Thoracic radiotherapy extended progression-free survival, reduced intrathoracic recurrences, and improved overall survival at 2 years when added to prophylactic cranial irradiation in patients with extended-stage small cell lung cancer in an international randomized controlled trial.1
“Thoracic radiation should be added to prophylactic cranial irradiation and be offered to all extended-stage small cell lung cancer patients with a response to initial chemotherapy to improve outcomes,” stated lead author Ben Slotman, MD, Professor and Chairman of Radiation Oncology at VU University Medical Center, Amsterdam.
Dr. Slotman presented these results at the 56th Annual Meeting of the American Society for Radiation Oncology (ASTRO) in San Francisco. The work was simultaneously published in
The Lancet. 2
CREST Trial
The multinational CREST trial enrolled 498 patients with extended-stage small cell lung cancer who had a complete, partial, or good response to initial platinum/etoposide chemotherapy. Patients were randomly assigned 1:1 to receive prophylactic cranial irradiation with or without thoracic radiotherapy within 2 to 7 weeks of chemotherapy. Thoracic radiotherapy was delivered in 10 fractions of 3 Gy.
“We know prophylactic cranial irradiation improves symptomatic brain metastases and overall survival at 1 year. We also know that persistent intrathoracic disease is seen in about three-quarters of extended-stage small cell lung cancer patients and intrathoracic progression in almost 90%,” Dr. Slotman told listeners. The present study was conducted to see if thoracic radiotherapy could improve intrathoracic and general outcomes.
No significant differences in baseline characteristics were seen between the two groups. Median age was 63 years; 55% were male and 45% were female. Median follow-up was 24 months. Eighty-nine percent of all patients were World Health Organization (WHO) performance status 0 or 1. Eighty-eight percent had persistent intrathoracic disease after chemotherapy.
Additionally, no significant differences in grades 3 and 4 toxicities were observed between the two treatment arms.
Survival and Recurrence Data
Over the first 9 to 12 months following treatment, survival curves were similar for the two arms, Dr. Slotman said. But by 24 months, survival was 13% in the group treated with thoracic radiotherapy vs 3% for prophylactic cranial irradiation alone (P = .004).
Subgroup analysis showed no significant differences in the effect of thoracic radiotherapy in survival related to age, degree of response to chemotherapy, or WHO status.
Progression-free survival was significantly longer in the group receiving thoracic radiotherapy, with a 27% reduced risk of recurrence compared with prophylactic cranial irradiation alone (P = .001). Among all patients, the rate of intrathoracic progression was 43.7% in the thoracic radiotherapy group vs 79.8% in the prophylactic cranial irradiation-only group (P < .001). Intrathoracic progression as the first site of relapse was observed in 41.7% and 77.8%, respectively (P < .001). Intrathoracic progression was the only site of progression in 19.8% and 46% of patients, respectively (P < .001).
Progression elsewhere, with or without progression in the thorax or brain, occurred in 60.3% of the thoracic radiotherapy group compared to 40.3% in the prophylactic cranial irradiation–alone group (P < .001). There was no significant difference between treatment arms in the risk of brain metastasis as site of first relapse.
Dr. Slotman said that the higher rate of progression outside the thorax in the thoracic radiotherapy arm warrants studies on consolidative radiation therapy to other sites of distant disease. ■
Disclosure: Dr. Slotman reported no potential conflicts of interest.
References
1. Slotman B, Faivre-Finn C, van Tinteren H, et al: ASTRO Annual Meeting. Abstract CT-05. Presented Sept 14, 2014.
2. Slotman BJ, van Tinteren H, Praag JO, et al: Lancet. Sept 12, 2014 (early release online).
