BackgroundDeciphering the correlation between immune-related adverse events (irAEs) categorized by organ system class and clinical benefit of immunotherapy is critical for clinical practice. The aim of this study is to investigate the incidence rates of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI).MethodsPubMed, Embase and Cochrane library were searched for eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were included. Logit transformation of the irAE incidences was applied for the generation of pooled estimate and Pearson correlation coefficient was calculated to evaluate the correlation between irAE and ORR.Results48 clinical trials involving 7936 patients treated with NIVO or NIVO+IPI were included. Compared to NIVO, NIVO+IPI led to more all-grade and grade 3 or higher irAEs categorized by system organ class (P < 0.05). The ORR of NIVO was positively correlated with the incidence rate of skin (r = 0.79, P < 0.001), gastrointestinal (r = 0.56, P = 0.006) and endocrine irAEs (r = 0.44, P = 0.05), but not hepatic, pulmonary and renal irAEs. The ORR of NIVO+IPI was positively correlated with the incidence rate of skin (r = 0.54, P = 0.04), and gastrointestinal irAEs (r = 0.60, P = 0.02), but not endocrine, hepatic, pulmonary and renal irAEs.ConclusionThis meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings highlight the potential of irAE to reflect response to NIVO or NIVO+IPI.

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A Type II collagen-binding peptide based NIR-II fluorescent probe for articular cartilage degeneration imaging and early osteoarthritis detection.

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Background: Histologically, SCLC are classified as pure (P-SCLC) and combined subtypes (C-SCLC). Currently, few studies compare the clinicopathological characteristics and explore the treatment strategies applied to them. Methods: Between July 2005 and April 2016, the clinical records of 297 postoperative patients with pathologically confirmed SCLC were retrospectively analyzed. Kaplan-Meier method and Cox regression model were separately used for stratified univariate and multivariate survival analysis. Results: A total of 46 cases (15.5%) of C-SCLCs and 251 cases (85.5%) of pure SCLCs (P-SCLCs) were included in this study. The average age of C-SCLCs was a little higher than that of P-SCLCs (59.65 AE 8.72 vs. 56.56 AE 10.12; P = 0.053). More patients had a history of smoking in C-SCLC (78.3% vs. 63.3%; P = 0.074). The five-year overall survival (OS) rate for P-SCLCs and C-SCLCs was 65.1% and 56.7%, respectively (P = 0.683). For P-SCLC, stage and an intervention of prophylactic cranial irradiation (PCI) were independent factors that affected OS. In C-SCLCs cases, performing sublobectomy was an independent risk factor for poor prognosis. Conclusions: We identified no significant difference in clinical characteristics and outcome between C-SCLCs and P-SCLCs. However, the factors affecting the prognosis of the two subtypes were slightly inconsistent. For C-SCLCs, the extent of resection had a greater impact on survival, and lobectomy combined with systemic lymph node dissection should therefore be performed as extensively as possible. In addition, PCI was beneficial in improving the SCLC OS rate. Key points • This study demonstrated the prognosis of C-SCLCs did not significantly differ from that of P-SCLCs, but was more susceptible to the extent of resection. Patients with C-SCLC who underwent limited resection had a significantly increased risk of shorter OS. • This study highlighted the importance of performing lobectomy for resectable C-SCLC patients. This study also proved the benefit of PCI in improving the OS rate for both P-SCLC and C-SCLC patients.