Timothy Crook1, Andrew Gaya2, Raymond Page3, Sewanti Limaye4, Anantbhushan Ranade5, Amit Bhatt5, Sanket Patil6, Prashant Kumar6,7,8, Darshana Patil6, Dadasaheb Akolkar9. 1. Department of Oncology, Broomsfield Hospital, Chelmsford, UK. 2. HCA Healthcare UK, London, W1G 6AF, UK. 3. Worcester Polytechnic Institute, Worcester, USA. 4. Department of Medical Oncology, Kokilaben Dhirubai Ambani Hospital, Mumbai, India. 5. Department of Medical Oncology, Avinash Cancer Clinic, Pune, India. 6. Datar Cancer Genetics, F-8 D-Road, Ambad, Nasik, 422010, India. 7. Institute of Bioinformatics, International Technology Park, Bangalore, 560066, Karnataka, India. 8. Manipal Academy of Higher Education (MAHE), Manipal, 576104, Karnataka, India. 9. Datar Cancer Genetics, F-8 D-Road, Ambad, Nasik, 422010, India. dadasaheb.akolkar@datarpgx.com.
Abstract
PURPOSE: Selection of cytotoxic chemotherapy agents (CCA) based on pre-treatment evaluation of drug sensitivities is a desirable but unmet goal for personalized anticancer treatment strategies. Prior attempts to correlate in vitro Chemo-Response Profiles (CRP) of tumor explants or Circulating Tumor Cells (CTCs) with clinical outcomes have been largely unsuccessful. METHODS: We present results from a large cohort (n = 5090, three Arms) of patients with various solid organ tumors, where CRP of Circulating Tumor-Associated Cells (C-TACs) was determined against cancer-specific CCA panels to generate a database of 56,466 unique CRP. RESULTS: In Arm 1 (n = 230), 93.7% concordance was observed between CRP of C-TACs and concurrently obtained Tumor tissue Derived Cells (TDCs). In arm 2 (n = 2201, pretreated), resistance of C-TACs to ≥ 1 CCA was observed in 79% of cases. In a blinded subset analysis of 143 pretreated patients with radiologically ascertained disease progression, CRP of C-TACs was 87% concordant with in vivo treatment failure. In Arm 3 (n = 2734, therapy naïve), innate resistance of C-TACs to ≥ 1 CCA was observed in 61% of cases. In a blinded subset analysis of 77 therapy naïve patients, in vitro chemo-sensitivity of C-TACs was concordant with radiologically ascertained treatment response to first line CCA in 97% of cases. CONCLUSION: To our knowledge, this is the first expansive and in-depth study demonstrating that real-time CRP of C-TACs is a viable approach for non-invasive assessment of response to CCA in solid organ cancers.
PURPOSE: Selection of cytotoxic chemotherapy agents (CCA) based on pre-treatment evaluation of drug sensitivities is a desirable but unmet goal for personalized anticancer treatment strategies. Prior attempts to correlate in vitro Chemo-Response Profiles (CRP) of tumor explants or Circulating Tumor Cells (CTCs) with clinical outcomes have been largely unsuccessful. METHODS: We present results from a large cohort (n = 5090, three Arms) of patients with various solid organ tumors, where CRP of Circulating Tumor-Associated Cells (C-TACs) was determined against cancer-specific CCA panels to generate a database of 56,466 unique CRP. RESULTS: In Arm 1 (n = 230), 93.7% concordance was observed between CRP of C-TACs and concurrently obtained Tumor tissue Derived Cells (TDCs). In arm 2 (n = 2201, pretreated), resistance of C-TACs to ≥ 1 CCA was observed in 79% of cases. In a blinded subset analysis of 143 pretreated patients with radiologically ascertained disease progression, CRP of C-TACs was 87% concordant with in vivo treatment failure. In Arm 3 (n = 2734, therapy naïve), innate resistance of C-TACs to ≥ 1 CCA was observed in 61% of cases. In a blinded subset analysis of 77 therapy naïve patients, in vitro chemo-sensitivity of C-TACs was concordant with radiologically ascertained treatment response to first line CCA in 97% of cases. CONCLUSION: To our knowledge, this is the first expansive and in-depth study demonstrating that real-time CRP of C-TACs is a viable approach for non-invasive assessment of response to CCA in solid organ cancers.
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