Stage IIIA-N2 Research Articles

Real-World Analysis of Survival and Treatment Efficacy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.

Prognostic Value of Preoperative N Subcategories in Patients with Stage IIIA N2 Non-Small Cell Lung Cancer.

Purpose To evaluate the preoperative risk factors in patients with pathologic IIIA N2 non-small cell lung cancer (NSCLC) who underwent upfront surgery and to evaluate the prognostic value of new N subcategories. Materials and Methods Patients with pathologic stage IIIA N2 NSCLC who underwent upfront surgery in a single tertiary center from January 2015 to April 2021 were retrospectively reviewed. Each patient's clinical N (cN) was assigned to one of six subcategories (cN0, cN1a, cN1b, cN2a1, cN2a2, and cN2b) based on recently proposed N descriptors. Cox regression analysis was used to identify the significant prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Results A total of 366 patients (mean age ± SD, 62.0 years ± 10.1; 202 male patients [55%]) were analyzed. The recurrence rate was 55% (203 of 366 patients) over a median follow-up of 37.3 months. Multivariable analysis demonstrated that cN (hazard ratios [HRs] for cN1 and cN2b compared with cN0, 1.66 [95% CI: 1.11, 2.48] and 2.11 [95% CI: 1.32, 3.38], respectively) and maximum lymph node (LN) size at N1 station (≥12 mm; HR, 1.62 [95% CI: 1.15, 2.29]), in addition to clinical T category (HR, 1.51 [95% CI: 1.14, 1.99]), were independent prognostic factors for RFS. For OS, clinical N subcategories (cN1, cN2a2, and cN2b vs cN0; HRs, 1.91 [95% CI: 1.11, 3.27], 1.89 [95% CI: 1.13, 2.18], and 2.02 [95% CI: 1.07, 3.80], respectively) and LN size at N1 station (HR, 1.75 [95% CI: 1.12, 2.71]) were independent prognostic factors. For clinical N1, OS was further stratified according to LN size (log-rank test, P < .001). Conclusion Assessing the proposed N subcategories by reporting single versus multistation involvement of N2 disease and maximum size of metastatic LN, reflecting metastatic burden, at preoperative CT may offer useful prognostic information for planning optimal treatment strategies. Keywords: CT, Lung, Staging, Non-Small Cell Lung Cancer Supplemental material is available for this article. ©RSNA, 2024.

Risk Factor Analysis of Morbidity and 90-Day Mortality of Curative Resection in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer after Induction Concurrent Chemoradiation Therapy.

Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

126 Exploring Real-World Treatment Patterns and Outcomes in Stage IIIA N2 Non-Small Cell Lung Cancer (NSCLC)

126 Exploring Real-World Treatment Patterns and Outcomes in Stage IIIA N2 Non-Small Cell Lung Cancer (NSCLC)

A review of perioperative treatment strategies with immunotherapy and tyrosine kinase inhibitors in resectable and stage IIIA-N2 non-small cell lung cancer.

Stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous group with different potential therapeutic approaches. Treatment is typically multimodal with either surgical resection after neoadjuvant chemotherapy and/or radiation or concurrent chemotherapy and radiation if unresectable. Despite the multimodal treatment and early stage, cure rates have traditionally been low. The introduction of immunotherapy changed the treatment landscape for NSCLC in all stages, and the introduction of immunotherapy in early-stage lung cancer has improved event free survival and overall survival. Tyrosine Kinase inhibitors (TKIs) have also improved outcomes in early-stage mutation-driven NSCLC. Optimal treatment choice and sequence is increasingly becoming based upon personalized factors including clinical characteristics, comorbidities, programmed death-ligand 1 (PD-L1) score, and the presence of targetable mutations. Despite encouraging data from multiple trials, the optimal multimodal sequence of stage IIIA-N2 NSCLC treatment remains unresolved and warrants further investigation. This review article summarizes recent major clinical trials of neoadjuvant and adjuvant treatment including stage IIIA-N2 NSCLC with a focus on immunotherapy and TKIs.

Prognostic Significance of the Highest Mediastinal Lymph Node Involvement in Patients with Stage III-N2 Non-small Cell Lung Cancer.

Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial. A total of 486 patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups-HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan-Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS). The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%; p<0.001) and stage IIIA (87.2% vs. 77.5%; p<0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%, p<0.001; OS: 42.1% vs. 59.2%, p=0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio [aHR] 1.26, 95% confidence interval CI 0.94-1.68; OS: aHR 1.45, 95% CI 1.07-1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06-2.02; OS: aHR 1.70, 95% CI 1.19-2.42); however, no such difference was observed within the stage IIIB group. HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.

