Pulmonary sarcomatoid carcinoma (PSC) is a rare, aggressive variant of NSCLC associated with emerging evidence of high programmed death-ligand 1 (PD-L1) expression, although its reported prevalence varies widely. We conducted a systematic review and meta-analysis to quantify the pooled prevalence of PD-L1 expression in PSC and identify factors associated with its variability. We searched PubMed, Web of Science, and the Cochrane Library up to November 2025. Studies reporting PD-L1 expression using the tumor proportion score (TPS) in confirmed PSC (≥ 10 patients) were included. A random-effects meta-analysis was performed for TPS thresholds of 50% and 1%. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. This study was registered with PROSPERO (CRD420251243606). Thirty-four studies, encompassing up to 1789 patients, were included. The pooled prevalence of high PD-L1 expression (TPS ≥ 50%) was 57.33%, and PD-L1 positivity (TPS ≥ 1%) was 79.61%. At a TPS of 50% or higher, non-Asian studies reported a numerically higher prevalence than Asian studies, although the difference was not statistically significant. A higher proportion of ever-smokers and a 100% pleomorphic carcinoma composition were each associated with a significantly higher prevalence at a TPS of 1% or higher. In the meta-regression, no covariate reached statistical significance at a TPS of 50% or higher, whereas the proportions of pleomorphic carcinoma, ever-smokers, and median age were significant predictors at a TPS of 1% or higher. PD-L1 expression is remarkably prevalent in PSC, substantially exceeding that in conventional NSCLC. These findings may inform immunotherapy decision-making for advanced PSC.
Background Stage III non-small cell lung cancer (NSCLC) represents one of the most heterogeneous and clinically challenging scenarios in thoracic oncology. The rapid integration of immunotherapy into multimodal treatment strategies has reshaped therapeutic algorithms, particularly for resectable and borderline resectable disease. However, uncertainty persists regarding optimal staging procedures, resectability assessment, and the integration of surgery, systemic therapy, and radiotherapy. Methods A multisocietal Delphi consensus was conducted to address key areas of uncertainty in the multidisciplinary management of stage III NSCLC. Experts in thoracic surgery, medical oncology, radiation oncology, interventional pulmonology, and pathology nominated by four Italian scientific societies participated in a structured consensus process. Sixty-five statements covering baseline evaluation, local treatment, and integrated therapeutic strategies were rated using a 9-point Likert scale across two Delphi rounds. Results Consensus was achieved for 62 of 65 statements. Strong agreement supported comprehensive baseline staging including contrast-enhanced CT, PET imaging, brain MRI, and systematic mediastinal staging with endosonographic techniques. Molecular characterization, including PD-L1 expression and testing for EGFR and ALK alterations, was considered essential for treatment selection. Neoadjuvant chemo-immunotherapy was endorsed as the preferred strategy for most patients with resectable stage III NSCLC without actionable driver alterations. Lung-sparing surgical procedures were strongly favored, while pneumonectomy should be reserved for highly selected cases. For unresectable disease, concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. Conclusions This multidisciplinary consensus provides an updated framework for the contemporary management of stage III NSCLC, emphasizing accurate staging, molecular profiling, and coordinated multidisciplinary decision-making to optimize multimodal treatment strategies.
Background KEYNOTE-A86 (NCT04956692) was a phase 3 randomized, open-label trial of pembrolizumab administered subcutaneously vs intravenously, plus chemotherapy, in participants with treatment-naive stage IV squamous or nonsquamous non-small cell lung cancer (NSCLC) without sensitizing EGFR, ALK, or ROS1 alterations. Methods Participants were randomized 2:1 to pembrolizumab 380 mg Q3W by subcutaneous injection or 200 mg Q3W by intravenous infusion (≤35 cycles), given in combination with platinum doublet chemotherapy. Dual primary endpoints were first dose (cycle 1) area under the curve (AUC0-3wks) and model-based steady state (cycle 6) trough concentration (Ctrough). The noninferiority margin for AUC0-3wks and Ctrough geometric mean ratios (GMR) of subcutaneous vs intravenous pembrolizumab was specified as 0.8. Secondary endpoints included other pharmacokinetic exposure measures, efficacy parameters, and safety. Results Participants (N=531) were randomized to the pembrolizumab subcutaneous (n=358) or intravenous (n=173) arms. Median time from randomization to data cutoff (04APR2023) was 9.9 months (range 4.2-19.3). The GMR (96% CI) for first dose AUC0-3wks was 1.04 (0.98-1.10; p <0.0001). The GMR (94% CI) for steady-state Ctrough was 1.85 (1.69-2.03; p <0.0001). Other pharmacokinetic endpoints fell within established bounds for pembrolizumab. The objective response rate ratio (subcutaneous vs intravenous arms) was 0.85 (95% CI 0.71-1.02). Incidences of treatment-related adverse events, including those serious, were similar between arms. Conclusions Overall AUC exposures and trough concentrations with subcutaneous pembrolizumab 380 mg Q3W were noninferior to those of intravenous pembrolizumab 200 mg Q3W, given with chemotherapy in participants with previously untreated metastatic NSCLC. Results demonstrate the feasibility of subcutaneous pembrolizumab administration.
