Resected Non-small Cell Lung Cancer Research Articles

Efficacy of radiolabelled PD-L1-targeted nanobody in predicting and evaluating the combined immunotherapy and chemotherapy for resectable non-small cell lung cancer.

This study aimed to assess the predictive and evaluative value of PD-L1 targeted 68Ga-THP-APN09 PET/CT in the neoadjuvant immunotherapy combined with chemotherapy for resectable non-small cell lung cancer (NSCLC), and to explore its potential in indicating immunotherapy-related adverse effects (irAEs). Fifty patients with resectable NSCLC enrolled in this prospective study underwent baseline 68Ga-THP-APN09 PET/CT and 18F-FDG PET/CT, with follow-up 18F-FDG PET/CT conducted, additionally, 36 patients received follow-up 68Ga-THP-APN09 PET/CT. Surgery was performed following 2-4 cycles of toripalimab combined with chemotherapy if R0 resection was feasible. The major pathologic response (MPR) state of the post-operative specimen and the adverse effects following combined therapy were documented. The correlation between PD-L1 expression and baseline 68Ga-THP-APN09 PET/CT uptake was determined. The predictive and evaluative efficacies of baseline and follow-up 68Ga-THP-APN09 PET/CT, along with 18F-FDG PET/CT, in determining MPR, were compared. The SUVmax values of baseline 68Ga-THP-APN09 PET/CT were significantly higher in patients exhibiting high-positive PD-L1 expression compared to those with low-positive and negative expression (P = 0.001). And the SUVmax values of baseline 68Ga-THP-APN09 PET/CT in the response group, as determined by 18F-FDG PET/CT evaluation, were significantly higher than those in the non-response group (3.4 vs. 2.4, P < 0.001). Totally, 41 patients underwent surgery, of which 27 achieved MPR, while 14 did not. The SUVmax in baseline 68Ga-THP-APN09 PET/CT demonstrated statistical significance between the MPR and non-MPR groups, with area under the ROC curve (AUC) of 0.88 (95%CI: 0.77-0.99) in identifying MPR. However, the SUVmax in baseline 18F-FDG PET/CT failed to demonstrated significant predictive power, with AUC values of 0.68 (95%CI: 0.50-0.86, P = 0.076). While the SUVmax in follow-up 68Ga-THP-APN09 and 18F-FDG PET/CT, along with their change rate (ΔSUVmax%), demonstrated good predictive efficacy in identifying MPR, with AUC values of 0.81 (0.64-0.98), 0.91 (0.82-1.00), 0.93 (0.84-1.00), and 0.96 (0.89-1.00), respectively. Furthermore, the follow-up 68Ga-THP-APN09 PET/CT could remarkedly indicate the potential for thyroiditis. Baseline 68Ga-THP-APN09 PET/CT alone could predict efficacy and assist in patient screening for immunotherapy combined chemotherapy in resectable NSCLC, and the follow-up 68Ga-THP-APN09 PET/CT and their change rates could aid in therapy evaluation. Additionally, follow-up 68Ga-THP-APN09 PET/CT could be utilized to monitor the immunotherapy-related thyroiditis during the therapy. NCT05156515, registered 8 December 2021, https://register. gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw .

Multiparameter body composition analysis on chest CT predicts clinical outcomes in resectable non-small cell lung cancer

