Clinical Utility of a Circulating Tumor Cell Detection Test for Detection of Soild Organ Cancers in Asymptomatic Individuals

According to the most recent predictions by the International Agency for Research on Cancer GLOBOCAN project, India’s cancer burden will nearly double in the next 20 years, from a million new cases in 2012 to more than 1.7 million by 2035. The age-standardized prevalence of cancer is estimated to be 97 per 100,000 persons with greater prevalence in urban areas. The evidence suggests that cancer prevalence is highest among the elderly and also among females in the reproductive age groups. In general, there is a consensus that about 60 percent of cancer deaths can be prevented with improved preventive (removing the causes of disease so theta exposure to risk is minimal) and screening (test or procedure used to detect disease) facilities. A key factor responsible for high cancer mortality (at 68% of the annual incidence) and lower survival in cancer patients is the late stage of diagnosis. Hence early detection is the key to improve disease outcomes with increased disease free and overall survival. Currently there are no high sensitivity and specificity screening tools available which can detect all cancers at early stage with minimal harm to the patient and can be used as a mass screening tool even for the patients without access to advanced healthcare facilities. Liquid biopsy involves the analysis of biomarkers like circulating tumor cells (CTCs), cell-free nucleic acids -circulating free DNA (cfDNA), exosomal messenger RNA (mRNA) and micro RNA (miRNA) in bodily fluids such as blood. However, development of methods for noninvasive detection of cancer has still not been standardized. Circulating tumor cells (CTCs) are the tumor cells which have detached from primary tumor site and have gained access to peripheral circulation. These may potentially lodge in distant organs giving rise to metastasis. Thus, CTCs are a pre-requisite for distant disease spread and are detectable before late stage/metastatic disease develops. CTCs have additional advantage of expressing tissue-of-origin specific markers giving rise to possibility of identification of primary tumor site. The evaluation of CTCs in cancer management, has potential to extend beyond prognostication. As technologies emerge to analyze CTCs at the molecular level, biological behavior of the tumor can be obtained in real time, with the promise of CTCs eventually acting as a ‘surrogate tumor biopsy’. All in all, CTC-based liquid biopsy has potential for non­invasive, accurate blood based cancer screening modality to improve patient care and quality of life. Current study is undertaken to evaluate the feasibility of a CTC based test for cancer screening in asymptomatic individuals. This is an observational study to evaluate the clinical utility and performance of a CTC based test for detection of solid organ cancers. The study has 2 cohorts, viz., suspected cases of cancers and asymptomatic individuals with no prior diagnosis of cancer or symptoms suspected of cancer. A cumulative enrollment of 10000 individuals is planned. The study investigator or an authorized representative will identify individuals eligible for the study, based on the inclusion/exclusion criteria. After providing all necessary information related to study, and after obtaining written informed consent from eligible participants, 15 ml blood will be drawn from all participants as per study protocol. The suspected cases will subsequently undergo a tumor tissue biopsy as part of standard diagnostic work up (outside the scope of the study), and the findings will be made available to the study investigators. Consenting participants in the asymptomatic cohort as well as those in the symptomatic cohort diagnosed with benign conditions will be telephonically followed up for 1 year for any diagnosis of cancer or symptoms suspected of cancer necessitating a diagnostic work-up. On the completion of the cohorts, data will be analyzed to evaluate the study objectives. The primary objective is to determine the performance characteristics of a Circulating Tumor Cell based Test for detection and tissue/organ of origin localization of cancers and differentiating cancer cases from benign cases and asymptomatic individuals. The secondary objective is to determine the clinical utility of a Circulating Tumor Cell based Test for molecular, theranostic and drug response-resistance profiling as well as longitudinal monitoring of cancer. The exploratory objectives is to identify and determine the performance characteristics of other additional biomarkers in cancers. The primary outcome measure is to determine Specificity and Sensitivity of the Test for detection and tissue/organ of origin localization of cancers and differentiating cancer cases from benign cases and asymptomatic individuals. The secondary outcome measure is to determine Specificity and Sensitivity of the Test for molecular, theranostic and drug response­ resistance profiling as well as longitudinal monitoring of cancer.