Postoperative Radiotherapy For Completely Resected Stage â…¢A(N2) Non-Small-Cell Lung Cancer Patients

Part I. Prognostic factors in patients with completely resected stage IIIA(N2) non-small-cell lung cancer on the basis of clinicopathologic characteristicPropose:To investigate the overall prognosis of stage ⅢA(N2) NSCLC patients who underwent curative surgery without PORT at our hospital. And we tried to analyze the influence of clinicopathologic characteristic on the survival of patients with completely resected stage ⅢA(N2) NSCLC patients and find out the factors related to high-risk locoregional recurrence after complete resection.Methods:From2005to2011, consecutive patients with stage Ⅲa(N2) NSCLC who underwent complete resection at our hospital were identified in this study. The eligibility criteria were margin-negative resection of all gross disease and systematic mediastinal sampling/dissection, stage pT1-3N2M0NSCLC and postoperative follow-up≥4months. Patients who received neoadjuvant therapy, had PORT, presented with other secondary primary cancer were excluded. The influence of clinicopathologic characteristic on the overall survival (OS), locoregional progression-free survival (LRFS), and distant metastasis free survival (DMFS) were analyzed.Results:Among264patients who met the eligibility criteria with completely resected stage≡a(N2) during the time interval,250with follow-up data included. The median follow-up time was24months for the living patients. The1-year,3-year, and5-year OS of all patients were90%,47.4%and32.8%respectively. The1-year,3-year, and5-year LRFS were87.7%,67.4%and61.1%respectively. According to multivariate analysis, the smoking history, clinical N status and lymph node metastasis ratio were independent prognostic-factor to LRFS (p<0.05).Conclusion:The prognosis of completely resected stage≡A(N2) patients without PORT in our hospital was similar to historical data. The smoking history, clinical N2status and higher lymph node metastasis ratio significantly influences the LRFS. Part Ⅱ. Patterns of Local-regional Failure in Completely Resected Stage Ⅲa(N2) Non-Small-Cell Lung Cancer Patients:Implications for Postoperative Radiotherapy Clinical Target Volumes DesignPurpose:We reviewed patterns of local-regional failure (LRF) for completely resected IIIa(N2) patients treated in our hospital and tried to provide objective evidence for the design of PORT CTV.Methods:From2005to2011, patients with stage IIIa(N2) NSCLC who underwent complete resection at our hospital were identified in this study. The eligibility criteria were margin-negative resection of all gross disease and systematic mediastinal sampling/dissection, stage pTl-3N2M0NSCLC and postoperative follow-up≥4months. Patients who received neoadjuvant therapy, had PORT, presented with other secondary primary cancer were excluded. The patterns of first LRF were evaluated whether they could be covered by the proposed PORT CTV in our hospital.Results:Among264patients who met the eligibility criteria with completely resected stage Ⅲa(N2) during the time interval,250with follow-up data included. With a median follow-up of24months,173of250patients experienced disease failures. Out of54patients with LRF as the first failure,48(89%) recurred in-field,6(11%) had both in-field and out-of-field failures.93%(104/112) of failure sites would have been contained in the proposed PORT CTV. The most common location for the left lung cancer was#4R station (22%), followed by#7(20%) and#4L (14%). The most common location for right lung cancer was#2R station (26%), followed by#10R (19%) and#4R (19%). The8out-of-field failures, located at#3a,#4L,#5,#6of right lung cancer, occurred with in-field nodal relapses also.Conclusion:The LRF sites of the right lung tumor basically occurred unilaterally at the ipsilateral superior mediastinum; in contrast, failure sites of the left lung tumor were found more frequently at bilateral superior mediastinum. Most of the relapse sites would have been covered by the proposed PORT CTV. Part Ⅲ. Study on the Rationale of Postoperative Radiotherapy Clinical Target Volumes in Completely Resected Stage Ⅲa (N2) Non-Small-Cell Lung CancerPurpose:Recent retrospective and