The Surg Onc Files

Latest Episodes:

Systemic Options for Pancreatic Adenocarcinoma Feb 17, 2018

Show notes

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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.

Gastric Cancer Review- Resident geared, ABSITE friendly Jan 07, 2018

Show notes

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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.

Minimally Invasive HPB and Oncologic Surgery Dec 19, 2017

Show notes

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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.

The Future of Surgical Lymph Node Management Nov 27, 2017

Show notes

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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.

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 <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.

ABSITE Breast Oncology Review Nov 20, 2017

Show notes

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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.

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<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 >1.7% are candidates for chemoprevention.

Radiation Oncology for Dummies Nov 13, 2017

Show notes

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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!

Lynch Syndrome- Modern management and outcomes Nov 06, 2017

Show notes

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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

Adjuvant Options for Advanced Melanoma Oct 30, 2017

Show notes

https://media.blubrry.com/surgoncfiles/www.surgoncfiles.com/wp-content/uploads/2017/10/1-Melanoma-Adjuvant-Compiled-10-30-1.mp3 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 Background Reading NCCN Guidelines on Melanoma . Updated overview of the current guidelines for the workup and treatment of patients with melanoma. 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. Behind the Knife Episode on MSLT II. Great discussion of MSLTII trial results, with guest Dr. Faries (lead author of MSLTII trial). 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. 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 Improved Survival with Ipilimumab in Patients with 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. Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma 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). Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer 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. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer 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. Nivolumab plus Ipilimumab in Advanced 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. Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma 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. Pembrolizumab versus Ipilimumab in Advanced 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. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma 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. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma 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 Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation 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. Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma 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. Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma Georgina V. Long, M.D., Ph.D., Daniil Stroyakovskiy, M.D., Helen Gogas, M.D., Evgeny Levchenko, M.D., Filippo de Braud, M.D., James Larkin, M.D., Claus Garbe, M.D., Ph.D., Thomas Jouary, M.D., Axel Hauschild, M.D., Ph.D., Jean Jacques Grob, M.D., Ph.D., Vanna Chiarion Sileni, M.D., Celeste Lebbe, M.D., Mario Mandalà, M.D., Michael Millward, M.D., Ana Arance, M.D., Ph.D., Igor Bondarenko, M.D., Ph.D., John B.A.G. Haanen, M.D., Ph.D., Johan Hansson, M.D., Ph.D., Jochen Utikal, M.D., Ph.D., Virginia Ferraresi, M.D., Nadezhda Kovalenko, M.D., Ph.D., Peter Mohr, M.D., Volodymyr Probachai, M.D., Dirk Schadendorf, M.D., Ph.D., Paul Nathan, M.D., Caroline Robert, M.D., Antoni Ribas, M.D., Ph.D., Douglas J. DeMarini, Ph.D., Jhangir G. Irani, M.A., Michelle Casey, Ph.D., Daniele Ouellet, Ph.D., Anne-Marie Martin, Ph.D., Ngocdiep Le, M.D., Ph.D., Kiran Patel, M.D., and Keith Flaherty, M.D. Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib 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…

Full show notes at the publisher

Short course versus Long course radiation for preoperative treatment of rectal cancer Part 2 Oct 29, 2017

Show notes

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–> 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%).

Short course versus Long course radiation for preoperative treatment of rectal cancer Part 1, and welcome! Oct 25, 2017

Show notes

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

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