Resected Non-small Cell Lung Cancer Research Articles

T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy (INT) targeting up to 34 patient-specific tumor neoantigens to induce T cell responses and potentiate anti-tumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T cell responses to neoantigens from the first-in-human phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1mg mRNA-4157 + 200mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event (AE); there were no grade 4/5 AEs or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo, and strengthened pre-existing, T cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.

Different DLCO Parameters as Predictors of Postoperative Pulmonary Complications in Mild Chronic Obstructive Pulmonary Disease Patients with Lung Cancer.

Numerous studies have investigated methods of predicting postoperative pulmonary complications (PPCs) in lung cancer surgery, with chronic obstructive pulmonary disease (COPD) and low forced expiratory volume in 1 second (FEV1) being recognized as risk factors. However, predicting complications in COPD patients with preserved FEV1 poses challenges. This study considered various diffusing capacity of the lung for carbon monoxide (DLCO) parameters as predictors of pulmonary complication risks in mild COPD patients undergoing lung resection. From January 2011 to December 2019, 2,798 patients undergoing segmentectomy or lobectomy for non-small cell lung cancer (NSCLC) were evaluated. Focusing on 709 mild COPD patients, excluding no COPD and moderate/severe cases, 3 models incorporating DLCO, predicted postoperative DLCO (ppoDLCO), and DLCO divided by the alveolar volume (DLCO/VA) were created for logistic regression. The Akaike information criterion and Bayes information criterion were analyzed to assess model fit, with lower values considered more consistent with actual data. Significantly higher proportions of men, current smokers, and patients who underwent an open approach were observed in the PPC group. In multivariable regression, male sex, an open approach, DLCO <80%, ppoDLCO <60%, and DLCO/VA <80% significantly influenced PPC occurrence. The model using DLCO/VA had the best fit. Different DLCO parameters can predict PPCs in mild COPD patients after lung resection for NSCLC. The assessment of these factors using a multivariable logistic regression model suggested DLCO/VA as the most valuable predictor.

Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies

The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC.

Robotic-assisted versus video-assisted lobectomy for resectable non-small-cell lung cancer: the RVlob randomized controlled trial

The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan-Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. A total of 320 patients were randomized to receive RAL (n=157) or VAL (n=163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0-98.3) in the RAL group and 91.5% (95% CI, 87.2-96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33-1.28; P=0.21); noninferiority of RAL was confirmed according to the predefined margin of-5% (absolute difference, 2.96%; a one-sided 90% CI,-1.39% to ∞; P=0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6-94.1) in the RAL group and 85.4% (95% CI, 80.0-91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50-1.52; P=0.62). This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04).

Recurrence-free survival after curative resection of non-small cell lung cancer between inhalational gas anesthesia and propofol-based total intravenous anesthesia: a multicenter, randomized, clinical trial (GAS TIVA trial): protocol description

BackgroundSurgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial.MethodsThis double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years.DiscussionConfirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management.Trial registrationThe study protocol was prospectively registered at the Clinical trials (https://clinicaltrials.gov, NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.

To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC). This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling. A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%). Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Neoadjuvant targeted therapy versus targeted combined with chemotherapy for resectable EGFR-mutant non-small cell lung cancer: a retrospective controlled real-world study.

This study aimed to assess the role and effect of neoadjuvant targeted therapy (TT) versus targeted combined with chemotherapy (TC) for resectable EGFR-mutant non-small cell lung cancer (NSCLC). Between March 2021 and June 2023, 20 patients with stage IA3-IIIB NSCLC were enrolled in the study. Eleven patients received EGFR-TKIs in the TT group, while nine patients received EGFR-TKIs and two cycles of cisplatin-based doublet chemotherapy (TC group). We compare the differences between the two groups through the following variables, including age, sex, surgical approach, postoperative complications, neoadjuvant therapy adverse events, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), major pathologic response (MPR), and pathologic complete response (pCR). Patients were predominantly female (75%) and never-smokers (95%). The average age was 59.2 years (range 46-79 years). Fifty-five percent harbored an exon 19 EGFR mutation and 45% an exon 21 mutation. The average targeted drug dosing time was 2.91 ± 1.7 (range 1-6) months in the TT group and 3.56 ± 3.54 (range 1-12) months in the TC group (P=0.598). The most common side effects were rash and diarrhea. No grade 5 events with neoadjuvant therapy were observed. The rate of R0 resection was 100% in all patients. Among the 11 patients in the TT group, 6 achieved a PR and 5 had SD, resulting in an ORR of 54.5%. Among the 9 patients in the TC group, 6 had PR and the remaining 3 had SD, resulting in an ORR of 66.6%. one patient (11.1%) in the TC group achieved pCR, while no patients in the TT group achieved pCR (P = 0.142). Two patients (18.2%) in the TT group reached MPR, and 2 patients (22.2%) in the TC group reached MPR (P = 0.257). The overall clinical downstage rate is 60%. Only 9 (45%) cases of yield clinical TNM (ycTNM) were consistent with yield pathologic TNM (ypTNM). Results from this retrospective controlled research indicate that the neoadjuvant TT group is likely to be more effective outcomes and has safer profile in patients with EGFR-positive NSCLC than the neoadjuvant TC group. However, our results need to be validated in a multicenter, large sample prospective study.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection

BackgroundReal-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC).MethodsElectronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan–Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years.ResultsData from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively.ConclusionsUse of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection

BackgroundReal-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC).MethodsElectronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan–Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years.ResultsData from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively.ConclusionsUse of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Comparison of radiotherapy versus surgical resection following neoadjuvant chemoimmunotherapy in potentially resectable stage III non-small-cell lung cancer: A propensity score matching analysis

BackgroundNeoadjuvant chemoimmunotherapy followed by surgery is recommended for resectable non-small-cell lung cancer (NSCLC). However, a considerable proportion of patients do not undergo surgery and opt for alternative treatments such as radiotherapy. The efficacy of radiotherapy in this context remains unclear. MethodsThis retrospective study analyzed data from patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by either surgery or radiotherapy. Propensity score matching (PSM) was used to balance the heterogeneity between the groups. Efficacy outcomes, safety profiles, and disease recurrence patterns were assessed. ResultsIn total, 175 patients were included; 50 underwent radiotherapy, and 125 underwent surgery. Prior to matching, radiotherapy was inferior to surgery in terms of progression-free survival (PFS; Hazard ratio [HR], 2.23; P = 0.008). Following a 1:1 PSM adjustment, each group consisted of 40 patients. The median PFS was 30.8 months in the radiotherapy group and not reached in the surgery group (HR, 1.46; P = 0.390). The 12- and 24-month PFS rates were 90.4 % and 69.0 % for the radiotherapy group compared to 94.1 % and 73.9 % for the surgery group, respectively. Subgroup analyses after PSM showed that patients with stage IIIA disease tend to benefit more from surgery than those with stage IIIB disease (HR, 3.00; P = 0.074). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 62.5 % of patients in the radiotherapy group and 55.0 % in the surgery group, with no grade 5 TRAEs reported. The incidence of grade 3–4 treatment-related pneumonitis or pneumonia was 7.5 % and 2.5 % in the radiotherapy and surgery groups, respectively. ConclusionRadiotherapy may be a viable alternative to surgery in patients with resectable NSCLC who do not undergo surgical resection after initial neoadjuvant chemoimmunotherapy, offering comparable efficacy and a manageable safety profile. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Associated With Recurrence and Survival of Resectable Non–Small Cell Lung Cancer (NSCLC): A Retrospective Study

IntroductionCurative lung resection remains the key therapeutic strategy for early-stage non–small cell lung cancer (NSCLC). However, a proportion of patients still experience variable outcomes and eventually develop recurrence or die from their disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as a deleterious factor that inhibits tumor cells apoptosis and leads to reduction of lymphocyte infiltration. However, there has been no research on the predicted role of PCSK9 as an immunohistochemical biomarker with survival in resectable NSCLC. MethodsOne hundred sixty-three patients with resectable NSCLC were retrospectively reviewed, and PCSK9 expression of resected NSCLC was analyzed by immunohistochemistry using tissue microarrays. ResultsPCSK9 was associated with recurrence (42.1% relapsed in the PCSK9lo group versus 57.9% relapsed in the PCSK9hi group, P = 0.006) and survival status (39.6% dead in PCSK9lo group versus 60.4% dead in PCSK9hi group, P = 0.004) in patients with resectable NSCLC. Moreover, resectable NSCLC patients with higher PCSK9 expression in tumor tissue experienced poorer disease-free survival (median disease-free survival: 10.5 versus 25.2 mo, hazard ratio = 1.620, 95% confidence interval: 1.124-2.334) and overall suvrival (median overall suvrival: 20.0 versus 54.1 mo, hazard ratio = 1.646, 95% confidence interval: 1.101-2.461) compared to those with lower PCSK9 expression. ConclusionsHigh PCSK9 expression of tumor was correlated with recurrence and worse survival status of resectable NSCLC in our retrospective study, which indicated that PCSK9 in NSCLC may be an immunohistochemical biomarker of poor prognosis for patients with resectable NSCLC. Further large-scale prospective studies are warranted to establish these results.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC

PurposeThe use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). MethodWe analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. ResultsPre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. ConclusionThese findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

PP01.101 Estimated Cost of Adverse Events and Surgery for Resectable Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Nivolumab Plus Platinum-Doublet Chemotherapy

PP01.101 Estimated Cost of Adverse Events and Surgery for Resectable Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Nivolumab Plus Platinum-Doublet Chemotherapy

Role of Pathologic Single-N and Multiple-N Descriptors in Resected Non-Small Cell Lung Cancer

BackgroundThe 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. Research QuestionDo the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and MethodsUsing the National Cancer Database, we analyzed patients with pathologically staged N1–2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan–Meier method and multivariate Cox regression models. ResultsIn the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. InterpretationNSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

Sublobar resection for small-sized non-small cell lung cancer: A comprehensive comparison between subsegmentectomy, segmentectomy and wedge resection

