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Background and purpose: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, 10%-30% of NSCLC patients with EGFR sensitive mutation still have primary drug resistance when receiving TKI targeted therapy. Therefore, to study the clinical efficacy of EGFR-TKI and find out its prognostic predictors has important significance for the treatment of advanced NSCLC patients with EGFR sensitive mutation. The purpose of this research was to evaluate the efficacy of icotinib as first-line treatment in patients with EGFR-mutant advanced NSCLC and investigate the prognostic predictors. Methods: A total of 258 stage ⅢB-Ⅳ NSCLC patients with EGFR mutation who were admitted to Fujian Cancer Hospital from January 2016 to November 2017 were selected. One hundred and eighteen advanced NSCLC patients with EGFR mutation were enrolled, and baseline circulating tumor DNA (ctDNA) EGFR-mutant status was determined using the plasma test. All these patients received icotinib 125mg three times a day. The χ2 test was used to compare the differences in clinicopathological characteristics between different EGFR mutation groups. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier survival curve. The log-rank test was used for univariate analysis, and the COX regression model was used for multivariate analysis. Results: The objective response rate (ORR) of 118 patients was 62.7% (95% CI: 53.9%-71.6%), the disease control rate (DCR) was 92.4% (95% CI: 87.5%-97.2%), and the median PFS was 11.3months (95% CI: 9.1-13.5 months), and the median OS was 32.0 months (95% CI: 26.9-37.1 months). No statistically significant difference was found in the clinicopathological characteristics between different EGFR expression types (P>0.05), while the best efficacy between different EGFR mutation groups was significantly different (P=0.040). Univariate analysis showed that EGFR mutation status in plasma ctDNA test was not correlated with PFS and OS of patients (P>0.05). Multivariate analysis showed that baseline lactate dehydrogenase (LDH) expression level, EGFR types, pleural effusion and the best curative effect might be independent factors of PFS. The patient’s N stage, bone metastasis, time to PFS and presence of EGFR T790M mutation might be independent predictors of OS. Conclusion: Icotinib as first-line treatment was effective in EGFR-mutant advanced NSCLC patients. The EGFR mutation status in plasma ctDNA test was not correlated with the clinical efficacy of patients. Bone metastasis was found to be an independent factor of worse prognosis.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms. Plain language summary: Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better. [ABSTRACT FROM AUTHOR]

Background: R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. Methods: Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high‐density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL‐focused microarray, comparative results based on event‐free survival at 24 months (EFS24) and lasso Cox regression models of progression‐free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme‐linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two‐AAb‐based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598). Results: Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p <.05) and superior PFS and OS (p <.05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R‐CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p <.05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p <.05). Conclusions: This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL. Autoantibodies (AAbs) have the potential for personalized monitoring of tumor recurrence. Serological AAbs against N4BP1, CREB1, DEAF1, and UBAP2 were independent of International Prognostic Index traditional risk factors for diffuse large B‐cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Notably, two of these biomarkers, CREB1 and N4BP1, exhibited prognostic significance at multiple levels, including messenger RNA, protein, and AAb. These findings suggest that monitoring AAb levels during treatment may be a useful tool for predicting prognosis and guiding personalized treatment strategies for patients with DLBCL. [ABSTRACT FROM AUTHOR]

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020., Methods: We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov., Findings: A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013-2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing ( n =273) and Shanghai ( n =257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors., Interpretation: In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy., Funding: This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001)., Competing Interests: All authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)