., Alan J. Korman, Ph.D., Susan M. Parker, Ph.D., Shruti Agrawal, Ph.D., Stacie M. Goldberg, M.D., Drew M. Pardoll, M.D., Ph.D., Ashok Gupta, M.D., Ph.D., and Jon M. Wigginton, M.D.
Suzanne L. Topalian, M.D., F. Stephen Hodi, M.D., Julie R. Brahmer, M.D., Scott N. Gettinger, M.D., David C. Smith, M.D., David F. McDermott, M.D., John D. Powderly, M.D., Richard D. Carvajal, M.D., Jeffrey A. Sosman, M.D., Michael B. Atkins, M.D., Philip D. Leming, M.D., David R. Spigel, M.D., Scott J. Antonia, M.D., Ph.D., Leora Horn, M.D., Charles G. Drake, M.D., Ph.D., Drew M. Pardoll, M.D., Ph.D., Lieping Chen, M.D., Ph.D., William H. Sharfman, M.D., Robert A. Anders, M.D., Ph.D., Janis M. Taube, M.D., Tracee L. McMiller, M.S., Haiying Xu, B.A., Alan J. Korman, Ph.D., Maria Jure-Kunkel, Ph.D., Shruti Agrawal, Ph.D., Daniel McDonald, M.B.A., Georgia D. Kollia, Ph.D., Ashok Gupta, M.D., Ph.D., Jon M. Wigginton, M.D., and Mario Sznol, M.D.
Pair of practice changing articles, appearing in the June 2012 edition of NEJM, establishing efficacy of PD-1 /PD-L1 blockade in a variety of cancers, including melanoma.
Jedd D. Wolchok, M.D., Ph.D., Harriet Kluger, M.D., Margaret K. Callahan, M.D., Ph.D., Michael A. Postow, M.D., Naiyer A. Rizvi, M.D., Alexander M. Lesokhin, M.D., Neil H. Segal, M.D., Ph.D., Charlotte E. Ariyan, M.D., Ph.D., Ruth-Ann Gordon, B.S.N., Kathleen Reed, M.S., Matthew M. Burke, M.B.A., M.S.N., Anne Caldwell, B.S.N., Stephanie A. Kronenberg, B.A., Blessing U. Agunwamba, B.A., Xiaoling Zhang, Ph.D., Israel Lowy, M.D., Ph.D., Hector David Inzunza, M.D., William Feely, M.S., Christine E. Horak, Ph.D., Quan Hong, Ph.D., Alan J. Korman, Ph.D., Jon M. Wigginton, M.D., Ashok Gupta, M.D., Ph.D., and Mario Sznol, M.D.
Michael A. Postow, M.D., Jason Chesney, M.D., Ph.D., Anna C. Pavlick, D.O., Caroline Robert, M.D., Ph.D., Kenneth Grossmann, M.D., Ph.D., David McDermott, M.D., Gerald P. Linette, M.D., Ph.D., Nicolas Meyer, M.D., Jeffrey K. Giguere, M.D., Sanjiv S. Agarwala, M.D., Montaser Shaheen, M.D., Marc S. Ernstoff, M.D., David Minor, M.D., April K. Salama, M.D., Matthew Taylor, M.D., Patrick A. Ott, M.D., Ph.D., Linda M. Rollin, Ph.D., Christine Horak, Ph.D., Paul Gagnier, M.D., Ph.D., Jedd D. Wolchok, M.D., Ph.D., and F. Stephen Hodi, M.D.
Phase I Trials appearing in NEJM in 2013 and 2015, respectively, established clinical efficacy of combination CTLA-4 + PD-1 blockade in melanoma.