ObjectivesThis study investigates the association between baseline CT body composition parameters and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC).MethodsPatients who underwent surgical resection for NSCLC between January 2006 and December 2017 were retrospectively enrolled in this multicenter study. Body composition metrics, including the area of skeletal muscle, intermuscular adipose tissue, subcutaneous adipose tissue, visceral adipose tissue, muscle radiodensity, and derivative parameters from five basic metrics mentioned before, were calculated based on preoperative non-contrast-enhanced chest CT images at L1 level. The Cox proportional hazards regression analysis was used to evaluate the association between body composition metrics and survival outcomes including overall survival (OS) and disease-free survival (DFS).ResultsA total of 2712 patients (mean age, 61.53 years; 1146 females) were evaluated. A total of 635 patients (23.41%) died. 465 patients (19.51%) experienced recurrence and/or distant metastasis. After multivariable adjustment, skeletal muscle index (SMI, HR = 0.86), intermuscular adipose index (IMAI, HR = 1.49), and subcutaneous adipose index (SAI, HR = 0.96) were associated with OS. Similar results were found after stratification by gender, TNM stage, and center. There was no significant association between all body composition metrics and DFS (all p > 0.05). The body composition metrics significantly enhance the model including clinicopathological factors, resulting in an improved AUC for predicting 1-year and 3-year OS, with AUC values of 0.707 and 0.733, respectively.ConclusionsSMI, IMAI, and SAI body composition metrics have been identified as independent prognostic factors and may indicate mortality risk for resectable NSCLC patients.Critical relevance statementOur findings emphasize the significance of muscle mass, quality, and fat energy storage in clinical decision-making for patients with non-small cell lung cancer (NSCLC). Nutritional and exercise interventions targeting muscle quality and energy storage could be considered for patients with NSCLC.Key PointsMultiparameter body composition analysis is associated with the clinical outcome in NSCLC patients.Assessing muscle mass, quality, and adipose tissue helps predict overall survival in NSCLC.The quantity and distribution of body composition can contribute to unraveling the adiposity paradox.Graphical

Postoperative radiotherapy improves survival in completely resected non-small cell lung cancer with pathologic N2 stage IIIA and positive lymph node count greater than one: a SEER-based retrospective cohort study

ObjectiveNon-small cell lung cancer (NSCLC) constitutes approximately 85% of lung cancer cases, with 20%–30% of patients diagnosed at stage III. While multimodal therapy is the standard for treating locally advanced NSCLC, the role of PORT remains controversial. This study seeks to evaluate the effect of postoperative radiotherapy (PORT) on overall survival (OS) and cancer-specific survival (CSS) in patients with resected pathologic N2 (pN2) stage IIIA NSCLC.MethodsData from the Surveillance, Epidemiology, and End Results Program (SEER) 17 registry (2010–2019) were analyzed. The cohort included 1,471 patients aged 65 years or older, diagnosed with stage IIIA pN2 NSCLC, who had undergone lobectomy or total pneumonectomy. Patients who had received neoadjuvant chemotherapy or radiotherapy were excluded. Univariate and multivariate analyses were conducted to assess the association of PORT with OS and CSS. Kaplan-Meier survival curves were employed to estimate survival outcomes, while the COX proportional hazards model was utilized for comparative analysis. PLN counts were stratified into two categories: ≤1 and &amp;gt;1.ResultsAmong the 1,471 patients included in the study, 613 (41.67%) received PORT, while 858 (58.33%) did not. PORT was associated with a significantly higher 1- and 3-year OS (89.96% and 68.49%, respectively) compared to the non-PORT group (87.44% and 61.88%, respectively, P = 0.03). However, no significant difference in CSS was observed between the groups (P = 0.15). Among patients with PLN counts &amp;gt;1, PORT significantly improved OS (HR = 1.32, 95% CI = 1.04–1.68, P = 0.0016) and CSS (HR = 1.32, 95% CI = 0.99–1.70, P = 0.026), whereas no significant differences were seen in patients with PLN counts ≤1.ConclusionsThis study underscores the potential of PORT in enhancing OS in patients with resectable pN2 stage IIIA NSCLC, particularly in those with PLN counts exceeding one. These findings suggest that PORT may offer improved outcomes in patients with extensive lymph node involvement, emphasizing the need for further prospective studies to validate and expand upon these observations.

Toripalimab plus platinum-doublet chemotherapy as perioperative therapy for initially unresectable NSCLC: An open-label, phase 2 trial.

