pIIIA-N2 Non-small Cell Lung Cancer Research Articles

Role of Postoperative Radiotherapy on High-Risk Stage pIIIA-N2 Non-Small Cell Lung Cancer Patients After Complete Resection and Adjuvant Chemotherapy: A Retrospective Cohort Study.

The aim of the study was to assess the effectiveness of postoperative radiotherapy in high-risk patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy. Data from NSCLC patients within the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. The study examined the association between lymph node ratio (LNR) and both cancer-specific survival (CSS) and overall survival (OS) using restricted cubic spline curves. Patients were categorized into high- and low-risk groups based on established LNR cut-off values, and survival outcomes were compared between those receiving postoperative radiotherapy and those who did not within the high-risk group. The study included 1,690 patients. An LNR threshold of 0.29 was identified for both CSS and OS. Patients with an LNR ≥ 0.29 demonstrated significantly worse CSS (hazard ratio (HR) = 1.56, 95% confidence interval (CI): 1.37 - 1.78; P < 0.001) and OS (HR = 1.44, 95% CI: 1.28 - 1.62; P < 0.001) compared to those with an LNR < 0.29. In the high-risk group (LNR ≥ 0.29), postoperative radiotherapy did not significantly affect CSS (HR = 0.98, 95% CI: 0.82 - 1.17; P = 0.809) or OS (HR = 0.95, 95% CI: 0.81 - 1.11; P = 0.533). LNR is a significant prognostic factor in patients with stage pIIIA-N2 NSCLC post complete resection and adjuvant chemotherapy. A higher LNR (≥ 0.29) is associated with poorer CSS and OS. However, postoperative radiotherapy does not confer survival benefits in these high-risk patients. Our findings suggest that postoperative radiotherapy should not be routinely performed in this subgroup. Further research is required to explore effective treatment strategies for these patients.

Clinical Verification of a Nomogram Model for Prediction of Brain Metastases in Patients with pⅢA-N2 Non-Small Cell Lung Cancer

Brain metastasis 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 risk factors that are associated with brain metastasis and subsequently provide instructions for selecting patients who will optimally benefit from PCI. We have reported a nomogram model which was established based on the condition of histology, bronchial invasion, perineural invasion, and adjuvant chemotherapy, through which we can predict high risk brain metastases in patients with pⅢA-N2 NSCLC. The purpose of this study is to verify the accuracy of the nomogram model by using new cases information. Between January 1, 2015 and December 31, 2019, patients of pⅢA-N2 NSCLC were retrospectively analyzed, to verify the consistency between actual and predictive brain metastases. The verification group was divided into two groups according to the years when genetic testing has been widely used in clinic (group1:2015-2016, group2:2017-2019). ROC curves and calibration curves were chosen for validation. A total of 770 patients were enrolled in our retrospective study (group1:294 patients, group2: 476patients). The 1-, 3- and 5-year survival rates were 97.2%, 76.5%, 63.2% in group1, and 95.8%, 84.5%, 76.9% in group2, respectively. The 1-, 3- and 5-year brain metastasis rates were 7.9%, 19.7%, 25.8%, and 5.4%, 14.5%, 26.3% in group2, respectively. The AUC were 0.74 (95% CI:0.72 - 0.76) in group1, and 0.71(95% CI:0.70 - 0.73) in group 2.The 1.3.5-year calibration curves of the two groups show that the prediction is in good agreement with the actual observation. The nomogram model can predict brain metastases high risk patients with pⅢA-N2 NSCLC. Whether gene test or not, it can be used as a basis to screening out patients of high-risk brain metastases in future clinical trials for PCI.

