Margriet Kwint

Safety and efficacy of reduced dose and margins 33 2 Table 2 : The mean dose and standard deviation (SD) of the organs at risk stratified for the reference-cohort and reduction-cohort. Organ at risk Reference (N=170) (Mean, SD) Reduction (N=138) (Mean, SD) P-value Heart V 2 (%) Mean (Gy) 53.8 (25.9) 13.8 (7.9) 51.7 (27.4) 12.0 (6.6) 0.491 0.030 Oesophagus V 50 (%) 27.6 (16.2) 20.8 (16.0) <0.001 Lung V 5 (%) MLD (Gy) 59.6 (13.9) 14.3 (3.4) 58.5 (14.9) 13.0 (3.2) 0.147 0.001 Spinal cord D max (Gy) 41.6 (7.9) 37.7 (9.9) <0.001 All doses are normalized total dose (EQD2) for spinal cord and plexus α/β=2 Gy; for lungs, heart and mediastinal envelope α/β=3 Gy and for the oesophagus α/β=10 Gy. SD = standard deviation; Heart V2=volume of the heart receiving ≥2 Gy; Oesophagus V50=volume of the oesophagus receiving ≥50 Gy (EQD210); Lung V5=volume of the lungs receiving ≥5 Gy; MLD=mean lung dose; Spinal cord Dmax=maximum dose to 0.1cc of the volume.L The overall ≥ grade 2 (G2) acute toxicity rates were significantly lower in the reduction- cohort ( Table 3A ). G2 and G3 pulmonary toxicity, consisting of cough, dyspnea and radiation pneumonitis, was significantly lower in the reduction-cohort (20.6% versus 4.3%; 1.8% versus 0.0%). G2 and G3 dysphagia was also significantly lower in the reduction-cohort: 48.2% vs. 37.0% and 12.9% versus 3.6%, respectively. However, the reduction in dose and margins did not result in a decreased late toxicity ( Table 3B ). Late toxicity rates were comparable between the 2 cohorts, except G2 cough (7.1% versus 1.4%). An additional comparison between the 2 cohorts treated with cCRT or sCRT/RT regarding the acute toxicity rates showed significant differences of dysphagia and cough (supplemental Table S1a-b ). This demonstrated the beneficial effect of the reduction-cohort independent of chemoradiotherapy-schedule. In total, 13 patients (4.2%) died due to a G5 adverse event. In 5 patients, an acute G5 toxicity was reported, all were treated in the reference-cohort: 1 (0.6%) patient died due to a pulmonary haemorrhage and 4 (2.4%) patients died because of pneumonitis. Eight patients died due to a possible G5 late toxicity, of which 5 patients (2.9%) were treated in the reference-cohort: an oesophageal fistula (n=1), a pulmonary haemorrhage (n=1), pneumonitis (n=3) and respiratory insufficiency (n=1). In the reduction-cohort, 3 patients (2.2%) died due to a possible G5: a fatal haemorrhage (n=1) and radiation pneumonitis (n=2). The proportion of patients that died due to an acute G5 adverse event was lower in the reduction-cohort (p=0.042), however, the incidence of late G5 adverse events did not differ (p=0.668).