Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

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.

Impact of a Pleural Care Program on the Management of Patients With Malignant Pleural Effusions.

BACKGROUND: Malignant pleural effusions (MPEs) are common and associated with a poor prognosis. Yet, many patients face suboptimal management characterized by repeated, nondefinitive therapeutic procedures and potentially avoidable hospital admissions. METHODS: We conducted a retrospective comparison of patients who underwent a definitive palliative intervention for MPE (indwelling pleural catheter or pleurodesis) at our center, before and after the implementation of a pleural care program. Targeted interventions included staff education, establishment of formal pleural drainage policies, a pleural clinic with weekday walk-in capacity, and a rapid access pathway for oncology patients. Outcomes assessed were the proportion of emergency room (ER) presentations, hospitalizations, number of nondefinitive pleural procedures, and time-to-definitive palliative procedure. RESULTS: A total of 144 patients were included: 69 in the preintervention group and 75 in the postintervention group. Although there was no difference in the proportion of ER presentations before and after interventions (43.5% vs. 38.7%, P =0.56), hospital admissions declined significantly (47.8% vs. 24.0%, P =0.003). The proportion of patients undergoing chest drain insertion decreased significantly (46.4% vs. 13.3%, P <0.001), with a stable low number of nondefinitive procedures per patient (1.6±1.1 vs. 1.3±0.9, P =0.32). A 7-day decrease in median time from presentation-to-definitive palliative procedure ( P =0.05) was observed. CONCLUSION: A targeted pleural care program improved MPE palliation through reduction in hospitalizations and chest drain use, and shorter time-to-definitive palliation, despite failing to reduce ER presentations.

Routine Clinically Detected Increased ROS1 Transcripts Are Related With ROS1 Expression by Immunohistochemistry and Associated With EGFR Mutations in Lung Adenocarcinoma.

Introduction: Translocations of the ROS1 gene were found to drive tumorigenesis in 1% to 2% of lung adenocarcinoma. In clinical practice, ROS1 rearrangements are often screened by immunohistochemistry (IHC) before confirmation with either fluorescence in situ hybridization or molecular techniques. This screening test leads to a non-negligible number of cases that have equivocal or positive ROS1 IHC, without ROS1 translocation. Methods: In this study, we have analyzed retrospectively 1021 cases of nonsquamous NSCLC having both ROS1 IHC and molecular analysis using next-generation sequencing. Results: ROS1 IHC was negative in 938 cases (91.9%), equivocal in 65 cases (6.4%), and positive in 18 cases (1.7%). Among these 83 equivocal or positive cases, only two were ROS1 rearranged, leading to a low predictive positive value of the IHC test (2%). ROS1-positive IHC was correlated with an increased mRNA ROS1 transcripts. Moreover, we have found a mean statistically significant relationship between ROS1 expression and EGFR gene mutations, suggesting a crosstalk mechanism between these oncogenic driver molecules. Conclusion: This study demonstrates that ROS1 IHC represents true ROS1 mRNA expression, and raises the question of a potential benefit of combined targeted therapy in EGFR-mutated NSCLC.

Neoadjuvant Prehabilitation Therapy for Locally Advanced Non-Small-Cell Lung Cancer: Optimizing Outcomes Throughout the Trajectory of Care.

BACKGROUND: Prehabilitation is well established for improving outcomes in cancer surgery. Combining prehabilitation with neoadjuvant treatments may provide an opportunity to rapidly initiate cancer-directed therapy while improving functional status in preparation for local consolidation. In this proof-of-concept study, we analyzed non-small-cell lung cancer patients who underwent simultaneous prehabilitation and neoadjuvant therapy. PATIENTS AND METHODS: We retrospectively analyzed all patients who underwent neoadjuvant treatment for non-small-cell lung cancer followed by curative intent surgery between 2015 and 2021. Patients who were screened for the prehabilitation program were identified. The screening included assessment of physical performance, nutritional status, and signs of anxiety and depression. RESULTS: We identified a total of 141 patients who underwent neoadjuvant therapy. Twenty patients were screened to undergo a prehabilitation program. Four patients did not complete the exercise program (1 surgical intervention too soon, 1 drop-out after the first session, and 2 patients were deemed fit without intervention). The postoperative median length of stay was 2 days (range 1-18). Patients improved their 6-minute-walk test despite undergoing neoadjuvant treatment by a mean of 33 meters (± 50, P = .1). Self-reported functional status (DASI) showed significant improvement by a mean of 10 points (± 11, P = .03), and HADS-anxiety-score was significantly reduced after the prehabilitation program by a mean of 1.5 points (± 1, P = .005). CONCLUSION: Neoadjuvant prehabilitation therapy is feasible and associated with encouraging results. The performance of all measures remains a logistic challenge. With multimodal strategies for lung cancer treatment becoming key to optimal outcomes, neoadjuvant prehabilitation therapy is a concept worthy of prospective multi-center evaluation.

Durvalumab therapy following chemoradiation compared with a historical cohort treated with chemoradiation alone in patients with stage III non-small cell lung cancer: A real-world multicentre study.

BACKGROUND: The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups. METHODS: In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use. RESULTS: Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression <1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006). CONCLUSIONS: This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Initial Clinical Experience With a Flexible Peripheral 21-G Needle Device.

BACKGROUND: Bronchoscopic techniques can be used to safely sample peripheral lung nodules (PLN), and transbronchial needle aspiration (TBNA) can further increase the diagnostic yield. Current needle devices not necessarily designed for this indication have limitations. We report our initial experience with a new flexible nitinol peripheral TBNA needle specifically designed for such sampling. METHODS: Retrospective case review describing the first clinical cases performed with a commercially available 21-G peripheral TBNA device in 4 centers. RESULTS: Eleven different operators performed 40 procedures for PLNs of a mean size of 35.1 mm (±18), and located 18.8 mm (±18.8) from the pleural surface, with 50% of them being present in the upper lobes. Bronchoscopists rated the use of the needle as good or excellent for reaching the PLN in 27/30 (90%) of cases. The TBNA sample was diagnostic in 18/40 cases (45%) overall and in 18/28 (64.3%) of cases where a diagnosis on bronchoscopy was possible. No episode of pneumothorax, significant bleeding, hypoxemia, escalation of care, or other complications were noted. CONCLUSION: Our initial experience with a novel peripheral TBNA device appears safe and effective, and may offer technical advantages over other available devices. Additional studies will be required to confirm the role of this device in the approach to bronchoscopic sampling of parenchymal lung nodules.