Real world practice of postoperative radiotherapy for patients with completely resected pIIIA-N2 non-small cell lung cancer: a national survey of radiation oncologists in China

BackgroundResults from Lung ART and PORT-C trials suggest that postoperative radiotherapy (PORT) cannot routinely be recommended as standard treatment in completely resected pIIIA-N2 NSCLC patients, but their effects on the real-world practice of PORT in China remain unclear.MethodsA national cross-section survey was conducted by using an online survey service. Participants were voluntarily recruited using a river sampling strategy. A link to the survey was posted on websites of radiation oncologist associations and tweets from public WeChat accounts. The survey collected the real names of participants to ensure that they were board-certified radiation oncologists.ResultsA total of 484 radiation oncologists were included with a median age of 40 years (IQR, 35–47). A total of 377 (77.9%) participants were male, and 282 (58.1%) had more than 10 years of clinical experience practicing thoracic radiotherapy. Before Lung ART and PORT-C trials were published, 313 (64.7%) respondents recommended PORT, 11 (2.3%) did not recommend it, and 160 (33.1%) reported that they made decisions based on risk factors. After the presentation of two trials, only 42 (8.7%) did not recommend PORT, while 108 (22.3%) recommended it, and 334 (69.0%) made decisions based on risk factors. The five most commonly considered risk factors among these 334 respondents were as follows: nodal extracapsular extension, the highest lymph node (LN) station involved, the number of dissected mediastinal LN stations, the number of positive mediastinal LN stations, and surgical approaches. In addition, the majority of all 484 respondents recommended a total dose of 50 Gy, lung stump + ipsilateral hilus + regions containing positive LNs as the targeted region, lung V20 < 25%, and heart V30 < 40% as dose constraints for PORT.ConclusionMost Chinese radiation oncologists recommended PORT for completely resected IIIA-N2 NSCLC patients based on risk factors, especially status of LN station.

Real World Practice of Postoperative Radiotherapy for Completely Resected pIIIA-N2 Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Two recently published clinical trials, the PORT-C and Lung ART, revealed that postoperative radiotherapy (PORT) cannot routinely be recommended for all patients with completely resected pIIIA-N2 non-small cell lung cancer (NSCLC). However, the real word decisions regarding PORT that physicians actually make is still unknown. This study was conducted to assess clinical decisions among radiation oncologists and factors influencing implementation of PORT for completely resected pIIIA-N2 NSCLC. <h3>Materials/Methods</h3> A 40-question survey was sent to radiation oncologists from 179 hospitals in China. Questions addressed demographics, the decision change of PORT from before to after the publishing of the two clinical trials, patient-related factors, operation-related factors, lymph nodes-related factors, systemic therapy-related factors, and radiotherapy-related factors influencing the implementation of PORT in completely resected pIIIA-N2 NSCLC. <h3>Results</h3> This research gathered 312 valid questionnaires. The median age of responders was 42 [IQR 38, 49]. Sixty-eight percentage of responders had more than 10 years practicing radiotherapy for treating lung cancers. Before the publishing of the PORT-C and Lung ART studies, PORT was routinely recommended and not recommended in 68.0% and 2.6% of responders, respectively, and 29.5% of responders made decision according to individual risk factors. After the two studies published, the proportion of responders routinely recommending PORT was decreased to 18.0%, however, only 9.6% of responders did not routinely recommend PORT while 72.4% of responders made decisions according to individual risk factors. The five most commonly considered risk factors that responders chose were as follows: the existence of tumor capsular invasion (81.1%), the existence of highest lymph node station metastasis (68.9%), the number of dissected lymph node stations (57.4%), the number of positive lymph nodes (45.5%), the choice of operation methods (43.9%). For the number of dissected lymph node stations, the proportions of responders reported ≤3, ≤2, ≤1, and not a consideration for recommending PORT were 38.5%, 41.0%, 9.3%, and 11.2%, respectively. For the number of positive lymph node stations except for hilar lymph nodes, the proportions of responders reported ≥3, ≥2, ≥1, and not a consideration for recommending PORT were 18.3%, 61.2%, 9.0%, and 11.5%, respectively. The proportions of operation methods chosen (multiple selection) for recommending PORT were as follows: pneumonectomy (2.9%), lobectomy (26.9%), sleeve lobectomy (54.8%), and not a consideration (47.4%). <h3>Conclusion</h3> After the publish of the PORT-C and Lung ART studies, most radiation oncologists made the clinical decisions according to individual risk factors other than not routinely recommending PORT for patients with completely resected pIIIA-N2 NSCLC. Additional studies are required to establish guidelines for use of PORT based on individual risk factors.

