Radiation Therapy To Prevent Brain Tumours Can Improve Survival For Small-Cell Lung Cancer Patients

Main Category: Lung Cancer
Also Included In: Neurology / Neuroscience;  Cancer / Oncology
Article Date: 18 Sep 2007 - 13:00 PDT

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Patients with small-cell lung cancer who receive a course of radiation therapy to their heads after responding to chemotherapy live longer and are less likely to develop secondary brain tumours, a common feature of this disease, than those who are offered no further treatment, according to the results of a randomised controlled trial, published in the New England Journal of Medicine (N Engl J Med 2007; 357: 664-72)

Small-cell lung cancer, which mainly occurs in current or former smokers, spreads quickly and is rapidly fatal. Advances in treatment have done little to improve survival rates over the past 25 years and brain metastases are common with this disease. At least 18% of patients already have secondary brain tumours when they get their diagnosis and at 2 years 80% of patients show symptoms of brain involvement.

Chemotherapy does not reduce the incidence of brain metastases, an observation scientists think might be because of the effect of a blood-brain barrier preventing drugs reaching the tumour site. However, combined analyses of clinical trial data suggest that treating patients' heads with radiotherapy before they develop any symptoms of brain tumours might slow down the progression of this aspect of the disease. It might even improve survival, which is just 9 months on average for patients with extensive disease.

Guidelines for the treatment of small-cell lung cancer generally recommend that all patients who achieve a complete remission after chemotherapy should undergo cranial irradiation, but how this treatment should be used and what benefits it confers are uncertain. To further elucidate the best use of this treatment in patients who have already responded to chemotherapy, the European Organisation for Research and Treatment of Cancer's Radiation Oncology and Lung Cancer Groups set up a multi-centre, phase 3, randomised trial with the primary objective of investigating whether cranial irradiation could reduce the incidence of symptomatic brain metastases.

Between February 2001 and March 2006, the researchers recruited 286 patients with small-cell lung cancer for their study; all the participants had responded to chemotherapy and had no evidence of brain metastases when they were enrolled. Half of this group was assigned to the intervention arm of the study, and the other half was kept as a control. Investigators at each of the trial's participating centres chose one of five radiotherapy schedules for their patients, and those in the intervention group began radiotherapy 4 to 6 weeks after they had finished chemotherapy.

Patients in both groups were seen by physicians for follow-up consultations at 6 weeks and at 3, 6, 9, and 12 months after the study began. At these meetings, the patients were assessed according to a checklist of key symptoms of brain metastases, including signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurological symptoms. The patients were also given a thorough physical examination and asked to fill in a quality-of-life questionnaire, which showed that cranial irradiation was generally well-tolerated, and the side effects didn't substantially influence patients' perception of their health status.

Analysis of the data was done in October 2006. At that time, brain metastases had been observed in 24 patients in the irradiation group (16.8%) and in 59 of the control group (41.3%). The difference in risk of developing brain metastases at 12 months was statistically significant: 14.6% for the irradiation group and 40.4% for controls. The study also showed that prophylactic radiation had a survival benefit: at 1 year, survival in the irradiation group was 27.1% as compared with 13.3% in the control group.

The authors concluded that even with moderate toxicity, cranial irradiation is associated with improved quality-adjusted life expectancy. "Our study shows a clear advantage of cranial irradiation with respect to the incidence of symptomatic brain metastases," they wrote. However, the question of the optimal dose for cranial irradiation in limited small-cell lung cancer remains unresolved, as does the issue of whether this treatment is appropriate for patients who do not have a complete response to chemotherapy. Nevertheless, the authors recommend that "Prophylactic cranial irradiation should be part of standard care for all patients with small-cell lung cancer who have a response to initial chemotherapy, and it should be part of the standard treatment in future studies involving these patients."

Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer.
Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S, for the EORTC Radiation Oncology Group and Lung Cancer Group.
N Engl J Med 2007; 357: 664-72

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