Margriet Kwint

Acute esophagus toxicity after IMRT and concurrent chemoradiation 125 6 was converted into NTD equivalent to fraction doses of 2 Gy with α/β=10, for which the derived results may also be applied to other fractionation schemes providing the same α/β is used. Uitterhoeve et. al. reported in a phase I/II EORTC trial that this fractionation-scheme was safe using 3DCRT and an EORTC phase III multicenter trial confirmed this[13,14]. In 2005 the NKI-AVL introduced IMRT for all lung cancer patients treated with radical intent and to our clinical experience the safety of this treatment is well established. Uyterlinde et. al. analyzed that our CCRT regimen with IMRT is well tolerated in cohort of 188 patients [15]. For the treatment of stage III NSCLC patients, a certain risk of grade 3 AET is deemed acceptable because the toxicity is often temporary and manageable. Late esophagus toxicity (LET) like a fistula or stricture of the esophagus may however cause life- threatening problems for the patient. For LET, proposed predictive parameters are Dmean and V50 [6], and V45 to V60 [4], but most studies analyzing LET were done in patient groups treated with heterogeneous radiotherapy and chemotherapy schedules. Belderbos et al. reported from the randomized trial comparing sequential (N=78) and concurrent (N=80) chemoradiation that a higher incidence of AET in the CCRT-arm did not result in a higher incidence of severe late toxicity (4 vs. 5 %). Follow- up of the patients included in the current study is ongoing to report LET in the future. Limitations of the study Limitations in general were the difficulties encountered with the scoring of AET in patients treated with CCRT. Although we scored prospectively, sometimes it is difficult to differentiate between AET and side effects of chemotherapy (e.g. anorexia). The dose-volume-parameters were all based on the position of the esophagus during the midV-scan and were not corrected for movements of the esophagus during treatment. Motion analysis of the esophagus, and also the influence of length and circumference of the irradiated esophagus on AET is currently being investigated to further increase our knowledge on AET. Our CCRT treatment consists of daily low dose Cisplatin but different chemotherapy- regimens are frequently used. Currently this radiotherapy scheme and full-dose concurrent chemotherapy is being tested in a randomized phase II trial (study identification-number NCT-01024829).