Higher Risk for Brain Metastases With Twice vs Once Daily Radiotherapy After Irradiation for SCLC

Patients with small-cell lung cancer (SCLC) who received radiotherapy twice daily were more likely to have brain metastases after prophylactic cranial irradiation than those who received radiotherapy once daily, according to a recent study (JAMA Netw Open. 2019;2[5]:e190103).

“Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown,” explained Haiyan Zeng, MD, Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China, and colleagues.

To evaluate the link between TDRT versus once-daily radiotherapy (ODRT) and brain metastases after prophylactic cranial irradiation in patients with SCLC, Dr Zeng et al conducted a multi-center cohort study of 778 patients with SCLC (median age, 55 years) who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation.

Date were collected from the databases of 8 hospitals across China between July 1, 2003, and June 30, 2016, and analyzed from November 1, 2017, to May 31, 2018; the data were later reanalyzed for revision. A 1:1 propensity score matching approach was used to control for confounding factors between the arms receiving ODRT and TDRT; these factors included 8 demographic variables and 8 treatment-related covariates.

Patients in the ODRT arm were given 50 to 66 Gy administered in 25 to 33 fractions. The TDRT arm received 45 Gy administered in 30 fractions. The primary end point of the study was brain metastases, and secondary end points included progression-free survival (PFS) and overall survival (OS).

Overall, 131 patients (16.8%) had brain metastases by a median follow-up of 23.6 months. The 3-year rate of brain metastasis was significantly higher in the TDRT arm versus the ODRT arm (26.0% vs 16.9%, respectively; hazard ratio [HR], 1.55; 95% CI, 1.06-2.26; P = .03).

Among the 338 matched patients (169 in the ODRT arm vs 169 in the TDRT arm), 60 (17.8%) had brain metastases, with a 3-year rate of 14.9% versus 26.0% in the ODRT and TDRT arms, respectively (HR, 1.71; 95% CI, 1.02-2.88; P = .04).

The PFS was revealed to be similar in the whole and matched cohort. The median OS, however, had a tendency to be significantly longer in the ODRT arm than in the TDRT arm after matching (47.2 vs 32.8 months, respectively; HR, 1.41; 95% CI, 0.99-2.01; P = .06).

“In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia,” Dr Zeng and colleagues concluded.—Hina Khaliq