Source
Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX The, Amsterdam, Netherlands.
Abstract
PURPOSE:
To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy.
PATIENTS AND METHODS:
The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status <or=2, weight loss <10% and no chemotherapy within 6 weeks prior to the start of the radiotherapy treatment. No elective nodal irradiation was given. Patients were treated 5 days a week with 2.25 Gy per fraction and a 6 weeks overall treatment time; two fractions a day were given if more than 30 fractions were prescribed. Five risk groups were defined according to the relative mean lung dose (rMLD). Within each group the dose was escalated with three fractions per step (6.75 Gy). The next dose level opened after a toxicity-free follow-up of 6 months in three patients. The maximum tolerable dose has been reached if two out of six patients experience a dose-limiting toxicity (pneumonitis >or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications).
RESULTS:
Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4.
CONCLUSION:
Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.