This trial was designed to compare the toxicity and effectiveness of PSPT with that of standard IMRT, both with concurrent chemotherapy, for patients with locally advanced NSCLC (Appendix: Protocol ). Patients were treated at The University of Texas MD Anderson Cancer Center and at Massachusetts General Hospital. The protocol was approved by the institutional review boards of both institutions, and all enrollees provided written informed consent to participate.
Eligibility criteria included age >18 years, Karnofsky Performance Status score ≥70, stage II–IIIB disease, or stage IV disease with a single brain metastasis, or recurrent tumor after surgical resection that could be treated definitively with concurrent chemoradiation, and baseline pulmonary function of forced expiratory volume in the first second of ≥1 liter. Patients who had received systemic chemotherapy regardless of response before enrollment were also eligible. Eligible patients consented to participate after they were evaluated and deemed suitable candidates for concurrent chemoradiation.
The primary endpoint was the first occurrence of either severe (grade ≥3) RP or local failure (LF). The choice to use two primary endpoints emphasized the importance of being free of RP, a potentially lethal form of toxicity, in addition to local disease control. From our historical data13 ,14 (link) we assumed 15% RP rates at 1 year in the IMRT group and 5% in the PSPT group; we further assumed a 25% LF rate in both groups (because the prescribed dose to tumor was the same in both arms by design). With a maximum of 150 randomized and evaluable patients, we would have 81% power to detect such a difference with a one-sided type I error rate of ≥10%. The posterior probability of PSPT being better than IMRT based on the primary endpoints was to be reported. The Bayesian adaptive design was constructed to possess the desirable frequentist properties. Detailed information on assumptions for the study design and trial operating characteristics can be found in the study protocol (Appendix: Protocol ).
Eligibility criteria included age >18 years, Karnofsky Performance Status score ≥70, stage II–IIIB disease, or stage IV disease with a single brain metastasis, or recurrent tumor after surgical resection that could be treated definitively with concurrent chemoradiation, and baseline pulmonary function of forced expiratory volume in the first second of ≥1 liter. Patients who had received systemic chemotherapy regardless of response before enrollment were also eligible. Eligible patients consented to participate after they were evaluated and deemed suitable candidates for concurrent chemoradiation.
The primary endpoint was the first occurrence of either severe (grade ≥3) RP or local failure (LF). The choice to use two primary endpoints emphasized the importance of being free of RP, a potentially lethal form of toxicity, in addition to local disease control. From our historical data13 ,14 (link) we assumed 15% RP rates at 1 year in the IMRT group and 5% in the PSPT group; we further assumed a 25% LF rate in both groups (because the prescribed dose to tumor was the same in both arms by design). With a maximum of 150 randomized and evaluable patients, we would have 81% power to detect such a difference with a one-sided type I error rate of ≥10%. The posterior probability of PSPT being better than IMRT based on the primary endpoints was to be reported. The Bayesian adaptive design was constructed to possess the desirable frequentist properties. Detailed information on assumptions for the study design and trial operating characteristics can be found in the study protocol (
