• The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial)

      van Diessen, DJ; De Ruysscher, D; Sonke, JJ; Damen, E; Sikorska, K; Reymen, B; van Elmpt, W; Westman, G; Fredberg, PG; Dieleman, E; et al. (2018)
      BACKGROUND AND PURPOSE: The PET-boost randomized phase II trial (NCT01024829) investigated dose-escalation to the entire primary tumour or redistributed to regions of high pre-treatment FDG-uptake in inoperable non-small cell lung cancer (NSCLC) patients. We present a toxicity analysis of the 107 patients randomized in the study. MATERIALS AND METHODS: Patients with stage II-III NSCLC were treated with an isotoxic integrated boost of ?72?Gy in 24 fractions, with/without chemotherapy and strict dose limits. Toxicity was scored until death according to the CTCAEv3.0. RESULTS: 77 (72%) patients were treated with concurrent chemoradiotherapy. Acute and late ?G3 occurred in 41% and 25%. For concurrent (C) and sequential or radiotherapy alone (S), the most common acute ?G3 toxicities were: dysphagia in 14.3% (C) and 3.3% (S), dyspnoea in 2.6% (C) and 6.7% (S), pneumonitis in 0% (C) and 6.7% (S), cardiac toxicity in 6.5% (C) and 3.3% (S). Seventeen patients died of which in 13 patients a possible relation to treatment could not be excluded. In 10 of these 13 patients progressive disease was scored. Fatal pulmonary haemorrhages and oesophageal fistulae were observed in 9 patients. CONCLUSION: Personalized dose-escalation in inoperable NSCLC patients results in higher acute and late toxicity compared to conventional chemoradiotherapy. The toxicity, however, was within the boundaries of the pre-defined stopping rules.
    • Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

      Apolle, R; Appold, S; Bijl, H; Blanchard, P; Bussink, J; Faivre-Finn, Corinne; Khalifa, J; Laprie, A; Lievens, Y; Madani, I; et al. (2019)
      Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and METHODS: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases eacH Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnairE RESULTS: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. CONCLUSION: IOV in target volume delineation increases during treatment, where a disparity in Institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needeD
    • Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer

      Defraene, G; Dankers, FJWM; Price, Gareth J; Schuit, E; van Elmpt, W; Arredouani, S; Lambrecht, M; Nuyttens, J; Faivre-Finn, Corinne; De Ruysscher, D; et al. (2019)