Introduction Stereotactic body radiotherapy (SBRT) to peripheral lung tumors is associated with radiation-induced bone effects that may predispose patients to chest wall pain (CWP) and radiation-induced rib fractures (RIRF). These effects may be inhibited by bisphosphonates. We aimed to determine the impact of risedronate on the radiologic biomarker rib cortical thickness (CTh) in patients with peripheral lung tumors treated with SBRT. Methods This randomized, double-blind, placebo-controlled phase 2 clinical trial enrolled patients with tumors within 2 cm of the chest wall, who were randomized 1:1 to risedronate 150 mg prior to SBRT or placebo. CTh was evaluated every 3 months for 1 year. The primary endpoint was percent change in rib CTh from baseline to 3 months within the >30 Gy isodose region. Results 73 patients (78 tumors) were randomized and eligible for analysis. Baseline CTh was 1.46 (±0.34) mm and 1.44 (±0.42) mm in the placebo and risedronate arms, respectively. Mean percent change from baseline to 3 months within the 30 Gy isodose region was: 6.4% (±18.0) for placebo versus 3.1% (±17.9) for risedronate (absolute difference: -3.3%, p=0.44). The absolute difference in percent CTh change from baseline to 6, 9, and 12 months in the risedronate (versus placebo) group was -4.7%, -8.3%, and -11.8%, respectively. Conclusion In patients with peripheral lung tumors treated with SBRT, risedronate did not result in statistically significant differences in rib CTh within the 30 Gy isodose region. This biomarker of bone changes after SBRT demonstrated increases over time within higher dose regions in the placebo group but remained similar to baseline in the risedronate group. Further studies are needed
Background Real-world (rw) use of rechallenge with platinum/pemetrexed (PP) in pleural mesothelioma (PM) has been recommended in international guidelines, but evidence is scarce and based on few very small retrospective studies. Methods 612 patients with PM treated with first-line PP between 2010 and 2023 across twelve centers were retrospectively identified. Outcomes and treatment patterns were analyzed across second-line regimens with particular focus on PP rechallenge. Platinum-free interval (PFI) was examined using a two-tier classification (platinum-sensitive ≥6 months, platinum-resistant <6 months) as a selection criterion. Results Among 375 patients (61%) receiving second-line therapy, median overall survival (OS) and rw progression-free survival (rwPFS) were 11.6 months and 4.7 months, respectively. Patients with PP rechallenge (n=78) showed a median OS of 20.5 months, median rwPFS of 6.8 months, and disease control rate (DCR) of 88%. Platinum-sensitive patients derived greater benefit from rechallenge, with OS differing across PFI categories (platinum-sensitive 21.4 months vs. platinum-resistant 11.9 months; p=0.007). Outcomes with Nivolumab/ipilimumab (n=29) were comparable to those observed with PP rechallenge (median OS 22.8 months, median rwPFS 8.0 months), with TFI (treatment-free interval) showing improved median OS in platinum-sensitive compared to platinum-resistant group (32 months vs. 18.1 months, p=0.03). Single-agent pemetrexed (n=32) and single-agent chemotherapy were associated with substantially shorter median OS of 11.6 and 8.0 months, respectively. Conclusion PP rechallenge demonstrated favorable outcomes and remains viable alternative in platinum-sensitive patients with PM, while nivolumab/ipilimumab may be considered in both TFI categories, particularly in platinum-resistant disease where PP rechallenge offers limited benefit. A PFI/TFI-guided approach to second-line treatment selection is supported, though prospective validation is warranted.
