The American College of Surgeons (ACS) Clinical Research Program (CRP) sponsored several sessions at Clinical Congress 2019, in San Francisco, CA. The following is a review of those programs that summarizes key learning points and outlines the ACS CRP’s efforts to promote education and quality improvement in oncology, as well as clinical trial participation among the ACS membership.
Designing and Running a Clinical Trial
Historically a five-day endeavor, this day-long didactic course for residents, fellows, and practicing surgeons interested in conducting clinical trials reviewed the path from trial design to completion and publication. Led by Judy Boughey, MD, FACS, Chair, ACS CRP Education Committee, and Kamal M.F. Itani, MD, FACS, chief of surgery, Veterans Affairs Boston Health Care System, and professor of surgery, Boston University, MA, the course began with guidance about how to identify a critical gap in surgical or medical knowledge and develop a well-designed scientific study question. Speakers reviewed schemas for clinical trial design, with a focus on two increasingly popular methodologies: neoadjuvant and window-of-opportunity trials. Attendees then learned about statistical analytical approaches, regulatory aspects, safety monitoring and reporting, and funding mechanisms, as well as the structure of the oncology cooperative groups. Edward Livingston, MD, FACS, AGAF, deputy editor of clinical reviews and education at the Journal of the American Medical Association, closed the session by providing insight into how to ensure successful publication of completed trials.
Clinical Trials in Personalized Medicine in Oncology
Systemic therapy for solid tumors traditionally has focused on histologic origin to define treatment strategies. Because tumor sequencing has evolved rapidly, the use of a patient’s unique mutational profile to determine treatment also has changed quickly. These transformations were the focus of a panel session co-moderated by Flavio Rocha, MD, FACS, member, CRP Cancer Care Standards Development Committee, CRP Education Committee, and Video-Based Education Committee, and Christina Roland, MD, MS, FACS, Vice-Chair, ACS CRP Education Committee.
Jason Sicklick, MD, FACS, assistant professor of surgery, University of California San Diego Health Moores Cancer Center, highlighted the impressive response rates that can be achieved when matching scores are used to determine treatment, with up to 30 percent of heavily pretreated patients with metastatic cancers achieving tumor response. Dennis Wigle, MD, PhD, FACS, consultant, division of general thoracic surgery, department of surgery, Mayo Clinic, Rochester, MN, emphasized the importance of enrolling patients with resected lung cancer in clinical trials, including in the ALCHEMIST trial (NCT02194738)—a unique trial platform designed to evaluate the combination of chemotherapy with immunotherapy in patients with resected lung cancer. Susan Tsai, MD, MHS, FACS, associate professor of surgery, Medical College of Wisconsin, Milwaukee, described the challenges of precision medicine in pancreatic cancer, particularly related to rapid tumor profiling for molecularly guided neoadjuvant therapy in localized pancreatic ductal adenocarcinoma. Dr. Rocha closed the session with a discussion of the differences in colon cancer based on “sidedness” (left versus right colon cancer), which is a topic that may be incorporated into the next iteration of National Cancer Center Network treatment guidelines.
Cracking the Code to Clinical Trial Enrollment
Physician participation in clinical trials can be challenging because of administrative barriers, such as the time required to complete training and certification. An open forum, Cracking the Code to Clinical Trial Enrollment, provided guidance on completing requirements, such as obtaining a Cancer Therapy Evaluation Program identification, enrolling in the National Cancer Institute Registrations and Credential Repository, and completing enhanced training requirements such as Good Clinical Practice. Materials from this session are available on the Clinical Research Program website at facs.org/crp.
Management of Peritoneal Malignancies
Garrett Nash, MD, MPH, FACS, FASCRS, vice-chair for quality and safety, department of surgery, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, and Rebecca Snyder, MD, MPH, FACS, member, CRP Cancer Care Standards Development Committee and CRP Education Committee, co-moderated a well-attended Panel Session. The session included a lively debate on the role of heated intraperitoneal chemotherapy (HIPEC) for patients with colorectal carcinomatosis, conducted by Olivier Glehen, MD, PhD, head, general and oncologic surgery department, Centre Hospitalier Lyon Sud (Hospices Civils de Lyon), France, and H. Richard Alexander, MD, FACS, chief surgical officer, and chief, surgical oncology, Rutgers Cancer Institute of New Jersey, and regional director, surgery, Monmouth Medical Center, Robert Wood Johnson Medical School, New Brunswick, NJ.