EP05.02-016 Aumolertinib after Adjuvant Chemotherapy/Radiotherapy in Stage pIIIA-N2 Non-Small-Cell Lung Cancer with EGFR Mutation

Several trials such as the ADJUVANT, ADAURA, EVAN, EVIDENCE, and SELECT have been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeting adjuvant therapy provides a dramatic response to patients with EGFR-mutation non-small cell lung cancer (NSCLC). Especially compared with stage II, patients with pIIIA-N2 may be the precise population for the clinical benefit of adjuvant targeted therapy. A number of multi-center, large-sample retrospective studies have evaluated that adjuvant chemotherapy/radiotherapy can also improve the local control rate and survival rate of pIIIA-N2 NSCLC.

Postoperative radiotherapy in pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis.

This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy. Electronic databases (PubMed, Web of Science databases, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched to extract randomized control trials comparing PORT with observation in pIIIA-N2 non-small cell lung cancer patients until October 2021. Main outcomes were disease-free survival (DFS), overall survival (OS), and local recurrence. Three-phase 3 randomized control trials involving 902 patients were included: 455 patients in the PORT group and 447 patients in the observation group. The methodological quality of the 3 randomized control trials were high quality. The pooled analysis revealed that PORT decreased local recurrence rate (odds ratio = 0.56, 95% confidence interval [CI]: 0.40-0.76). However, PORT did not improve median DFS (hazard ratio = 0.84, 95% CI: 0.71-1.00) and OS (hazard ratio = 1.02, 95% CI: 0.68-1.52). PORT decreased the incidence of local recurrence. However, PORT did not improve DFS and OS.

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.

Predictive Risk Factors for Early Recurrence of Stage pIIIA-N2 Non-Small Cell Lung Cancer.

PurposeInflammatory biomarkers and clinical pathological factors have been reported to predict survival of patients with non-small cell lung cancer (NSCLC). The goal of this study was to identify risk factors for early recurrence in patients with pIIIA-N2 NSCLC who had undergone radial resection.MethodsA retrospective analysis was conducted on 238 patients with pIIIA-N2 NSCLC who underwent surgical treatment at the First Affiliated Hospital of Wenzhou Medical University between December 2006 and August 2018. The early recurrence (ER) group included patients who recurred within one year of curative resection, while the non-early recurrence (NER) group included patients who did not recurrence or recurrence beyond one year. The univariate and multivariate Cox proportional risk analyses were used to identify prognostic factors associated with early recurrence, while the chi-square test was used for categorical data. Overall survival and recurrence-free survival were assessed by Kaplan–Meier estimates.ResultsA total of 69 patients experienced an early recurrence, while the remaining 169 patients did not relapse within one year. ER patients had a much worse prognosis than NER patients, with median survival times of 20.6 and 83.1 months, respectively. Multivariate analysis showed that smoking status, tumor size, metastatic lymph node ratio (LNR) and platelet-to-lymphocyte ratio (PLR) were independent risk factor of early recurrence. Patients with early recurrence were more likely to develop bone metastases.ConclusionSmoking history, large tumour size, and elevated LNR and PLR values in pIIIA-N2 NSCLC patients after complete resection may have a significant risk of early recurrence. Based on these independent risk indicators, this prediction model may successfully predict early recurrence and advise individual treatment.

Risk Factors of Brain Metastases in IIIA-N2 Non-Small Cell Lung Cancer After Complete Resection

