IIIA-N2 Non-small Cell Lung Cancer 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.

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.

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.

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.

ASO Author Reflections: Upfront Surgery Followed by Adjuvant Therapy: An Option for IIIA-N2 Non-small Cell Lung Cancer.

ASO Author Reflections: Upfront Surgery Followed by Adjuvant Therapy: An Option for IIIA-N2 Non-small Cell Lung Cancer.

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.

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.

Postoperative Radiotherapy in Completely Resected IIIA-N2 Non-small Cell Lung Cancer: Quit or Not?

This commentary highlights the potential role of postoperative radiotherapy for patients with completely resected ⅢA-N2 non-small cell lung cancer.

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.

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.

Value of postoperative radiotherapy for stage IIIa-N2 non-small cell lung cancer: an analysis based on SEER database.

BackgroundThe role of postoperative radiotherapy (PORT) in resected stage IIIa-N2 non-small cell lung cancer (NSCLC) patients who have received adjuvant chemotherapy remains controversial. This study aimed to explore the value of PORT and determine which patients could benefit from PORT.MethodsStage IIIa-N2 NSCLC patients treated with surgery and adjuvant chemotherapy were identified from the Surveillance, Epidemiology and End Results (SEER) databases from 2004 to 2015. Eligible patients were divided into the following two groups: PORT group and non-PORT group. Overall survival (OS) was estimated by the Kaplan-Meier (KM) method, and differences in survival were evaluated with log-rank test. Long-term cause-specific mortality consisted of lung cancer-related mortality and non-lung cancer-related mortality was investigated through competing risk analysis. Cox regression analysis was performed to identify variables that significantly affected OS.ResultsWe identified 2,347 eligible patients, after propensity score matching (PSM), 877 pairs were selected. Overall, there was no significant difference in OS between two groups, but the patients who received PORT had a lower lung cancer-related mortality rate. Subgroup analysis showed that PORT was associated with a significantly better OS and lower lung cancer-related mortality rate in patients with T2, grade I–II and positive/resected lymph node ratio (LNR) ≥0.31. The non-lung cancer-related mortality of PORT group was higher in the patients with squamous cell carcinoma, although the difference was not significant. The independent prognostic factors for OS were age, sex, grade, histology, the American Joint Committee on Cancer (AJCC) T stage and LNR.ConclusionsOur results revealed that PORT appears to be the optimal treatment strategy in patients with AJCC T2, grade I–II and LNR ≥0.31. PORT may not be recommended for patients with squamous cell carcinoma.

Is Surgery Worthwhile in Locally-advanced NSCLC Patients with Persistent N2-disease After Neoadjuvant Therapy?

To explore the long-term survival in lung cancer patients with persistent mediastinal lymph nodal disease after neoadjuvant followed by surgical resection and to analyse prognostic factors in this specific subset of patients. Surgery in non-small-cell lung cancer (NSCLC) patients with N2-disease after neoadjuvant therapy (NAD) has been debated and has been even more questioned with the advent of immunotherapy. Describe long-term results of a multimodal approach in locally-advanced NSCLC patients with persistence of N2-disease and identify prognostic factors to target the strategy of care. We retrospectively reviewed data of 121 consecutive Stage IIIA-N2 NSCLC patients who underwent NAD (chemoradiotherapy or chemotherapy) from 01/00 to 12/19, focusing our analysis on 37 patients with persistent N2s status after surgery. Kaplan-Meier and Cox regression analysis explored the associations between mortality and potential risk factors. The 5-year survival was 29.8%. Cox regression analysis suggested that young age (HR=0.98, C.I.95%: 0.97- 1.00; p=0.062), male sex (HR=3.8,C.I.95%:1.06-13.73;p=0.04), and adjuvant therapy (HR=6.81,C.I.95%:0.96-53.94;p=0.06) influenced long-term outcomes in these patients. We herein observed suboptimal long-term results in this NSCLC patient subset, and, considering emerging results adopting immunotherapy following chemoradiotherapy, surgery should be carefully considered in very selected cases (young and clinically fit patients) and combined with adjuvant therapy after surgery.

