The CAUSAL study: a prospective cohort of sarcoma survivors across the lifespan

Abstract

Sarcomas affect individuals across the lifespan, yet no cohort study exists evaluating contributors to treatment response, survival and health outcomes among contemporarily treated sarcoma patients. Determining disease, treatment, lifestyle, and genomic factors that contribute to oncologic and non-oncologic outcomes and survival in sarcoma patients is critical for strategic surveillance for current survivors and to inform future therapies. Furthermore, strategies to monitor disease through circulating tumor DNA (ctDNA) approaches have tremendous potential as both a prognostic and predictive biomarker, to guide therapeutic interventions. This cohort is designed as a mixed retrospective and prospective study of sarcoma patients across the lifespan, treated with contemporary therapies, in the Sarcoma Treatment Center at the Vanderbilt-Ingram Cancer Center. Data are systematically being collected on disease, treatment, response, relapse, treatment-related toxicity, sociodemographic, lifestyle, functional status, quality of life, physical health outcomes, and survival, together with tumor and germline biospecimens to evaluate oncologic and non-oncologic health outcomes among sarcoma patients seen for follow up or treatment since 2012 to present. At enrollment and annually, participants complete patient reported outcome (PRO) measures as well as health history and lifestyle surveys. In addition to general demographics, surveys provide data regarding family history, medication, and general health history. PROs assess financial toxicity, psychosocial and functional wellbeing, caregiver quality of life and function, post-traumatic stress, and physical symptoms. Lifestyle surveys describe participants’ diet, physical activity, and substance use. Permission is secured to bank tumor specimens and germline samples, as well as for medical record review and ongoing follow up. Germline whole genome sequencing is conducted at 30X coverage. Tumor tissue sequencing is carried out by the Tempus xT, a panel of 648 cancer related genes at Tempus, Inc. Establishment of a cohort of sarcoma survivors across the lifespan, with extensive and well characterized clinical and epidemiologic data, patient reported outcomes, tumor tissue, germline DNA, and serial blood samples builds a foundation for a long-term prospective investigation on life after sarcoma. Identification of health outcomes and their predictive and prognostic factors can lead to precision treatment and survivorship care, which are currently clinically unmet needs. Clinicaltrials.gov, NCT06482957, Registered June 12, 2024.