Purpose/Objective(s)Brain metastasis (BM) is one of the most common failure pattern of locally advanced non-small cell lung cancer (NSCLC) after multidisciplinary therapy. Prophylactic Cranial Irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify risk factors associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Materials/MethodsBetween 2003 and 2015, patients with pIIIA-N2 NSCLC who underwent complete resection in our single institution were reviewed and enrolled into the study. Clinical characteristics, pathological parameters, treatment mode, BM time and overall survival (OS) were analyzed. The cumulative incidence of BM was estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Multivariate Cox regression analysis was used to assess risk factors of BM. Statistically significant difference was set as P < 0.05.ResultsTotally 1400 patients were enrolled, including 900 (64.3%) males and 500 (35.7%) females. The median age was 58.0 (25.0-84.0) years old. 1003 (71.6%) patients were non-squamous cell carcinoma, and 397 (28.4%) were squamous cell carcinoma. The number of patients with pT1, pT2, and pT3 were 174 (12.4%), 995 (71.1%), and 231 (16.5%), respectively. 899 patients (64.2%) received adjuvant chemotherapy, and 334 patients (23.9%) underwent postoperative radiotherapy. The median follow-up time was 38.7 months. The 1, 3 and 5-year OS rates were 92.9%, 66.4% and 52.1%, respectively. The 1, 3 and 5-year cumulative incidence of BM were 6%, 13.9% and 22.2%, respectively. In univariate analysis, patients ≤ 60 years old, non-smokers, non-squamous cell carcinoma, lymph node metastases number≥ 4, lymph node metastases rate > 30%, and adjuvant chemotherapy were more likely to develop BM. In multivariate analysis, non-squamous cell carcinoma (HR:2.789, 95༅CI:1.779-4.372;P < 0.001), lymph node metastasis number≥4 (HR:1.448, 95༅CI:1.042-2.011;P = 0.027) and adjuvant chemotherapy (HR:2.168, 95༅CI:1.507-3.120;P < 0.001) were independent risk factors of BM.ConclusionNon-squamous cell carcinoma, lymph node metastasis number ≥ 4 and adjuvant chemotherapy are the high-risk factors of BM in patients with pIIIA-N2 NSCLC after complete resection. These groups of patients may benefit from PCI and can be enrolled in the further study. Brain metastasis (BM) is one of the most common failure pattern of locally advanced non-small cell lung cancer (NSCLC) after multidisciplinary therapy. Prophylactic Cranial Irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify risk factors associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI. Between 2003 and 2015, patients with pIIIA-N2 NSCLC who underwent complete resection in our single institution were reviewed and enrolled into the study. Clinical characteristics, pathological parameters, treatment mode, BM time and overall survival (OS) were analyzed. The cumulative incidence of BM was estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Multivariate Cox regression analysis was used to assess risk factors of BM. Statistically significant difference was set as P < 0.05. Totally 1400 patients were enrolled, including 900 (64.3%) males and 500 (35.7%) females. The median age was 58.0 (25.0-84.0) years old. 1003 (71.6%) patients were non-squamous cell carcinoma, and 397 (28.4%) were squamous cell carcinoma. The number of patients with pT1, pT2, and pT3 were 174 (12.4%), 995 (71.1%), and 231 (16.5%), respectively. 899 patients (64.2%) received adjuvant chemotherapy, and 334 patients (23.9%) underwent postoperative radiotherapy. The median follow-up time was 38.7 months. The 1, 3 and 5-year OS rates were 92.9%, 66.4% and 52.1%, respectively. The 1, 3 and 5-year cumulative incidence of BM were 6%, 13.9% and 22.2%, respectively. In univariate analysis, patients ≤ 60 years old, non-smokers, non-squamous cell carcinoma, lymph node metastases number≥ 4, lymph node metastases rate > 30%, and adjuvant chemotherapy were more likely to develop BM. In multivariate analysis, non-squamous cell carcinoma (HR:2.789, 95༅CI:1.779-4.372;P < 0.001), lymph node metastasis number≥4 (HR:1.448, 95༅CI:1.042-2.011;P = 0.027) and adjuvant chemotherapy (HR:2.168, 95༅CI:1.507-3.120;P < 0.001) were independent risk factors of BM. Non-squamous cell carcinoma, lymph node metastasis number ≥ 4 and adjuvant chemotherapy are the high-risk factors of BM in patients with pIIIA-N2 NSCLC after complete resection. These groups of patients may benefit from PCI and can be enrolled in the further study.

Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non–Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy

The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC). To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy. The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020. Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects. In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed. In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed. ClinicalTrials.gov Identifier: NCT00880971.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: a preferential benefit for squamous cell carcinoma.

