Sequential Hypofractionated Radiotherapy can Offer Similar Disease Control and Survival of Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer?

Abstract

Concurrent conventional fractionated chemoradiation (ccCRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC) when compared with convectional fractionated radiation therapy (cfRT) after chemotherapy. The main benefit of ccCRT is associated to disease locoregional control. Sequential Hypofractionated Radiation therapy (s-HypoRT) is a treatment option for these patients. We compared the outcomes of the ccCRT with sequential treatment cfRT and s-HypoRT. It was a retrospective analysis of all inoperable stage III LA-NSCLC submitted to radical radiotherapy (RT) in a single institution from January 2013 to October 2018. Patients submitted to ccCRT and cfRT received 60Gy in 30 fractions. The patients submitted to s-HypoRt received 55Gy in 20 fractions. All patients were treated with conformal RT or IMRT. All chemotherapy schedule was platinum doublet based. Patients submitted All Patients were (re)staged according to the AJCC 8a ed. The criteria for disease progression was based on RECIST v1.1 and the toxicity criteria used was the CTCAE.v4. Survival analysis was evaluated by Kaplan–Meier method and log-rank test. Multivariate models were tested including all covariates with p values < .20 in the univariate analysis. It was recorded the medical charts and treatment planning of 140 patients. The median age was 63 years (range, 25–83). Most were male (61%) and had ECOG Performance Status 1 (72%). The stage distribution was IIIA 32%, IIIB 51% and IIIC 17%. The patient populations were divided in 3 groups: 52 patients (37%) were submitted to cc-CRT, 38 patients (27%) was submitted to sequential cfRT (cfRTSeq) and 50 patients (36%) received s-HypoRT. With the median follow up of 16 months, the median Overall Survival (OS) for the entire population was 23 months and there was no difference in OS between the 3 groups (p = 0,686). Large tumor volume (p = 0,039) and use of IMRT (p = 0,031), was associated with OS on univariate analysis. The 2-years Locoregional Progression Free Survival (LPFS) 62.9% for ccCRT, x 60.0% for s-HypoRT and 41.0% for cfRTSeq (p = 0.031). On multivariate analysis the cfRTSeq (HR 2,11, IC 1,06—4,19) was associated with worse LRPFS. The treatment was well tolerated for all groups, and the rates of grade ≥ 3 acute esophagitis of 1.9% for ccCRT and 4.0% for s-HypoRT (p = ns). Only one case of grade 3 fatigue was evidenced in the cfRTSeq and one case of grade 3 pneumonitis was evidenced in the ccCRT and cfRT group. Our data demonstrated that s-HypoRT results in similar LRPFS when compared with the standard ccCRT. There was no difference in OS. S-HypoRT is a safe and fast treatment strategy for patients not suitable for ccCRT and can be considered a better option than cfRTSeq.