A landmark meta-analysis in 1998 showed that postoperative radiotherapy (PORT) was adversely associated with the survival of patients with non–small cell lung cancer (NSCLC).¹ This was primarily due to the low risk of locoregional recurrence in nonselective patients (including pI-II or pN0-1), high rate of distant metastasis (DM) due to the lack of systemic treatment, and high toxicity due to outdated radiotherapy techniques.¹ With the rapid improvement of modern radiotherapy techniques and focusing on the subgroup of pN2 NSCLC, there is increasing evidence that PORT results in better survival.^2-5 However, the definitive role of PORT in pIIIA-N2 NSCLC, especially in patients receiving adjuvant chemotherapy, remains controversial. To the best of our knowledge, there have been 3 phase 3 randomized clinical trials (RCTs) (Cancer and Leukemia Group B [CALGB] 9734 in North America,⁶ LungART in Europe,⁷ and PORT-C in China). The CALGB 9734 trial was initiated in 1998 and closed in 2000 without meeting the accrual target because of slow accrual⁶; the LungART trial⁷ began in 2007 and completed patient accrual in 2018. The present trial, PORT-C, conducted between 2009 and 2017, was a single-institutional RCT aimed at evaluating the efficacy and safety of PORT using 3-dimensional conformal radiotherapy (3D-CRT)/intensity-modulated radiotherapy (IMRT) in patients with pIIIA-N2 NSCLC after complete resection followed by adjuvant chemotherapy. In this article, we present the results of the PORT-C study, which is the first to complete patient accrual and meets its primary end point among the aforementioned phase 3 RCTs.

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60–66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m² on days 1–5 and cisplatin 50 mg/m² on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m² and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%–28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55–1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558.

Lung adenocarcinoma (LAD) is considered to be a highly aggressive disease with heterogeneous prognosis and the molecular mechanisms underlying tumor progression remain elusive. Growing evidence demonstrates that the dysregulation of microRNAs (miRNAs) plays an important role in various tumor processes. The aim of this study is to discover prognostic miRNA and investigate its role involved in progression of LAD. Prognosis related miRNA was detected by miRNA microarray using formalin-fixed paraffin-embedded (FFPE) specimens from 87 patients with IIIA-N2 LAD. The cell proliferation was evaluated by Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS), and the migration/invasion was evaluated by transwell assay. The bioinformatics methods and luciferase reporter assay were applied to detect the relationship between miRNA and its target. The mRNA and protein levels of miRNA target were determined by quantitative real time polymerase chain reaction (qRT-PCR) analysis, western blot and enzyme-linked immunosorbent assay (ELISA). Changes of angiogenesis induced by miRNA was evaluated by human umbilical vein endothelial cell (HUVEC) tube formation assay. Immunohistochemistry (IHC) analysis was performed in FFPE specimens of patients to evaluate the correlation between miR-29c with microvessel density (MVD) and vascular endothelial growth factor A (VEGFA) expression. MiR-29c expression downregulation was significantly associated with unfavorable prognosis in IIIA-N2 LAD. MiR-29c inhibited cell proliferation, migration and invasion in cell lines. Integrated analysis revealed that VEGFA was a direct target of miR-29c. MiR-29c reduced the capability of tumor cells to promote HUVEC tube formation. The compromised cell proliferation, migration/invasion and angiogenesis induced by miR-29c mimic transfection were reversed by transfection of VEGFA expression plasmid. Furthermore, the correlation of miR-29c with MVD and VEGFA was confirmed in patients’ samples. MiR-29c acts as a tumor suppressor by targeting VEGFA and may represent a promising prognostic biomarker as well as a potential therapeutic target for LAD.

BACKGROUND: The authors conducted a retrospective study to evaluate the effects of thoracic radiation therapy (TRT) for patients with extensive-stage small cell lung cancer (ED-SCLC). METHODS: Between January 2003 and December 2006, the records of 119 patients who were diagnosed with ED-SCLC (all with distant metastasis [M1]) were included in the study. Sixty patients received chemotherapy (ChT) and TRT (ChT/TRT), and 59 patients received ChT alone. The ChT regimens consisted of either carboplatin and etoposide (CE) or cisplatin and etoposide (PE). The total dose of TRT ranged from 40 to 60 grays (Gy) at 1.8 to 2.0 Gy per fraction. RESULTS: For the entire group, the median survival was 13 months, and the 2-year and 5-year overall survival (OS) rates were 26.1% and 6.5%, respectively. The median survival and the 2-year and 5-year OS rates were 17 months, 35%, and 7.1%, respectively, in the ChT/TRT group and 9.3 months, 17%, and 5.1%, respectively, in the ChT group (P = .014). However, this improvement was achieved at the expense of low toxicity. Multivariate analysis revealed that receiving ≥4 cycles of ChT (P = .032) and TRT (P = .005) were favorable prognostic factors for OS. Of all toxicities, only high-grade leucopenia (grade >3) was more frequent in the ChT/TRT group. CONCLUSIONS: The addition of TRT to ChT improved the OS of patients with ED-SCLC. Furthermore, receiving ≥4 cycles of ChT and TRT were independent, favorable prognostic factors for OS. Cancer 2011;. © 2011 American Cancer Society.