Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated vs conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC)

Konference: 2009 34st Congress ESMO a 15th Congress ECCO - účast ČR

Kategorie: Zhoubné nádory plic a průdušek

Téma: Presidential session

Číslo abstraktu: 4LBA

Autoři: M. Baumann; T. Herrmann; R. Koch; B. Wahlers; L. Kepka; G. Marschke; Prof. MUDr. David Feltl, Ph.D., MBA; R. Fietkau; V. Budach; J. Dunst

Background: Accelerated radiotherapy counteracts repopulation of tumor cells during treatment and may significantly improve local control and survival in patients with locally advanced NSCLC (CHART-trial, Saunders 1997). Nevertheless local failure rates ˇÝ80% call for radiation dose escalation, using conformal techniques. We report here the final results of the CHARTWEL trial (CHART weekend less).

Patients and Methods: Between 1997 and 2005 406 pts. with NSCLC were randomized by 15 centres in Germany, Poland and Czech Republic. Inclusion criteria: UICC stage (I: 10%, II: 6%, IIIA:38% IIIB:46%), WHO performance 0¨C1. Randomization was stratified according to stage, histology, neoadjuvant chemotherapy (CTx; no = 300/yes = 106) and center. All patients were treated with 3D RT using a linear accelerator to 60 Gy/40 f/2.5 w (CHARTWEL) or 66 Gy/33 f/6.5 w (CF). The trial was carried out within the Arbeitsgemeinschaft Radioonkologie (trial # ARO 97-1) of the Deutschen Krebsgesellschaft and sponsored by the Deutsche Krebshilfe.

Results: Intent-to-treat analysis did not reveal significant differences of overall survival (primary endpoint) at 2, 3 and 5 yrs after CHARTWEL (31%, 22% and 11%) vs CF (32%, 18% and 7%; HR 0.92, 95% CI 0.75¨C1.13, p = 0.43). Also local tumor control rates (LC; HR 0.86; 0.68¨C1.09; p = 0.22) and distant metastasis rates (HR 1.06; 0.78¨C1.44; p = 0.71) did not significantly differ between the arms. Acute dysphagia was more pronounced after CHARTWEL. Pneumonitis determined by imaging was increased after CHARTWEL, without clinical differences. Exploratory analysis revealed a significant trend for improved LC after CHARTWEL vs CF with increasing UICC, T or N stage (p = 0.006¨C0.025) and after CTx (HR 0.48, 0.26¨C0.89, p = 0.019).

Conclusions: OS and LC were not significantly different after CHARTWEL and CF in the overall trial population. The impact of higher total dose in CF on LC was compensated by the shorter overall treatment time in CHARTWEL. This confirms a time factor of fractionated radiotherapy in NSCLC, and cautions treatment prolongation. The efficacy of CHARTWEL vs CF was higher in advanced stages and after CTx. From this we hypothesize that CHARTWEL after neoadjuvant CTx is a promising avenue to intensify treatment of locally advanced NSCLC which may overcome current limitations by toxicity of simultaneous radiochemotherapy.

Publikováno v: European Journal of Cancer Supplements, Vol. 7, No 3, September 2009, Page 4

Datum přednesení příspěvku: 23. 9. 2009