Corrigendum to "Timing of first pembrolizumab infusion and long-term outcomes in non-small cell lung cancer: A retrospective multicenter study" [Eur J Cancer. 2025;228:115748

Timing of first pembrolizumab infusion and long-term outcomes in non-small cell lung cancer: A retrospective multicenter study.

NU01.05 Indigenous Population with Lung Cancer

The Impact of Persistent Smoking After Surgery on Long-term Outcomes After Stage I Non-small Cell Lung Cancer Resection

Racial Disparities in the Surgical Treatment of Clinical Stage I Non-Small Cell Lung Cancer Among Veterans

BackgroundWhile immune checkpoint inhibitors (ICIs) have significantly improved outcomes for many non-small cell lung cancer (NSCLC) patients, phase 3 trials have shown limited efficacy in programmed cell death ligand 1 (PD-L1) negative subgroups. This study aimed to evaluate the real-world effectiveness and safety of ICI-containing regimens vs. chemotherapy alone in PD-L1 negative NSCLC patients.MethodsThis multicenter, retrospective study analyzed advanced or recurrent NSCLC patients treated between 2015 and 2022 in Japan. From an initial screening of 1,382 patients, we identified patients with PD-L1 negative [tumor proportion score (TPS) <1%] NSCLC. We excluded patients who received molecular targeted therapy, chemoradiotherapy, or had epidermal growth factor receptor (EGFR) mutations. Overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs) were analyzed.ResultsAmong the 86 eligible patients identified, 54 received ICI-containing regimens (IC group) and 32 received chemotherapy alone (C group). No significant difference in OS (C vs. IC: median 14.9 vs. 23.8 months, P=0.87) and PFS (C vs. IC: median 6.6 vs. 7.8 months, P=0.20) was observed after covariates adjustment. The overall response rate was higher in the IC group (C vs. IC: 34.4% vs. 50.0%), as was the disease control rate (C vs. IC: 65.6% vs. 81.5%). AEs profiles were similar between groups, with grade 3–4 events occurring in 56.2% of C patients and 59.2% of IC patients. Treatment discontinuation rates due to AEs were comparable (C vs. IC: 21.9% vs. 24.1%, P=0.71).ConclusionsIn this real-world study of PD-L1 negative NSCLC patients, ICI-containing regimens did not demonstrate significantly improved OS or PFS compared to chemotherapy alone. Limited efficacy in this population highlights the need for further investigation and advancement in treatment strategies.

Simple SummaryThe superior vena cava (SVC)’s involvement in non-small-cell lung cancer (NSCLC) has been considered a technical and oncological contraindication for surgery. In recent decades, different studies have demonstrated that surgery should not be contraindicated per se, but in highly selected cases and specialized centers, it could be curative with acceptable risks. Nevertheless, the tangential resection of the SVC or patch reconstruction have different surgical risks from prosthetic replacement. Moreover, the percentage of SVC involvement may influence the prognoses of these selected patients. Our intention was to investigate the relation between the rate of SVC involvement and surgical and oncological outcomes. The conclusions of our retrospective study may improve the management of patients with T4 NSCLC and SVC invasion.Background: Surgery for non-small-cell lung cancers (NSCLCs) invading the superior vena cava (SVC) is rarely performed due to surgical complexities and reported poor prognoses. Different methods have been described to reconstruct the SVC, such as direct suture, patch use or prosthesis, according to its circumferential involvement. The aim of our study was to analyze the short- and long-term results of different types of SVC resection and reconstruction for T4 NSCLCs. Methods: Between January 2000 and December 2019, 80 patients received an anatomical lung resection with SVC surgery in this multicenter retrospective study. The partial resection and direct suture or patch reconstruction group included 64 patients, while the complete resection and prosthesis reconstruction group included 16 patients. The primary endpoints were as follows: long-term survival and disease-free survival. The secondary endpoints were as follows: perioperative complications and 30- and 90-day mortality. Unpaired t-tests or Mann–Whitney U tests for non-parametric variables were applied to discrete or continuous data, and the chi-square test was applied to dichotomous or categorical data. Survival rates were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: No differences were found between the two groups in terms of general characteristics and surgical, oncological and survival outcomes. In particular, there were no differences in terms of early (50.0% vs. 68.8%, p = 0.178) and late complication frequency (12.5% vs. 12.5%, p = 1.000), 30- and 90-day mortality, R status, recurrence, overall survival (33.89 ± 40.35 vs. 35.70 ± 51.43 months, p = 0.432) and disease-free survival (27.56 ± 40.36 vs. 31.28 ± 53.08 months, p = 0.668). The multivariate analysis demonstrated that age was the only independent predictive factor for overall survival. Conclusions: According to our results, SVC resection has good oncological and survival outcomes, regardless of the proportion of circumferential involvement and the type of reconstruction.