Caroline Robert, M.D., Ph.D., Jacob Schachter, M.D., Georgina V. Long, M.D., Ph.D., Ana Arance, M.D., Ph.D., Jean Jacques Grob, M.D., Ph.D., Laurent Mortier, M.D., Ph.D., Adil Daud, M.D., Matteo S. Carlino, M.B., B.S., Catriona McNeil, M.D., Ph.D., Michal Lotem, M.D., James Larkin, M.D., Ph.D., Paul Lorigan, M.D., Bart Neyns, M.D., Ph.D., Christian U. Blank, M.D., Ph.D., Omid Hamid, M.D., Christine Mateus, M.D., Ronnie Shapira-Frommer, M.D., Michele Kosh, R.N., B.S.N., Honghong Zhou, Ph.D., Nageatte Ibrahim, M.D., Scot Ebbinghaus, M.D., and Antoni Ribas, M.D., Ph.D., for the KEYNOTE-006 investigators
Keynote-006 trial, appearing in NEJM in 2015, either Q2 or Q4 wk PD-1 pembrolizumab (PD-1 inhibitor) vs. ipilimumab (10mg/kg), with a 12 mo OS of 74.1% (HR for death 0.63) and 68.4%, respectively, in advanced melanoma, versus ipilimumab group 58.2% 1 yr OS.
James Larkin, M.D., Ph.D., Vanna Chiarion-Sileni, M.D., Rene Gonzalez, M.D., Jean Jacques Grob, M.D., C. Lance Cowey, M.D., Christopher D. Lao, M.D., M.P.H., Dirk Schadendorf, M.D., Reinhard Dummer, M.D., Michael Smylie, M.D., Piotr Rutkowski, M.D., Ph.D., Pier F. Ferrucci, M.D., Andrew Hill, M.D., John Wagstaff, M.D., Matteo S. Carlino, M.D., John B. Haanen, M.D., Michele Maio, M.D., Ph.D., Ivan Marquez-Rodas, M.D., Ph.D., Grant A. McArthur, M.D., Paolo A. Ascierto, M.D., Georgina V. Long, M.D., Margaret K. Callahan, M.D., Ph.D., Michael A. Postow, M.D., Kenneth Grossmann, M.D., Mario Sznol, M.D., Brigitte Dreno, M.D., Lars Bastholt, M.D., Arvin Yang, M.D., Ph.D., Linda M. Rollin, Ph.D., Christine Horak, Ph.D., F. Stephen Hodi, M.D., and Jedd D. Wolchok, M.D., Ph.D.
CheckMate-067 trial, NEJM 2015, unresectable stage III/IV melanoma PFS 11.3mo combined group vs. 6.9months nivolumab alone group (3mg/kg) vs. 2.9mo ipilimumab alone group. In tumors PD-L1 + (5%+ tumor cells PD-L1 staining) 14mo median PFS combined and PD-1 alone group (vs. 3.9 months ipilimumab alone group). PD-L1 low tumors combined group 11.2mo median PFS, 5.3mo nivolumab alone group, and 2.9 months ipilimumab alone group. Grade 3/4 toxicity 43% nivolumab alone, 56% ipilimumab alone, 69% combined. Treatment related event leading to d/c therapy <15% both alone groups, and 36% in combined group. Most common tx related adverse events: diarrhea, fatigue, rash, pruritus, nausea, vomiting, colitis, headache.
Jedd D. Wolchok, M.D., Ph.D., Vanna Chiarion-Sileni, M.D., Rene Gonzalez, M.D., Piotr Rutkowski, M.D., Ph.D., Jean-Jacques Grob, M.D., C. Lance Cowey, M.D., Christopher D. Lao, M.D., M.P.H., John Wagstaff, M.D., Dirk Schadendorf, M.D., Pier F. Ferrucci, M.D., Michael Smylie, M.D., Reinhard Dummer, M.D., Andrew Hill, M.D., David Hogg, M.D., John Haanen, M.D., Matteo S. Carlino, M.D., Oliver Bechter, M.D., Ph.D., Michele Maio, M.D., Ph.D., Ivan Marquez-Rodas, M.D., Ph.D., Massimo Guidoboni, M.D., Grant McArthur, M.D., Celeste Lebbé, M.D., Ph.D., Paolo A. Ascierto, M.D., Georgina V. Long, M.B., B.S., Ph.D., Jonathan Cebon, M.B., B.S., Ph.D., Jeffrey Sosman, M.D., Michael A. Postow, M.D., Margaret K. Callahan, M.D., Ph.D., Dana Walker, M.D., M.S.C.E., Linda Rollin, Ph.D., Rafia Bhore, Ph.D., F. Stephen Hodi, M.D., and James Larkin, F.R.C.P., Ph.D.
