lunes, 30 de diciembre de 2013

Hypofractionated RT in Locally Advanced NSCLC: Phase I Trial Yields M

Dose-escalated hypofractionated radiotherapy yielded a maximum tolerated dose for patients with locally advanced non-small-cell lung cancer (NSCLC) and shed light on dangerous toxicity at higher doses, according to a new study. The toxicity was dominated by late radiation toxicity to the central and perihilar structures including the proximal bronchial tree and surrounding vasculature.

The new phase I study, published online ahead of print on October 21 in the Journal of Clinical Oncology, enrolled 79 patients with NSCLC at a single institution. After five patients were treated on a pilot study at a dose of 57 Gy of hypofractionated radiotherapy, the study’s dose escalation protocol (without any concurrent chemotherapy) proceeded. Forty-seven of the patients ended up receiving only the 57 Gy base dose; 11 patients received 63.25 Gy, 3 received 69.25 Gy, 12 received 75 Gy, 4 received 80.5 Gy, and 2 received 85.5 Gy. The median dose was 57 Gy in 25 fractions.
After a median follow-up period of 17 months, the median overall survival rate was 16 months; 29% of the cohort survived to 3 years. There was no difference seen in rates of local control between those treated at 69.25 Gy and higher and those treated at the lower 57 and 63.25 Gy doses (P = .81).
The maximum tolerated dose was established at 63.25 Gy. There were no cases of grade 3 or higher radiation pneumonitis, and 12 patients (16%) had grade 2 pneumonitis. There were also no instances of grade 3 or worse acute or late esophageal toxicities, though 48% of the cohort experienced grade 2 esophagitis.
Six grade 4 or 5 toxicities were deemed likely to be related to radiotherapy. One patient treated at 63.25 Gy died from progressive hypoxemia with bilateral lung infiltrates without disease progression 1 month after therapy. Three patients treated at 75 Gy and above died from massive hemoptysis 8 or more months after the therapy. Univariate analysis showed that higher delivered dose was significantly associated with development of any grade 4 to 5 toxicity, with a hazard ratio of 1.13 (95% CI, 1.04-1.23; P = .0036).
While the study suggests this therapy up to 63.25 is well tolerated, the authors noted that “our results are a reminder that the spectrum of toxicities from dose-intensified thoracic radiotherapy can be broad.” The results have implications for design of trials aiming to improve rates of local control. “In addition to controlling for pneumonitis risk, radiation dose-escalation studies in lung cancer should require strict limits to doses received by the proximal bronchial tree,” they concluded.

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