Background In the global phase 3 randomized LEAP-006 study (NCT03829319), addition of lenvatinib to pembrolizumab plus chemotherapy did not significantly improve efficacy outcomes in metastatic nonsquamous non-small–cell lung cancer (NSCLC). We present findings from an extension study of LEAP-006 (NCT04716933) including participants from China. Methods Adults (≥18 years) from mainland China with untreated metastatic nonsquamous NSCLC without targetable genetic alterations were randomized 1:1 to lenvatinib 8mg once daily or placebo, plus pembrolizumab 200mg plus cisplatin or carboplatin plus pemetrexed for 4 cycles, followed by lenvatinib or placebo plus pembrolizumab plus pemetrexed for ≤35 cycles. PFS and OS were dual primary endpoints. No alpha was assigned to these analyses. Results Of 201 enrolled participants from China, 101 received lenvatinib plus pembrolizumab and chemotherapy (lenvatinib arm) and 100 to placebo plus pembrolizumab and chemotherapy (placebo arm). Median follow-up was 32.7 months (data cutoff August 11, 2023). Median PFS (95% CI) was 15.3 (12.2‒19.6) and 9.2 (8.2‒12.5) in the lenvatinib and placebo arms, respectively (HR, 0.68; 95% CI, 0.48‒0.97); median OS (95% CI) was 26.6 (22.2‒35.0) months and 22.0 (16.6‒24.8) months (HR, 0.78; 95% CI, 0.54‒1.12). Grade ≥3 treatment-related adverse events occurred in 83.2% and 62.0% of participants in the lenvatinib and placebo arms, respectively; treatment-related AEs that led to death were reported in 7.9% and 3.0% of participants. Conclusions In the China extension of LEAP-006, addition of lenvatinib to pembrolizumab plus chemotherapy was associated with numerical improvements in PFS and OS with manageable safety in previously untreated metastatic nonsquamous NSCLC.
Background Distinguishing separate primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs) is essential for staging and treatment, yet histology alone may be inconclusive. Molecular profiling can enhance diagnostic accuracy, but most supporting evidence to date stems from North America and Asia. Methods We retrospectively analyzed 49 patients (111 tumour nodules) with multiple lung cancers (MLCs) surgically resected at a Swiss tertiary centre (2015–2023). Tumours were classified histologically using three algorithms (Martini and Melamed, comprehensive histologic assessment [CHA], and CHA with low-grade lepidic features) and compared with molecular classification using a 52-gene targeted next-generation sequencing (NGS) panel integrating somatic mutation and copy number alteration (CNA) analysis to assess clonal relatedness. Results Histologic algorithms showed high internal concordance (up to 96.1%) but only modest agreement with molecular classification (69–75%). NGS enabled definitive classification in 85.5% of tumour pairs. CNA analysis contributed to clonality assessment in 28% of tumours and was the sole discriminatory feature in two mutation-negative cases. Discordance between CHA and molecular classification was frequent when tumours harboured common driver mutations (e.g., KRAS p.G12C, EGFR p.L858R). Overall, 31% of comparisons showed disagreement between CHA-based histologic assessment and molecular profiling. Conclusions In this first Swiss cohort, targeted NGS with CNA analysis improved discrimination between SPLCs and IPMs, but the standard routine NGS panel size was limited when tumours shared common driver mutations, particularly KRAS p.G12C and EGFR p.L858R. These findings underscore the potential need for broader genomic approaches, alongside histology, to achieve accurate classification and guide precise staging and treatment.