BackgroundThe beneficial effect of postoperative radiotherapy (PORT) on completely resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of the study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC.Patients and methodsBetween October 2010 and September 2016, 288 consecutive patients with completely resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed, which consisted of 194 cases of LADC and 85 cases of LSCC. There were 42 (21.6%) patients treated with PORT in LADC cases and 19 (22.3%) patients treated with PORT in LSCC cases. The 5-year overall survival (OS), loco-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The prognostic factors were determined using Cox’s regression model.ResultsAmong 194 cases of LADC, the 1-, 3-, and 5-year OS in the PORT group were 95.2%, 61.9% and 40.0%, respectively, while in the non-PORT group were 90.1%, 63.3% and 45.0% (p = 0.948). The use of postoperative chemotherapy (POCT) and smoking index ≥ 400 were both prognostic factors of 5-year rates of OS, LRFS and DMFS. On the other hand, among 85 cases of LSCC, the 1-, 3-, and 5-year OS in the PORT group were 94.7%, 63.2% and 63.2%, respectively, whereas in the non-PORT group were 86.4%, 48.5% and 37.1% (p = 0.026). In this group, only the use of PORT was a favorable prognostic factor for 5-year OS, LRFS and DMFS.ConclusionsDue to clinicopathological differences among completely resected pIIIA-N2 NSCLC, PORT may not be suitable to all patients. Our study distinguishes pIIIA-N2 LSCC from LADC by their positive responses to PORT.

The Efficacy of Local Radiotherapy after Failure of First-Line Treatment for Piiia-N2 Non-Small Cell Lung Cancer

A large portion of patients with pIIIA-N2 non-small cell lung cancer (NSCLC) experience local recurrence and distant metastasis after radical surgery despite postoperative adjuvant chemotherapy ± radiotherapy, and the best option for these relapses remains unclear. This study retrospectively analyzed the correlation between follow-up treatment and survival of these patients and explored the optimal therapy for these patients. From January 2003 to January 2015, patients with pIIIA–N2 NSCLC who experienced local recurrence or distant metastasis after radical first-line treatment in our hospital were retrospectively analyzed to find the correlation between the choice of follow-up treatment and survival of the patients. The Kaplan-Meier, Log Rank test, and Cox regression were used for survival analysis and identification of prognostic factors. A total of 739 patients were enrolled for this study, including 440 males and 299 females, aged 25∼80 years old with an average of 57 years. The first-line treatment was surgery alone for 170 (23.00%) of the patients, surgery + adjuvant chemotherapy for 389 (52.64%), surgery + adjuvant radiotherapy for 13 (1.76%), surgery + adjuvant chemoradiotherapy for 167 (22.60%). Recurrences included 141 case of local-regional recurrence (19.08%), 390 cases of distant metastasis (52.77%), and 208 cases of local recurrence + distant metastasis (28.15%). In the follow-up treatment, chemotherapy was performed for 289 patients (39.11%), local radiotherapy for 279 (37.75%), target therapy (TKI) for 195 (26.39%). As a whole, median survival time of the patients was 47.5 months, and the 2-year and 5-year survival rates were 76.4% and 41.8% respectively. Multivariate Cox regression revealed age, KPS, pathological differentiation, pathological T staging, use of radiotherapy after recurrence, use of targeted therapy after recurrence, and type of recurrence as independent prognostic factors affecting survival. Subgroup analysis showed that for patients who had EGFR- or ALK-positive recurrence and received targeted therapy (TKI) after failure of first-line treatment, local radiotherapy in the follow-up treatment brings no significant benefits to survival, and may even have adverse effects on median survival time (53.26 months for those had local radiotherapy vs. 163.88 months for those didn't); but for those who did not receive targeted therapy, local radiotherapy significantly improved OS (median survival time: 59.14 months vs. 34.43 months, p <0.001). For patients with pIIIA–N2 NSCLC who had relapses after first-line radial therapy, local radiotherapy for local recurrence or distant metastasis may improve OS of those who did not receive targeted therapy (TKI) after recurrence, but may have adverse effect on survival of patients who received targeted therapy and is not recommended as follow-up treatment for the latter.