non-randomized studies provide evidence of the benefit of postoperative radiotherapy (PORT) in patients of stage Ⅲa non-small cell lung cancer (NSCLC) with mediastinal nodal involvement (N2stage). However, the clinical target volume (CTV) of PORT in patients with completely resected stage Ⅲa (N2) NSCLC has not been reached the consensus. The CTV contouring guideline for PORT was developed in2004. The rationale of the CTV was evaluated in this study.Methods:Basing on comprehensive evidence, PORT CTV contouring guideline for completely resected stage Ⅲa(N2) patients was developed in our hospital. The postoperative CTV of the left lung cancer include#2R,#2L,#4R,#4L,#5,#6,#7and#10-11L station lymph nodes (LN); the right lung cancer including#2R,#4R,#7and#10-11L station LN (according to the2009AJCC lymph node grouping). From2005to2011,63patients with stage IIIA(N2) NSCLC patients who underwent complete resection and received PORT in accordance with the CTV contouring guideline at our hospital were included in this study. The patterns of first failure after PORT were evaluated to help determine whether or not the PORT CTV was appropriate.Results:Of the63patients,61patients had the reliable follow-up data and included in the analysis. No patient received neoadjuvant chemotherapy or radiotherapy and all patients underwent postoperative chemotherapy in this study. The median radiation dose was50.4Gy at1.8Gy per fraction. The median follow-up time for the42living patients was27.5months (range,13.1-88.8). The median survival time was58months. Up to the last follow-up,42patients experienced disease failure, including2with locoregional recurrence alone,39(93%) with distant metastases, and1with both. There were6patients (14%) with supraclavicular LN metastasis. Out of the3patients presented with the mediasinal LN relapses, all patients had the in-field recurrence sites within the irradiated field of the postoperative radiotherapy.Conclusions:Basing on the available information, the CTV delineation protocol for completely resected stage IIIA (N2) patients is relatively adequate and appropriate. Part IV. Effectiveness of Postoperative Radiotherapy in Completely resected Stage ⅢA(N2) Non-Small-Cell Lung Cancer According to Analyses of Locoregional Recurrence risksPurpose:For completely resected stage ⅢA(N2) NSCLC patients, about20%-40%of patients still have a risk of local-regional failure and the role of PORT remains controversial. We tried to subcategorize these patients into high-and low-risk groups with respect to local-regional recurrence rates, and to determine whether there were certain subgroups of patients who were particularly likely benefit from PORT.Methods:From2005to2011, patients with stage Ⅲa(N2) NSCLC who underwent complete resection were retrospectively analyzed in this study. The PORT group were patients with stage ⅢA(N2) NSCLC who underwent complete resection and received PORT in accordance with the CTV contouring guideline at our hospital. Patients who experienced disease failure before the PORT were excluded. The non-PORT group were patients with stage ⅢA(N2) NSCLC who underwent complete resection at our hospital without PORT. The eligibility criteria were detailed in Part Ⅰ and Ⅲ. Overall survival was estimated using Kaplan-Meier method. Significance between groups was assessed by log-rank test. The prognostic model related LRFS constructed by the Prognostic Index.Results:The median duration of follow-up was24.5months. The5-year cumulative LRR was10.5%in the PORT group and38.9%in the non-PORT group (p=0.001). The5-year OS was48.8%in the PORT group and32.8%in non-PORT group (p=0.006). However, the greatest level of improvement in LRFS and survival (p<0.001) associated with the PORT was in the high-risk group and in patients with heavy smoking history, clinical N2, or lymph node metastasis>4. For the low-risk group, the LRFS and OS were not statistically different between the patients who received PORT and those who underwent observation.Conclusion:Patients with completely resected stage IIIA(N2) NSCLC and who are at high-risk for local-regional recurrence are likely to benefit from adjuvant PORT. Prospective confirmation of these observations is warranted.