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Journal of Thoracic Oncology:
doi: 10.1097/01.JTO.0000283803.40306.60
Poster Abstracts: Novel Therapeutics:New Horizon and Others: NT: Radiation Posters, Wed, Sept 5 - Thur, Sept 6

Personalized High-Dose Continuous Hyperfractionated Accelerated Radiotherapy (HI-CHART) of non-small cell lung cancer (NSCLC) based on normal tissue constraints: a prospective clinical trial: P3-046

van Baardwijk, Angela1; Wanders, Rinus1; Boersma, Liesbeth1; Dingemans, Anne-Marie2; Bootsma, Gerben3; Geraedts, Wiel4; Pitz, Cordula5; Simons, Jean6; Lambin, Philippe1; De Ruysscher, Dirk1

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1 Dept. of Radiation Oncology (MAASTRO), GROW Research Institute, University Hospital Maastricht, Maastricht, The Netherlands 2 Dept. of Pulmonology, University Hospital Maastricht, Maastricht, The Netherlands 3 Dept. of Pulmonology, Atrium Medical Center, Heerlen, The Netherlands 4 Dept. of Pulmonology, Maasland Hospital, Sittard, The Netherlands 5 Dept. of Pulmonology, Laurentius Hospital, Roermond, The Netherlands 6 Dept. of Pulmonology, Sint Jans Gasthuis, Weert, The Netherlands

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Local recurrence is a major problem after (chemo-)radiation for NSCLC. We hypothesized that for each individual patient the highest therapeutic ratio could be achieved by increasing the total tumor dose (TTD) to the limits of the normal tissues, delivered within 5 weeks. In a theoretical model this resulted in an increase in tumor control probability from approximately 5% for a classical scheme (60 Gy in 6 weeks) to 25% for the study scheme. Here, we report the first results of a prospective clinical trial.

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Twenty-nine patients with medically inoperable (stage I, n=2) or locally advanced NSCLC (stage III, n=27), in a good general condition (WHO-PS 0-1) and with a reasonable lung function (FEV1 >50% of predicted) were included. Most patients (25/29) received induction chemotherapy. All patients were irradiated using an individualized prescribed TTD, based on normal tissue constraints (mean lung dose 19 Gy, maximal spinal cord dose 54 Gy, no constraints for esophagus) up to a maximal TTD of 79.2 Gy. Radiotherapy was delivered in 1.8 Gy fractions, twice daily. Acute and late (>3 months) toxicity was scored using the CTCAE-criteria. A FDG-PET-CT scan (n=27) was performed to evaluate (metabolic) response 70 days after radiotherapy according to EORTC-criteria (PET) and RECIST-criteria (CT). The Kaplan-Meier method was used to compute overall survival.

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The mean delivered dose was 62.7 Gy (range 46.8-79.2 Gy). This corresponds to a mean biological equivalent dose of approximately 80 Gy (2 Gy fractions, once daily, in 8 weeks). Most patients experienced mild acute toxicity, while only 2 patients (6.8%) developed acute grade 3 toxicity (n=1 dysphagia, n=1 cough) as depicted in figure 1. Concerning late toxicity, 93% of patients (n=25) showed radiographic changes (75% in <25% and 18% in >25% of the lungs), while 12 out of 28 patients (43%) had clinical symptoms (>gr 1 pneumonitis). One patient (3.4%) died 51 days after radiotherapy due pneumonitis (treatment related mortality).

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The post-radiotherapy PET-CT showed in 18 patients a metabolic response (41% complete metabolic response, 26% partial metabolic response), whereas only in 9 patients (33.3%) a response was seen on CT (p=0.01). Eight patients (29.6%) showed progressive disease, consisting of loco-regional progression (n=4), metastases (n=3) or a combination of both (n=1). With a mean FU of 13 months the mean overall survival was 16.7 months and a 1-yr survival of 65%.

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Personalized HI-CHART radiation prescription based on normal tissue constraints is tolerable and initial results are promising.

Copyright © 2007 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.


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