Should we distinguish between intra and extrapericardial pulmonary artery involvement in NSCLC? A multicenter retrospective case-control study

Gender Differences: Implications for Clinical Trials and Practice

IntroductionCompared to platinum-based therapies, a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) has demonstrated improved outcomes in advanced non-small cell lung cancer (NSCLC), albeit with higher rates of immune-related adverse events (irAEs). This multicenter retrospective study evaluated the efficacy and safety of nivolumab and ipilimumab with or without chemotherapy (NI and NICT) in real-world clinical settings.MethodsWe enrolled 215 treatment-naïve NSCLC patients who received NI or NICT between December 2020 and May 2023 at 14 institutions in Japan. Severe irAEs (Grade ≥ 3) were assessed using the Common Terminology Criteria for Adverse Events. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier methods and propensity score matching.ResultsOf 215 patients, 104 and 111 received NI and NICT, respectively. The median PFS was 5.3 and 5.9 months for NI and NICT, respectively. The median OS was 22.1 and 19.2 months for NI and NICT, respectively. High fever within 3 weeks of treatment initiation and high tumor burden were indicators of severe irAEs. Grade 3 or higher irAEs occurred in 36.5% patients in the NI group and 50.5% patients in the NICT group, with higher treatment-related mortality in the NICT group (5.4% vs. 1.9% in NI).ConclusionsNI and NICT showed comparable efficacies in PFS and OS. However, NICT had a higher incidence of severe irAEs and treatment-related mortality. High tumor burden and early high fever were predictors of severe irAEs. Further research is warranted to optimize the efficacy and safety of NICT for NSCLC treatment.

Simple SummaryIn this retrospective study including 580 patients with metastatic (Stage IV) non-small cell lung cancer, we investigated whether KRAS mutational status had any impact on clinical outcome. First, we analyzed overall survival of patients grouped based on absence (KRASWT) or presence (KRASMUT) of mutations in KRAS. Next, we assessed the effect of first-line therapies on both groups: platinum doublet chemotherapy (PT), the backbone treatment for most patients with metastatic non-small cell lung cancer, and immune checkpoint blockade (ICB) given to Stage IV patients with high PD-L1 expressing tumors. We found that KRASMUT patients had better response to ICB, but worse response to PT compared to KRASWT patients and that KRASWT patients with high PD-L1 expressing tumors responded better to PT than ICB. Our findings will have immediate clinical value, as KRAS mutations and PD-L1 expression are routinely assessed in most patients diagnosed with lung cancer.There is an urgent need to identify new predictive biomarkers for treatment response to both platinum doublet chemotherapy (PT) and immune checkpoint blockade (ICB). Here, we evaluated whether treatment outcome could be affected by KRAS mutational status in patients with metastatic (Stage IV) non-small cell lung cancer (NSCLC). All consecutive patients molecularly assessed and diagnosed between 2016–2018 with Stage IV NSCLC in the region of West Sweden were included in this multi-center retrospective study. The primary study outcome was overall survival (OS). Out of 580 Stage IV NSCLC patients, 35.5% harbored an activating mutation in the KRAS gene (KRASMUT). Compared to KRAS wild-type (KRASWT), KRASMUT was a negative factor for OS (p = 0.014). On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.478, 95% CI 1.207–1.709, p < 0.001). When treated with first-line platinum doublet (n = 195), KRASMUT was a negative factor for survival (p = 0.018), with median OS of 9 months vs. KRASWT at 11 months. On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.564, 95% CI 1.124–2.177, p = 0.008). KRASMUT patients with high PD-L1 expression (PD-L1high) had better OS than PD-L1high KRASWT patients (p = 0.036). In response to first-line ICB, KRASMUT patients had a significantly (p = 0.006) better outcome than KRASWT patients, with a median OS of 23 vs. 6 months. On multivariable Cox analysis, KRASMUT status was an independent prognostic factor for better OS (HR 0.349, 95% CI 0.148–0.822, p = 0.016). kRAS mutations are associated with better response to treatment with immune checkpoint blockade and worse response to platinum doublet chemotherapy as well as shorter general OS in Stage IV NSCLC.

