Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

During the past 2 decades, genetic predictors of prognosis have been used with increasing frequency for patients with colorectal liver metastasis (CRLM).¹ Several investigators have reported on the prognostic value of somatic mutations in the KRAS (OMIM 190070) in patients with resectable CRLM.^2-6 Although only 2 studies had assessed KRAS mutational status as a prognostic factor in the 1990s, at least 14 additional studies have been published since 2000.^7,8 A 2015 meta-analysis demonstrated the adverse effect of KRAS mutations on prognosis by pooling survival data from 326 patients with KRAS-mutated tumors.⁹

This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0–1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. ICC makes up about 10% of all cholangiocarcinomas. It arises from the peripheral bile ducts within the liver parenchyma, proximal to the secondary biliary radicals. Histologically, the majority of ICCs are adenocarcinomas. Only a minority of patients (15%) present with resectable disease, with a median survival of less than 3 years. Multidisciplinary management of ICC is complicated by large differences in disease course for individual patients both across and within tumor stages. Risk models and nomograms have been developed to more accurately predict survival of individual patients based on clinical parameters. Predictive risk factors are necessary to improve patient selection for systemic treatments. Molecular differences between tumors, such as in the epidermal growth factor receptor status, are promising, but their clinical applicability should be validated. For patients with locally advanced disease, several treatment strategies are being evaluated. Both hepatic arterial infusion chemotherapy with floxuridine and yttrium-90 embolization aim to downstage locally advanced ICC. Selected patients have resectable disease after downstaging, and other patients might benefit because of postponing widespread dissemination and biliary obstruction.

Objective: To examine the impact of surgical margin width on survival following R0 hepatic resection for colorectal metastases (CRLM). Summary of Background Data: Although negative resection margin is considered of paramount importance for the prognosis of patients with colorectal liver metastases, optimal resection margin width remains controversial. Methods: Eligible studies examining the association between margin status after R0 hepatic resection for CRLM and survival, including overall survival (OS) and disease-free survival (DFS) were sought using the Medline, Cochrane, and EMBASE databases. Random-effects models were used for the calculation of pooled relative risks (RRs) with their 95% confidence intervals (95% CIs). Results: Thirty-four studies were deemed eligible for inclusion representing a cohort of 11,147 hepatic resections. Wider resection margin (>1 vs 1 cm resection margin at 3, 5, and 10 years. Interestingly, >1 mm (vs 1 mm margin is associated with better prognosis than a submillimeter margin, achieving a margin >1 cm may result in even better oncologic outcomes and should be considered if possible.