The use of helical tomotherapy in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer with concurrent chemotherapy was feasible and resulted in acceptable toxicity, according to the results of a clinical trial published in the January issue of Cancer.
Various strategies have been tried to improve outcomes for later stage lung cancer, including increasing dose by increasing the number of fractions, increasing dose by increasing fraction size (hypofractionation), and by using chemotherapy at the same time as radiation (concurrent chemotherapy).
The researchers said that the phase 1/2 study determined the maximum tolerated dose of radiotherapy in patients with stage III non-small cell lung cancer (NSCLC) administered concurrently with docetaxel and cisplatin and showed that a moderately aggressive hypofractionation schedule can be used along with concurrent chemotherapy, with low side effects.
Radiotherapy was delivered using helical tomotherapy. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6 percent per dose cohort in the study.
Samuel Bral, MD, from the department of radiation oncology at Universitair Ziekenhuis in Brussels, Belgium and colleagues performed dose escalation in 34 patients over five dose cohorts to a dose per fraction of 2.48 Gy. Early and late toxicity to esophagus, lungs and heart were monitored by the researchers and scored using Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer criteria.
Bral and colleagues observed no differences in acute toxicity between the different dose cohorts. However, a significant increase in late lung toxicity in a dose cohort, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the maximum tolerated dose defined as 2.24 Gy per fraction, they wrote.
“The overall incidence of acute grade esophageal and pulmonary toxicity was 24 percent and 3 percent, respectively. The overall incidence of late lung toxicity was 21 percent, but the incidence was an acceptable 13 percent in dose cohorts I, II and III. The local response rate was 61 percent on CT images,” said Bral and colleagues.
The researchers observed complete metabolic tumor response on FDG-PET scans in 55 percent of patients and the median survival was calculated to be 17.9 months.
Guy Storme, MD, PhD, director of the oncologic center at Universitair Ziekenhuis in Brussels said, “We are hopeful that this work—and the growing body of published tomotherapy-focused work from Universitair Ziekenhuis—will result in positive outcomes for patients with locally advanced NSCLC.”
A full phase 2 study has been initiated to further investigate toxicity and treatment efficacy with a helical tomotherapy dose of 67.2 Gy in 30 fractions and concurrent chemotherapy, according to Bral and colleagues.