TOXICITY PROFILING: CREATING NOVEL PARADIGMS TO PERSONALIZE CANCER TREATMENT
Led by Michael Scheurer at Baylor College of Medicine
Advances in genomic technologies have generated great interest in the concept of personalized patient care, particularly in oncology where there is great variability in both toxicity and response to treatment. Development of clinical and genomic screens would enable prospective identification of patients at high risk for toxicity and potentially heightened tumor response, allowing alterations in treatment planning and management. Using data and specimens from the RTOG 0825 clinical trial, specific aims to be addressed include: (1) refine and validate our clinical and germline candidate pathway-based modeling (genetic polymorphisms) of the myelotoxicity associated with temozolomide in newly diagnosed GBM patients; (2) develop clinical and germline candidate pathway-based modeling of vascular toxicity associated with antiangiogenic therapy (bevacizumab) in newly-diagnosed GBM patients; (3) determine the relationship
between germline candidate pathway polymorphisms and survival with cytotoxic chemotherapy. Our proposal includes both clinical and genomic factors, uniquely enabling us to develop a two-stage model that will, ultimately, utilize clinical factors to screen for patients at increased risk and then perform genetic testing only on those select patients to refine the risk assessment, thereby improving clinical utility and feasibility. Clinical data and biospecimens will be used to develop clinical risk models supplemented with genomic
variants related to myelotoxicity due to temozolomide, vascular toxicities due to bevacizumab, and response to therapy in patients treated for newly diagnosed GBM. Furthermore, this paradigm combining clinical factors with genomics is designed to evaluate the relationship between toxicity and tumor response, thereby achieving the goal of establishing a modified “therapeutic window”. The findings of this study have strong potential for translation to personalized care by identifying patient-specific variability in treatment toxicity and response. In addition, the paradigm of creating a clinically based assessment that can better define the patients at risk will improve the utility, feasibility, and cost-benefit of genomic screening.
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