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As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment., Competing Interests: Declaration of interests Y.-L.W reports grants and personal fees from AstraZeneca, BMS, and Pfizer and personal fees from Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, and Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation., Methods: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS., Results: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20)., Conclusion: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed., (© 2023. The Author(s).)

Objective: This study aimed to investigate the impact of tumor mutational burden (TMB) and DNA damage repair (DDR) gene alteration on overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients., Patients and Methods: A DNA library of cancer cells from 67 NSCLC patients in stages III-IV was constructed for next-generation sequencing (NGS). Geneseeq422 probes were used for hybridization enrichment. The target-enriched library was sequenced on HiSeqNGS platforms, and we analyzed the relevant signaling pathways. Then, we correlated the OS of the patients with TMB and DDR mutations., Results: Many significant alterations were found, including in the EGFR, p53, KRAS, RB1, ERBB2, NF1, DNMT3A, ALK, MYC, PIK3CA, ROS1, BRAF, ARID1A, PTEN, CDKN2A, and FGF19 genes. We also identified many mutations in the genes relevant to the DDR pathway. Interestingly, we found that the TMB of patients with DDR gene mutations was dramatically higher than that in the DDR wild-type (WT). Univariable analysis showed that DNMT3A, RB1, DDR pathway-related gene mutations, and TMB were critical factors for the effects on OS. Multivariable analysis confirmed that DNMT3A and mutations in the DDR pathway-related genes were important for predicting OS., Conclusions: Multiple mutations in the genes of the DDR pathway caused higher TMB levels, which resulted in longer OS. By contrast, OS was significantly longer in patients with non-DNMT3A mutations than in those with DNMT3A variants. DNMT3A alteration in NSCLC patients led to poor outcomes.

Background: CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor (EGFR)., Patients and Methods: Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m(2)) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data., Results: From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40-0.75, P < 0.001] as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38-0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49-1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43-2.08, P = 0.877)., Conclusions: CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients., Clinicaltrialsgov Identifier: NCT00891579., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Objective: Neoadjuvant chemotherapy for stage IIIA non-small cell lung cancer (NSCLC) remains controversial. The role of the expressions of P53, K-ras, HER2, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), CD44, and matrix metalloproteinase-9 (MMP-9) in predicting efficacy of neoadjuvant chemotherapy on stage IIIA NSCLC is still unclear although they have been found to be related to prognosis. This study was to determine the predictive effect of multi-gene expression on treatment outcome of neoadjuvant chemotherapy for resectable stage IIIA NSCLC., Methods: Expressions of p53, K-ras, HER2, VEGF, EGFR, CD44, MMP-9 in the patients enrolled in the prospective randomized controlled trial were detected by immunohistochemistry. The treatment efficacies of combination (neoadjuvant chemotherapy combined with surgery) group (36 patients) and surgery alone group (32 patients) were compared., Results: The high gene expression rate was 58.3% in combination group, and 40.6% in surgery alone group(P=0.145). In combination group, no significant difference of disease-free survival rate (P=0.903) and survival time (P=0.238) was found between patients with histopathologic regression and patients without histopathologic regression; high gene expression had no correlation with pathologic regression (P= 0.862); the mean disease-free survival time was significantly lower in high gene expression subgroup than in low gene expression subgroup [(14.1+/-9.8) months vs. (27.2+/-13.6) months, P=0.032]; the 2-year disease-free survival rate was 38.1% in high gene expression subgroup, and 46.7% in low gene expression subgroup (P=0.607)., Conclusions: Pathologic regression after neoadjuvant chemotherapy has no correlation with disease-free survival rate and survial time. The high gene expression maybe indicate high risk of postoperative metastasis; the necessity of postoperative chemotherapy needs further study.

Objective: To study the reasonable dosage for paraplatin according to different dosage calculations., Methods: A prospective, randomized, single-blinded study on 54 patients with advanced non-small-cell lung cancer (NSCLC) treated with paraplatin was conducted. Patients were divided to 2 groups. In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS). Hematological toxicity, response rate and survival rate in the two groups of patients were compared., Results: Neutropenia in group A and group B was seen in 77.8% and 37.0% (P < 0.05), and thrombocytopenia in 18.5% and 3.7% (P > 0.05) of patients, respectively. Hemoglobin decrease was seen in 48.2% of patients in both groups. The average quantity of paraplatin given in one cycle of treatment was 535.93 +/- 106.71 mg and 398.52 +/- 71.72 mg (P < 0.01) respectively. The average time interval between treatment cycles was 27.04 +/- 5.30 d and 22.85 +/- 2.80 d (P < 0.05). The response rate and survival rate of patients in group A and B were 22.2% versus 48.2% (P < 0.05), and 40.7% versus 44.4% (P > 0.05) respectively, but the median survival time was identical (12 months) in the two groups., Conclusion: NSCLC patients given paraplatin with dosages calculated on the basis of AUC have higher response rate and less severe hematological toxicity than those given paraplatin with dosages on the basis of body surface. However, the median survival time and survival rate have no statistical differences between the two groups of patients.