Top Line: How safe and effective is hypofractionated chemoradiation for stage III NSCLC?
The Study: For patients who aren’t candidates for concurrent chemotherapy, a recent randomized trial found that accelerated hypofractionated RT consisting of 60 Gy in 15 fractions did not improve survival outcomes compared to conventional fractionation. In this single arm, phase 2 trial, 75 patients with stage III NSCLC were treated with hypofractionated radiation and concurrent chemotherapy. The GTV was contoured on a 4DCT, and the target volume was the GTV plus a 5mm margin. The overall treatment plan consisted of two phases. In the first phase, patients received 40 Gy in 10 fractions with two cycles of weekly docetaxel and nedaplatin. In phase 1, the lung V15 was limited to 20% and the esophagus Dmax was limited to 34 Gy with a V30 <30%. Of note, the PTV was modified adjacent to the esophagus to limit esophageal exposure to the prescription dose. Half (52%) of patients had grade 2+ toxicity after phase 1 requiring a treatment break. The most frequent toxicity was esophagitis (28%). Patients who didn’t progress on restaging CT and who had resolution of any grade 2+ toxicity (94.7%) then received another 24-28 Gy in 6-7 fractions adapted to the new GTV with another 2 cycles of docetaxel and nedaplatin. The patients who didn’t receive the boost had persistent grade 2+ pneumonitis. The median time from the end of phase 1 to the start of phase 2 was 20 days. The average GTV volume was reduced by 42% after the first phase. In the second phase, the lung V15 was limited to 10%, and the esophagus Dmax was limited to 24 Gy with a V20 <15%. The median total dose was 64 Gy. At the completion of all treatment, 26.7% had grade 2 esophagitis, 5.3% had grade 3 esophagitis, and 17.3% had grade 2 pneumonitis with no grade 3+ pneumonitis. Three patients (4%) experienced fatal hemoptysis 10-12 months after treatment highlighting the ever-present risk of severe toxicity when hypofractionating near central structures. Locoregional recurrence occurred in 17.3%, 18.7% had distant failure, and 5.3% had both distant and locoregional failure. At 2 years, the rate of PFS was 43.3%, and the rate of OS was 72.4%.
TBL: The two-phase approach used in this single arm trial of hypofractionated concurrent chemoradiation allowed for significant reduction in the treatment volume and mostly manageable toxicity. However, over half of patients required a treatment break between phases mainly due to esophagitis. | Zhou, Int J Radiat Oncol Biol Phys 2023
The Study: For patients who aren’t candidates for concurrent chemotherapy, a recent randomized trial found that accelerated hypofractionated RT consisting of 60 Gy in 15 fractions did not improve survival outcomes compared to conventional fractionation. In this single arm, phase 2 trial, 75 patients with stage III NSCLC were treated with hypofractionated radiation and concurrent chemotherapy. The GTV was contoured on a 4DCT, and the target volume was the GTV plus a 5mm margin. The overall treatment plan consisted of two phases. In the first phase, patients received 40 Gy in 10 fractions with two cycles of weekly docetaxel and nedaplatin. In phase 1, the lung V15 was limited to 20% and the esophagus Dmax was limited to 34 Gy with a V30 <30%. Of note, the PTV was modified adjacent to the esophagus to limit esophageal exposure to the prescription dose. Half (52%) of patients had grade 2+ toxicity after phase 1 requiring a treatment break. The most frequent toxicity was esophagitis (28%). Patients who didn’t progress on restaging CT and who had resolution of any grade 2+ toxicity (94.7%) then received another 24-28 Gy in 6-7 fractions adapted to the new GTV with another 2 cycles of docetaxel and nedaplatin. The patients who didn’t receive the boost had persistent grade 2+ pneumonitis. The median time from the end of phase 1 to the start of phase 2 was 20 days. The average GTV volume was reduced by 42% after the first phase. In the second phase, the lung V15 was limited to 10%, and the esophagus Dmax was limited to 24 Gy with a V20 <15%. The median total dose was 64 Gy. At the completion of all treatment, 26.7% had grade 2 esophagitis, 5.3% had grade 3 esophagitis, and 17.3% had grade 2 pneumonitis with no grade 3+ pneumonitis. Three patients (4%) experienced fatal hemoptysis 10-12 months after treatment highlighting the ever-present risk of severe toxicity when hypofractionating near central structures. Locoregional recurrence occurred in 17.3%, 18.7% had distant failure, and 5.3% had both distant and locoregional failure. At 2 years, the rate of PFS was 43.3%, and the rate of OS was 72.4%.
TBL: The two-phase approach used in this single arm trial of hypofractionated concurrent chemoradiation allowed for significant reduction in the treatment volume and mostly manageable toxicity. However, over half of patients required a treatment break between phases mainly due to esophagitis. | Zhou, Int J Radiat Oncol Biol Phys 2023