Introduction Blood-based tumor mutation burden (bTMB) has been proposed as a potential biomarker for identifying patients with advanced non–small cell lung cancer (NSCLC) who may benefit from immunotherapy. Prior studies have primarily focused on the high-bTMB groups, which may lead to an incomplete or misleading assessment of the predictive value of bTMB. In this study, we used data from the POPLAR (NCT01903993) and OAK (NCT02008227) trials to re-evaluate the predictive role of bTMB for immunotherapy response in advanced NSCLC by analyzing all patients with available bTMB measures and examining outcomes in both high- and low-bTMB groups. Methods Patients with evaluable bTMB from the POPLAR and OAK trials were included. For each study, hazard ratios (HRs) for both progression-free survival (PFS) and overall survival (OS) were calculated separately for the high- and low-bTMB groups across a range of cut points. Results A total of 211 and 583 patients with evaluable bTMB were included from the POPLAR and OAK trials, respectively. bTMB cut points from 4 to 26 (in increments of 2) were evaluated. At a cut point of 14, one of the evaluated thresholds, in POPLAR, high-bTMB patients had PFS HR = 0.50 (95% CI: 0.30–0.83) and OS HR = 0.51 (0.30–0.86), while low-bTMB patients had PFS HR = 1.23 (0.86–1.76) and OS HR = 0.82 (0.55–1.21). In OAK, high-bTMB patients had PFS HR = 0.68 (0.50–0.91) and low-bTMB patients had PFS HR = 0.98 (0.79–1.12) with no difference between the two groups for OS (HR: 0.63 (0.45-0.88) vs. 0.63 (0.50-0.80)). Conclusions The predictiveness of bTMB for identifying patients with NSCLC who may benefit from immunotherapy was evident for PFS but not OS. Observing a differential treatment efficacy trend solely within the high-bTMB group across multiple cut points was insufficient to establish predictive utility. A valid assessment requires a comprehensive evaluation of both high- and low-bTMB populations, with predictiveness established by demonstrating differential treatment efficacy between these two groups.
Introduction:Tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3, demonstrated clinical activity both in previously treated SCLC and as intensification of maintenance immunotherapy. Owing to its action mechanism, tarlatamab exerts a new toxicity profile, needing careful management. Based on these premises, we performed a systematic review and meta-analysis to evaluate treatment-related adverse events (TRAEs) among available clinical trials enrolling patients with SCLC receiving tarlatamab monotherapy. Methods:The research protocol was recorded in PROSPERO register with ID no. 1163787. We included the following keywords: phase I, phase II, phase III, small cell lung cancer, and tarlatamab. We conducted research in Embase, PubMed, Scopus, and Web of Science databases. Results:A total of four studies with 457 observations were included. Although Egger's test was performed, the results must be interpreted with caution as the small number of included studies (n = 4) limits the statistical power to reliably detect publication bias.For TRAEs, grades 3 to 4, 385 events were registered assessing the overall prevalence of 42% (95% confidence interval [CI]: 23%-64%). For serious TRAEs, 178 events were registered, and the overall prevalence was estimated at 40% (95% CI: 18%-67%). For TRAEs leading to dose interruptions and dose reduction, 105 events were included, and the prevalence was 24% (95% CI: 16%-34%). For TRAEs leading to discontinuation, 16 events were recorded, and the pooled prevalence was 4% (95% CI: 1.4%-8.2%). For TRAEs for grade 5 events, 12 events were analyzed, and the pooled prevalence was 3.2% (95% CI: 0.4%-22%). For cytokine release syndrome, 255 events were recorded, and the overall was 55.8% (95% CI: 48%-63%). For immune effector cell-associated neurotoxicity syndrome, 40 events were recorded, and the pooled prevalence was 8.9% (95% CI: 3.3%-21.8%). For decreased appetite, 146 events were reported, and the overall prevalence was 31% (95% CI: 23%-41%). For pyrexia, 139 events were analyzed, and the pooled prevalence was 30% (95% CI: 24%-38%). As regards dysgeusia, 457 observations and 139 cases were included, and the pooled prevalence was estimated at 32.5% (95% CI: 20%-48%). Conclusions:Future research should be focused on identifying risk factors for TRAEs and developing prophylactic strategies to mitigate this risk without blunting antitumor efficacy in patients with SCLC receiving tarlatamab. By improving our understanding and management of tarlatamab TRAEs, we can maximize its clinical efficacy while minimizing harm and ultimately improving outcomes for patients with SCLC.