Optimal Timing of Postoperative Radiotherapy (PORT) for Patients with pⅢA-N2 Non-Small Cell Lung Cancer (NSCLC) Receiving Complete Resection Followed by Adjuvant Chemotherapy

Optimal Timing of Postoperative Radiotherapy (PORT) for Patients with pⅢA-N2 Non-Small Cell Lung Cancer (NSCLC) Receiving Complete Resection Followed by Adjuvant Chemotherapy

Patterns of Local-Regional Failure (LRF) in Completely Resected pⅢA-N2 Non-Small Cell Lung Cancer (NSCLC) after Adjuvant Chemotherapy and Postoperative Radiotherapy (PORT)

Patterns of Local-Regional Failure (LRF) in Completely Resected pⅢA-N2 Non-Small Cell Lung Cancer (NSCLC) after Adjuvant Chemotherapy and Postoperative Radiotherapy (PORT)

Postoperative Radiotherapy (PORT) Improves Survivals of Resected pN2 Non-Small Cell Lung Cancer (NSCLC): A Propensity Score-Matched (PSM) Analysis

To evaluate the effect of PORT on survivals as well as tumor control in patients with pN2 NSCLC after complete resection. From Jan. 2003 to Dec. 2015, patients with resected pN2 NSCLC at our institution were retrospectively studied. PSM analysis was conducted to generate comparable study arms. The effect of PORT on survivals (OS, DFS, LRFS, and DMFS) were evaluated using the Kaplan–Meier method and log-rank tests. Cox’s proportional hazards model was used for multivariate analysis. A statistically significant difference was set as p＜0.05. Totally 1434 patients were enrolled, including 341 (23.8%) in the PORT group and 1093 (76.2%) in the non-PORT group. The median follow-up time was 41.8 months. Patients treated with PORT had significantly longer OS (p＜0.001) and DFS (p=0.001) when compared with the control, as well as LRFS (p＜0.001) and DMFS (p=0.015). Multivariate analyses showed that PORT was an independent prognostic factor associating with better OS (HR=0.756, p=0.012). Moreover, we analyzed the effect of PORT on survivals for pⅢA–N2 NSCLC patients who received adjuvant chemotherapy using PSM to balance several covariates. After adjustment, PORT also significantly improved the survivals. The 3- and 5-year OS rates were 72.9% and 56.1%, respectively in the PORT group and were 62.6% and 41.7%, respectively in the control group (p=0.01). The 3- and 5-year DFS rates were 38.9% and 29.5%, respectively in the PORT group and were 21.6% and 13.2%, respectively in the control group (p＜0.001). The 3- and 5-year LRFS rates were 59.0% and 43.8% versus 38.3% and 20.5% in the PORT versus control group, respectively(p＜0.001). The 3- and 5-year DMFS rates were 44.5% and 33.2% versus 30.6% and 15.0% in the PORT versus control group, respectively (p＜0.0001). For NSCLC patients with resected pN2 or pⅢA-N2 receiving adjuvant chemotherapy, PORT can significantly improve the rates of OS, DFS, LRFS and DMFS. A prospective randomized multicenter clinical trial led by our institution is ongoing now.

The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis.

Background: The role of postoperative radiotherapy (PORT) in completely resected pathological stage IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis aimed to assess the effect of PORT in patients with pIIIA-N2 NSCLC on the basis of clinicopathological features.Methods: The PubMed, PubMed Central (PMC), Embase, Web of Science, and Cochrane Library were searched for relevant studies. The main outcomes were overall survival (OS) and disease-free survival (DFS), which were compared using the hazard ratio (HR).Results: One randomized trial and 12 retrospective studies were eligible for the analysis. PORT significantly improved both OS [HR = 0.85; 95% confidence interval (CI): 0.79-0.92] and DFS (HR = 0.57; 95% CI: 0.38-0.85) compared with non-PORT treatment in patients with multiple N2 metastases or multiple N2 station involvement. No significant difference in either OS (HR = 1.03; 95% CI: 0.86-1.24) or DFS (HR = 1.08; 95% CI: 0.70-1.65) was found between PORT and non-PORT groups for patients with single N2 station involvement. No significant heterogeneity was observed. No significant differences in OS were observed between PORT and non-PORT groups for patients of different ages, sex, tumor sizes or pT stages, and histological types.Conclusions: The findings of this meta-analysis supported a role for PORT in patients with completely resected pIIIA-N2 NSCLC having multiple N2 metastases and favored withholding PORT to patients with single N2 station involvement. Further prospective randomized controlled trials are needed to confirm the findings.