Prognostic Value of Pretreatment FDG-PET Parameter for Early Stage Non-small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy

The association between anaesthetic technique and cancer specific survival following surgical resection of non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival. This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required. The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test). TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC). We conducted a retrospective cohort study of patients with clinical stage I NSCLC who underwent surgical resection in the Veterans Health Administration (VHA) between 10/01/2006 and 09/30/2016. Details of all outpatient prescriptions filled by patients within the VHA system from 1-year up to 14 days before surgery were collected. Medications were categorized using the Anatomical Therapeutic Chemical (ATC) Level One classification system. We assessed the association of medications prescribed in the year prior to surgery with postoperative adverse events (composite of death or major complication) at 30 and 90 days following surgery and overall survival (OS). We included 9,741 veterans in the analysis. The median number of prescription medications filled in the year preceding surgery was 11 (interquartile range: 7-16). In multivariable-adjusted analyses, a higher number of prescription medications was associated with increased risk of 30-day [multivariable-adjusted odds ratio (aOR): 1.016; 95% confidence interval (CI): 1.007-1.026] and 90-day postoperative adverse events (aOR: 1.015; 95% CI: 1.006-1.024) and decreased OS (adjusted hazard ratio: 1.019; 95% CI: 1.014-1.023). Within a subgroup of patients with a high comorbidity burden (Charlson-Deyo Comorbidity Index score of 6-8), a higher number of prescription medications was also associated with reduced OS (P<0.001). Patients prescribed medications from the ATC respiratory system class had elevated risk of postoperative adverse events at 30 days (aOR: 1.255; 95% CI: 1.095-1.439) and 90 days (aOR: 1.254; 95% CI: 1.097-1.434) compared to patients without these prescription medications. Significantly increased odds for 90-day postoperative adverse events were observed with each additional prescription medication from the ATC respiratory (aOR: 1.057; 95% CI: 1.027-1.088) and nervous system (aOR: 1.035; 95% CI: 1.005-1.066) classes. The number of medications prescribed preoperatively is associated with short- and long-term postoperative outcomes for early-stage NSCLC, even when adjusting for several covariates including age and comorbidity burden. Patients prescribed a higher number of medications acting primarily on the respiratory and nervous systems are at elevated risk for postoperative adverse events after curative-intent resection. Prescription medications may be a reliable tool to assess comorbidities and perioperative risk for patients with NSCLC.

BackgroundImmune checkpoint inhibitors (ICIs) have improved outcomes in advanced lung cancer. β-adrenergic signaling may promote tumor initiation and progression, and β-blockers (BBs) have emerged as anti-tumor sensitizing agents. This study evaluates the impact of BBs use during ICIs treatment in advanced lung cancer.MethodsThis multicenter retrospective real-world study included 462 patients treated with ICIs from June 2019 to December 2024. Patients were divided into BBs and No BBs groups. Primary endpoints were overall survival (OS) and progression-free survival (PFS); efficacy evaluation and objective response rate (ORR) were secondary. Propensity score matching (PSM) balances baseline characteristics. Kaplan–Meier method, Cox, and logistic regression models were used for survival and multivariate analyses. Subgroup analyses assessed clinical factors. A P value < 0.05 is considered statistically significant.ResultsAfter PSM, 318 patients were included (88 BBs, 230 No BBs). BBs use was associated with longer median PFS (mPFS) (15.8 vs. 11.8 months; HR = 0.67, 95% CI: 0.49–0.92, P = 0.038) and higher ORR (51.1% vs. 35.2%, P = 0.014), but not improved median OS (mOS) (29.0 vs. 31.5 months; HR = 1.38, 95% CI: 0.93–2.03, P = 0.108). BBs use independently predicted improved ORR (OR = 0.45, 95% CI: 0.26–0.78, P = 0.004) and longer PFS (HR = 0.67, 95% CI: 0.49–0.92, P = 0.014). In patients with cardiovascular comorbidities (CVD), BBs use was linked to longer mPFS (15.8 vs. 10.9 months, P = 0.0066) and higher ORR(51.1% vs 27.0%, P<0.001), with no mOS difference (P = 0.82). Among non-small cell lung cancer (NSCLC) patients, mPFS (17.5 vs. 12.3 months, P = 0.04) and ORR (56.0% vs 35.9%, P = 0.004) were also improved in the BBs group, whereas OS did not differ significantly (P = 0.3).ConclusionIn stage-advanced lung cancer, BBs combined with ICIs were associated with improved ORR and prolonged PFS, but did not significantly improve OS. PFS and ORR benefits were also observed in patients with CVD or NSCLC. Further prospective studies are needed to validate these findings and clarify whether BBs directly contribute to ICIs’ efficacy.