Tumor volum in lung cancer
GTV differentially impacts locoregional control of non-small cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWEL trial

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Abstract

Purpose

To evaluate the impact of fractionation schedule on the size of the gross tumour volume (GTV) effect on tumour control after radiotherapy of NSCLC.

Material and methods

A subgroup analysis on 163 patients treated in a randomized phase III trial of CHARTWEL (continuous hyperfractionated accelerated radiotherapy-weekend less) vs conventional radiotherapy was performed. The influence of GTV and other baseline factors on local failure (LF), disease-free survival (DFS), distant metastases (DM), and overall survival (OS) was estimated using the Cox Proportional Hazards model.

Results

Superior local control was achieved by CHARTWEL compared to conventional radiotherapy (HR 0.54, p = 0.015). The hazard of LF increased with increasing GTV for both conventional fractionation and CHARTWEL, however the increase for the latter was less pronounced and not significant.

Conclusion

Highly accelerated CHARTWEL treatment was significantly more effective than conventional radiotherapy for locoregional control of NSCLC. GTV had a significant effect on locoregional control after conventional fractionation, an effect that was not significant with CHARTWEL. This is the first study to demonstrate that the magnitude of the time factor of fractionated radiotherapy increases with tumour volume.

Section snippets

The CHARTWEL trial

The phase III multi-centre randomized CHARTWEL trial (ARO 97-1) was performed between 1997 and 2005. One hundred and sixty three of the 406 patients with NSCLC were treated in the Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Germany, and this was the largest subgroup in the study. Of the 163 patients, 81 were randomly assigned to conventional fractionation (CF) and 82 patients were randomized to CHARTWEL (CW). The treatment protocol has

Results

In contrast to the intent-to-treat complete dataset of all 406 patients treated in the randomized multicentre CHARTWEL trial [6], the analysis of this largest single centre subset revealed a significant decrease of locoregional failure (LF), which was found after accelerated hyperfractionated radiotherapy in univariate analysis (Table 2a). Disease free survival (DFS), distant metastases rate (DM) and overall survival (OS) did not differ significantly between the treatment arms (Table 2a). The

Discussion

The present re-analysis of a large single-centre subset of the CHARTWEL-bronchus randomized trial provides evidence that the size of the negative impact of GTV on tumour control after radiotherapy of NSCLC differs between conventional fractionation and hyperfractionated-accelerated treatment. While the hazard of LF increases with increasing tumour volume for both conventional fractionation and CHARTWEL, the increase for the latter was found to be much less pronounced and not significant, i.e.

Conflict of Interest

The authors have no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work.

Acknowledgements

The CHARTWEL trial was supported by the Deutsche Krebshilfe (German Cancer Foundation, grant number T1/Ba1, #70-2206). M.S. was supported by a grant from the DAAD-GERLS (German academic exchange service – German Egyptian Research Long-term Scholarship), financed by DAAD and the Egyptian Ministry of Higher Education. MK and MB receive support by the Bundesministerium für Bildung und Forschung (BMBF, BMBF-ZIK program 01KS9602) and the German Consortium for Translational Cancer Research (DKTK).

References (33)

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1

Current address: MAASTRO (Maastricht Radiation Oncology), Radiotherapy Dept., Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands

2

Current address: Dept. of Radiation Oncology and OncoRay, Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

3

Current address: Universitätsklinik für Radioonkologie, Eberhard-Karls-Universität Tübingen, Germany.

4

Shared first authorship.

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