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

Abstract

BackgroundColorectal 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.ResultsWe 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.ConclusionsResults 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: NCT02305368Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0765-4) contains supplementary material, which is available to authorized users.

Clinical Usefulness of Tools to Support Decision-making for Palliative Treatment of Metastatic Colorectal Cancer: A Systematic Review

“…We identified 10 prognostic scores, [13][14][15][17][18][19][20][22][23][24] 3 nomograms, 16,21,25 and 1 chemotherapy sensitivity and resistance assay. 26 Of the 14 tools, Embase "colon tumor"/exp OR "colorectal tumor"/exp OR "colonic neoplasm*":ab,ti OR "colon neoplasm*":ab,ti OR "cancer of colon":ab,ti OR "cancer of the colon":ab,ti OR "colon cancer*":ab,ti OR "colonic cancer*":ab,ti OR "colorectal neoplasms*":ab,ti OR "colorectal tumor*":ab,ti OR "colorectal tumour*":ab,ti OR "colorectal carcinoma*":ab,ti OR "colorectal cancer*":ab,ti AND "decision support system"/exp OR "nomogram"/exp OR "probability"/exp OR "decision support system*":ab,ti OR "decision support technique*":ab,ti OR "decision aid*":ab,ti OR "decision support model*":ab,ti OR "decision analys*":ab,ti OR decision AND modeling:ab,ti OR "prediction rule*":ab,ti OR probabilit*:ab,ti OR nomogram*:ab,ti OR (prognos*:ab,ti AND (index:ab,ti OR score*:ab,ti OR model*:ab,ti)) OR markov:ab,ti AND "prognosis"/exp OR "incidence"/exp OR "mortality"/exp OR "follow up"/exp OR predict*:ab,ti OR course*:ab,ti OR mortalit*:ab,ti OR "life expectancy"/exp OR "survival rate"/exp OR "longevity"/exp OR "longevity":ab,ti OR "life expectancy":ab,ti OR "life expectance":ab,ti OR "life expectation":ab,ti OR "survival":ab,ti OR prognos*:ab,ti OR toxicit*:ab,ti OR "toxic potential*":ab,ti OR "margin of safety":ab,ti OR "adverse effect*":ab,ti AND ("article"/it OR "article in press"/it OR "review"/it) Cochrane Library "Incidence" OR mortality OR follow up studies OR prognos* OR predict* OR course* OR mortalit* OR "life expectancy" OR "longevity" OR "life expectancy" OR "life expectance" OR "life expectation" OR "survival" OR toxicit* OR toxic potential* OR "margin of safety" OR adverse effect* OR survival:ti,ab,kw AND "decision support system*" OR "decision support technique*" OR "decision aid*" OR "decision support model*" OR "decision analys*" OR "decision modeling OR prediction rule*" OR nomogram* OR (prognos* and (index or score* or model*)) or markov:ti,ab,kw AND "colonic neoplasm*" OR "colon neoplasm*" OR "cancer of colon" OR "cancer of the colon" OR "colon cancer*" OR "colonic cancer*" OR "colorectal neoplasms*" OR "colorectal tumor*" OR "colorectal tumour*" OR "colorectal carcinoma*" OR "colorectal cancer*":ti,ab,kw Cutoffs were determined by when the last major changes in treatment advice were introduced in the Dutch treatment guidelines (which roughly coincided with international guidelines).…”

“…[17][18][19][20][21][22] Eight of the DSSs identified were developed and/ or only validated in Asian [13][14][15]25 or European populations. 16,20,21,26 Furthermore, great variation was found in the factors included in the DSSs. Only 3 factors were incorporated in > 2 DSSs (ie, patient age, performance status, and distant metastasis location; Figure 3).…”

“…[17][18][19][20][21]23,24 One DSS aimed to help oncologists select the most effective chemotherapy regimen. 26 Finally, 1 DSS aimed to help oncologists select patients likely to develop a severe side effect a priori to take preventive measures. 25…”

Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment

“…Patient-derived models of cancer, including PDCOs show great promise in trialling therapies before they reach the patient and evidence supporting how accurately these ex vivo models can predict patient response is beginning to emerge [32,[38][39][40][41][42]. A recent report showed convincing data from ten patients that a viability assay could be used to predict patient response to irinotecan-based therapies using CRC-derived PDCOs [39].…”

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

“…Viable and dead cells are counted using a fluorescent microscope. Preliminary studies in metastasized colorectal cancer specimen reported a good sensitivity (84.6%) for the assay, although specificity was low at 33.3% .…”