||4UH3CA260318-03 Interpret this number
||Vanderbilt University Medical Center
||CAUSAL: Cohort to Augment the Understanding of Sarcoma Survivorship Across the Lifespan
Sarcomas represent a rare and highly heterogeneous subtype of tumors that may develop across the lifespan.
In the United States (US), there are approximately 14,000 new cases annually, with approximately 65% survival.
Aside from those included in pediatric cancer survivor cohort studies, there are no sarcoma survivor cohorts in
which to systematically study recurrence, organ toxicity, function, quality of life, and survival as well as their
predictors. We propose to address these critical gaps in knowledge by establishing a cohort of approximately
2100 sarcoma survivors through the Vanderbilt University Medical Center (VUMC) Sarcoma Treatment Center,
which is amongst the largest sarcoma programs in the US, in existence since 1987. In this cohort, we will
systematically collect repeated information on disease, treatment, response, relapse, treatment-related toxicity,
sociodemographics, lifestyle, functional status, quality of life, physical health outcomes, and survival, together
with biospecimens (tumor tissue and peripheral blood samples). We hypothesize that: 1) extrinsic factors, tumor
biology, and germline genomics contribute to oncologic outcomes and long-term organ toxicity; 2) healthy
lifestyle, e.g., high quality of diet, exercise, abstinence from cigarette smoking and alcohol drinking mitigate the
adverse health consequences, improve survival and quality of life among sarcoma survivors; and 3) liquid biopsy
tools, developed through identifying genomic drivers of sarcoma, will be of predictive and prognostic utility. Our
aims for current grant period are to evaluate1) the impact of disease, treatment, sociodemographic and lifestyle
contributors on adverse oncologic and non-oncologic outcomes and mortality in the cohort; 2) the role of drug
metabolism and DNA repair gene functional polymorphisms, genetically predicted gene expression levels, and
polygenic risk scores, on treatment efficacy and therapy-induced normal tissue toxicity; and 3) genomic drivers
of sarcoma to develop personalized liquid biopsy assays for monitoring treatment response, recurrence, and
minimal residual disease. Establishment of a prospective cohort of sarcoma survivors across the lifespan, with
extensive and well characterized clinical and epidemiologic data, patient reported outcomes, tumor tissue and
serial blood samples builds a foundation for a long-term prospective investigation on life after sarcoma. This
effort is critically important to improve the understanding of a rare tumor affecting the lifespan but seriously
underrepresented in research. Identification of health outcomes and their predictive and prognostic factors can
lead to precision treatment and survivorship care, which are currently clinically unmet needs.
Accuracy and Reliability of Chatbot Responses to Physician Questions.
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JAMA network open, 2023-10-02; 6(10), p. e2336483.