Patterns of Local-Regional Failure in Completely Resectable IIIA-N2 Non-Small Cell Lung Cancer: Implications for Postoperative Radiation Target Volumes Design

This study aimed to analyze patterns of local-regional failure (LRF) in completely resected pIIIA-N2 non-small cell lung cancer (NSCLC) to guide the design of target volumes for postoperative radiotherapy (PORT). From Jan. 2003 to Jan. 2015, consecutive patients with pIIIA-N2 NSCLC who had undergone complete resection with or without adjuvant chemotherapy in our hospital were retrospectively reviewed. Those who had received no PORT, with margin-negative resection and exact failure patterns were included in this study. Patterns were constructed to illustrate sites of first failure on the basis of the location of primary tumor. The clinicopathological factors related to LRF were assessed. With a median follow-up of 27 months, 554 of 1024 patients (54.1%) experienced treatment failure. Of the 233 patients with LRF as the first event, the most frequent site of LRF was the ipsilateral lymph node station 4 (16.3%), followed by lymph node station 7 (10.8%), ipsilateral lymph node station 2 (10.7%) and bronchial stump (9.5%). For left-sided lung cancer, the most common LRF site was 4L (13.8%), followed by 4R (12.2%), bronchial stump (11.4%), 7 (10.3%) and 6 (9.4%). For right-sided lung cancer, the most common site was 4R (18.2%), followed by 2R (15.3%), 7 (11.0%), right supraclavicular fossa (10.1%) and bronchial stump (8.1%). Patients with squamous cell carcinoma were more likely to experience bronchial stump recurrence than those with non-squamous cell carcinoma (35.5% vs. 19.1%, p=0.006). While, the patterns of failure in the hilum, mediastinum and supraclavicular fossa did not differ significantly between squamous cell carcinoma and non-squamous cell carcinoma. Patients with preoperative cN2 were more likely to have recurrence of the contralateral hilum than those with cN0-1 (7.4% vs. 1.0%, p=0.03). No difference in patterns of LRF was observed among T1, T2 and T3. Adjuvant chemotherapy had no significant impact on patterns of LRF. For patients with completely resected pIIIA-N2 NSCLC, the ipsilateral lymph node station 4, 7, 2 and bronchial stump are the most common LRF sites. Besides, LRF of 4R and 6 for left-lung cancer and contralateral hilum for cN2 disease is more common, which should also be included in PORT.

Postoperative Radiation Therapy (PORT) May Not Improve Overall Survival (OS) of Patients with pIIIA-N2 Non-Small-Cell Lung Cancer (NSCLC) with Positive Surgical Margins

For pN+ NSCLC patients with positive surgical margins, the standard treatment is chemoradiotherapy. However, high level evidence is lacking. This study is to evaluate the effect of PORT on survivals of pIIIA-N2 NSCLC patients with positive surgical margins and identify the prognostic factors. Between Jan. 2003 and Dec. 2015, patients who had undergone lobectomy or pneumonectomy plus mediastinal lymph node dissection or systematic sampling in our single institution were respectively reviewed. Those with pIIIA–N2 NSCLC and positive surgical margins were included in this study. The Kaplan–Meier method was used to calculate survival rates, and the log-rank test was used to analyze differences between the groups. Multivariate analysis was done using the Cox hazard regression with entry factors of which the p-value <0.10. Statistically significant difference was set as p-value <0.05. Of all the 1547 pIIIA–N2 NSCLC patients, 113 were with positive surgical margins, including 76 with R1-resection and 37 with R2-resection. Of the 113 patients, 32 (28.3%) received radiotherapy. There was no significant difference in OS between patients with R1-resection and with R2-resection. The 5-year OS rates were 35.1% and 19.2% respectively (p=0.373). OS was more favorable for patients with less positive lymph nodes (p=0.039). In PORT group, the 3- and 5-year OS rates were 33.9% and 22.6% respectively, which were similar with 40.1% and 35.3% in non-PORT group (p=0.970). Subset analysis showed that for patients with R1-resection and non-squamous cell carcinoma (n=44), PORT trended to improve OS, with the 5-year OS rates of 35.7% versus 23.8% (p=0.082). In multivariate analysis with entry factors including age, the number of positive lymph nodes and different adjuvant therapies, there was no significant independent factor in predicting OS. For pIIIA-N2 NSCLC patients with positive surgical margins in our study, PORT does not improve OS, but trends to improve the OS of those with R1-resection and non-squamous cell carcinoma. Further study with a larger population is needed to validate our conclusion.

