Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or metastatic pancreatic cancer (mPC). However, no randomized trials comparing the two schemes have been performed. This meta-analysis aims to compare GEM-NAB and FOLFIRINOX in terms of safety and effectiveness, taking into account data from real-life studies on mPC. We systematically searched PubMed, EMBASE and Cochrane library up to November 2018 to identify retrospective or cohort studies on mPC comparing GEM-NAB and FOLFIRINOX. We included 16 retrospective studies, including 3813 patients (2123 treated with GEM-NAB and 1690 treated with FOLFIRINOX). Despite a median weighted overall survival (OS) difference in favor of FOLFIRINOX (mean difference: 1.15, 95% confidence interval CI 0.08–2.22, p = 0.03), in whole population OS was similar (hazard ratio (HR = 0.99, 95% CI 0.84–1.16; p = 0.9). PFS was also not different between the two arms (HR = 0.88, 95% CI 0.71–1.1; p = 0.26). The overall response rate was similar (25 vs. 24% with GEM-NAB and FOLFIRINOX). Among grade 3–4 toxicities, neutropenia, febrile neutropenia, and nausea were lower with GEM-NAB, while neurotoxicity and anemia were lower with FOLFIRINOX. In conclusion, despite a numerically longer median OS with FOLFIRINOX as compared to GEM-NAB, the overall risk of death and progression were similar. Their toxicity was different with less nausea, neutropenia, and febrile neutropenia with GEM-NAB, as compared to less neurotoxicity and anemia with FOLFIRINOX. Therefore, analysis of non-randomized “real world” studies to date has not provided evidence of a major benefit of one regimen over the other.

Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of irAEs versus no irAEs according to fixed or random-effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. A total of 30 studies that included a total of 4324 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death [HR=0.49, 95% confidence interval (CI): 0.38–0.62; P<0.001]. Similarly, the occurrence of irAEs was associated with a reduced risk of progression (HR=0.51, 95% CI: 0.42–0.64; P<0.001). The odds of response was 4.56 (95% CI: 3.72–5.59; P<0.001). In patients treated with ICIs, irAEs predict survival and response. Although this correlation cannot be fully explained, it may be related to the strongest T-cell activation.

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Background/Aim: About 15-20% of colorectal cancers (CRCs) have deficiency in a mismatch repair (MMR) protein. MMR has a high level of microsatellite instability (MSI-H). We have conducted this review and meta-analysis to determine the prognostic role of MSI-H status in stage II CRC. Materials and Methods: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, and SCOPUS for studies reporting data on overall survival (OS) and disease-free or relapse-free survival (DFS or RFS) for MSI-H compared to microsatellite stable (MSS) CRC. Results: A total of 39 studies were analysed, including 12,110 patients. MSI-H status was associated with a significantly reduced risk of death (HR=0.64, 95%CI=0.52-0.8, p<0.01) and relapse (HR=0.59, 95%CI=0.45-0.77, p<0.01) in stage II CRC. Conclusion: MSI-H represents an important prognostic determinant in stage II CRC and may be considered when estimating the risk of recurrence in stage II CRC. Stage II colorectal cancer (CRC) is usually associated with a good prognosis; five-year overall survival (OS) rates range from 75 to 87.5% (1). However, the administration of postoperative 5-fluorouracil (5-FU)-based chemotherapy in this group of patients remains controversial, since it has been shown that survival gain generally does not exceed 5% (2). Several prognostic factors have been evaluated in order to identify a high-risk stage II CRC subgroup, for which adjuvant chemotherapy would have a better indication. High-risk features include an inadequate sampling of lymph nodes (less than 12), extension of primary tumor (pT4), poor differentiation (grade 3), acute onset of the disease with obstruction or perforation, lymph-vascular and perineural invasion, and close, indeterminate or positive resection margins (3). Recently, microsatellite instability status (MSI) has been identified as a reliable prognostic indicator in stage II CRC, with an additional role in predicting the lack of benefit of 5-FU-based adjuvant chemotherapy (4-6). These data have been replicated in the large randomized phase III Quick and Simple and Reliable (QUASAR) trial, where 2,291 patients with stage II CRC were randomized to receive adjuvant chemotherapy with 5-FU and folinic acid or to undergo observation. An analysis performed on these patients found a prognostic role for MMR status, even if it was not shown to be predictive of any benefit from adjuvant chemotherapy (6). Although a number of molecular markers of outcome in CRC has been proposed (BRAF/KRAS), there has been no clear consensus about their role in early stage CRC. Despite that a series of studies have investigated the relationship between MSI status and survival in CRC patients, they often included mixed populations of early (stage II-III) and advanced CRCs (stages IV). The aim of our study was to evaluate the prognostic significance of MMR status in stage II CRC by analyzing all the available data coming from prospective and retrospective studies.

We evaluated the prognosis of colorectal cancer in patients with diabetes mellitus. The present meta-analysis involved 82 observational studies (5,267,980 participants). Diagnosis of diabetes was associated with an increased risk of mortality.

The aim of this meta analysis was to evaluate the benefit of adding concomitant trastuzumab to neoadjuvant(anthracycline and taxane-based) chemotherapy, which was assessed based on two published randomized controlled trials. The eligible patients were randomized to receive either neoadjuvant chemotherapy alone or with concurrent administration of trastuzumab. Relative risks(RRs) with 95% confidence intervals of pathologically complete response in breast and nodes, relapse-free survival, overall survival, and cardiotoxicity were calculated.The RR of obtaining a pathologically complete response in breast and nodes was 2.07 in the experimental arms(1.41–3.03; P = 0.0002; P for heterogeneity 0.63; fixed effect model). The RR of being disease free was 0.67 in favor of the experimental arms (0.48–0.94; P = 0.02; P for heterogeneity 0.22; fixed affect model). The RR of being alive was 0.67 in favor of the experimental arms (0.39–1.15;P= 0.15). The RR of a cardiac event was 1.09 in the arms treated with chemotherapy and concomitant trastuzumab, but that is not significant (0.6–1.98; P =0.77). The addition of concomitant trastuzumab to neoadjuvant chemotherapy doubles the risk of obtaining a pathologically complete response in both breast and nodes compared with controls. Trastuzumab significantly reduces the risk of relapse and does not increase the risk of cardiotoxicity,despite being associated with anthracyclines. The largest benefit was observed in a locally advanced patient study.

A high m-GPS is associated with poor OS in colorectal cancer. The m-GPS is a cheap and easily evaluable biomarker, and its incorporation into known prognostic scores for clinical decision making warrants further investigation in this setting.