Siteman Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center in Missouri and is ranked as one of the nation’s top cancer facilities by U.S. News & World Report. In 2020, Siteman earned the highest possible rating— exceptional—by the National Cancer Institute, as part of a rigorous, peer-reviewed five-year evaluation of Siteman’s research programs.
Siteman Cancer Center | Department of Surgery 2020 Annual Report
Colon and Rectal Surgery Section Chief Matthew Mutch, MD, and surgeon Steven Hunt, MD, have introduced a new standard of care for the treatment of locally advanced rectal cancer (LARC). This new regimen utilizes total neoadjuvant therapy to reduce the length of care, improve disease-free survival and increase the chance of complete pathologic response in rectal cancer patients.
This new treatment administers five days of short course radiotherapy, delivering the same biologic dose of radiation as the current standard of treatment in the United States in a shorter time. Systemic chemotherapy is then administered pre- operatively. For patients with complete pathologic response to these therapies, nonoperative management can replace surgery if there is no residual tumor. Close surveillance ensures that, if the tumor grows back, it will be identified and treated with surgery.
The regimen is the result of an international multicenter clinical trial to study the impact of neoadjuvant therapies on disease-free survival of patients with LARC. Researchers at Washington University School of Medicine in St. Louis and Siteman Cancer Center were the only participants from North America involved in this Phase III clinical trial.
The Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) Trial compared conventional treatment of rectal cancer with an experimental treatment involving more pre-operative therapy and shorter Department of Surgery overall treatment time. The results of the RAPIDO Trial were published in the Journal of Clinical Oncology in May 2020.
The RAPIDO trial is the first trial to demonstrate an improvement in a lower rate of distant metastases in high-risk LARC patients, meaning the new treatment regimen reduced the rate of disease- related treatment failure and longer survival. Colorectal surgeons at Washington University have found that systemic chemotherapy is better tolerated before surgery than after, patients receive more systemic chemotherapy when given before than after surgery, and more total patients receive systemic chemotherapy—and their rectal cancers are more likely to shrink—with total neoadjuvant therapy.
Surgeons in the section continue to participate in further clinical trials researching the impact of total neoadjuvant therapy on rectal cancer treatment.
At the School of Medicine, surgeons, radiologists and oncologists take a truly multidisciplinary approach to managing rectal cancer, ensuring the most effective diagnosis, staging and treatment.
“Patients with rectal cancer will receive multidisciplinary care every step of the way, including diagnosis, staging and treatment,” Mutch says. “We work closely with our colleagues in radiation oncology and medical oncology to ensure that patients see all of the physicians they need in a timely fashion and receive the best possible care.”
Through the National Cancer Institute-funded Specialized Programs of Research Excellence (SPORE) in Pancreatic Cancer, Siteman Cancer Center and Washington University School of Medicine have developed the Career Enhancement Program (CEP).
The primary objective of the CEP is to enhance pancreatic cancer research by providing financial support and mentoring for investigators who are new to the field to help build translational research careers in pancreatic cancer. Research initiatives funded by the CEP have a major translational component, focusing on etiology, prevention, diagnosis, early detection, treatment or population science in pancreatic cancer.
One of the main objectives of the program is to promote participation of women and under- represented minorities in pancreatic cancer research. The CEP specifically seeks to increase the diversity of those participating in pancreatic cancer research through outreach, recruitment, training and retention activities.
The CEP selects awardees from collaborating SPORE institutions and other qualified institutions. Financial support—including salary, research supplies and tuition—is provided for awardees for up to two years. The CEP facilitates interactions between awardees and all members of the SPORE, emphasizing the basic and clinical science cross-fertilization that is essential to translational research.
Siteman, Washington University and collaborating SPORE institutions provide outstanding opportunities for career development in translational pancreatic cancer research.
The program has established intra-SPORE collaborations with the University of North Carolina, University of Rochester and Johns Hopkins University, broadening the CEP applicant pool and helping to match the interests of junior investigators with local expertise and need.
The CEP has funded projects leading to clinical trials in pancreatic cancer, and CEP-funded investigators have published in top-tier journals, including Cancer Discovery, Clinical Cancer Research and Cancer Immunology Research.
A better understanding of how tumors progress to metastasis could lead to improved methods of diagnosis and treatments of cancer that has spread to other organs, such as the liver or brain.
Two recently published studies outline colorectal cancer evolution from primary tumor to metastasis. These studies are the culmination of cross-disciplinary research between the labs of co-senior authors, Chief of Surgical Oncology Ryan Fields, MD, and Assistant Director of the McDonnell Genome Institute Christopher Maher, PhD.
The first study, published in Nature Communications, led to the discovery of 150 long noncoding RNAs that may contribute to metastasis.
This study analyzed normal tissue, colon tumors and metastatic tumors from the
same patient, finding that a molecule called RAMS11 was associated with metastatic tumor progression and resistance to chemotherapy. Using CRISPR gene editing technology, the researchers turned off RAMS11 in colorectal cancer cells, which caused the cells to become less aggressive.
“There is a significant unmet need in clinical oncology to identify new markers of cancer that can reliably predict and stratify low- and high-risk patients,” Fields says. “This will allow oncologists to move from ‘one size fits all’ to a ‘personalized and precision-based’ approach that will reserve aggressive and higher risk treatments to those who need it most, sparing those who do not need it the unnecessary side effects. We hope to explore further the ability of RAMS11 and other biomarkers to do just that.”
The second study, published in Science Advances, sequences the genome of nearly 100 tumor samples collected from 11 patients with metastatic colorectal cancer who underwent treatments at Siteman Cancer Center. The researchers detailed the heterogeneity of these tumors and reconstructed how the cancer evolved in these patients.
These findings will impact future strategies to target, and ultimately inhibit, the progression of metastases.
“Tumor heterogeneity is a challenge in treatment of advanced colorectal cancer,” Fields says. “The more complex the tumors are, the more difficult to treat them.”
These two companion studies provide novel insights into the biology of colorectal cancer. The ongoing work of Fields and Maher will further explore and validate these findings and may lead to novel diagnostics and therapeutics in solid tumors.