Dataset Information

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

ABSTRACT: BACKGROUND:Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. METHODS:This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. RESULTS:Baseline splenic volume > 180 mL was associated with poor PFS (median PFS = 9.2 versus 11.1 months; log-rank p = 0.0125), but was not statistically associated with OS (median OS = 22.6 versus 28.5 months; log-rank p = 0.1643). The increase in splenic volume at 3 months had no impact on PFS (HR 0.928; log-rank p = 0.56) or on OS (HR 0.843; log-rank p = 0.21). Baseline splenic volume was positively correlated with the level of baseline circulating mMDSC (r = 0.48, p-value = 0.031). CONCLUSION:Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation.

SUBMITTER: Niogret J

PROVIDER: S-EPMC7352427 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

Niogret Julie J Limagne Emeric E Thibaudin Marion M Blanc Julie J Bertaut Aurelie A Le Malicot Karine K Rinaldi Yves Y Caroli-Bosc François-Xavier FX Audemar Franck F Nguyen Suzanne S Sarda Corinne C Lombard-Bohas Catherine C Locher Christophe C Carreiro Miguel M Legoux Jean-Louis JL Etienne Pierre-Luc PL Baconnier Mathieu M Porneuf Marc M Aparicio Thomas T Ghiringhelli Francois F

Cancers 20200531 6

<h4>Background</h4>Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan.<h4>Methods</h4>This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by u ...[more]

PMID: 32486421

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Project description:ObjectiveRecognizing what physicians know and do not know about a particular disease is one of the keys to designing clinical decision support systems, since these systems can fulfill complementary role by recognizing this boundary. To our knowledge, however, no study has attempted to quantify how many diseases physicians actually know and thus the boundary is unclear. This study explores a method to solve this problem by investigating whether the vocabulary assessment techniques developed in the linguistics field can be applied to assess physicians' knowledge.MethodsThe test design required us to pay special attention to disease knowledge assessment. First, to avoid imposing unnecessary burdens on the physicians, we chose a self-assessment questionnaire that was straightforward to fill out. Second, to prevent overestimation, we used a "pseudo-word" approach: fictitious diseases were included in the questionnaire, and positive responses to them were penalized. Third, we used paper-based tests, rather than computer-based ones, to further prevent participants from cheating by using a search engine. Fourth, we selectively used borderline diseases, i.e., diseases that physicians might or might not know about, rather than well-known or little-known diseases, in the questionnaire.ResultsWe collected 102 valid answers from 109 physicians who attended the seminars we conducted. On the basis of these answers, we estimated that the average physician knew of 2008 diseases (95% confidence interval: (1939, 2071)). This preliminary estimation agrees with the guideline for the national license examination in Japan, suggesting that this vocabulary assessment was able to evaluate physicians' knowledge. The survey included physicians with various backgrounds, but there were no significant differences between subgroups. Other implication for researches on clinical decision support and limitation of the sampling method adopted in this study are also discussed, toward more rigorous estimation in future surveys.

Project description:Background: The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. The utility of zFOLFIRI after bevacizumab+FOLFIRI is unknown and not recommended in NCCN guidelines. We explored whether zFOLFIRI may be active beyond progression on bevacizumab+FOLFIRI. Methods: We undertook a retrospective analysis of patients treated in routine clinical practice. A chart review was conducted for a cohort (N = 19) of advanced cancer patients (18 mCRC) who received zFOLFIRI from 2014 to 2018 at Fox Chase Cancer Center (FCCC). Analysis included time on zFOLFIRI, PFS, OS, CEA trends and adverse events. A second mCRC cohort (N = 26) from the Flatiron Health EHR-derived database treated with zFOLFIRI after prior bevacizumab+FOLFOX and bevacizumab+FOLFIRI was analyzed for time-on-treatment and overall survival. Results: Median age of mCRC cohort at zFOLFIRI treatment was 54 (FCCC; N = 18) and 62 (Flatiron Health-cohort; N = 26). Of 18 FCCC mCRC patients, 1 patient had prior bevacizumab+FOLFOX and ramucirumab+irinotecan prior to zFOLFIRI for 8.5 months. Of 17 FCCC mCRC patients with prior bevacizumab+FOLFIRI who received zFOLFIRI, 13 had mutant-KRAS, 3 WT-KRAS, and one BRAF-V600E. The patient with BRAF-V600E mutation achieved stable disease on zFOLFIRI after multiple BRAF-targeted therapies. One patient (WT-KRAS mCRC) remained on zFOLFIRI for 14 months. Of 14 patients with mutated-KRAS, 8 remained on zFOLFIRI for >5 months including 3 for >15 months. The rate-of-change in CEA measures on zFOLFIRI was significantly different (p = 0.004) between rapid progressors and those with PFS>4 months. For mCRC patients treated with zFOLFIRI in the 3rd line or greater (N = 18), median PFS was 7.1 months (214 days) and median OS was 13.8 months (416 days). Median time-on-treatment with zFOLFIRI in the Flatiron Health cohort was 4.4 months, median OS was 7.8 months, and longest time-on-treatment with zFOLFIRI was 266 days. Conclusions: In these small real-world cohorts, clinical meaningful stable disease and overall survival on zFOLFIRI beyond progression on bevacizumab+FOLFIRI was observed in patients with mCRC. Further exploration of this approach is warranted.

Dataset Information

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

Publications

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

Similar Datasets

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