Introduction Osimertinib is the standard first-line therapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the clinical significance of high programmed death-ligand 1 (PD-L1) expression in this setting remains unclear. This study aimed to evaluate the association between high PD-L1 tumor proportion score (TPS) (≥50%) and clinical outcomes in patients treated with first-line osimertinib. Methods This multicenter retrospective study used the REAL-WIND database from 16 Japanese institutions. Among 486 patients with EGFR-mutated NSCLC treated with first-line osimertinib, 385 with known PD-L1 status formed the full cohort (Cohort B). After excluding 185 patients overlapping with the published OSI-FACT dataset, 200 formed the non-overlapping validation cohort (Cohort A). Patients were stratified by PD-L1 TPS (≥50% vs. <50%). The primary endpoint was real-world progression-free survival (rwPFS) and secondary endpoints were overall survival (OS) and time to treatment failure (TTF). Outcomes were evaluated using unadjusted analyses and propensity score–based analyses to assess the robustness of the observed associations. Results In Cohort A, high PD-L1 expression was associated with shorter rwPFS (hazard ratio [HR]=1.95; 95% confidence interval [CI]: 1.30–2.92; p = 0.001) and OS (HR=1.72; 95% CI: 1.02–3.09; p = 0.044). Similar associations were observed in Cohort B for rwPFS (HR=1.76; 95% CI: 1.30–2.37; p < 0.001) and OS (HR=1.92; 95% CI: 1.28–2.87; p = 0.002). These associations were consistent in unadjusted analyses and in propensity score–based analyses adjusting for baseline confounding, supporting the reproducibility of the findings in this real-world cohort. Conclusions High PD-L1 expression was associated with reduced clinical benefit from first-line osimertinib in EGFR-mutated NSCLC. These findings should be interpreted as a consistent clinical association observed in real-world practice rather than definitive evidence of a predictive biomarker.
Introduction:Transformed small-cell lung cancer (tSCLC) is a clinically important resistance mechanism to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. This study characterizes clinical features, treatment outcomes, and biomarker profiles in patients with tSCLC. Methods:Data from 45 patients with EGFR-mutant NSCLC who developed tSCLC between 2014 and 2023 were analyzed. Demographic characteristics, treatment histories, and delta-like ligand 3 (DLL3) and B7-H3 expression were collected. Objective response rate, progression-free survival (PFS), and posttransformation survival (PTS) were assessed. Spatial transcriptomic profiling was performed in selected cases. Results:Most patients were women (60%) and never-smokers (75.6%). Exon 19 deletion was the predominant EGFR mutation (57.8%). Median PFS and PTS were 3.3 and 9.2 months, respectively. Etoposide plus platinum (EP) was the predominant first-line regimen (69.8%), with 23.2% of the patients receiving EP plus immune checkpoint or tyrosine kinase inhibitors. EP-based combination regimens yielded a numerically higher objective response rate and a significantly longer PFS than EP alone (7.5 versus 2.8 months, p = 0.002). PTS was longer with EP-based regimens than with other regimens (10.4 versus 6.4 months, p = 0.035). DLL3 and B7-H3 were expressed in 87.5% and 66.7% of tumors, respectively, without prognostic significance. Multivariable analysis identified brain metastasis and liver progression at transformation as adverse prognostic factors. Spatial transcriptomic analysis revealed neuroendocrine lineage reprogramming, stromal depletion, and immune exclusion. Conclusions:tSCLC remains an aggressive resistance phenotype with poor outcomes. EP-based combination strategies may provide clinical benefit, whereas frequent DLL3 expression supports further evaluation of targeted therapies.
Background Small cell lung cancer (SCLC) is an aggressive malignancy where platinum-based chemotherapy is the cornerstone of treatment. While immunotherapy has redefined the standard of care, the optimal choice between cisplatin and carboplatin remains debated. This study evaluated the impact of platinum backbone selection on survival outcomes across the SCLC spectrum in the immunotherapy era. Methods A systematic review and meta-analysis were performed on randomized controlled trials evaluating first-line chemoimmunotherapy with platinum-based regimens in SCLC. Outcomes were stratified by disease stage and platinum backbone (carboplatin vs. cisplatin). Survival endpoints included progression-free survival (PFS) and overall survival (OS). Results Seven trials (3,059 patients) were analyzed. In extensive-stage SCLC (n= 1,843), both backbones provided comparable benefits when combined with immunotherapy; pooled OS HR for cisplatin was 0.71 (95% CI: 0.57–0.89; p=0.003) and 0.76 for carboplatin (95% CI: 0.68–0.85; p<0.001). In limited-stage SCLC (n=1,216), carboplatin improved OS (HR: 0.71; 95% CI: 0.54-0.92; p=0.01) and PFS (HR: 0.70; 95% CI: 0.56-0.87; p=0.002). In contrast, cisplatin did not reach statistical significance for OS (HR: 1.15; 95% CI: 0.77-1.72; p=0.49) or PFS (HR: 1.02; 95% CI: 0.81-1.28; p=0.96). Conclusion These findings invite a reconsideration of the platinum hierarchy in SCLC management. By demonstrating that carboplatin provides a more effective backbone in the limited-stage setting and comparable efficacy in the extensive-stage setting, this analysis suggests that the historical prioritization of cisplatin may no longer be justified in the immunotherapy era. Prioritizing carboplatin as a preferred agent may optimize tolerability while preserving or improving survival outcomes across the SCLC spectrum.
