SAN ANTONIO, TX—Treatment with stereotactic body radiotherapy (SBRT) was well-tolerated by patients whose lung cancer tumors were located centrally in the chest and who were not candidates for surgery. The highest dose level allowed by the protocol was reached (12 Gy delivered in 5 fractions over 1.5 to 2 weeks, for a total dose of 60 Gy). These findings were reported at the 2015 American Society for Radiation Oncology (ASTRO) Annual Meeting.

The trial is the first to implement a phase 1/2 continuous reassessment design employed to collect toxicity and efficacy data safely and expeditiously in the evaluation of dose-escalating SBRT treatment. The presentation, by principal investigator, Andrea Bezjak, MD, MSc, FRCPC, a professor of radiation oncology at the University of Toronto in Ontario, Canada, focused on toxicity results of the phase 1/2 NRG Oncology/RTOG 0813 trial.

SBRT is widely used in the treatment of non-small cell lung cancer (NSCLC) tumors located in the periphery of the lung.

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“What has remained unclear are the dose and fractionation schedule of SBRT that are safe and efficacious for treating patients with early stage, inoperable NSCLC tumors that are located more centrally in the chest, close to critical organs and structures. So we planned this trial to establish a dose standard for these patients who are being treated for cancer cure,” said Bezjak.

The starting radiation dose was 10 Gy delivered in 5 fractions over 1.5 to 2 weeks (total dose 50 Gy). As part of the continuous reassessment study design, the dose level for the next patient was determined based on all dose-limiting toxicity (DLT) reported as of the time of patient registration. DLT was defined as any grade 3 or worse toxicity occurring within the first year that was related to SBRT.

“Rather than as with a classical phase I study holding accrual while awaiting toxicity reporting on the cohort of patients at a given dose, and then proceeding to a phase 2 study, once the maximum tolerated dose was achieved, this seamless phase 1/2 study allowed all patients to contribute to determining the maximally tolerated dose levels and to the information about dose efficacy within 1 trial,” explained Bezjak. He noted that such a trial design requires a concerted effort on the part of research sites to rapidly report toxicity data as it may influence the dose that next patient will be assigned.

Bezjak reported that the highest dose level allowed by the protocol was associated with a 7.2 probability of DLT. The phase 2 efficacy analysis is expected to begin in early 2016.

“These results are especially important in light of the new lung cancer screening guidelines, which are likely to lead to significantly more early stage lung cancers being detected,” said Walter J. Curran Jr, MD, an NRG Oncology Group chairman and executive director of the Winship Cancer Institute of Emory University in Atlanta, Georgia.