Is there role of adjuvant radiotherapy after complete resection of locally advanced nonsmall cell lung cancer?

This review aims to provide a timely and relevant overview of the role of postoperative radiotherapy (PORT) in completely resected stage IIIA-N2 nonsmall cell lung cancer (NSCLC). Given the controversy surrounding the use of PORT and the emergence of advanced radiation techniques and therapies, this review provides valuable insight into current and potential treatment strategies. The Lung ART and PORT-C trials have provided valuable insights into the efficacy of PORT in stage IIIA-N2 NSCLC. While the results have been mixed, studies have shown that advanced radiation techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy, can reduce cardiopulmonary toxicities associated with PORT. Molecular targeted therapies and immunotherapies have also shown potential in improving NSCLC treatment outcomes. The role of radiotherapy becomes smaller and smaller in new era. However, it is too early to abolish radiotherapy for all the patients after complete resection of locally advanced NSCLC. Nowadays, it is recommended to adopt individualized treatment approaches guided by multidisciplinary team consultations. The integration of IMRT, proton therapy, and emerging therapies offers the potential to enhance treatment efficacy while minimizing toxicity. Further research is needed to optimize the use of PORT and explore the method to identify the patients who can really benefit from PORT.

Long-Term Outcomes of Selected Patients with IIIA-N2 Non-small Cell Lung Cancer Receiving Upfront Surgical Resection.

Stage IIIA non-small cell lung cancer (NSCLC) is a diverse group that requires multimodality treatment. The aim of this study was to report the long-term outcomes for patients with IIIA-N2 disease. We conducted a retrospective review of cases with IIIA-N2 (T1-2N2) NSCLC who underwent upfront surgery. Kaplan-Meier curves and Cox proportional hazard analyses were used to assess the impact of various variables on survival. A total of 475 patients were ultimately included. With a median follow-up time of 108 months, the 5- and 10-year overall survival (OS) rates were 42.2% and 27.7%, respectively. R0 resection was found to be associated with improved progression-free survival (PFS) and OS compared with R1/R2 resection (p=0.041 for PFS; p=0.015 for OS). Patients with single-station N2 disease demonstrated significantly better PFS and OS than those with multiple-station N2 disease (p<0.001 for PFS; p=0.002 for OS). Following surgical resection, adjuvant therapy was significantly correlated with prolonged PFS and OS compared with those patients without any treatment. However, there was no significant difference in PFS and OS between chemotherapy and radiochemotherapy (p=0.915 for PFS; p=0.287 for OS). Patients with EGFR exon 19 deletion had significantly improved OS compared with those with L858R (p=0.040). Our study shows promising long-term outcomes for selected patients with stage IIIA-N2 NSCLC treated with upfront surgery followed by adjuvant therapy, especially those with R0 resection and single-station N2. This study sheds light on the potential management and treatment options for this challenging population.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer

ObjectivesAlthough postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC.Materials and methodsThis study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan–Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability.ResultsOf all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85–0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93–1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85–1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94–1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98–1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99–1.23, P = 0.07).ConclusionPORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

Outcomes of Stage IIIa and Well-Selected Stage IIIb or Oligometastatic Stage IV Non-Small Cell Lung Cancers Managed by Multimodal Therapy Including Immunotherapy and Surgery

Abstract Background Resectable locally advanced non-small cell lung cancers (NSCLCs) are managed by multimodal approaches including systemic therapies followed by surgery. The recent inclusion of immunotherapy in neoadjuvant protocols has significantly improved tumor responses. In selected situations, bulky N2, N3 or oligometastatic NSCLCs with treated metastasis have shown excellent regression following chemo-immunotherapy and could be considered for surgery. Aims We here compare the oncological outcomes of stage IIIA (single N2) with stage IIIB (bulky N2, N3) or oligometastatic stage IV NSCLCs managed by chemo-immunotherapy followed by surgery. Methods We reviewed all patients treated in our institution between April 2017 and June 2022 for a locally advanced or oligometastatic NSCLC with chemo-immunotherapy followed by surgery in our prospectively collected database. We recorded, for each patient, the clinico-pathological characteristics, perioperative complications and oncological outcomes. Results Forty-eight patients (27 single station N2 stage IIIA (group 1) and 21 bulky N2, N3 or oligometastatic NSCLC (group 2)) were identified. Patient characteristics were comparable between groups. Surgery consisted in lobectomy (81%), bilobectomy (17%) or pneumonectomy (2%). Complete resection was achieved in 46 (95%) patients with R1 resection in two patients due to lymph node effraction. Complete tumor pathological response was achieved in 26% in group 1 and 33% in group 2. Postoperative morbidity was 48% in group 1 and 81% in group 2 (p=0.05). There was no mortality. Median follow-up was 16 months (IQR: 9-32). Progression-free survival was 6 months (IQR: 3-18) in group 1 and 5 months (IQR: 2-7) in group 2 (p=0.04). Overall recurrence rate was 40% (comparable between groups (p=0.08)) and consisted, in majority, of distant metastasis. Overall survival was comparable between groups (p=0.05). Conclusions The inclusion of immunotherapy in induction protocols has improved tumor response and allowed to consider advanced NSCLCs for surgical resection with good postoperative and oncological outcomes.

