The John Wayne Cancer Institute has long been at the forefront of research on colorectal cancer and other gastrointestinal (GI) malignancies, under the direction of Anton J. Bilchik, MD, professor of surgery, chief of medicine and director of the gastrointestinal research program. Dr. Bilchik and his team are investigating key questions in GI cancers, which are helping to establish standards of care worldwide. Here is a look at some of the Institute’s projects and their implications for improved patient care.
Improving the accuracy of colon cancer staging
Advances in screening and treatment mean that far fewer people today die of colorectal cancer. Nevertheless, the disease remains the third most common cancer in both men and women in the United States, with about 140,000 new cases each year. One prominent question in the field centers on how to assess colon cancer to better predict which patients diagnosed with nonmetastatic colon cancer—disease that has not spread—may have a recurrence of disease.
Dr. Bilchik and Institute investigators have examined this problem, noting that even in patients whose lymph nodes appear negative (noncancerous) when the tumor is removed, about one-quarter of patients will experience cancer recurrence. The researchers have proposed a more focused analysis of lymph nodes by other techniques, including sentinel lymph node biopsy and sophisticated molecular analysis of the tumor to look for known genetic mutations that predict recurrence. These results improve the selection of patients for chemotherapy or avoid the toxicity of chemotherapy in those patients cured by surgery alone.
In a 2013 paper published in the journal Advances in Surgery, Dr Bilchik and Institute scientists suggest that the staging of colon cancer needs further refinement to identify high-risk patients within each stage. Ongoing research is exploring newer laboratory techniques for molecular tumor cell identification and sentinel node biopsy.
Advocating for improved colon cancer staging
Another study, in which Institute fellow Danielle Hari, MD, appears as the first author, showed that the current methods for staging colon cancer published in the seventh edition of the American Joint Commission on Cancer (AJCC) Cancer Staging Manual, do not address all of the discrepancies seen in patient survival, regardless of the number of lymph nodes examined. The paper suggests that other prognostic factors should be included to make the best decisions regarding therapy, particularly for patients with stage II colon cancer. Since the AJCC staging manual is the most important reference used by cancer doctors and pathologists worldwide, these findings are very important to further refine staging accuracy.
Using immune system markers to better predict outcomes
Institute fellow Simon Lavotshkin, MD, under the supervision of Dr. Bilchik, has proposed a technique called immunoprofiling to better understand the role the immune system plays in determining cancer spread. In the first prospective study of its kind, they showed that the patient’s immune response to the cancer can be scored and then used to predict patient outcomes. The research was recently published in the Journal of Gastrointestinal Surgery and presented as a plenary presentation at the Society of Surgeons of the Alimentary Tract.
Ultrastaging of colon cancer – first international prospective trial.
In a study appearing in 2012 in the Annals of Surgery, a consortium of international researchers led by Dr. Bilchik compared various methods of examining lymph nodes to predict recurrence. The study was the first to demonstrate that the number of lymph nodes evaluated—called lymph node yield—impacts survival estimates in early colon cancer. The research helps further refine quality benchmarks for lymph node examination in colon cancer with a methodology called targeted nodal assessment and ultrastaging and has contributed to quality measures that have now been instituted nationwide.
Selecting treatment for high-risk colon cancer patients using statistical modelling
Treatments for colon cancer have improved, but puzzling questions remain about why some patients with early stage, node-negative (suggesting no spread of the cancer) colon cancer recover while similar patients have recur. Researchers at the Institute are interested in understanding whether a statistical model can be developed to differentiate those patients at risk for recurrence and which patients need more aggressive treatment to prevent recurrence.
A paper published last year in the in The American Surgeon, an international research consortium including Institute researchers, suggests that statistical models using data from large tumor registries may help accurately predict clinical outcomes and guide physicians and patients in the selection of treatments. The study demonstrated that such models can be useful.
For example, it showed a benefit to giving chemotherapy to node-negative, non-metastatic colon cancer patients older than 72. Yet typically those individuals are far less likely to receive chemotherapy compared to people younger than 55. The paper encourages the use of such models to reliably identify patients with worse prognoses and to help educate patients and family members on prognoses.
Exploring cancer stem cells as the driver of tumor development
Despite many advances in cancer care, researchers are still not able to explain why cancer arises. A new theory, called the cancer stem cell theory, has been proposed by leading researchers including Dr. Bilchik to reinvigorate investigations into cancer’s cause and optimal treatment.
This theory suggests that cancer stem cells—a cell within a tumor that possesses the capacity to self-renew—are responsible for the start of a tumor and its growth and resistance to treatment. This means that only a small fraction of cells with a tumor, the stem cells, are capable of propelling tumor growth. Shifting the focus of research to identify biomarkers for colorectal cancer stem cells may lead to new progress in the field.
Cancer stem cells may be a “rational target for the development of more efficacious screening, early detection, prevention, treatment, surveillance modalities, and interventions,” wrote the authors of an editorial in 2013 in the Journal of Surgical Oncology. As the cost for genomic sequencing declines, it may be possible to investigate the role of various types of colorectal cancer stem cells in individual patients.
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