SAN FRANCISCO – Patients with extensive small cell lung cancer that responds to chemotherapy fare better when given thoracic radiation in addition to prophylactic cranial irradiation, investigators reported at the annual scientific meeting of the American Society for Radiation Oncology.
“Thoracic radiotherapy – 30 Gy in 10 fractions – improves overall survival, progression-free survival, and intrathoracic control,” concluded Dr. Ben J. Slotman, professor and head of the department of radiation oncology at Vrije Universiteit Medical Center, Amsterdam. “We think that this should now be offered in addition to prophylactic cranial irradiation to patients with a response after initial chemotherapy,” he said.
“What are your thoughts about building on these results by using perhaps a higher dose of radiation or perhaps radiation to other extrathoracic sites using [stereotactic body radiation therapy] or other approaches like that?” asked session cochair Dr. Benjamin Movsas, a radiation oncologist at Henry Ford Hospital in Detroit.
“That’s an excellent point. The dose was chosen on the safe side – 10 times 3 Gy – and was given without much toxicity, so I think the next step would be to move … to a higher dose, perhaps 15 times 3 Gy,” Dr. Slotman replied. The findings also support use of radiation therapy to manage other sites of metastases. “I think this study really shows that if you give local treatment to this group of patients with disseminated disease, that you are still able to make a great impact,” he maintained.
In this patient population, prophylactic cranial irradiation alone reduces the risk of symptomatic brain metastases and improves overall survival, he noted, giving some background to the trial (N. Engl. J. Med. 2007;357:664-72). The large majority of patients, however, have persistent intrathoracic disease (76%) and experience intrathoracic progression (89%).
Patients from the Netherlands, United Kingdom, Norway, and Belgium were eligible for the phase III trial, known as the Chest Radiotherapy Extensive Stage Trial (CREST), if they had extensive-stage small cell lung cancer (disease beyond the hemithorax, hilar, mediastinal, and supraclavicular nodes) and had experienced a complete, partial, or good response to platinum-based chemotherapy. Additionally, they could not have any brain, leptomeningeal, or pleural metastases and could not have previously received radiation therapy to the thorax or brain.
The 498 patients were randomized evenly to receive thoracic radiation or no thoracic radiation. All received prophylactic cranial irradiation.
Overall survival curves for the two groups first began to diverge at about 9 months, Dr. Slotman noted.
Thoracic radiation was associated with a trend toward better 1-year overall survival (33% vs. 28%; hazard ratio, 0.84; P = .066) and significantly better 2-year overall survival (13% vs. 3%, P = .004), according to results reported at the meeting and simultaneously published online (Lancet 2014 Sept. 14 [doi:10.1016/S0140-6736(14)61085-0]).
Subgroup analyses suggested that thoracic radiation was similarly efficacious regardless of a variety of disease, clinical, and demographic characteristics, except for possibly having less benefit in patients who had had a complete response to chemotherapy and in patients who did not have intrathoracic disease, he said.
Thoracic radiation also was associated with better progression-free survival (HR, 0.73; P = .001).
The rate of intrathoracic progression was significantly lower in the thoracic radiation group as well, regardless of whether this applied to intrathoracic progression events overall (44% vs. 80%), to those that were the first site relapse (42% vs. 78%), or to those that were the only site of relapse (20% vs. 46%), Dr. Slotman reported.
The thorax was the leading site of first relapse in the control group. In contrast, sites outside the thorax and brain were most often the site of first relapse in the thoracic radiation group.
About 8% of patients overall experienced grade 3 or worse toxicity, with no significant difference between groups in the rate or nature of the events.
Dr. Slotman disclosed no relevant conflicts of interest.