NEJM Sept 2017, 3 year OS outcomes of above discussed CheckMate-067 trial, OS 58% combined group, 52% nivolumab group (3mg/kg), 34% ipilimumab group. Combined therapy with trend to improved OS and PFS at all PD-L1 expression levels, although CI crossed 1 at all levels with PD-L1 expression 1%+, suggesting predominance of benefit from PD-1 therapy at these higher PD-L1 tumor levels. Discussion of risks/benefits to be had at these levels of PD-L1 expression, as clearly combined therapy comes at the cost of increased side effects.
Major papers establishing efficacy of targeting the MAPK signal transduction pathway in advanced melanoma
Paul B. Chapman, M.D., Axel Hauschild, M.D., Caroline Robert, M.D., Ph.D., John B. Haanen, M.D., Paolo Ascierto, M.D., James Larkin, M.D., Reinhard Dummer, M.D., Claus Garbe, M.D., Alessandro Testori, M.D., Michele Maio, M.D., David Hogg, M.D., Paul Lorigan, M.D., Celeste Lebbe, M.D., Thomas Jouary, M.D., Dirk Schadendorf, M.D., Antoni Ribas, M.D., Steven J. O’Day, M.D., Jeffrey A. Sosman, M.D., John M. Kirkwood, M.D., Alexander M.M. Eggermont, M.D., Ph.D., Brigitte Dreno, M.D., Ph.D., Keith Nolop, M.D., Jiang Li, Ph.D., Betty Nelson, M.A., Jeannie Hou, M.D., Richard J. Lee, M.D., Keith T. Flaherty, M.D., and Grant A. McArthur, M.B., B.S., Ph.D., for the BRIM-3 Study Group
BRIM-3 study group, Phase III RCT NEJM 2011, established efficacy of BRAF inhibition in advanced BRAF V600E melanoma, with OS at 6 months 84% BRAF inhibition group (Vemurafenib) vs. 64% chemo group.
Keith T. Flaherty, M.D., Caroline Robert, M.D., Ph.D., Peter Hersey, M.D., Ph.D., Paul Nathan, M.D., Ph.D., Claus Garbe, M.D., Mohammed Milhem, M.B., Lev V. Demidov, M.D., Jessica C. Hassel, M.D., Piotr Rutkowski, M.D., Ph.D., Peter Mohr, M.D., Reinhard Dummer, M.D., Uwe Trefzer, M.D., James M.G. Larkin, M.D., Jochen Utikal, M.D., Brigitte Dreno, M.D., Marta Nyakas, M.D., Mark R. Middleton, Ph.D., Jürgen C. Becker, M.D., Ph.D., Michelle Casey, Ph.D., Laurie J. Sherman, R.N., Frank S. Wu, M.D., Ph.D., Daniele Ouellet, Ph.D., Anne-Marie Martin, Ph.D., Kiran Patel, M.D., and Dirk Schadendorf, M.D., for the METRIC Study Group
METRIC Study Group, phase III RCT, NEJM 2012, established survival benefit MEK inhibition with Trametinib (OS @ 6mo 81%) vs. chemo (OS @ 6mo 67%) in BRAF V600E or V600K unresectable stage IIIc or stage IV melanoma.
Caroline Robert, M.D., Ph.D., Boguslawa Karaszewska, M.D., Jacob Schachter, M.D., Piotr Rutkowski, M.D., Ph.D., Andrzej Mackiewicz, M.D., Ph.D., Daniil Stroiakovski, M.D., Michael Lichinitser, M.D., Reinhard Dummer, M.D., Florent Grange, M.D., Ph.D., Laurent Mortier, M.D., Vanna Chiarion-Sileni, M.D., Kamil Drucis, M.D., Ph.D., Ivana Krajsova, M.D., Axel Hauschild, M.D., Ph.D., Paul Lorigan, M.D., Pascal Wolter, M.D., Georgina V. Long, M.D., Ph.D., Keith Flaherty, M.D., Paul Nathan, M.D., Ph.D., Antoni Ribas, M.D., Ph.D., Anne-Marie Martin, Ph.D., Peng Sun, Ph.D., Wendy Crist, B.A., Jeff Legos, Ph.D., Stephen D. Rubin, M.D., Shonda M. Little, M.P.H., and Dirk Schadendorf, M.D.
