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.
Highlights
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide [1,2]
This study underlines that splenic volume could be a predictive marker of progression-free survival (PFS) in patients treated with FOLFIRI plus bevacizumab
Levels, this study raises the hypothesis that monocytic Myeloid derived suppressor cells (mMDSC) could modulate the efficacy of FOLFIRI plus bevacizumab in metastatic colorectal cancer (mCRC)
Summary
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide [1,2]. For metastatic CRC (mCRC), the typical chemotherapy backbone comprises a fluoropyrimidine (intravenous 5-FU or oral capecitabine) used in various combinations and schedules with irinotecan or oxaliplatin [4]. The classical first line chemotherapies consist in bi-chemotherapy, comprising an injection of irinotecan, fluorouracil and leucovorin (FOLFIRI) or the combination of an injection of oxaliplatin, fluorouracil and leucovorin (FOLFOX) with a biotherapy targeting VEGF or EGFR. 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 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). Conclusion: Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation
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