Perioperative treatment with toripalimab combined with chemotherapy was efficacious and safe in resectable stage II-IIIA non-small cell lung cancer (NSCLC); however, little is known about whether this treatment regimen could convert unresectable NSCLC to resectable. This study enrolled 40 treatment-naive patients with initially unresectable stage IIIA-IIIB NSCLC. Toripalimab (240mg) and platinum-doublet chemotherapy were administered every 3weeks for 2-4 cycles. Surgical resection was decided after assessing the efficacy of induction therapy. The primary outcome was the R0 resection rate. The secondary outcomes included safety, overall survival, disease-free survival, event-free survival, objective response rate, major pathological response (MPR), and pathological complete response (pCR). Available baseline tumor biopsy samples were used for molecular biomarker analyses, including bulk RNA sequencing and multiplex immunostaining. This study was registered at ClinicalTrials.gov: NCT04144608. Of the 40 patients who received induction toripalimab plus chemotherapy, 29 (72.5%) patients received surgery, and all achieved R0 resection (100% R0 rate). Of these patients, 17 (58.6%) achieved MPR, with 10 (34.5%) patients evaluated as pCR. With a median follow-up of 31.8months (95% confidence interval [CI]: 24.2-39.4), the median event-free survival and overall survival were not reached. Molecular analyses revealed highly expressed gene sets for germinal center B cells (signatures of tertiary lymphoid structure [TLS]) at baseline among patients with pCR compared to patients with non-pCR, suggesting that the TLS status of the patients was associated with the induction of immunotherapy responses. Toripalimab-based induction treatment of initially unresectable NSCLC yielded a high R0 rate and MPR rate, with a good safety profile and encouraging survival outcomes. This work was funded by the National Natural Science Foundation of China.

Prognostic significance of pathological response and lymph node status in neoadjuvant immunotherapy for potentially resectable non-small cell lung cancer

Objective To evaluate the predictive value of pathological response and lymph node status on progression-free survival (PFS) in patients with potentially resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant immunotherapy. Methods A retrospective analysis was conducted on 143 patients with potentially resectable NSCLC who underwent neoadjuvant immunotherapy followed by surgical resection. Pathological response, lymph node involvement, and clinical outcomes were comprehensively assessed using Kaplan-Meier analysis and Cox regression. Results Both major pathological response (MPR) and complete pathological response (CPR) significantly correlated with improved PFS (p < .01), with no statistically significant difference between them (p = .15). Lymph node involvement adversely affected PFS (p < .01). A novel risk stratification approach based on pathological response and nodal status effectively distinguished prognostic groups, with 3-year PFS rates of 98.9%, 78.9%, and 53.3%. Cox regression identified gender (HR = 0.25, p = .03), pathological response (HR = 6.02, p < .01), and lymph node stage (HR = 2.30, p = .01) as independent PFS predictors. Conclusion In potentially resectable NSCLC, MPR and CPR demonstrate similar PFS benefits after neoadjuvant immunotherapy. Lymph node status significantly influences prognosis, even in initially unresectable cases. The proposed risk stratification provides a valuable tool for personalized management in this challenging patient population.

Brain Imaging in Patients with Non-Small Cell Lung Cancer—A Systematic Review

Background: Lung cancer frequently metastasizes to the brain, liver, and adrenal glands with a significant negative prognostic impact on overall survival and quality of life (QoL). To optimize treatment and prognosis, adequate staging with the detection of distant metastases is crucial. The incidence of brain metastases in potentially resectable early-stage non-small cell lung cancer (NSCLC) is as low as 3%; hence, the need for preoperative brain imaging has been a constant matter of debate, especially in stage II. In stages III and IV NSCLC, neuroimaging is an essential part of staging. Methods: A systematic literature search was performed. Publications from 1999 to 2024, focusing on preoperative brain imaging (BI) in the staging of stages I–IV NSCLC, were included. Data extraction included study population characteristics, the modality of BI, the incidence of brain metastases (BMs), and the main outcomes of the studies. The final included studies were selected according to the PRISMA criteria. In the second step, guidelines on BI in NSCLC staging of major importance were identified and compared. Results: A total of 530 articles were identified, of which 25 articles were selected. Four prospective studies and 21 retrospective investigations were included. Most of the investigations focused on BI in the early stages. The main imaging modality for BI was magnetic resonance imaging (MRI), followed by computed tomography (CT). Besides the identified 25 studies, the most important internationally applied guidelines on brain imaging in the staging of NSCLC were reviewed. While some guidelines agree on preoperative BI in NSCLC stage III (Union for International Cancer Control—UICC eighth edition) patients, other guidelines recommend earlier BI starting from clinical stage II. All mentioned guidelines homogenously recommend BI in patients with symptoms suggestive of brain pathologies. Conclusions: BI in NSCLC staging is recommended in neurologically symptomatic patients suggestive of brain metastases as well as NSCLC patients with stage III disease. Neuroimaging in stage IA patients, as well as in pure GGO (Ground-Glass Opacity) lesions, was considered unnecessary. The predominantly applied imaging modality was ce-MRI (contrast-enhanced magnetic resonance imaging). Inconsistency exists concerning BI in stage II. The identification of prognostic factors for developing BM in patients with early-stage NSCLC could help to clarify which subgroup might benefit from preoperative BI.

