Deliwala, Smit

e14591 Background: Combined immune checkpoint inhibitors (ICPI) have revolutionized treatment of solid tumors. Their use can lead to treatment-related adverse events (TRAEs) resulting in hospital admissions, treatment discontinuation and increased morbidity. We aim to evaluate gastrointestinal (GI) TRAEs of different combination ICPI. Methods: A comprehensive search of multiple databases from inception to October 2021 was performed. Phase 2 and 3 trials assessing safety and efficacy of combined ICPI in solid tumors were included. Trials reporting concurrent use of chemotherapy, immunosuppressants, targeted therapy, or sequential ICPI therapy were excluded. Primary outcome was pooled luminal, hepatic and pancreatic TRAEs. A meta-analysis of proportions was done for outcomes using a random-effects model. I2 % was used to assess heterogeneity. Results: Out of 3696 citations screened, 53 trials reporting TRAEs in 6186 patients were included. Data from 41 study arms of 35 trials in nivolumab plus ipilimumab (N+I), 15 study arms of 15 trials in durvalumab plus tremelimumab (D+T), 4 study arms of 3 trials in pembrolizumab plus ipilimumab (P+I). The most common indications for combined ICPI were melanoma (26.4%) and lung cancer (24.5%). Pooled GI TRAE rates from the D+T, P+I and two different dosing combinations of N+I are shown in the table. Conclusions: Our study provides pooled data of TRAEs from different combination ICPI use in solid tumors and demonstrates high incidence of all grades and ≥ 3 GI TRAEs. Combined ICPI related TRAEs should be recognized early, as it may require treatment discontinuation. Further studies are required to assess overall impact of TRAEs on treatment course and outcomes.[Table: see text]

Abstract Background and study aims Endoscopic mucosal resection (EMR) of laterally spreading tumors (LSTs) > 20 mm in size can be challenging. Piecemeal EMR of these lesions results in high rates of adenoma recurrence at first surveillance colonoscopy (SC1). Snare tip soft coagulation (STSC) of post resection margins is a safe and effective technique to prevent adenoma recurrence. We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of this technique. Patients and methods Multiple databases were searched through April 2021 for studies that reported on outcomes of post EMR STSC for LSTs > 20 mm in size. Meta-analysis was performed to determine pooled odds of adenoma recurrence as well as pooled proportion of adverse events including intraprocedural and delayed bleeding as well as intraprocedural perforation events. Results Six studies including two randomized controlled trials (RCT) and four cohort studies with 2122 patients were included in the final analysis. Overall pooled odds of adenoma recurrence at SC1 with post EMR STSC compared to no STSC was 0.27 (95 % 0.18–0.42; I2 = 0 %), P < 0.001. Pooled rate of adenoma recurrence at SC1 in post EMR STSC cohort was 6 %. Rates of intraprocedural bleeding, delayed bleeding and intraprocedural perforation were 10.3 %, 6.5 % and 2 % respectively. Conclusions Our results show that thermal ablation of resection margins with STSC in LSTs > 20 mm is a safe and effective technique in reducing the incidence of adenoma recurrence.