Dana-Farber / Brigham and Women's Cancer Center

Cutting-edge Medical, Surgical, and Radiation Approaches and Genetic Findings in Colorectal Cancer

Barrett Rollins, MD, PhD, Janina Longtine, MD, Monica Bertagnolli, MD, Philip Kantoff

From left to right: Harvey J. Mamon, MD, PhD, Radiation Oncology Director, Center for Gastrointestinal Oncology; Michael J. Zinner, MD, Clinical Director, Dana-Farber/Brigham and Women's Cancer Center; Charles S. Fuchs, MD, MPH, Director, Center for Gastrointestinal Oncology

Comprised of a multidisciplinary team of experts, the Colorectal Cancer Program — part of the Center for Gastrointestinal Oncology – is offering new trials that combine multiple agents, advanced radiation and surgical techniques, and genetic testing and discoveries for patients with colorectal cancer.

Medical Therapy Advances
Specialists in the Program are offering clinical trials of newer agents, as well as new combinations of agents, to help improve outcomes of patients with colorectal cancer. Current trials include:

  • Led by Principal Investigator Kimmie Ng, MD, MPH, a randomized Phase II trial for previously untreated metastatic colorectal cancer patients has recently been initiated comparing standard therapy with 5-FU, leucovorin and oxaliplatin (FOLFOX) to FOLFOX with vitamin D supplementation based on observational data from the team on the impact of vitamin D on outcomes in colorectal cancer patients;
  • NCI-sponsored, randomized Phase III trial (CALGB 80702), led by Principal Investigator Jeffrey A. Meyerhardt, MD, MPH, is comparing the effectiveness and side effects of two durations of adjuvant chemotherapy (three months versus six months) and celecoxib as adjunctive therapy to standard surgical treatment for Stage III colon cancer;
  • Phase II trial, led by Principal Investigator Jeffrey A. Meyerhardt, MD, MPH, of cetuximab, 5-FU (chemotherapeutic drug 5-fluorouracil) and radiation as neoadjuvant therapy for patients with locally advanced rectal cancer;
  • Randomized Phase II trial for previously treated patients with metastatic colorectal cancer with either KRAS or BRAF mutation comparing 5-FU, leucovorin and irinotecan (FOLFIRI) to FOLFIRI with GS6624, a monoclonal antibody against the LOXL2 extracellular matrix enzyme; 
  • Phase I trial of two novel agents, SAR245408 (PI3K inhibitor) and MSC1936369B (MEK inhibitor), in previously treated colorectal and pancreatic cancer patients;
  • Phase I trial of two novel agents, SAR245409 (dual PI3K and mTOR inhibitor) and MSC1936369B (MEK inhibitor), in previously treated colorectal and pancreatic cancer patients.

For more information regarding these trials and other novel studies in colorectal cancer, please contact Eileen Regan, RN, BSN, OCN, at (617) 632-5960 or eregan@partners.org.

In addition, medical oncologists in the Program work collaboratively with interventional radiologists to employ localized approaches for treatment of isolated colorectal cancer metastases, including radiofrequency ablation and cryoablation.

Advanced Surgical Treatments and Outcomes
“We have continually expanded our use of minimally invasive surgical techniques for colorectal cancers,” said Ronald Bleday, MD, Section Chief of the Division of  Colorectal Surgery. “In addition, our studies of the long-term outcomes of patients who have been surgically treated for colorectal cancers provide data to support decisions regarding the treatment of our patients.” 

In 2008, surgeons in the Program published a study of patients who had undergone local excisions for early-stage rectal cancers and found excellent outcomes seven-to-10 years following surgical treatment (Dis Colon Rectum. 2008 Aug;51(8):1185-91). Overall ten-year survival rates were 84 percent for patients with T1 rectal cancer and 66 percent for patients with T2 rectal cancer.

Innovative surgical techniques offered at the Program include:

  • Cylindrical abdominal perineal resection (APR) – Surgeons in the Program are among few in the nation to offer this technique, which changes the patient’s position during surgery to achieve better short- and long-term outcomes among patients with large rectal cancers who require complete resection of the rectum with permanent colostomy;
  • Total mesorectal excision (TME) – Surgeons in the Program are among the most experienced in the nation in nerve- and sphincter-sparing techniques, designed to avoid permanent colostomy in patients with rectal cancer;
  • Transanal endoscopic microsurgery (TEM) – Used to remove small cancers or carcinoids from the mid-rectum, this technique offers a faster recovery and less risk of complications compared with open procedures;
  • Laparoscopic colectomy – Laparoscopic approaches are applied for the vast majority of colon cancers to reduce pain and complications, shorten hospital stay, and improve cosmesis. The colon is typically dissected from its attachments using the laparoscope, and a small incision is made to remove the tumor and perform the anastomosis. 

New Techniques in Radiation Oncology
Radiation oncologists in the Program deliver conformal radiation prior to surgical excision to improve outcomes among patients with locally advanced rectal tumors. Having recently completed a retrospective analysis among older patients who have undergone radiation therapy for rectal cancer, similar analyses are ongoing with the goals of improving outcomes and reducing toxicities. Shorter courses of radiation treatment for rectal cancer to help reduce side effects in appropriately selected patients also are being evaluated.

Genetic Discoveries in Colorectal Cancers
All patients in the Program are genotyped for tumor types that are likely to respond to targeted therapies. Specialists in the Program also have conducted studies establishing the prognostic and predictive value of common mutations, including KRAS, BRAF and PIK3CA, in treatment response and survival in patients with metastatic colorectal cancer. (Br J Cancer. 2009 Aug 4;101(3): 465-72.)

Genetic Screening Tools
Based on extensive research in hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) – including large patient registries – Sapna Syngal, MD, MPH, Director of the Familial Gastrointestinal Cancer Program, led the development of an online tool for physicians (www.dana-farber.org/premm) to help assess patients’ family and personal history of cancer and guide who should be genetically tested for colon cancer genes.

Endoscopic Management of Large Colorectal Polyps
Endoscopists in the Program, led by John R. Saltzman, MD, have special expertise in the evaluation and removal of large colorectal polyps. Newer techniques, such as endoscopic mucosal resection (EMR), are utilized to remove polyps that otherwise would require surgery. In addition, endoscopists in the Program were among the first in the nation to employ confocal endomicroscopy imaging to evaluate colonic mucosa at the cellular level with more precision than is capable with a standard endoscope. This technology also facilitates improved targeting of areas for biopsy and identification of margins to guide removal of dysplastic tissue.

Role of Diet, Exercise, and Medication in Colon Cancer
Program specialists have conducted numerous studies showing the impact of diet, exercise and medication on both the development and recurrence of colon cancer. More recent studies have shown that exercise (J Clin Oncol. 2006 Aug 1;24(22):3517-8), aspirin (JAMA. 2009;302(6):649-658.), and higher levels of plasma 25-vitamin D (J Clin Oncol. 2008 June 20; Vol 26, No 18: 2984-2991) may reduce the risk of the recurrence of early-stage colon cancer and that a Western dietary pattern high in red meat and refined sugars and grains increases the risk of colon cancer recurrence (JAMA. 2007;298:754-764.). Based on the promising results of aspirin and NSAIDs in patients with stage III colon cancer, the team has initiated a large Phase III trial assessing the addition of celecoxib to standard post-operative adjuvant chemotherapy.

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