120P Efficacy of postoperative radiotherapy (PORT) in stage IIIA-N2 non-small cell lung cancer: Meta-analysis of randomized controlled studies

Although adjuvant systemic therapy is the standard in patients with stage 3A-N2 non-small cell lung cancer (NSCLC) who underwent curative surgical resection, discussions about radiotherapy (RT) continue. This meta-analysis evaluated the efficacy of randomized controlled trials (RCTs) investigating the addition of RT (PORT) (sequential or concurrent) to adjuvant ChT in patients with operated stage 3A-N2 NSCLC. Pubmed, Embase, Cochrane Library, and Clinical Trials databases were scanned, and original research articles published until December 01, 2021, were included. Data on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMSF) were extracted from the included studies and jointly analyzed. As a result of the database search, 5 RCTs involving a total of 1138 patients were included in the analysis (three phase 3, two phase 2). In the joint analysis of these 5 studies, it was seen that PORT did not contribute to OS (HR: 0.99, CI 95% 0.82-1.18, p = 0.87). In the analysis for DFS, it was observed that PORT provided a survival advantage (HR:0.84, CI 95% 0.72-0.97, p= 0.02). In the joint analysis of 4 RCTs (n:637) reporting LRFS and DMFS results, it was observed that PORT provided a significant survival advantage in terms of RLFS (HR:0.66, CI 95% 0.51-0.84, p= 0.001), but it did not contribute significantly to DMSF ( HR:0.84, CI 95% 0.70-1.02, p= 0.06). In this meta-analysis; In stage 3A-N2 NSCLC, it was observed that PORT prolonged DFS and LRFS, but did not contribute to OS and DMSF. Considering the possible cardiopulmonary toxicities of RT in this patient group, it would be more appropriate to make a patient-based decision.

Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer.

Simple SummaryMultimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Is the landscape in this hotly debated stage changing the role for surgery as immunotherapy and targeted therapies are being investigated and implemented? A review on multimodality therapeutic options for stage IIIA-N2 NSCLC is presented.For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement.

Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial

BackgroundThe phase III PACIFIC trial (NCT02125461) established consolidation durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression following chemoradiotherapy (CRT). In some cases, patients with stage IIIA-N2 NSCLC are considered operable, but the relative benefit of surgery is unclear. We report a post hoc, exploratory analysis of clinical outcomes in the PACIFIC trial, in patients with or without stage IIIA-N2 NSCLC.Materials and methodsPatients with unresectable, stage III NSCLC and no disease progression after ≥2 cycles of platinum-based, concurrent CRT were randomized 2 : 1 to receive durvalumab (10 mg/kg intravenously; once every 2 weeks for up to 12 months) or placebo, 1-42 days after CRT. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review according to RECIST version 1.1) and overall survival (OS). Treatment effects within subgroups were estimated by hazard ratios (HRs) from unstratified Cox proportional hazards models.ResultsOf 713 randomized patients, 287 (40%) had stage IIIA-N2 disease. Baseline characteristics were similar between patients with and without stage IIIA-N2 NSCLC. With a median follow-up of 14.5 months (range: 0.2-29.9 months), PFS was improved with durvalumab versus placebo in both patients with [HR = 0.46; 95% confidence interval (CI), 0.33-0.65] and without (HR = 0.62; 95% CI 0.48-0.80) stage IIIA-N2 disease. Similarly, with a median follow-up of 25.2 months (range: 0.2-43.1 months), OS was improved with durvalumab versus placebo in patients with (HR = 0.56; 95% CI 0.39-0.79) or without (HR = 0.78; 95% CI 0.57-1.06) stage IIIA-N2 disease. Durvalumab had a manageable safety profile irrespective of stage IIIA-N2 status.ConclusionsConsistent with the intent-to-treat population, treatment benefits with durvalumab were confirmed in patients with stage IIIA-N2, unresectable NSCLC. Prospective studies are needed to determine the optimal treatment approach for patients who are deemed operable.

Postoperative radiotherapy for patients with completely resected stage IIIA-N2 non-small cell lung cancer: opt-in or opt-out.

The role of adjuvant radiotherapy in completely resected pIIIA‐N2 non‐small cell lung cancer (NSCLC) has long been debated. Evidence from previous retrospective and prospective studies showed that postoperative radiotherapy could reduce the incidence of local recurrence and prolong disease‐free survival, while two recently reported randomized controlled trials (lung ART and PORT‐C) both demonstrated no survival benefit of postoperative radiotherapy. The great gap between our knowledge and reality has made us rethink the value of postoperative radiotherapy. In this mini review, we elaborate on the role of postoperative radiotherapy in completely resected pIIIA‐N2 NSCLC.