Clinical significance of the preoperative prognostic nutritional index in patients with resectable non-small cell lung cancer: a multicenter study.

To validate the clinical impacts of the prognostic nutritional index (PNI), an immune-nutritional blood marker, in patients with resectable non-small cell lung cancer (NSCLC) using multicenter cohort data. The subjects of this retrospective multicenter study, involving 11 hospitals, were patients who underwent curative lung resection for pathological stage IA-IIIA NSCLC. We analyzed the relationship between the preoperative PNI and postoperative outcomes. Patients were divided into a high PNI group and a low PNI group (cutoff: 45). We also performed exact matching and three propensity score-based methods to validate the results. Among the total 2,770 patients, 2,272 (82.0%) had a high PNI (>45) and 498 (18.0%) had a low PNI (≤45). A low preoperative PNI was a predictor of increased overall postoperative complications (relative risk 1.49; 95% confidence interval (CI) 1.31-1.69) and an independent adverse prognostic factor for overall survival (hazard ratio 1.77; 95% CI 1.45-2.17) and recurrence-free survival (1.34; 95% CI 1.14-1.59). All the methods we used (whole cohort, exact matching, and three propensity score methods) showed consistent results. The findings of this multicenter study suggest that immune-nutritional assessment using the PNI will provide useful prognostic information for patients with resectable NSCLC.

ACUTE MYOCARDIAL INJURY AFTER SURGICAL LUNG RESECTION: INCIDENCE, CLINICAL FEATURES, PREDICTORS

HighlightsAcute perioperative myocardial injury develops in 38.5% of patients with non – small cell lung cancer and is associated with the ThRCRI major cardiac events risk index, preoperative hemoglobin level and postoperative heart rate. Aim. To determine the incidence and predictors of acute myocardial injury after surgical treatment of patients with non – small cell lung cancer (NSCLC).Methods. The study included 104 men aged 63.0 [58–67] years who underwent lung resection for NSCLC. Blood levels of cardiac troponin I (cTnI) were determined before and 24 and 48 hours after surgery. Myocardial injury after noncardiac surgery (MINS) was diagnosed when postoperative cTnI increased &gt; 99th percentile of the upper reference limit. Two patients with elevated cTnI of non-ischemic origin were excluded from the analysis. In groups with and without MINS, clinical parameters were compared and their relationships with the MINS development were assessed using univariate regression. Multivariate logistic regression analysis was performed to identify independent MINS predictors. ROC curves were constructed and threshold values of quantitative variables associated with the study outcome were determined.Results. MINS was diagnosed in 40 patients (38.5%). In 36 of them, the cTnI increase was asymptomatic. Among patients with MINS, in contrast to the group without MINS, the share of pneumonectomy, heart rate (HR) after surgery and the cardiac events risk index ThRCRI were higher, as well as hemoglobin level before surgery was lower. Using multiple logistic regression, a combination of factors that provides the greatest accuracy in predicting MINS was identified: ThRCRI index ≥ 1 (adjusted odds ratio (OR) 5.85, 95% confidence interval [1.41–24.28]), hemoglobin before surgery (OR 0.68 [0.5–0.91] for every 10 g/L), HR after surgery (OR 1.99 [1.26–3.13] for every 10 min–1). Threshold levels were established for hemoglobin before surgery (135 g/L), below which the OR for MINS was 2.54 [1.12–5.75], and postoperative HR (88 min–1), above which the OR for MINS was 2.64 [1.16–5.99].Conclusion. The incidence of acute myocardial injury after NSCLC surgery is 38.5%. In 90% of cases the MINS was asymptomatic. A mathematical model was created and following independent predictors of MINS were established: ThRCRI index ≥ 1, hemoglobin level before and heart rate after the surgery. At a threshold hemoglobin value &lt; 135 g/L and HR&gt;88 min–1, the risk of MINS increases significantly.

Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.

Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non-small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial. Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety. A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively. Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.

