Lung Cancer-specific Survival Research Articles

A European multicentre study evaluating the prognosis of peripheral early-stage lung adenocarcinoma patients operated on by segmentectomy or lobectomy.

To analyze impact of segmentectomy on oncological outcomes of different peripheral early-stage lung adenocarcinoma patterns. Retrospective multicentre study including patients who underwent either lobectomy or segmentectomy in 6 European centres from 2015-2021, for ≤ 2 cm pathological peripheral lung adenocarcinoma. Overall and disease-free survivals were assessed by cox-regression and lung cancer specific survival by competing regression analyses to adjust for patient- and tumour- related factors both in the entire dataset and the in aggressive adenocarcinoma patterns dataset. Lobectomy and segmentectomy were performed in 481 (71%) and 193 (29%) patients, respectively. Propensity score matching was performed (n = 191). 108 patients had a least an aggressive pattern. 5-year disease-free, overall and lung cancer specific survivals were similar between patients who underwent lobectomy or segmentectomy in both entire and aggressive pattern datasets. In patients with aggressive pattern, 5-year disease-free (lobectomy 87.3%; segmentectomy 86.6%, p = 0.62), overall (lobectomy 86.4%; segmentectomy 95.6%, p = 0.61) and lung cancer specific (lobectomy 100%; segmentectomy 95.6%, p = 0.13) survivals did not differ.Segmentectomy was not an independent risk factor for disease-free survival, neither for overall survival nor for lung cancer specific survival in any of the 2 datasets.In patients with aggressive pattern, loco-regional recurrence (linearized risks: lobectomy 8.21; segmentectomy 11.3) was higher in patients who underwent segmentectomy. Resection should not be extended (to lobectomy) on patients who underwent segmentectomy for pathologically proven early-stage adenocarcinoma with aggressive patterns.

Choice of wedge resection for selected T1a/bN0M0 non-small cell lung cancer

Recently, several studies have reported that the survival benefit of wedge resection might not be inferior to that of lobectomy in early-stage NSCLC patients, but there is no unified definition of the details or cutoff value. Patients with early-stage NSCLC with a tumour size ≤ 2.0 cm were chosen from the SEER database. The influence of confounding factors was minimized by 1:1 propensity score matching (PSM). Kaplan‒Meier curves and Cox proportional hazards models were used to evaluate the overall survival (OS) and lung cancer-specific survival (LCSS) of patients undergoing lobectomy and wedge resection. A total of 3891 patients with early-stage NSCLC with tumour size ≤ 2.0 cm were enrolled, of whom 2839 underwent lobectomy and 1052 underwent wedge resection. Both before and after PSM, lobectomy significantly improved OS and LCSS compared with wedge resection in the unstratified study population. In the tumour size ≤ 1 cm group, lobectomy had better OS and LCSS than wedge resection (P < 0.05) before PSM; after PSM, there was no significant difference in OS (P = 0.16) and LCSS (P = 0.17). In Grade I patients, before PSM, lobectomy was superior to wedge resection in LCSS (P = 0.038), while there was no significant difference in OS (P = 0.16); after PSM, there were no significant differences in either OS (P = 0.78) or LCSS (P = 0.11). For early-stage NSCLC patients with a tumour size ≤ 1 cm or with a tumour size ≤ 2 cm and with Grade I, there was no significant difference in survival between wedge resection and lobectomy.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

Impact on Prognosis of Stage I Non-Small Cell Lung Cancer Secondary to Delays in Diagnostic Workup.

