FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting

ASO Visual Abstract: FOLFIRINOX or Gemcitabine Based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-Institutional, Patient-Level Meta-Analysis and Systematic Review

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The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma

The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers. Programmed death ligand 1 (PDL1) overexpression, a possible biomarker predicting response to immune checkpoint inhibitors, approaches forty percent in esophageal and gastric cancers. Translational and molecular studies have shown that esophageal cancers are possible candidate malignancies for immune checkpoint inhibition. In this review, we plan to highlight the mechanisms, preclinical, and early clinical data that provide insight on the role of immune therapeutics in esophageal cancers

Predictive and prognostic effects of primary tumor size on colorectal cancer survival

Background: Pathologic staging is crucial in colorectal cancer (CRC). Unlike the majority of solid tumors, the current staging model does not use tumor size as a criterion. We evaluated the predictive and prognostic impact of primary tumor size on all stages of CRC. Methods: Using the National Cancer Database (NCDB), we conducted an analysis of CRC patients diagnosed between 2010 and 2015 who underwent resection of their primary cancer. Univariate and multivariate analyses were used to identify predictive and prognostic factors, Kaplan-Meier analysis and Cox proportional hazards models for association between tumor size and survival. Results: About 61,000 patients met the inclusion criteria. Median age was 63 years and majority of the tumors were colon primary (82.7%). AJCC stage distribution was: I - 20.1%; II - 32.1%; III - 34.7% and IV - 13.1%. The prognostic impact of tumor size was strongly associated with survival in stage III disease. Compared to patients with tumors \u3c2cm; those with 2-5cm (HR 1.33; 1.19-1.49; p\u3c0.001), 5-10cm (HR 1.51 (1.34-1.70; p\u3c0.001) and \u3e10cm (HR 1.95 (1.65-2.31; p\u3c0.001) had worse survival independent of other variables. Stage II treated without adjuvant chemotherapy had comparable survival outcomes (HR 1.09; 0.97-1.523; p=0.148) with stage III patients who did, while Stage II patients who received adjuvant chemotherapy did much better than both groups (HR 0.76; 0.67-0.86; p\u3c0.001). Stage III patients who did not receive adjuvant chemotherapy had the worst outcomes among the non-metastatic disease subgroups (HR 2.66; 2.48-2.86; p\u3c0.001). Larger tumors were associated with advanced stage, MSI high, non-rectal primary and positive resection margins. Conclusions: Further studies are needed to clarify the role of tumor size in prognostic staging models, and how to incorporate it into therapy decisions