Clinical utility of circulating tumor-associated cells to predict and monitor chemo-response in solid tumors

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 C...

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Veröffentlicht in:Cancer chemotherapy and pharmacology 2021-02, Vol.87 (2), p.197-205
Hauptverfasser: Crook, Timothy, Gaya, Andrew, Page, Raymond, Limaye, Sewanti, Ranade, Anantbhushan, Bhatt, Amit, Patil, Sanket, Kumar, Prashant, Patil, Darshana, Akolkar, Dadasaheb
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Sprache:eng
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Zusammenfassung: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.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-020-04189-8