Background Diagnostic workup of small pulmonary nodules often requires follow-up CT scans to confirm nodule growth before invasive diagnostics or treatment. Purpose To confirm prior results from the International Early Lung Cancer Action Program (I-ELCAP) on quantifying decreases in lung cancer prognosis by using two large databases, the National Lung Screening Trial (NLST) and International Association for the Study of Lung Cancer (IASLC). Materials and Methods In this retrospective study, a model was developed to predict cure rates based on size of solid nodules using the NLST (August 2002 to summer 2007) and IASLC (January 2011 to December 2019) databases, focusing on stage I non-small cell lung cancer (NSCLC). Kaplan-Meier methods were used to calculate 10-year lung cancer-specific survival and 5-year overall survival rates for different tumor sizes. Tumor diameter increases after 90-, 180-, and 365-day delays were estimated using volume doubling times (VDTs) of 60, 120, and 240 days corresponding to fast, moderate, and slow tumor growth. Initial and delayed lung cancer cure rates were assessed across nine scenarios of time delays and tumor growth rates and compared with the previous results of the I-ELCAP database. Results Using regression models based on 166 NLST and 22 590 IASLC patients with NSCLC, 10-year lung cancer-specific survival and 5-year overall survival, respectively, for tumors 4.0-20.0 mm in diameter were estimated. For a 20.0-mm tumor with a 60-day VDT in the NLST database, the lung cancer-specific survival decreased from 83.4% to 76.5%, 66.8%, and 32.3% after 90, 180, and 365 days, respectively. The IASLC database showed similar decreases in 5-year overall survival, from 81.2% to 73.4%, 62.4%, and 23.3% after 90, 180, and 365 days, respectively. Comparison across NLST, IASLC, and I-ELCAP databases revealed minor variations in lung cancer cure rates between 79.9% and 83.4%, with reductions of 6.9%-8.3% after a 180-day delay with a 120-day VDT. Conclusion The NLST and IASLC databases confirmed prior estimates from the I-ELCAP database for the decrease in lung cancer prognosis due to diagnostic delays. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Park and Lee in this issue.

Survival and recurrence rates following SBRT or surgery in medically operable Stage I NSCLC

ObjectivesSurgery is the standard of care for early-stage non-small cell lung cancer (NSCLC), with SBRT reserved for patients who are not surgical candidates. We hypothesized overall survival (OS), lung cancer-specific survival (LCSS), progression free survival (PFS), and recurrence rates following SBRT or surgery in medically operable patients with Stage I NSCLC from the Veterans’ Health Care System (VAHS) would be equivalent. Materials and methodsMedically operable patients diagnosed with Stage I NSCLC between 2000–2020 from the VAHS, determined by an FEV1 or DLCO > 60 % of predicted and Charlson comorbidity index (CCI) of 0 or 1, treated with SBRT or surgery were identified. SBRT patients were propensity score matched in a 1:1:1 ratio to those undergoing resection (SBRT:lobectomy:sub-lobar resection). OS, LCSS, and PFS and site of recurrence were determined. Results103 patients were included in each cohort. With a median follow-up of 7.9 years 5-year OS for all patients was 51 % (95 % CI 46–57 %). After propensity score matching, OS (HR 2.08, 1.59), LCSS (HR 2.28, 1.97), and PFS (1.97, 1.45) were significantly worse with SBRT compared to either lobectomy or sub-lobar resection, respectively, (p < 0.05 for each comparison). Regional recurrence was significantly higher following SBRT (15.5 % vs 6.8 % or 4.9 %; p < 0.05), but there was no significant difference in local (28.2 % vs 21.4 % or 21.4 %; p > 0.05) or distant recurrence (10.7 % vs 9.7 % or 13.6 %; p > 0.05) when compared to lobectomy or sub-lobar resection, respectively. ConclusionIn medically operable patients, OS, LCSS, and PFS following either lobectomy or sub-lobar resection were superior to that for SBRT for Stage I NSCLC, likely due in part to higher regional recurrence following SBRT. This suggests that pulmonary function test results and CCI alone are insufficient to define a cohort of medically operable patients suited for SBRT. These data support strategies to overcome regional recurrences seen with SBRT.

Histological Assessment and Interobserver Agreement in Major Pathologic Response for Non-Small Cell Lung Cancer with Neoadjuvant Therapy.

Major pathologic response (MPR), defined as ≤10% of residual viable tumor (VT), is a prognostic factor in non-small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction. This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images. Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; IoU score, 0.92). Excellent agreement was achieved for VT (%) (ICC=0.959) and MPR using 10% cutoff (Fleiss' kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p<0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012). While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.

Effect of family history of cancer on postoperative survival in patients with non-small cell lung cancer.

Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC. Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed. A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC. FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

Sublobar resection for lung adenocarcinoma less than 2 cm containing solid or micropapillary components radiologically presented as consolidation-to-tumor ratio (CTR) ≤0.25 [ground-glass opacity (GGO)

The suitability of sublobar resection as a surgical approach for early-stage non-small cell lung cancer (NSCLC) remains unclear. This study investigated the feasibility of sublobar resection in patients with pathological-stage IA adenocarcinoma less than 2 cm characterized by a high-risk pathological subtype but exhibiting radiologically noninvasive features. We conducted a retrospective review of patients diagnosed with pathological stage IA lung adenocarcinoma who underwent surgical intervention between 2013 and 2017. The inclusion criteria included a maximum tumor diameter of 2.0 cm or less, a consolidation-to-tumor ratio (CTR) of 0.25 or less, and a histopathological confirmation of a solid or micropapillary component. Patients were categorized into sublobar resection and lobectomy groups, and propensity score matching was employed to mitigate potential confounders. The primary endpoints were lung cancer-specific survival (LCSS) and overall survival (OS). The study comprised 149 patients, with 84 in the lobectomy group and 65 in the limited resection group. In the overall cohort, the 5-year LCSS was 100% for both groups, while the 5-year OS was 97.6% (95% CI: 94.41-100.00%) in the lobectomy group and 100% in the sublobar resection group (P=0.21). After propensity score matching, the LCSS remained at 100% for both groups, and the 5-year OS was 97.14% in the lobectomy group and 100% in the sublobar resection group (P=0.32). Based on our experience, for lung adenocarcinoma containing solid/micropapillary subtype, a size less than 2 cm, and a CTR ≤0.25, the oncological outcomes appeared to be comparable between sublobar resection and lobectomy, suggesting that sublobar resection might serve as an equivalent alternative to lobectomy for such lesions.

Impact of Margin Distance on Locoregional Recurrence and Survival After Thoracoscopic Segmentectomy

BackgroundThis study aimed to identify the impact of margin distance on locoregional recurrence (LRR) and survival outcomes after thoracoscopic segmentectomy for non-small cell lung cancer. MethodsWe retrospectively analyzed data from prospectively collected consecutive thoracoscopic segmentectomies in a single center from January 2008 to February 2023. The restricted cubic spline of the adjusted Cox regression model for LRR displayed the breakpoint of margin distance. The Kaplan-Meier estimator with log-rank test evaluated the overall survival between the 2 groups stratified by the breakpoint, and the Aalen-Johansen estimator with the Gray test assessed the LRR-free survival and lung cancer-specific survival in the competing model. ResultsThe study included 155 patients. LRR was observed in 22 patients (14.2%), with a median time to LRR of 17.1 months (interquartile range, 6.3-26.3 months). Margin distance was found to be a predictor for LRR (hazard ratio, 0.92; P = .033). The identified breakpoint for margin distance in this cohort was 19.8 mm. Compared with this cutoff, a margin distance of 15 mm increased the risk of LRR by 65%, whereas 25 mm decreased the risk to LRR with 31%. A segmentectomy with a margin distance ≥20 mm resulted in significant improvements in overall survival (P = .020), lung cancer-specific survival (P = .010), and LRR-free survival (P < .001) compared with cases with a margin distance of <20 mm. ConclusionsMargin distance ≥20 mm decreased LRR and improved survival outcomes for thoracoscopic segmentectomy in this study.

Impact of Tumor Size and Differentiation Grade on Survival After Lobectomy and Segmentectomy for Patients with Early-Stage Lung Adenocarcinoma.

The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.

Impact of lung cancer screening on stage migration and mortality among the national Veterans Health Administration population with lung cancer.

