Cost input.

Cost input.</p

Summary of cost (US dollars) and outcome results in the base-case analysis.

Summary of cost (US dollars) and outcome results in the base-case analysis.</p

Health utilities and disutilities of advanced NSCLC.

NSCLC: non-small-cell lung cancer; PFS: progression-free survival; OS: overall survival.</p

Probabilistic sensitivity analysis (PSA) results.

(A) Cost-Effectiveness Acceptability Curves Comparing the Cost-effectiveness of Crizotinib Treatment with the ALK Rearrangement Testing (NGS and multiplex PCR) Versus Standard Chemotherapy, with PAP; (B) Scatter Plot of Monte Carlo Probabilistic Sensitivity Analysis, NGS vs. Control Strategy, with Patient Assistance Program (PAP); (C) Scatter Plot of Monte Carlo Probabilistic Sensitivity Analysis, Multiplex PCR vs. Control Strategy, with Patient Assistance Program (PAP). Blue line indicates NGS and yellow one is multiplex PCR, ALK: anaplastic lymphoma kinase; NGS: next-generation sequencing; PAP: patient assistance program; QALY: quality-adjusted life-year; PCR: polymerase chain reaction.</p

One-way sensitivity analyses for NGS panel tests and multiplex PCR versus control (with PAP).

(A) NGS vs. control; (B) multiplex PCR vs. control. NGS: next-generation sequencing; PAP: patient assistance program; QALY: quality-adjusted life-year.</p

Key clinical data.

Key clinical data.</p

Table_1_Immunotherapy strategies for EGFR-mutated advanced NSCLC after EGFR tyrosine-kinase inhibitors failure.docx

BackgroundThis study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test.ResultsA total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group.ConclusionNSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.</p

Image1_Comprehensive molecular characterizations of stage I–III lung adenocarcinoma with tumor spread through air spaces.JPEG

Purpose: The aim of this study is to investigate integrative genomic spectra of stage I–III lung adenocarcinoma with tumor spread through air spaces (STAS).Methods: We retrospectively identified 442 surgically resected lung adenocarcinoma patients of pathological stage I–III in Shanghai Chest Hospital from January 2018 to February 2021. Surgically resected tissues were used for next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes to profile comprehensive molecular characterizations.Results: A total of 442 cases were analyzed, including 221 (50%) STAS-positive (SP) and 221 (50%) STAS-negative (SN) lung adenocarcinoma patients. In total, 440 cases (99.6%) were positive for the overall mutational spectrum, and the higher mutational genes were EGFR, TP53, KRAS, ALK, SMAD4, and ERBB2 (62%, 42%, 14%, 10%, 7%, and 7%, respectively). Compared with the SN population, there was significantly lower EGFR alteration in the single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, p Conclusion: Significant differences exist in stage I–III lung adenocarcinoma patients with STAS in molecular characterizations.</p

Table1_Comprehensive molecular characterizations of stage I–III lung adenocarcinoma with tumor spread through air spaces.DOCX

Purpose: The aim of this study is to investigate integrative genomic spectra of stage I–III lung adenocarcinoma with tumor spread through air spaces (STAS).Methods: We retrospectively identified 442 surgically resected lung adenocarcinoma patients of pathological stage I–III in Shanghai Chest Hospital from January 2018 to February 2021. Surgically resected tissues were used for next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes to profile comprehensive molecular characterizations.Results: A total of 442 cases were analyzed, including 221 (50%) STAS-positive (SP) and 221 (50%) STAS-negative (SN) lung adenocarcinoma patients. In total, 440 cases (99.6%) were positive for the overall mutational spectrum, and the higher mutational genes were EGFR, TP53, KRAS, ALK, SMAD4, and ERBB2 (62%, 42%, 14%, 10%, 7%, and 7%, respectively). Compared with the SN population, there was significantly lower EGFR alteration in the single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, p Conclusion: Significant differences exist in stage I–III lung adenocarcinoma patients with STAS in molecular characterizations.</p

Image2_Comprehensive molecular characterizations of stage I–III lung adenocarcinoma with tumor spread through air spaces.JPEG

Purpose: The aim of this study is to investigate integrative genomic spectra of stage I–III lung adenocarcinoma with tumor spread through air spaces (STAS).Methods: We retrospectively identified 442 surgically resected lung adenocarcinoma patients of pathological stage I–III in Shanghai Chest Hospital from January 2018 to February 2021. Surgically resected tissues were used for next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes to profile comprehensive molecular characterizations.Results: A total of 442 cases were analyzed, including 221 (50%) STAS-positive (SP) and 221 (50%) STAS-negative (SN) lung adenocarcinoma patients. In total, 440 cases (99.6%) were positive for the overall mutational spectrum, and the higher mutational genes were EGFR, TP53, KRAS, ALK, SMAD4, and ERBB2 (62%, 42%, 14%, 10%, 7%, and 7%, respectively). Compared with the SN population, there was significantly lower EGFR alteration in the single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, p Conclusion: Significant differences exist in stage I–III lung adenocarcinoma patients with STAS in molecular characterizations.</p