The emerging outcome of postoperative radiotherapy for stage IIIA(N2) non-small cell lung cancer patients: based on the three-dimensional conformal radiotherapy technique and institutional standard clinical target volume

Abstract

BackgroundThe aim of this study was to evaluate the clinical efficacy of postoperative radiotherapy (PORT), administered using three-dimensional conformal radiotherapy (3D-CRT) and our institutional standard clinical target volume (CTV) delineation, for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC).MethodsFrom 2005 to 2012, consecutive patients with pT1-3N2 NSCLC who were treated with PORT employing our institutional CTV delineation after complete surgery or who underwent complete resection in our hospital but without PORT were identified. We excluded patients who had received neoadjuvant chemotherapy or radiation therapy (RT). Kaplan-Meier estimates for locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were performed. In the OS estimation, patients who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) during follow-up were censored at the time of TKI initiation.ResultsData from 70 patients in the PORT group and 287 in the non-PORT group were analysed. All 70 cases received 3D-CRT following our institutional CTV guideline, with a median total dose of 50.4 Gy at 1.8 Gy/fraction. At a median follow-up of 34.3 months for the PORT group and 31.2 months for the non-PORT group, PORT significantly improved local control (5-yr LRFS 91.9% for PORT vs 66.4% for non-PORT, P < 0.001) and OS (5-yr OS 57.5% for PORT vs 35.1% for non-PORT, P = 0.003), whereas no differences in DMFS were noted (P = 0.18). In multivariable analyses, PORT was independently associated with an improved LRFS (HR 0.2, P = 0.001) and OS (HR 0.4, P = 0.001). All patients completed the planned RT dose without interruption of RT due to treatment-related complications.ConclusionsOur data suggested that PORT administered using the 3D-CRT technique following our institutional CTV delineation guideline resulted in a promising outcome with favourable survival for completely resected IIIA(N2) NSCLC, after controlling for subsequent EGFR-TKI confounding in the OS analysis. Prospective trials are needed to further corroborate these results.

Early postoperative radiotherapy is associated with improved outcomes over late postoperative radiotherapy in the management of completely resected (R0) Stage IIIA-N2 non-small cell lung cancer

“…Recently, Feng et al . designed a patterns-of-failure study after R0 surgery in resected N2 disease to evaluate the rationale of the proposed PORT CTVs based on the most likely sites of nodal failure, and the institutional standard CTV delineation for PORT was developed in their hospital [ 29 – 30 ]. Similar to these studies, our CTV encompassed the bronchial stump and involved mediastinal nodal stations and their next draining stations.…”

PLNR&le;20% may be a benefit from PORT for patients with IIIA-N2 NSCLC: a large population-based study

“… 23 – 26 Feng et al have demonstrated that PORT was an independent prognostic factor for improved locoreginal free Survival (HR=0.2, 95% CI 0.1–0.5; P =0.001) and improved OS (HR=0.4, 95% CI 0.2–0.7; P =0.001). 27 The Lung Adjuvant Radiotherapy Trial (LungART, NCT00410683), a randomized trial of modern PORT vs no PORT in patients with resected NSCLC, is ongoing. 28 …”

“…Feng et al showed that PORT was an independent prognostic factor for improved OS (HR=0.4, 95% CI 0.2–0.7; P =0.001); female sex (HR=0.5, 95% CI 0.3–0.7; P <0.001) and LNR>20% (HR=2.4, 95% CI 1.7–3.3; P <0.001) were the other factors for OS. 27 Wang et al demonstrated that in stage IIIA-pN2 NSCLC, the use of PORT demonstrated better survival results than no PORT for patients with positive LNs with n>3, but not for patients with positive LNs with n≤3. 17 Other studies have reported that several clinical and pathological factors, such as the number of pathologically involved lymph node stations, 32 , 33 extracapsular extension, 34 lymph node skip status and positive LNR 12 – 16 should be considered when evaluating the risks and benefits of PORT.…”

Postoperative Radiotherapy for Resected Stage IIIA–N2 Non-small-cell Lung Cancer: a Review of Outcomes

“…3,24 Nonetheless, the rate of distant failure remained high (66.7%), consistent with that in other studies. 3,13,25,26 There is an association between pN2 disease and distant failure.…”