Margriet Kwint

Safety and efficacy of reduced dose and margins 39 2 Heart dose parameters (V 5 and V 30 ) and the presence of dysphagia were associated with OS. In addition to the RTOG-0617, Hallqvist et al. recently published their toxicity results of a randomized phase II-trial [22]. Thirty-six patients were treated with an escalated dose up to 84 Gy to the tumour and involved mediastinum concurrently with 3-weekly Cisplatin-Vinorelbin. Seven patients died due to a possible G5 toxicity (pneumonitis and oesophageal fistulae) of which 5 patients were included in the 84 Gy-arm. The study was stopped after this pre-planned safety analysis. The conclusion of the RTOG-0617 and the Hallqvist-trial was that the acute and late toxicities were at least partly responsible for the negative results. It should be emphasized that the primary tumour as well as the involved lymph nodes were exposed to the escalated dose. In the current study, we reduced the total dose to the mediastinum, but not the primary tumour. Combining a lower mediastinal dose with a reduction of the PTV- margins resulted in a significantly lower exposure of the OAR (Table 2), a significantly lower incidence of severe ≥G3 acute dysphagia and acute pulmonary toxicity as well as an improved OS. The lower toxicity rates favoured the reduction-cohort, but the safety of this regimen also depends on the RF rate. No increase in RF with or without LF was observed ( Table 4 ). A previously published study by Van den Bosch et al. supported our results by demonstrating that an increased RT dose was not associated with a lower RF rate [23]. Seventy-five stage IIB-IV NSCLC patients were treated with a dose between 42- 66 Gy (EQD2 10 ) to the tumour as well as the lymph nodes, of which 63% received sCRT. The RF rate was not different between lower and higher radiation dose to involved lymph nodes and varied between 6-8%. However, the primary tumour did show a dose-effect relationship. Several papers showed similar results, although the RTOG-0617 did not reveal lower LF rates [1, 13]. In addition to the already mentioned potential causes of the detrimental outcome of the 74Gy-arm, the extended overall treatment time probably resulted in reduced effectiveness. This disadvantage may be countered by hypofractionated RT with a positive effect on OS [3, 24]. However, the hypofractionated schedule used in the current analysis differs from the conventionally fractionated schedule and could potentially increase the toxicity. Since the introduction of our hypofractionated schedule, after being tested within a phase II and III EORTC-trial, we have monitored the toxicity closely and published about the acute and long term outcome [25-28]. The acute and late toxicity rates are favorable compared to the toxicity of the conventional fractionated schedules with full dose chemotherapy [1].