Chemotherapy outcome predictive effectiveness by the Oncogramme: pilot trial on stage-IV colorectal cancer

Abstract

Background: Colorectal cancer (CRC) remains a major public concern. While conventional chemotherapeutic regimens have proved useful against advanced/metastatic diseases, progresses are to be made to effectively cure the large portion of patients not benefiting from these treatments. One direction to improve response rates is to develop chemosensitivity and resistance assays (CSRAs) efficiently assisting clinicians in treatment selection process, an already long preoccupation of oncologists and researchers. Several methods have been described to this day, none achieving yet sufficient reliability for recommended use in the clinical routine.

Methods: We led a pilot study on 19 metastatic CRC patients evaluating capacity of the Oncogramme, a standardized process using tumor ex vivo models, to provide chemosensitivity profiles and predict clinical outcome of patients receiving standard CRC chemotherapeutics. Oncogramme responses were categorized according to the method of percentiles to assess sensitivity, specificity and concordance.

Results: We report from a primary analysis a success rate of 97.4 %, a very good sensitivity (84.6 %), a below-average specificity (33.3 %), along with a global agreement of 63.6 % and a concordance between Oncogramme results and patients' responses (Kappa coefficient) of 0.193. A supplementary analysis, focusing on CRC patients with no treatment switch over a longer time course, demonstrated improvement in specificity and concordance.

Conclusions: Results establish feasibility and usefulness of the Oncogramme, prelude to a larger-scale trial. Advantages and drawbacks of the procedure are discussed, as well as the place of CSRAs within the future arsenal of methods available to clinicians to individualize treatments and improve patient prognosis.

Trial registration: ClinicalTrials.gov database, registration number: NCT02305368.

Fig. 1

a Overview of patient selection process in the pilot trial, from initial recruitment to final inclusion. From the 64 individuals originally recruited, exclusion and inclusion criteria allowed to finally select 19 patients with stage-IV CRC, pre- + post- or post-surgery treatment, RECIST 1.1-measurable lesions and consistent clinical follow-up. b Overview of the Oncogramme experimental procedure, from surgery to readout. Viable samples were recovered and processed to obtain primary cultures that were subsequently utilized for realization of the Oncogramme by exposure to chemotherapeutic drugs and cell death analysis. Whole time course was inferior to 2 weeks