Above papers, NEJM 2014 and 2015, respectively, established combined BRAF/MEK inhibition in advanced BRAF V600 mutant melanoma as being superior to BRAF inhibition alone. Median PFS 11.4mo Dabrafenib + Trametinib vs. 7.3mo Vemurafenib alone (Robert et. al.), and 9.3mo Dabrafenib + Trametinib vs. 8.8mo Debrafenib alone (Long et. al.). OS also increased in both combined groups.
Alexander M.M. Eggermont, M.D., Ph.D., Vanna Chiarion-Sileni, M.D., Jean-Jacques Grob, M.D., Ph.D., Reinhard Dummer, M.D., Jedd D. Wolchok, M.D., Ph.D., Henrik Schmidt, M.D., Omid Hamid, M.D., Caroline Robert, M.D., Ph.D., Paolo A. Ascierto, M.D., Jon M. Richards, M.D., Céleste Lebbé, M.D., Ph.D., Virginia Ferraresi, M.D., Michael Smylie, M.D., Jeffrey S. Weber, M.D., Ph.D., Michele Maio, M.D., Ph.D., Lars Bastholt, M.D., Laurent Mortier, M.D., Ph.D., Luc Thomas, M.D., Ph.D., Saad Tahir, M.D., Axel Hauschild, M.D., Ph.D., Jessica C. Hassel, M.D., F. Stephen Hodi, M.D., Corina Taitt, M.D., Veerle de Pril, M.Sc., Gaetan de Schaetzen, Ph.D., Stefan Suciu, Ph.D., and Alessandro Testori, M.D.
EORTC 18071 Phase III RCT, NEJM 2016, adjuvant Ipilimumab (10mg/kg) vs. placebo in resected stage III melanoma. OS at 5 years 65% Ipilimumab group vs. 54% placebo group (p=0.001). Grade 3/4 adverse events 54% tx group vs. 26% placebo group, with 5 patients (1%) dying due to adverse immune related events in the tx group.
Karl D. Lewis, Michele Maio, Mario Mandalà, Betty J Nelson, Grant R. Goodman, Dirk Schadendorf
Vemurafenib alone as an adjuvant agent showed benefit in resected Stage IIC-IIIA patients, but did not show a statistically significant benefit in DFS in Stage IIIC patients. Results recently presented at ESMO 2017.