Use of neoadjuvant immunotherapy strategies in locally advanced melanoma has shown great promise, allowing for real-time assessment of tumor response, as well as tissue acquisition to identify novel mechanisms of resistance.
In this session, the authors discussed the recently presented PRODIGE-7 trial, which randomized patients with colorectal carcinomatosis to treatment with systemic chemotherapy and either cytoreductive surgery or cytoreductive surgery + HIPEC. Median overall survival in both groups was approximately 41 months, a significant improvement in survival compared with historical data. The study did not show an association between intraperitoneal chemotherapy and improved survival in this study, prompting significant controversy among surgeons who treat this disease. Professor Glehen attributed the lack of observed benefit of HIPEC to the specific chemotherapy agent (oxaliplatin) and short duration of administration (30 minutes). Dr. Alexander said earlier studies demonstrated similar efficacy of intraperitoneal mitomycin-C and oxaliplatin, suggesting that perhaps neither agent will provide a meaningful survival benefit in the setting of modern systemic chemotherapy.
The panel included an overview of the data regarding HIPEC for gastric cancer by Brian Badgwell, MD, FACS, professor, department of surgical oncology, division of surgery, The University of Texas MD Anderson Cancer Center, Houston, and ovarian cancer by Oliver Zivanovic, MD, PhD, surgeon, section, ovarian cancer surgery, and director, innovative surgical technology, gynecology service, department of surgery, MSKCC.
Immunotherapy for the Treatment of Solid Tumors
Immunotherapy is increasingly used to treat patients with solid tumors such as metastatic melanoma and advanced lung cancer with significant benefit. This session, Immunotherapy in the Treatment of Solid Tumors: Emerging Roles of the Surgeon, moderated by Dr. Roland, focused on how best to incorporate surgery in the multidisciplinary management of these complex cases, as well as the treatment of immunotherapy complications requiring surgical intervention.
Charlotte Ariyan, MD, PhD, FACS, a general surgeon at MSKCC, noted that understanding the incidence, unique toxicity profile, and optimal management of immunotherapy-related surgical issues not previously seen with traditional cytotoxic chemotherapy is critical. Use of neoadjuvant immunotherapy strategies in locally advanced melanoma has shown great promise, allowing for real-time assessment of tumor response, as well as tissue acquisition to identify novel mechanisms of resistance.
Surgeon involvement… is critical to unlocking the full potential of this promising class of agents.
Rebecca Auer, MD, MSc, FRCSC, FACS, associate professor, department of surgery and department of biochemistry, microbiology, and immunology, University of Ottawa, ON, described the spectrum of the inflammatory environments seen in patients with colorectal cancer, highlighting the first Food and Drug Administration approval of immunotherapy for patients with mismatch-repair deficient tumors.
George Plitas, MD, Jeanne A. Petrek Junior Faculty Chair, MSKCC, reviewed emerging data on differences in response to immunotherapy seen in patients with localized versus metastatic breast cancer, as well as variable responses based on hormone-receptor expression.
John Stewart, MD, MBA, FACS, physician executive, oncology services, and associate director, clinical research, University of Illinois at Chicago Cancer Center, rounded out the session with an insightful review of oncolytic viruses currently on clinical trial for peritoneal malignancies and head and neck cancers. Surgeon involvement in future clinical trials for patients with early-stage disease and rare tumors is critical to unlocking the full potential of this promising class of agents.
Cancer Care Standards
Led by co-moderators Matthew H.G. Katz, MD, FACS, Chair, CRP Cancer Care Standards Development Committee, and Kelly Hunt, MD, FACS, Program Director, ACS CRP, and member, CRP Cancer Care Standards Development Committee, this session focused on best practices from Operative Standards for Cancer Surgery Volumes 1 and 2 and featured a panel of experts who reviewed data demonstrating the benefits of these standards. The session, which emphasized how incorporating these recommendations into practice can lead to improved patient outcomes, was especially timely because the operative standards for melanoma, breast, colon, lung, and rectal cancers recently have been incorporated into the 2020 Commission on Cancer accreditation standards.* This integration is a notable step toward improving oncologic outcomes by reducing variation in the way cancer operations are performed across the U.S.
*Optimal Resources for Cancer Care: 2020 Standards. American College of Surgeons. Available at: facs.org/-/media/files/quality-programs/cancer/coc/optimal_resources_for_cancer_care_2020_standards.ashx. Accessed December 4, 2019.