Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomised trial.

BACKGROUND: Heart exposure to ionizing irradiation can cause ischemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients.

PATIENTS AND METHODS: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomised to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis.

RESULTS: 161 patients were randomised in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these (male/female:105/50, median age 58 [33-74] years, stage IIIA/IIIB:54/101). Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumor and clinical characteristics with (hazard ratio 1.005 [0.995-1.015], P=0.30) or without lower lobe tumor location (hazard ratio 0.999 [0.986-1.012], P=0.83). There was no influence of heartV5 on death without tumor progression. Tumor progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths.

CONCLUSIONS: HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumor progression was the predominant cause of death.