Optimal Timing of Postoperative Radiotherapy for Patients with Piiia-N2 Non-Small Cell Lung Cancer after Resection

Optimal Timing of Postoperative Radiotherapy for Patients with Piiia-N2 Non-Small Cell Lung Cancer after Resection

Contemporary Postoperative Radiation Therapy Improves the Survival of Patients with Resected Pathological IIIA-N2 Non–small Cell Lung Cancer Treated With Adjuvant Chemotherapy

For pIIIA–N2 non-small cell lung cancer (NSCLC) after complete resection followed by adjuvant chemotherapy (ACT), the effect of PORT on survival may be counterbalanced by severe toxicities induced by suboptimal RT techniques. Our study is to evaluate the effect of contemporary PORT using 3D-CRT/IMRT techniques on survival of patients with resected pIIIA–N2 NSCLC treated with ACT. Between Jan. 2006 and Mar. 2015, patients with pIIIA–N2 NSCLC after complete resection followed by ACT in our single institution were retrospectively analyzed. Using 3D-CRT/IMRT techniques, PORT was given by 2 Gy per fraction to a total dose of 50 Gy. The effect of PORT on overall survival (OS) and disease free survival (DFS) was evaluated with Kaplan-Meier method and log-rank test. The impact of PORT on loco-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) was also analyzed. Statistically significant difference was set as p<0.05. Overall, 545 consecutive patients were enrolled, including 187 (34.3%) in the PORT group and 358 (65.7%) in the non-PORT group. The characteristics were comparable between the two groups except that the patients with less positive lymph nodes were more prevalent in the PORT group. The median follow-up time for survival patients was 37.4 months. The median survival time of whole group was 60.0 months. PORT significantly improved the OS (p=0.003). The median survival time was 56.1 months in the non-PORT group and not reached in the PORT group. The 3- and 5-year OS rates were 76.5%, and 65.7%, respectively in the PORT group and were 67.1%, and 47.8%, respectively in the non-PORT group. The differences of the DFS, LRFS and DMFS between the two groups were all statistically significant (p=0.001, p=0.001, and p=0.006, respectively). The 3-, and 5-year DFS rates were 41.4%, and 33.6% in the PORT group and 33.8%, and 19.5% in the non-PORT group, respectively. The 3-, and 5-year LRFS rates were 68.2%, and 51.9% in the PORT group and 58.1%, and 36.9% in the non-PORT group, respectively. The 3-, and 5-year DMFS rates were 45.7%, and 37.7% in the PORT group and 40.0%, and 23.6% in the non-PORT group, respectively. Multivariate analyses also showed that PORT was significantly associated with longer OS (HR=0.640, 95% CI: 0.432-0.947; p=0.025). The other independent prognostic factors included age≤60 year (HR=0.563, 95% CI: 0.420-0.754; p=0.000) and the number of positive nodes ≤4 (HR=0.564, 95% CI: 0.421-0.756; p=0.000). In the PORT group, IMRT was used in 145 patients (75.9%) and 3D-CRT was used in 46 patients (24.1%). Up to the last follow up, none irradiation toxicity-related deaths were observed. Based on our study, postoperative 3D-CRT/IMRT is safe and can significantly improve the survival of patients with pIIIA–N2 NSCLC treated with surgery followed by ACT. A prospective randomized multicenter clinical trial is ongoing to evaluate the definitive role of PORT using contemporary techniques.