Despite randomized trials demonstrating a mortality benefit to low-dose computed tomography screening to detect lung cancer, uptake of lung cancer screening (LCS) has been slow, and the benefits of screening remain unclear in clinical practice. This study aimed to assess the impact of screening among patients in the Veterans Health Administration (VA) health care system diagnosed with lung cancer between 2011 and 2018. Lung cancer stage at diagnosis, lung cancer-specific survival, and overall survival between patients with cancer who did and did not receive screening before diagnosis were evaluated. We used Cox regression modeling and inverse propensity weighting analyses with lead time bias adjustment to correlate LCS exposure with patient outcomes. Of 57,919 individuals diagnosed with lung cancer in the VA system between 2011 and 2018, 2167 (3.9%) underwent screening before diagnosis. Patients with screening had higher rates of stage I diagnoses (52% vs. 27%; p ≤ .0001) compared to those who had no screening. Screened patients had improved 5-year overall survival rates (50.2% vs. 27.9%) and 5-year lung cancer-specific survival (59.0% vs. 29.7%) compared to unscreened patients. Among screening-eligible patients who underwent National Comprehensive Cancer Network guideline-concordant treatment, screening resulted in substantial reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.67-0.92; p=.003) and lung-specific mortality (aHR, 0.61; 95% CI, 0.50-0.74; p<.001). While LCS uptake remains limited, screening was associated with earlier stage diagnoses and improved survival. This large national study corroborates the value of LCS in clinical practice; efforts to widely adopt this vital intervention are needed.

The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non–small-cell lung cancer (NSCLC).

TPS8116 Background: Pembrolizumab (pembro; anti–PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309–1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145–0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II–IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1–4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS ( &lt; 1% vs 1%–49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). The abstract was originally presented and published in: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281. Clinical trial information: NCT06077760 .

The population-based effects of the FDA’s approval of durvalumab as consolidative therapy in patients with locally-advanced non-small cell lung cancer.

e20086 Background: In 2018, consolidative durvalumab (D) was FDA-approved in patients with locally advanced non-small cell lung cancer(NSCLC) because it increased PFS and was later found to increase overall survival (OS). This analysis will check the real-world effects of this agent prior to and after its approval. Methods: The SEER-17 database was queried from 2015-2020 and assessed for differences in OS/lung cancer specific survival (LCSS) and rates of second cancers (2C). Patients included were those with NSCLC who received chemotherapy and radiation with at least 7 months of follow-up. The population was split into two different groups, those diagnosed before and after D’s approval (2015-2017(BA) and 2018-2020(AA). Multi-variate analyses (MVA) were used to find prognostic factors which were used to adjust OS/LCSS rates for the BA and AA at 12, 24, and 30 months. Variables analyzed included patient characteristics, histopathology, and previous cancers (separated into alcohol, diet, smoking, virus and hormone related). Inverse propensity scores were weighted for OS factors to determine rates of second cancers. Results: Of 12,022 patients, 501 patients developed 2Cs. The OS was significantly better for AA group than the BA group ( p &lt; 0.001, HR = 0.79(0.74, 0.85) with rates at 12, 24, and 30 months of 0.86, 0.68, and 0.62%; and 0.83, 0.62, and 0.55%. Multivariate analyses for OS demonstrated similar prognostic factors in both year groups and were worse with advanced age, male sex, unmarried status, squamous histology, advanced stage and non-Hispanic white race. The LCSS was significantly better in AP than the BA group ( p &lt; 0.001, HR = 0.84 (0.7, 0.89) with rates at 12, 24, and 30 months of groups of 0.82,0.61, and 0.55%; and 0.80,0.56,and 0.48%. The prognostic factors for LCSS were the same in both group and included age, male sex, squamous histology, and advanced stage. The adjusted rates of 2C in 2018-2020 group were trending less than in 2015-2017 (HR = 0.80(0.63-1.03), p =0.07), largely driven by a reduction in smoking-related cancers (HR = 0.74(0.53-1.02, p= 0.07). The 2C rates at 12, 24, and 30 months were 1.0, 2.7, and 3.5% in the 2015-2017 and 0.9, 1.6, and 1.9% in 2018-2020 groups. MVA significant risk factors for 2Cs were age, history of previous cancer, male sex, and squamous histology in the BA group, but no factors were significant for 102 second cancers in the AA group. Conclusions: In the years after durvalumab's approval, there was a significant benefit in terms of overall survival and lung cancer specific survival, but prognostic factors remained similar. In addition to the OS/LCSS benefit, durvalumab's approval was associated with a strong trend for reducing the incidence of second cancers, especially in those with previous smoking related cancers.

Is wedge resection equivalent to segmentectomy in pathological stage IA (≤2 cm) non-small cell lung cancers?

Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early-stage patients with non-small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients. We identified patients with pT1a-bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity-score matching (PSM) analysis were used. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p < 0.001). Before PSM, patients undergoing segmentectomy had a higher 5-year OS rate (87.75% vs. 82.72%; p = 0.0023), while exhibiting a similar LCSS rate (93.45% vs. 92.73%; p = 0.32). After PSM, segmentectomy consistently demonstrated significantly better OS and there was no statistically significant difference in LCSS. Analysis of causes of death revealed that a higher incidence of deaths related to other causes among patients undergoing wedge resection compared to those undergoing segmentectomy. Both wedge resection and segmentectomy yield comparable oncological outcomes for patients with NSCLC ≤ 2 cm, although segmentectomy exhibits superior OS due to less death related to other causes.

Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer–specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern–based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer–specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern–based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Treatment strategies for stage IA non-small cell lung cancer: A SEER-based population study.

There are various therapeutic methods for treating stage IA (T1N0M0) non-small cell lung cancer (NSCLC), but no studies have systematically assessed multiple treatments to determine the most effective therapy. Stage IA NSCLC patient data collected between 2004 and 2018 were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Treatment modalities included observation, chemotherapy alone (CA), radiation alone (RA), radiation+chemotherapy (RC), surgery alone (SA), surgery+chemotherapy (SC), surgery+radiation (SR) and surgery+radiation+chemotherapy (SRC). Comparisons were made of overall survival (OS) and lung cancer-specific survival (LCSS) among patients based on different therapeutic methods by survival analysis. Ultimately, 89147 patients with stage IA NSCLC between 2004 and 2018 were enrolled in this study. The order of multiple treatment modalities based on the hazard ratio (HR) for OS for the entire cohort revealed the following results: SA (HR: 0.20), SC (HR: 0.25), SR (HR: 0.42), SRC (HR: 0.46), RA (HR: 0.56), RC (HR: 0.72), CA (HR: 0.91) (P<0.001), and observation (HR: Ref). The SA group had the best OS and LCSS, and similar results were found in most subgroup analyses (all P<0.001). The order of surgical modalities based on the HR for OS for the entire cohort revealed the following results: lobectomy (HR: 0.32), segmentectomy (HR: 0.41), wedge resection (HR: 0.52) and local tumor destruction (HR: Ref). Lobectomy had the best effects on OS and LCSS, and similar results were found in all subgroup analyses (all P<0.001). SA appeared to be the optimal treatment modality for patients with stage IA NSCLC, and lobectomy was associated with the best prognosis. There may be some indication and selection bias in our study, and the results of this study should be confirmed in a prospective study.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma

ObjectivesInvasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm.MethodsData were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model.ResultsIn SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830).ConclusionsLimited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Surgical outcomes for non-small cell lung cancer in younger adults: A population-based study.

The surgical outcomes for younger patients with non-small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long-term survival outcomes in younger individuals with NSCLC following surgery. We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer-directed surgery. Younger patients were defined as those aged 18-50 years, while older patients were 51-80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non-white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5-year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p < 0.001), as were the 5-year LCSS rates (82.4% vs. 71.8%; p < 0.001). Post-PSM, younger patients consistently demonstrated significantly better OS and LCSS. Further stage-specific analysis revealed significantly improved 5-year OS rates at each stage and superior 5-year LCSS for stages I-II among younger patients. However, there was no statistically significant difference in LCSS for stages III-IV. Overall, younger patients with NSCLC treated surgically exhibit superior OS and LCSS compared to their older counterparts, although no statistically significant difference in LCSS for stages III-IV was observed between the two age groups.

The characteristics and prognosis of different disease patterns of multiple primary lung cancers categorized according to the 8th edition lung cancer staging system.

The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.

Abstract CT281: The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC)

Abstract Background: Pembrolizumab (pembro; anti-PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309-1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145-0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II-IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1-4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS (&amp;lt;1% vs 1%-49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). Citation Format: Jonathan D. Spicer, Santosh M. Nair, Adnan Khattak, Jay M. Lee, Michelle Brown, Robert S. Meehan, Nazly Shariati, Xuan Deng, Ayman Samkari, Jamie E. Chaft. The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281.