Cross-sectional study of lung cancer patients as a potential high-risk factor for abdominal aortic aneurysm

Background Abdominal aortic aneurysm (AAA) is more common in Non-small cell lung cancer (NSCLC) patients. Considering that ruptured AAA is potentially fatal, timely management of AAA would result in long-term survival benefits. We assess the prevalence and characteristics of AAA in resectable NSCLC patients who would benefit from AAA surveillance. Methods 1,019 resectable NSCLC patients in Severance and Kangbuk Samsung Hospitals were reviewed from January 2019 to November 2020. The control group comprised 2,899 cancer-free people who had a health check-up CT scan in Severance between January 2018 and December 2019. Results Among resectable primary NSCLC patients, 39/1,019 (3.8%; odds ratio [OR], 19.19; 95% confidence interval [CI], 8.10–46.46) had AAA compared with 6/2,899 (0.2%) in the control (P&lt;0.001). In multivariable regression analysis, male (OR, 13.24; 95% CI, 1.50–117.48; P = 0.020), aging (OR, 1.10; 95% CI, 1.04–1.15; P&lt;0.001), current smoker (OR, 4.20; 95% CI, 1.20–14.62; P = 0.024), and coronary artery disease (OR, 3.13; 95% CI, 1.48–6.62; P = 0.003) were independent risk factors for AAA in NSCLC. Conclusion The present study found that the incidence of AAA in resectable early-stage lung cancer patients was significantly higher than in the cancer-free control group. Therefore, we suggest that early-stage NSCLC patients, especially smokers older than 60 years, undergo regular AAA surveillance as part of their lung cancer monitoring.

Navigating the landscape of neoadjuvant immunotherapy for NSCLC: progress and controversies.

Recently, attention has increasingly centered on non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors application. Numerous clinical studies have underscored the potential of immunotherapy in treating resectable NSCLC, highlighting its role in improving patient outcomes. However, despite these promising results, there is ongoing debate regarding the efficacy of immunological combination therapy strategies, the prevalence of treatment-related side effects, the identification of predictive biomarkers, and various other challenges within the neoadjuvant context. Careful consideration is essential to maximize the benefits of immunotherapy for patients with resectable NSCLC. This article offers a detailed overview of recent advancements in neoadjuvant immunotherapy for resectable NSCLC. By examining these developments, we aim to provide new perspectives and valuable insights into the benefits and challenges of applying neoadjuvant immunotherapy in clinical settings.

Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer

Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer remains clinically challenging. In this study, we investigated the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase 2 trial. Blood samples were prospectively collected from 45 patients with stage IIIA (N2) non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the computed tomography-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 mutations/megabase was associated with significantly greater MPR rates (77.8% vs 38.5%, P=.042), and longer disease-free survival (P=.043), but not overall survival (P=.131), compared with bTMB <11 mutations/megabase in 35 patients with bTMB available. The developed DL model achieved an area under the curve of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an area under the curve of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathologic response and survival. Compared with ctDNA residual, ctDNA clearance before surgery was associated with significantly greater MPR rates (88.2% vs 11.1%, P<.001) and improved disease-free survival (P=.010). The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

CT Predictors of Angiolymphatic Invasion in Non-Small Cell Lung Cancer 30 mm or Smaller.

