The Lancet Oncology
Volume 18, No. 5, p663–671, May 2017
Toshiaki Takahashi, MD, Prof Takeharu Yamanaka, PhD, Takashi Seto, MD, Hideyuki Harada, MD, Hiroshi Nokihara, MD, Hideo Saka, MD, Makoto Nishio, MD, Hiroyasu Kaneda, MD, Koichi Takayama, MD, Osamu Ishimoto, MD, Koji Takeda, MD, Hiroshige Yoshioka, MD, Motoko Tachihara, MD, Hiroshi Sakai, MD, Koichi Goto, MD, Prof Nobuyuki Yamamoto, MD
Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer. However, because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses, concerns have been raised about these findings. We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer.
We did this randomised, open-label, phase 3 study at 47 institutions in Japan. Patients with extensive-disease small-cell lung cancer who had any response to platinum-based doublet chemotherapy and no brain metastases on MRI were randomly assigned (1:1) to receive prophylactic cranial irradiation (25 Gy in ten daily fractions of 2·5 Gy) or observation. All patients were required to have brain MRI at 3-month intervals up to 12 months and at 18 and 24 months after enrolment. Randomisation was done by computer-generated allocation sequence, with age as a stratification factor and minimisation by institution, Eastern Cooperative Oncology Group performance status, and response to initial chemotherapy. The primary endpoint was overall survival, analysed in the intention-to-treat population. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001755, and is closed to new participants.