ObjectivesSubsegmentectomy has been adopted for non-small cell lung cancer (NSCLC) for decades. This study aimed to compare the features between subsegmentectomy, segmentectomy and wedge resection for NSCLC. Materials and methodsNSCLC patients who underwent subsegmentectomy, segmentectomy, or wedge resection between 2014 and 2019 were retrospectively screened. Demographic, radiomic, and perioperative characteristics between patients were compared. Further, log-rank test, univariate and multivariate Cox regression were used for prognostic evaluation. ResultsThere were 276, 670, and 494 patients undergoing subsegmentectomy, segmentectomy, and wedge resection, respectively. Patients with segmentectomy and subsegmentectomy had larger tumor sizes and greater distances to the pleura than those with wedge resection. Subsegmentectomy and segmentectomy were more likely to achieve adequate surgical margins than wedge resection (82.0 % vs. 79.5 % vs. 64.7 %, P < 0.001), which was especially true for nodules away from the pleura (80.2 % vs. 81.4 % vs. 55.8 %, P < 0.001). In addition, anatomic resection allowed for more lymph node dissection and required less preoperative localization than wedge reception. Subsegmentectomy preserved about two subsegments than segmentectomy (P < 0.001). The incidence of prolonged air leakage after subsegmentectomy (3.3 %) and wedge (1.8 %) was similar (P = 0.308). Notably, 66.8 % of patients who underwent segmentectomy or subsegmentectomy were considered unsuitable for wedge. During the follow-up (55.1 months), no tumor recurrence or death occurred in patients undergoing subsegmentectomy. No significant recurrence-free survival (P = 0.140) or overall survival (P = 0.370) difference existed between these groups. ConclusionsSubsegmentectomy could achieve more adequate surgical margins than wedge resection and showed superiority for deep nodules. Compared to segmentectomy, subsegmentectomy could preserve more lung parenchyma.

Predictive Value of PERCIST for Locally Advanced Non-Small Cell Lung Cancer Treated with Preoperative Induction Therapy - A Multicenter Study in Japan.

Induction therapy followed by surgery is recommended as an alternative treatment strategy for locally advanced non-small cell lung cancer (NSCLC). Patients who achieve pathologic response after induction therapy have better outcomes than non-responders; therefore, therapeutic response must be evaluated. Recently, new approaches for monitoring therapeutic responses, which are based on 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), have been developed. In this study, we evaluated the predictive value of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which uses standardized uptake values corrected for lean body mass (SUL) and total lesion glycolysis (TLG). A total of 130 patients in the Setouchi Lung Cancer Group who underwent FDG-PET imaging before and after induction therapy prior to a planned surgical resection for NSCLC between 2007 and 2016 were studied retrospectively. The pathologic responses of the primary lung tumors and metastatic lymph nodes were compared with their responses based on evaluation using PERCIST. Postoperative pathologic studies revealed pathologic complete response (pCR) in 42 (32.3%) patients. PERCIST was significantly correlated with pathologic response (p < 0.001). The sensitivity, specificity, and accuracy of PERCIST for predicting pCR were 16.7% (7/42), 88.6% (78/88), and 65.4% (85/130), respectively. Patients with pCR had significantly higher reduction rates in SULpeak for both primary lung tumors and metastatic lymph nodes and TLG for primary tumors than non-responders. In a multivariate Cox regression analysis, tumor site in upper lobes, reduction rate of TLG in primary tumor, and pathologic N0 were independent predictors of favorable recurrence-free survival (RFS). Our study suggested that PERCIST, especially the rate of TLG reduction rate, are useful to predict the pathological response and prognosis after induction therapy. Although improvement is necessary, PERCIST can be a promising method of the post-induction status in lung cancer. Further research is needed to confirm our findings.

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

The Role of Environmental Exposures on Survival After Non-Small Cell Lung Cancer Resection

BackgroundSocioeconomic status and pollution exposure have been described as risk factors for poor survival in patients with non-small cell lung cancer (NSCLC). However, the relationship between these factors is complex and inadequately studied. This study aimed to evaluate the relationship between environmental and social factors and their impact on survival after NSCLC resection. MethodsA prospective database for all patients with NSCLC who underwent primary resection from 2006 to 2021 was analyzed. Ambient fine particulate matter (air pollution smaller than 2.5 μm [PM2.5]), greenness, and deprivation index (a measure of neighborhood-level material deprivation composed of 6 factors) were linked to individual patients by geocoding their residential address. ResultsA total of 661 patients who underwent pulmonary resection for NSCLC were evaluated. Black patients had increased levels of community deprivation compared with White patients; however, there was no difference in PM2.5 exposure or overall survival between races. Increased PM2.5 exposure was an independent predictor of worse survival on univariable and multivariable analysis (hazard ratio, 1.06; P = .003). ConclusionsIncreased PM2.5 exposure is associated with worse overall survival in resected NSCLC and was a more significant factor than race and material deprivation in this population. Interventions to reduce environmental air pollution could improve lung cancer survival.