CTOS Op Ed |
Understanding Rare Cancers:
The NIH Pediatric and wildtype GIST Clinic Paradigm
An ESUN Article
Editor's Note: This editorial is part of an ongoing series of Op Ed pieces written by one of the members of the Board of Directors of the Connective Tissue Oncology Society (CTOS). Dr. Helman has served CTOS in a number of different capacities including Treasurer (1998-1999); Secretary (1999-2000); Vice President (2000-2001), President (2001-2002), and Immediate Past President (2002-2003). These editorials are intended to address important and controversial issues in the field. The "Questions, Comments & Counterpoint" column allows readers to express their opinions in response to these Op Ed pieces. Click here to send in an opinion.
One of the missions of the National Institutes of Health (NIH) is to advance healthcare in areas that are not currently addressed, such as the study of rare diseases. Gastrointestinal Stromal Tumor (GIST) is a rare cancer, and even more uncommon in the pediatric population. Estimates suggest a prevalence of less than 200 children in North America. Two major differences distinguish adults from younger patients with GIST. In adults, 50% of patients are female. In contrast, 80% of pediatric patients are female. In addition, 85% of adults with GIST have activating mutations in KIT or PDGFRA. In contrast, almost all pediatric patients do not have such mutations, therefore termed wildtype. Adults have had dramatic improved overall survival due to therapy using KIT/PDGFRA targeted tyrosine kinase inhibitors, such as Imatinib. Pediatric patients have not had a similar response. How do we address this discrepancy, in order to achieve the same remission rates in pediatrics, currently seen in adults?
In conversations and planning with many others, we proposed a gathering of physicians who have clinical and research knowledge of pediatric GIST, along with young patients with GIST. The dilemma was how to bring together so many people in a short amount of time. The solution was to implement a two-day clinic and conference, termed the NIH Pediatric and wildtype GIST Clinic. Although this concept is not new, our implementation of an innovative clinic design, made it very successful.
We describe a novel paradigm that has allowed us to begin answering many of the questions posed by differential responses of KIT/PDGFRA-mutated versus wildtype GIST to therapy. The NIH Pediatric and wildtype GIST Clinic was started to address many basic questions. 1) what are the biological determinants of wildtype and pediatric GIST? 2) what current treatment modalities are effective? 3) what new therapy is required? 4) what research endeavors will help answer these questions? Our goal was to collect information for all patients with either pediatric or wildtype GIST, including medical history, treatment regimens, radiographic scans and pathology slides.
The inaugural clinic brought together 12 patients and 6 physicians from across the nation. Each patient had a 30-minute appointment to ask questions they had about their medical care, or about GIST in general. The presence of physicians with expertise in surgery, medical treatments and genetic alterations associated with pediatric GIST, allowed us to address their questions and concerns. The short time frame, also allowed us to speak to all 12 patients in one day. Summaries that had been compiled by NIH physicians precluded the need to obtain a history, thus allowing us to concentrate only on the questions that the patients had. Following this meeting, patients then met with a host of specialists at the NIH including geneticists, nutritionists, pain management specialists, psychologists and social workers. They also had the opportunity to attend many seminars such as coping with anxiety, complementary and alternative medicine, exercise and maintaining an active lifestyle, nutrition tips and others.
The patient perspective of the clinic. We received 9 responses to 12 post-clinic questionnaires. Everyone said that the clinic was excellent. The 30-minute limitation was not a detriment and all patients had their most pressing questions answered. The opportunity to discuss any aspect of their care was one of the highlights of the clinic. Another high point was the ability for patients to meet so many other patients and families with this rare disorder.
What did we learn?
We have completed two clinics to date and will continue them twice every year. The complete medical histories of all of these patients, has allowed us to begin answering many of the questions posed previously
1. The results from 24 patients allowed us to examine the natural history of pediatric GIST. 25% of patients presented with widespread disease and were not amenable to surgery. 25% of patients had resection at presentation and remain in remission. The longest follow-up in this group has been four years, but our hope is that these patients have a less aggressive form of GIST. Prolonged follow-up will allow us to answer this question. The remaining 50% of patients had complete surgical resection, but have recurred.
2. Physical examination revealed some interesting observations suggesting that there are two distinct groups of patients with wildtype GIST. We are performing photographic assessments and innovative three-dimensional facial videography to correlate these phenotypic findings with genotype and also clinical course.
3. There is a much higher percentage of patients than we expected who have increased genetic predisposition for GIST. These preliminary findings will be announced during the 3rd NIH Pediatric and wildtype GIST clinic, scheduled for June 17-19, 2009.
4. The lack of tumor samples is hindering research endeavors. Tumor samples from all young patients should be tested for known causative mutations, since the results will dictate therapy. More importantly, the NIH and many other institutions have the ability to perform sequence analysis of all 600 tyrosine kinases in the genome. This is only one of many tests that we can perform. The only limitation is the lack of appropriately preserved tumor sample. If you have GIST and you are about to undergo surgery, please make it clear to your surgeon and your oncologist that you would like your tumor sample preserved in such a way to make it amenable for research. Although this may not affect you directly, it will further research efforts immensely and help others with GIST. Patients who attend our clinic have been asked to submit as many unstained slides as possible, so that we can begin interrogating new pathways. Members of the Pediatric and wildtype GIST team at the NIH will be glad to answer any questions from patients and physicians.
Additional information is available on our website, and specific questions can be sent via e-mail.
V6N1 ESUN Copyright © 2009 Liddy Shriver Sarcoma Initiative.