Introduction:Pivotal clinical trials have reported the survival benefits of both nivolumab plus ipilimumab (NI) and nivolumab plus ipilimumab with 2 cycles of platinum-based chemotherapy (NICT) compared with chemotherapy. However, real-world evidence comparing NI and NICT with long-term follow-up remains limited. Methods:We retrospectively analyzed 181 patients treated with NICT or NI across 13 institutions in Japan. The primary end points were median overall survival (OS) and the 36-month OS rate. Secondary end points included progression-free survival (PFS), objective response rate, disease control rate, and treatment-related adverse events (TRAEs). To reduce treatment-selection bias, 1:1 propensity score matching was performed using 11 covariates. Results:In the post-propensity score matching cohort (47 pairs; n = 94; median follow-up, 42.6 and 44.1 months), the median PFS was 8.7 months with NICT versus 4.7 months with NI (hazard ratio [HR] 0.86; p = 0.51). The median OS was 19.5 months with NICT versus 16.3 months with NI (HR 0.79; p = 0.37), with similar 36-month OS rates (34.3% versus 30.9%). The objective response rate was significantly higher with NICT than with NI (68.1% versus 34.0%) (p = 0.002), as was the disease control rate (83.0% versus 53.2%) (p = 0.004). NICT was associated with a higher cumulative incidence of TRAEs of grade 3 or higher (HR 2.25 [95% confidence interval, 1.03-4.91]) (Gray's test p = 0.039). Treatment discontinuation and treatment-related deaths were comparable between the groups. Conclusions:With more than 40 months of follow-up, NICT was associated with higher response rates and a higher incidence of TRAEs of grade 3 or higher than NI, without a clear PFS or OS advantage. Adding 2-cycles of chemotherapy may enhance early disease control but at the cost of increased toxicity, and this balance should be considered when selecting treatment for patients for whom tolerability is a major concern.
Introduction Current or former smokers with 20-pack year history between ages 50-80 years old are eligible for lung cancer screening (LCS) under current guidelines. Despite age restrictions for screening, older patients remain at risk for lung cancer and without screening are diagnosed with advanced stage disease that limits curative treatment options.Treatment for early-stage lung cancer has improved with minimally invasive surgical techniques and reduced toxicity with stereotactic body radiation therapy (SBRT). Robust older patients can tolerate surgical resection or SBRT with similar rates of recovery to younger peers. Given the advancements in treatment and improved tools to identify frailty, chronologic age should not be a gatekeeper for lung cancer screening. Methods A taskforce within the International Society of Geriatric Oncology was created to address challenges of LCS within older patients. Taskforce members represented 5 different specialties with clinical expertise in lung cancer and/or the care of older adults. Results For patients >80 years old that qualify for LCS, we recommend performing geriatric assessment (GA) to assess functional status and age-related vulnerabilities. Robust patients determined by GA should be eligible for screening and discuss their health care priorities in shared decision-making conversations. GA should be performed every 2 years while enrolled in LCS to determine the appropriateness of continued screening efforts. Conclusions Age should not be an exclusion criteria for lung cancer screening. Patients over 80 years old should be thoughtfully co-managed by geriatric and lung cancer specialists to determine which older patients would benefit from screening efforts.
The combination of amivantamab (an EGFR/MET bispecific antibody) and lazertinib (a third-generation EGFR tyrosine kinase inhibitor [TKI]) has emerged as a first-line option for EGFR-mutant non-small cell lung cancer (NSCLC), demonstrating superior progression-free and overall survival versus osimertinib in the MARIPOSA trial. Pneumonitis/interstitial lung disease (ILD) occurs in approximately 3% of patients receiving this combination. Following treatment discontinuation and corticosteroid therapy, the optimal subsequent systemic treatment strategy—particularly the feasibility of switching to another EGFR-targeted agent—remains undefined. We report two patients with advanced EGFR-mutant NSCLC who developed Grade 2 pneumonitis during first-line amivantamab-lazertinib therapy. After corticosteroid-induced resolution, both patients were successfully transitioned to osimertinib 80 mg/day. Neither patient experienced pneumonitis recurrence during follow-up periods of 14 and 12 months, respectively. To our knowledge, these are among the first reported cases describing the initiation of osimertinib following resolution of amivantamab-lazertinib-associated pneumonitis. These cases suggest that sequential EGFR-targeted therapy with osimertinib after amivantamab-lazertinib-associated ILD may be feasible and warrants prospective evaluation.
