Jessie A. Elliott, Lisa O’Byrne, Gemma Foley, Conor F. Murphy, Sinead King, Emer M. Guinan, Narayanasamy Ravi, John V. Reynolds
Background: Neoadjuvant chemoradiation (nCRT) results in lung exposure to radiation, but the impact of modern quality-assured nCRT with respect to pulmonary morbidity is unclear. This prospective observational study aimed to systematically examine pulmonary physiology through multimodal therapy, and in survivorship.
Methods: Consecutive patients with locally advanced oesophageal cancer treated with curative intent between 2010 and 2016 were studied. A dose-volume histogram of V20 <25% was set for nCRT (40–44 Gy). DLCO, FEV1 and FVC were assessed at baseline and one month post-neoadjuvant therapy. Radiation-induced lung injury (RILI, EORTC ≥2), comprehensive complications index (CCI), Clavien-Dindo (CDC), pulmonary morbidity (PPCs) and HR-QL were monitored.
Results: A total of 384 patients were studied [nCRT, n=228; neoadjuvant chemotherapy (nCT), n=156]. Neoadjuvant therapy decreased FEV1 (P=0.0002), FVC (P=0.003) and DLCO (P<0.0001), with a greater reduction in DLCO (14%±14% vs. 7%±15%; P=0.002) post-nCRT vs. nCT. Post-nCRT 5 (2.2%) patients developed RILI precluding resection, associated with baseline DLCO (P=0.03). Smoking and age independently predicted pulmonary function decline. Comparing nCRT and nCT, major PPCs (CDC ≥ IIIb) occurred in 14.3% and 6.6% (P=0.037) and pneumonia in 30.9% and 24.8% (P=0.30). FEV1 (P=0.004, P=0.017, P=0.03), FVC (P=0.004, P=0.006, P=0.04) and DLCO (P=0.001, P=0.04, P=0.04) post-treatment, but not at baseline, were associated with CCI, inpatient LOS, and pneumonia, respectively, while post-treatment DLCO predicted prolonged intubation (P=0.03). In survivorship, post-treatment DLCO (P=0.03) independently predicted physical function score.
Conclusions: Modern nCRT rarely results in RILI precluding surgery, however these data highlight for the first time a significant impact on pulmonary function, associated with major short- and long-term respiratory morbidity.