Background Angiolymphatic invasion (ALI) is an important prognostic indicator in non-small cell lung cancer (NSCLC). However, few studies focus on radiologic features for predicting ALI in patients with early-stage NSCLCs 30 mm or smaller. Purpose To identify radiologic features for predicting ALI in NSCLCs 30 mm or smaller in maximum diameter. Materials and Methods This study was a secondary review of pathologic and CT findings from an integrated health care system between January 2016 and November 2023 for participants in the prospective study Initiative for Early Lung Cancer Research on Treatment, or IELCART. Preoperative diagnostic radiologic features possibly related to ALI, volume doubling time (VDT), and PET maximum standardized uptake value were evaluated. Multivariable logistic regression analysis, adjusted for sex, age, nodule size, and smoking status, was used to determine predictors of ALI. Model performance was analyzed with the area under the receiver operating characteristic curve (AUC). Results Of 778 resected NSCLCs 30 mm or smaller (median patient age, 69 years [IQR, 63-76 years]; 458 female patients), 715 (92%) were solid, 41 (5%) were part-solid, and 22 (3%) were nonsolid. ALI was documented in 271 (35%) resected NSCLCs, all in solid NSCLCs, representing 37.9% (95% CI: 34.4, 41.5) of solid NSCLCs. None of the 63 subsolid NSCLCs had ALI (0% [95% CI: 0, 5.75]). For the 715 solid NSCLCs (median patient age, 69 years [IQR, 63-76 years]; 420 female patients), multivariable logistic regression analysis showed that lollipop sign (odds ratio [OR] = 4.12 [95% CI: 2.82, 6.04]; P < .001) and spiculation (OR = 2.05 [95% CI: 1.42, 2.97]; P < .001) were independent predictors of ALI (AUC = 0.77 [95% CI: 0.73, 0.80]). Considering only the 474 patients in whom VDT could be calculated based on CT scans, VDT was also an independent predictor for ALI (OR = 0.96 [95% CI: 0.94, 0.98]; P < .001). Incorporating VDT into the model improved ALI prediction (AUC = 0.82 [95% CI: 0.77, 0.86]; P < .001). Conclusion For patients with NSCLCs 30 mm or smaller, ALI was present in 37.9% of solid NSCLCs and none of the 63 subsolid NSCLCs. Among solid NSCLCs, lollipop sign, spiculation, and VDT were independent radiologic predictors of ALI. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Czum in this issue.

Recurrence as a small cell lung cancer transformation in a resected stage IIIA EGFR-mutated non-small cell lung cancer treated with adjuvant osimertinib: a case report

Recurrence as a small cell lung cancer transformation in a resected stage IIIA EGFR-mutated non-small cell lung cancer treated with adjuvant osimertinib: a case report

Explainable PET-Based Habitat and Peritumoral Machine Learning Model for Predicting Progression-free Survival in Clinical Stage IA Pure-Solid Non-small Cell Lung Cancer: ATwo-center Study.

This study aimed to develop and validate machine learning (ML) models utilizing positron emission tomography (PET)-habitat of the tumor and its peritumoral microenvironment to predict progression-free survival (PFS) in patients with clinical stage IA pure-solid non-small cell lung cancer (NSCLC). 234 Patients who underwent lung resection for NSCLC from two hospitals were reviewed. Radiomic features were extracted from both intratumoral, peritumoral and habitat regions on PET. Univariate and multivariate logistic regression analyses were employed to determine significant clinical variables. Subsequently, a radiomics nomogram was developed by combining the radiomics signature with these identified clinical variables. Kaplan-Meier (KM) analysis was performed to investigate the prognostic value of the nomogram. Shapley Additive Explanations (SHAP) were used to interpret the ML models. The combination model which contained peritumoral 5mm and habitat regions radiomics features, clinical variables obtained a strong well-performance, achieving area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.854-0.957) in the train set and 0.875 (95% CI 0.789-0.962) in the internal validation set. The radiomics signature was significantly associated with PFS, the model significantly discerned high and low-risk patients, and exhibited a significant benefit in the clinical use showed low-risk score given have far longer RFS than those with high-risk score (log-rank P＜0.001). The habitat and peritumoral radiomics signatures serve as an independent biomarker for predicting PFS in patients with early-stage NSCLC, effectively stratified survival risk among patients with clinical stage IA pure-solid non-small cell lung cancer.

EGFR status assessment using reflex testing targeted next-generation sequencing for resected non-squamous non-small cell lung cancer.

EGFR status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR versus next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making. We aimed to describe the clinico-pathological and molecular features, as well as the prognostic factors of resected EGFR-mutant NS-NSCLC evaluated with reflex NGS and RT-PCR, so as to compare the results of the two methods. We retrospectively included and collected data from patients with resected EGFR-mutant NS-NSCLC diagnosed in our institution between 2005 and 2024. Additional cases from another center were included. Tumors were analyzed using targeted NGS and RT-PCR. A total of 153 patients were selected. The median follow-up after surgery was 22months. The positive percent agreement of RT-PCR compared to NGS for the detection of an EGFR mutation was 88%. Common single EGFR mutations (L858R/del19) were observed in 117/153 (77%) cases; 22/153 (14%) and 14/153 (9%) cases had uncommon single and compound EGFR mutations, respectively. 63/153 (41%) patients had a co-occurring mutation, including a TP53 mutation in 43/63 (68%) co-mutated patients. EGFR/TP53-mutant tumors were associated with positive PD-L1 expression compared to EGFR-mutant/TP53-wild-type tumors (62% vs 39%; p = 0.006). Shorter median event-free survival (EFS) in patients with an EGFR exon 18 mutation and those with TP53 exon 7 co-mutation was recorded. The EGFR status should be systematically evaluated using targeted NGS reflex testing for resected NS-NSCLC since future therapeutic decision-making could soon consider integrating the presence of co-occurring mutations.

Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade.

Co-mutations of the Kirsten rat sarcoma virus (KRAS) and serine/threonine kinase 11 (STK11) genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. Although neoadjuvant chemoimmunotherapy is now a standard-of-care treatment for resectable NSCLC, the clinical and immunologic impacts of KRAS and STK11 co-mutations in this setting are unknown. We evaluated and compared recurrence-free survival of resectable KRAS-mutated NSCLC tumors, with or without co-occurring STK11 mutations, treated with neoadjuvant ICB. Single-cell transcriptomics was performed on tumor-infiltrating T cells from seven KRASmut/STK11wt tumors and six KRAS and STK11 co-mutated (KRASmut/STK11mut) tumors. Relative to KRASmut/STK11wt tumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased prostaglandin E2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TILs from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT). These divergent T-cell transcriptional fates suggest that T-cell maintenance and residence may be detrimental to antitumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning prostaglandin E2 signaling and IL-2 signaling as they relate to T-cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB.

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy. This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers. Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM. Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.

Circulating TERT serves as the novel diagnostic and prognostic biomarker for the resectable NSCLC

BackgroundTelomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase and required for cancer development. This study aims to reveal its clinical utility for diagnosis and prognosis of resectable NSCLC.MethodsTERT was quantitatively evaluated by the enzyme-linked immunosorbent assay (ELISA) from 69 patients before and after the surgery. The prognostic value was evaluated by disease-free survival (DFS) and overall survival (OS).ResultsCirculating TERT in NSCLC patients were significantly higher than that in the healthy group, possessing the AUC of 0.90. Importantly, TERT change between pre- and post- operation was significantly correlated with OS and DFS (p = 0.022, p = 0.046 respectively), acted as the independent prognostic factors for DFS and OS, indicating it can serve as the promising diagnostic and prognostic biomarker for resectable non-small cell lung cancer (NSCLC).ConclusionsTERT change between pre- and post- resection can serve as the promising biomarker for prognosis of resectable NSCLC.

Efficacy of neoadjuvant PD-1/PD-L1 inhibitor in resectable NSCLC: a meta-analysis based on randomized controlled trials

BackgroundThe efficacy of neoadjuvant immunotherapy in resectable non-small-cell lung cancer (NSCLC) is controversial. The aim of this study is to explore the efficacy of additional PD-1/PD-L1 inhibitors in the neoadjuvant treatment of resctable NSCLC.MethodsData sources included Cochrane Library, Embase, Web of Science, and PubMed from beginning of the database creation to May 2024. The primary outcomes of the study included event-free survival (EFS), overall survival (OS), pathological complete response (pCR), major pathological response (MPR).ResultsSeven RCTs, including 2929 patients, were included in the analysis. The results showed that the experimental group had significantly higher rates of pCR (RR = 5.9, p < 0.001) and MPR (RR = 2.88, p < 0.001) compared to the control group. OS (HR = 0.57) and EFS (HR = 0.58) was also significantly improved in the experimental group. Subgroup analysis of EFS revealed that the benefit was higher in the East (HR = 0.56) than in the West (HR = 0.70). Additionally, the benefit seemed to rise with PD-L1 tumor cell proportion score (TPS) (TPS < 1%, HR = 0.76; 1% < TPS < 49%, HR = 0.56; TPS ≥ 50%, HR = 0.38). The benefit degree seemed to be higher in the III period patients (HR = 0.75) than I-II period patients (HR = 0.52). It is important to emphasize that smokers (HR = 0.54, p < 0.001) benefited from neoadjuvant immunotherapy but nonsmokers (HR = 0.68, p = 0.055) did not.ConclusionNeoadjuvant PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the short-term and long-term prognosis of patients with resectable NSCLC. Moreover, the efficacy of this treatment regimen may be affected by different clinicopathological characteristics of patients.