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Background: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC., Methods: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses., Results: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017)., Conclusions: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective., Competing Interests: Disclosure JDS has received honoraria and consulting fees from Roche, Merck, BMS, AstraZeneca, Regeneron, Novartis, Protalix Biotherapeutics, Xenetic Biosciences and Protalix Biotherapeutics. JS also received grants to his institution from Roche, AstraZeneca, Protalix Biotherapeutics, CLS Therapeutics, BMS and Merck. BS received speakers’ fees from AstraZeneca, Medscape, and PEER VIEW, and consulting fees from AstraZeneca. SO received honoraria from Astra Zeneca, Bayer, BMS, and Novocure., (Copyright © 2023. Published by Elsevier Inc.)

Background: PD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay., Methods: A total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as <1%, 1%-49% and ≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy., Results: Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04), and 29% of surgical resections (P = 0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001)., Conclusion: Our results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

Introduction: As treatments for non-small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation., Methods: We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples., Results: We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients., Conclusion: Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC.

Background: Non-small-cell lung cancer (NSCLC) has a significant impact on patients' health-related quality of life (HRQOL). This study aimed to measure health state utility values representing the individual's preferences for specific health-related outcomes in advanced NSCLC patients and to assess predictive parameters., Methods: We conducted a prospective quality-of-life survey on advanced NSCLC patients in 25 hospitals in Europe, Canada, Australia, and Turkey. HRQOL was assessed using the EuroQol (EQ-5D) questionnaire and EQ-5D utility and EQ-visual analog (EQ-VAS) scores were estimated., Results: Three hundred nineteen patients were recruited of which 263 had evaluable data. Mean utility for progression-free (PF) patients on first-, second-, and third-/fourth-line treatment was 0.71 (SD = 0.24), 0.74 (SD = 0.18), and 0.62 (SD = 0.29), respectively. Mean utility for patients with progressive disease (PD) while on first-, second- and third-/fourth-line treatment was 0.67 (SD = 0.2), 0.59 (SD = 0.34), and 0.46 (SD = 0.38), respectively. Overall, patients with PD had lower mean utility scores than PF patients (0.58 versus 0.70). The results of the EQ-VAS showed that the score decreased with later treatment lines. Patients with PD had a 10-point decrease in VAS scores compared with PF patients (53.7 versus 66.6). The regression analysis revealed that stage IV disease, higher lines of treatment, and health state were significant predictors of utility at the 10% level., Conclusion: The results presented indicate a substantial impact of lung cancer on patients' HRQOL, with stage IV disease, line of treatment, and PD, resulting in considerable deterioration of utility. The values obtained here will inform evaluations of cost-utility for NSCLC therapies.