A non-parametric approach for jointly combining evidence on progression free and overall survival time in network meta-analysis.

Randomised controlled trials of cancer treatments typically report progression free survival (PFS) and overall survival (OS) outcomes. Existing methods to synthesise evidence on PFS and OS either rely on the proportional hazards assumption or make parametric assumptions which may not capture the diverse survival curve shapes across studies and treatments. Furthermore, PFS and OS are not independent; OS is the sum of PFS and post-progression survival (PPS). Our aim was to develop a non-parametric approach for jointly synthesising evidence from published Kaplan-Meier survival curves of PFS and OS without assuming proportional hazards. Restricted mean survival times (RMST) are estimated by the area under the survival curves (AUCs) up to a restricted follow-up time. The correlation between AUCs due to the constraint that OS > PFS is estimated using bootstrap re-sampling. Network meta-analysis models are given for RMST for PFS and PPS and ensure that OS=PFS + PPS. Both additive and multiplicative network meta-analysis models are presented to obtain relative treatment effects as either differences or ratios of RMST. The methods are illustrated with a network meta-analysis of treatments for stage IIIA-N2 non-small cell lung cancer. The approach has implications for health economic models of cancer treatments, which require estimates of the mean time spent in the PFS and PPS health-states. The methods can be applied to a single time-to-event outcome, and so have wide applicability in any field where time-to-event outcomes are reported, the proportional hazards assumption is in doubt, and survival curve shapes differ across studies and interventions.

A Nomogram for Predicting Brain Metastasis in IIIA-N2 Non-Small Cell Lung Cancer After Complete Resection: A Competing Risk Analysis.

BackgroundBrain metastasis (BM) is one of the most common failure patterns of pIIIA-N2 non-small cell lung cancer (NSCLC) after complete resection. Prophylactic cranial irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify the risk factors that are associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Methods and MaterialsBetween 2011 and 2014, patients with pIIIA-N2 NSCLC who underwent complete resection in our institution were reviewed and enrolled in the study. Clinical characteristics, pathological parameters, treatment mode, BM time, and overall survival were analyzed. A nomogram was built based on the corresponding parameters by Fine and Gray’s competing risk analysis to predict the 1-, 3-, and 5-year probabilities of BM. Receiver operating characteristic curves and calibration curves were chosen for validation. A statistically significant difference was set as P <0.05.ResultsA total of 517 patients were enrolled in our retrospective study. The median follow-up time for surviving patients was 53.2 months (range, 0.50–123.17 months). The median age was 57 (range, 25–80) years. Of the 517 patients, 122 (23.6%) had squamous cell carcinoma, 391 (75.6%) received adjuvant chemotherapy, and 144 (27.3%) received post-operative radiotherapy. The 1-, 3-, and 5-year survival rates were 94.0, 72.9, and 66.0%, respectively. The 1-, 3-, and 5-year BM rates were 5.4, 15.7, and 22.2%, respectively. According to the univariate analysis, female, non-smokers, patients with non-squamous cell carcinoma, bronchial invasion, perineural invasion, and patients who received adjuvant chemotherapy were more likely to develop BM. In a multivariate analysis, non-squamous cell carcinoma (subdistribution hazard ratios, SHR: 3.968; 95% confidence interval, CI: 1.743–9.040; P = 0.0010), bronchial invasion (SHR: 2.039, 95% CI: 1.325–3.139; P = 0.0012), perineural invasion (SHR: 2.514, 95% CI: 1.058–5.976; P = 0.0370), and adjuvant chemotherapy (SHR: 2.821, 95% CI: 1.424–5.589; P = 0.0030) were independent risk factors for BM. A nomogram model was established based on the final multivariable analysis result. The area under the curve was 0.767 (95% CI, 0.758–0.777).ConclusionsFor patients with IIIA-N2 NSCLC after complete resection, a nomogram was established based on clinicopathological factors and treatment patterns for predicting the BM. Based on this nomogram, patients with a high risk of BM who may benefit from PCI can be screened.