Jeffrey Weber, M.D., Ph.D., Mario Mandala, M.D., Michele Del Vecchio, M.D., Helen J. Gogas, M.D., Ph.D., Ana M. Arance, M.D., Ph.D., C. Lance Cowey, M.D., Stéphane Dalle, M.D., Ph.D., Michael Schenker, M.D., Vanna Chiarion-Sileni, M.D., Ivan Marquez-Rodas, M.D., Ph.D., Jean-Jacques Grob, M.D., Marcus O. Butler, M.D., Mark R. Middleton, Ph.D., Michele Maio, M.D., Ph.D., Victoria Atkinson, M.B., B.S., Paola Queirolo, M.D., Rene Gonzalez, M.D., Ragini R. Kudchadkar, M.D., Michael Smylie, M.D., Nicolas Meyer, M.D., Laurent Mortier, M.D., Ph.D., Michael B. Atkins, M.D., Georgina V. Long, Ph.D., M.B., B.S., Shailender Bhatia, M.D., Celeste Lebbé, M.D., Ph.D., Piotr Rutkowski, M.D., Ph.D., Kenji Yokota, M.D., Naoya Yamazaki, M.D., Ph.D., Tae M. Kim, M.D., Ph.D., Veerle de Pril, M.Sc., Javier Sabater, Pharm.D., M.Sc., Anila Qureshi, M.D., M.P.H., James Larkin, F.R.C.P., Ph.D., and Paolo A. Ascierto, M.D., for the CheckMate 238 Collaborators
The CHECKMATE 238 trial: adjuvant nivolumab provided significant improvements in RFS at 18 month compared to ipilimumab (10mg/kg) in Stage IIIB-IV patients after complete resection, and was significantly better tolerated than ipilimumab. 12mo RFS 70% Nivolumab group vs. 61% Ipilimumab group (p<0.0001). Relationship held true for most subgroups as well, including both PD-L1 low and high tumors. Grade 3/4 treatment events 14% Nivulumab group vs. 46% Ipilimumab group. (Ipilimumab dose 10mg/kg)
Georgina V. Long, M.B., B.S., Ph.D., Axel Hauschild, M.D., Ph.D., Mario Santinami, M.D., Victoria Atkinson, M.D., Mario Mandalà, M.D., Vanna Chiarion-Sileni, M.D., James Larkin, Ph.D., Marta Nyakas, M.D., Caroline Dutriaux, M.D., Andrew Haydon, M.B., B.S., Ph.D., Caroline Robert, M.D., Laurent Mortier, M.D., Ph.D., Jacob Schachter, M.D., Dirk Schadendorf, M.D., Ph.D., Thierry Lesimple, M.D., Ruth Plummer, M.D., Ran Ji, Ph.D., Pingkuan Zhang, M.D., Bijoyesh Mookerjee, M.D., Jeff Legos, Ph.D., Richard Kefford, M.B., B.S., Ph.D., Reinhard Dummer, M.D., and John M. Kirkwood, M.D.
The ‘COMBI-AD’ trial: in patients with BRAF V600E or V600K mutated tumors, combination of dabrafenib and trametinib significantly improved the primary end point of relapse free survival over placebo (3yr RFS 58% vs 39%) in patients who had undergone complete resection and lymphadenectomy for Stage III disease.
Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS.
Phase III Optim trial comparing T-VEC intralesional therapy vs. subcutaneous GMCSF in patients with non-resectable stage IIIB-IV melanoma. Median survival nearly 2 years with T-VEC vs. ~1.5 years with GMCSF (HR T-VEC 0.79). Favorable side effect profile for T-VEC.
Igor Puzanov, Mohammed M. Milhem, David Minor, Omid Hamid, Ai Li, Lisa Chen, Michael Chastain, Kevin S. Gorski, Abraham Anderson, Jeffrey Chou, Howard L. Kaufman, and Robert H.I. Andtbacka
Phase Ib trial demonstrating that oncolytic immuntherapy with T-VEC can be combined with anti-CTLA4 therapy, with a 50% objective response rate in advanced melanoma, with 44% of responses lasting >6months. Combination therapy appears to have > efficacy than either therapy alone.
Antoni Ribas, Reinhard Dummer, Igor Puzanov, Ari VanderWalde, Robert H.I. Andtbacka, Olivier Michielin, Anthony J. Olszanski, Josep Malvehy, Jonathan Cebon, Eugenio Fernandez, John M. Kirkwood, Thomas F. Gajewski, Lisa Chen, Kevin S. Gorski, Abraham A. Anderson, Scott J. Diede, Michael E. Lassman, Jennifer Gansert, F. Stephen Hodi, and Georgina V. Long
In combination with anti-PD-1 therapy, intratumoral injection of an oncolytic virus engineered to enhance immune recognition of cancer resulted in a high response rate (33% complete response rate!!) in patients with advanced melanoma.
This episode was produced by Linda Jin and Brad Krasnick.
You can email us at surgoncfiles@gmail.com.
Short course versus Long course radiation for preoperative treatment of rectal cancer Part 2
Oct 29, 2017
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
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.
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.
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.
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.
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.
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).
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.
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 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–> 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.
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 1, and welcome!
Oct 25, 2017
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
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 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.
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.
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.
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.
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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