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List of Ethics Committes that approved the study protocol. (DOCX 116Â kb)

Objective: We built and externally validated a nomogram for predicting the overall survival (OS) probability of advanced gastric cancer patients receiving second-line treatment. Methods: The nomogram was developed on a set of 320 Italian patients and validated on two independent sets (295 Italian and 172 Korean patients). Putative prognostic variables were selected using a random forest model and included in the multivariable Cox model. The nomogram’s performance was evaluated by calibration plot and C index. Results: ECOG performance status, neutrophils to lymphocytes ratio, and peritoneal involvement were selected and included into the multivariable model. The C index was 0.72 (95% CI 0.68–0.75) in the development set, 0.69 (95% CI 0.65–0.73) in the Italian validation set, but only 0.57 (95% CI 0.52–0.62) in the Korean set. While Italian calibrations were quite good, the Korean one was poor. Regarding 6-month OS predictions, calibration was best in both Caucasian cohorts and worst the in Asian one. Conclusions: Our nomogram may be a useful tool to predict 3- or 6-month OS in Caucasian gastric cancer patients eligible for second-line therapy. Based on three easy-to-collect variables, the Gastric Life nomogram may help clinicians improve patient selection for second-line treatments and assist in clinical trial enrollment.

Background Obesity is associated with an increased risk of development and recurrence of colorectal cancer. The role of obesity in mCRC patients (pts) is still unclear, especially in those treated with triplet plus bevacizumab (bev). The aim of our study was to evaluate the prognostic and predictive role of BMI in mCRC pts treated with FOLFOXIRI plus bev or FOLFIRI/FOLFOX plus bev in the TRIBE and TRIBE-2 trial. Methods 1160 pts enrolled in TRIBE and TRIBE-2 trials were included. Baseline height and weight were used to assign patients to one of the following BMI categories: underweight (group A = BMI 30 kg/m2; 156 pts). Results In our population, no differences in terms of PFS (p = 0.38) or OS (p = 0.93) resulted between three groups. No interaction effect between treatment arm and BMI was evident in terms of PFS (HR: 0.70 [95%CI: 0.40-1.22]; HR: 0.78 [95%CI: 0.68-0.89]; HR: 0.66 [95%CI: 0.48-0.91]; p for interaction= 0.61, in group A,B,C respectively) or OS (Group A HR: 0.62 [95%CI: 0.31-1.25]; Group B HR: 0.84 [95%CI: 0.72-0.98];Group C HR: 0.67 [95%CI: 0.46-0.99] p for interaction= 0.44). No statistically significant difference in terms of dose reductions due to toxicities were required according to BMI in overall population (p = 0.48) and in pts treated with FOLFOXIRI plus bev (p = 0.57). Conclusions BMI was not prognostic either for PFS or for OS in our population. Our analyses showed that the advantage of FOLFOXIRI plus bev versus FOLFIRI/FOLFOX plus bev was independent from BMI. Legal entity responsible for the study Daniele Santini. Funding Has not received any funding. Disclosure A. Falcone: Advisory / Consultancy, advisory board and Institutional funding to research: Amgen; Advisory / Consultancy, advisory board and Institutional funding to research: Roche; Advisory / Consultancy, advisory board and Institutional funding to research: Bayer; Advisory / Consultancy, advisory board and Institutional funding to research: Merck; Advisory / Consultancy, advisory board and Institutional funding to research: Servier; Advisory / Consultancy, advisory board and Institutional funding to research: Lilly. All other authors have declared no conflicts of interest.

Aim: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). Materials & methods: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. Results: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. Conclusion: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.