ER predicts poor prognosis in male lung squamous cell cancer of stage IIIA-N2 disease after sequential adjuvant chemoradiotherapy.

The efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study. A total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay. The median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors. PORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT.

The prognostic value of postoperative radiotherapy in right tumor for lung related death: based on SEER database and real-world data.

Postoperative radiotherapy (PORT) is a therapeutic strategy for patients with non-small cell lung cancer (NSCLC). Nevertheless, some studies suggesting PORT does not improve overall survival (OS) including Lung ART phase III trial. The role of PORT and high-risk groups need to be confirmed. Patients from the Surveillance, Epidemiology, and End Results program (SEER) from 2004 to 2015 were eligible. Aged ≥18 years with stage IIIA-N2 NSCLC, accepted PORT or not were considered for the study. Cox regression analyses and multivariate competing risk model were performed. Propensity score matching (PSM) was conducted. Data from a single-center study in China were used for validation. In all patients with IIIA-N2 NSCLC, death from respiratory illness increased year by year, with right lung-related deaths accounting for the main proportion. In SEER database, PORT was detrimental for OS after PSM (hazard ratio [HR], 1.088; 95% CI, 1.088-1.174; P = 0.031), with a same trend for death from the lungs (HR, 1.13; 95% CI, 1.04-1.22; P = 0.005). Right tumor receiving PORT were prone to death from lung disease(HR, 1.14; 95% CI, 1.02-1.27; P = 0.018). In China single-center cohort, PORT was significantly correlated with deteriorated OS (HR 1.356; 95% CI 1.127-1.632; P <0.01), especially in the right laterality (HR 1.365; 95% CI 1.062-1.755; P = 0.015). PORT was a risk factor for stage IIIA-N2 NSCLC patients, particularly with characters of right laterality, male sex, age ≥65 years, and advanced tumor stage. These patients are more likely to death from lung disease after PORT.

Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial

EMERGING-CTONG 1103 showed improved progression-free survival (PFS) with neoadjuvant erlotinib vs. chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) (NCT01407822). Herein, we report the final results. Recruited patients were randomly allocated 1:1 to the erlotinib group (150 mg/day orally; neoadjuvant phase for 42 days and adjuvant phase to 12 months) or to the GC group (gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously; 2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase). Objective response rate (ORR), complete pathologic response (pCR), PFS, and overall survival (OS) were assessed along with safety. Post hoc analysis was performed for subsequent treatments after disease recurrence. Among investigated 72 patients (erlotinib, n = 37; GC, n = 35), the median follow-up was 62.5 months. The median OS was 42.2 months (erlotinib) and 36.9 months (GC) (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.47–1.47; p = 0.513). The 3- and 5-year OS rates were 58.6% and 40.8% with erlotinib and 55.9% and 27.6% with GC (p3-y = 0.819, p5-y = 0.252). Subsequent treatment was administered in 71.9% and 81.8% of patients receiving erlotinib and GC, respectively; targeted therapy contributed mostly to OS (HR, 0.35; 95% CI, 0.18–0.70). After disease progression, the ORR was 53.3%, and the median PFS was 10.9 months during the EGFR-TKI rechallenge. During postoperative therapy, grade 3 or 4 adverse events (AEs) were 13.5% in the erlotinib group and 29.4% in the GC group. No serious adverse events were observed. Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.

Reaching multidisciplinary consensus on the management of non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer

IntroductionThe optimal management of patients with non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer (NSCLC) remains controversial. In this modified Delphi study from France, we aimed to generate agreement through multidisciplinary decision-making on the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC. MethodsAn expert panel of 30 physicians from different specialities completed two Delphi rounds of a 76-item questionnaire, pertaining to: pathological confirmation of N2 disease; initial treatment approach; treatment approach in case of disease progression/stability following neoadjuvant chemotherapy; treatment approach taking into account various patient and tumour characteristics. Each questionnaire item was scored using a 9-point Likert scale. Consensus in agreement was achieved if ≥ 80 % of responses to a questionnaire item were scored between 7 and 9 and if the median value of the score to the item was ≥ 7. ResultsRegarding the pathologic confirmation of N2 disease, agreement (up to 100 %) was reached on endobronchial ultrasound/endoscopic ultrasound as the preferred method of initial mediastinal staging for paratracheal lymph nodes. There was also panellist agreement (up to 93 %) on the adoption as first-line treatment of surgery and (neo)adjuvant chemotherapy in patients with single-station disease, and of concurrent chemoradiotherapy followed by adjuvant immunotherapy in those with multi-station N2 disease. Panellists further agreed on the use of a non-surgical strategy, i.e., concurrent chemoradiotherapy with adjuvant immunotherapy, in patients with single-station N2 disease in case of: involvement of ≥ 2 mediastinal lymph nodes; disease progression following neoadjuvant chemotherapy; compromised cardiopulmonary function if compatible with radiotherapy; anticipated right pneumonectomy. ConclusionsThis Delphi study reinforces the importance of multidisciplinary discussions leading to the best individual approach to the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC, a challenging heterogeneous population.

Operative versus Nonoperative Treatment in Patients with Advanced Non-Small-Cell Lung Cancer: Recommended for Surgery.

There is currently limited evidence for a correlation between the recommended operation and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). NSCLC patients with stages III and IV, recommended for operation, were identified in the US National Cancer Institute Surveillance, Epidemiology, and End Results database (SEER).We used propensity score matching (PSM) and multivariable Cox proportional hazards regression to ensure the robustness of our findings. The cumulative rates of death were compared between patients with and without recommended operations using the Kaplan-Meier curves. Operation was recommended for 3331 patients but was not performed in 912 (27.4%) patients (then on-operative group). After PSM, 553 pairs matched. Compared to the nonoperative group, the hazard ratios (HRs) in the operative group were 0.46 (95% CI 0.23-0.95 and p=0.037) in stage IIIA and 0.54 (95% CI 0.42-0.68 and p < 0.001) in stage IVA. However, in stages IIIB, IIIC, and IVB, the recommended operative group was not associated with better OS. The OS was not different in stage IIIA-N2, stage IVA-N1, and stage IVA-N3 patients between groups (p=0.28, p=0.14, and p=0.79, respectively). Moreover, the recommended operative group had better OS than the nonoperative group in stage IIIA-N0 (p=0.00085), stage IIIA-N1 (p=0.009), stage IVA-N0 (p < 0.001), and stage IVA-N2 (p=0.034). Compared to the nonoperative group, recommended operation improved survival in NSCLC patients with stage IIIA-N0, stage IIIA-N1, stage IVA-N0, and stage IVA-N2. However, in stages IIIA-N2, IIIB, IIIC, IVA-N1, IVA-N3, and IVB, recommended operation did not lead to significantly improved survival time.

Effects of Neoadjuvant Radiotherapy on Survival in Patients with Stage IIIA-N2 Non-Small-Cell Lung Cancer Following Pneumonectomy.

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan−Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients.

Improved survival in N2 non-small cell lung cancer: better staging or better treatment; a SEER database retrospective cohort analysis

Background: Over the past several decades, there has been an apparent improvement in survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). Positron emission tomography (PET)-scanning for NSCLC staging/restaging was approved by the Centers of Medicare and Medicaid Services (CMS) in 2001. We sought to determine whether this survival improvement was due to more sensitive staging-modalities and/or an evolution in surgical practice.

Postoperative radiotherapy with modern techniques does not improve survival for operable stage IIIA-N2 non–small cell lung cancer

ObjectivesThis study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non–small cell lung cancer (NSCLC) who underwent complete resection. MethodsThe overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded. ResultsA total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not. ConclusionsIn this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

EP05.02-009 Aumolertinib Versus Erlotinib/Chemotherapy for Neoadjuvant Treatment of Stage IIIA EGFR-mutant NSCLC (ANSWER)

For stage IIIA-N2 EGFR-mutant NSCLC, there have been several randomized controlled studies comparing various EGFR-TKI targeted therapy versus chemotherapy as neoadjuvant therapy. However, the role of third-generation EGFR-TKIs in neoadjuvant settings remains inconclusive. Aumolertinib (formerly almonertinib; HS-10296) is a novel, third-generation EGFR-TKI approved in China to treat EGFR-mutant NSCLC. The ANSWER study (NCT04455594) will assess the efficacy and safety of aumolertinib compared with erlotinib or platinum doublet chemotherapy (pemetrexed plus carboplatin or cisplatin) as neoadjuvant therapy in resectable patients with EGFR-mutant stage IIIA NSCLC.

Neoadjuvant Immunotherapy Combined with Chemotherapy for Local Advanced Non-Small-Cell Lung Cancer in a Patient with a History of Breast Cancer: A Case Report

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.