Introduction Bronchoscopic microwave ablation (BMA) is a minimally invasive treatment for pulmonary nodules, yet up to 50% of initial ablations may not achieve the manufacturer-predicted ablation zone size (AZS). We aimed to identify factors that may affect AZS reaching the predicted at the first energy administered. Methods We conducted a single-center retrospective study of 235 nodules in 149 patients treated with BMA guided by cone-beam CT (CBCT) between March 2019 and June 2024. Nodule, lung and patient factors including nodule size, morphology, intra-nodular vessel, bronchus sign, pathology, and previous lung interventions were analyzed using logistic regression, Bayesian network modeling, random forests, and differential classification and regression tree (CART) analysis. The primary endpoint was first-pass predicted AZS attainment, defined as the first energy delivery to the nodule resulting in an ablation zone size on intraoperative CBCT reaching or exceeding the manufacturer predicted AZS, based on the delivered power and duration. Results First-pass predicted AZS attainment was achieved in 47.7% of nodules (112/235). Larger nodules (>1 centimeter) (odds ratio [OR] per 10 millimeters increase, 1.74; p<0.001), presence of a bronchus sign (OR, 1.18; p=0.01), and intra-nodular vessel ≥3 mm (OR, 1.20; p<0.001) were independently associated with first-pass predicted AZS non-attainment. Ground-glass and metastatic nodules were more likely to achieve first-pass predicted AZS attainment (p<0.05). In matched within-patient analysis, absence of prior lung surgery, bronchus sign, and smooth border were associated with first-pass predicted AZS non-attainment (p<0.05). CART showed that first-pass predicted AZS non-attainment in the preceding nodule was followed by non-attainment in the subsequent nodule in 77% of cases. Finally, we constructed a simple bedside risk stratification tool for first-pass predicted AZS non-attainment. Conclusions First-pass predicted AZS attainment was primarily associated with nodule size and airway, or intra-nodular vascular structures consistent with heat sink effects, with nodule morphology providing additional influence. These findings could identify nodules at increased risk of first-pass predicted AZS non-attainment.
Introduction Although lung cancer screening reduces deaths, U.S. uptake is low, and disparities persist in eligibility. Our objectives were to examine how smoking intensity and duration shaped screening eligibility across demographic groups, and whether alternative criteria could promote more equitable screening. Methods We conducted a retrospective observational study of adults who underwent resection for primary lung cancer. Eligibility was defined using period-specific AATS/USPSTF criteria and three alternatives: (1) One PPD (≥1 pack/day), (2) Upper 75th (smoking duration ≥75% of lifetime), and (3) 20 YS (≥20 years smoking). Multivariable linear models related demographics to smoking behaviors; logistic models estimated odds of eligibility for each criterion. Results Smoking behaviors varied across demographic groups: female and racial/ethnic minority patients smoked at lower intensities but for longer durations than White males. Among 995 participants, eligibility was 35.6% (AATS/USPSTF), 68.9% (One PPD), 25.9% (Upper 75th), and 81.9% (20 YS) under respective criteria. Females were less likely to be eligible under AATS/USPSTF (Odds Ratio [OR]adj 0.65; 95% Confidence Interval [CI]: 0.50-0.85). Black patients had higher odds of eligibility under Upper 75th (ORadj 1.87; 95% CI: 1.27-2.72), as did Hispanic patients (ORadj 1.99; 95% CI: 1.11-3.49), and under 20 YS (ORadj 1.72; 95% CI: 1.07-2.89). Early-stage (I/II, n=910) cases captured as screening-eligible varied by criteria: 35.7% (AATS/USPSTF), 68.6% (One PPD), 26.4% (Upper 75th), and 81.9% (20 YS). Conclusion Duration-focused eligibility criteria may better capture patient groups with low-intensity, long-duration smoking behaviors, potentially improving equity and early detection.
