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24-05-2019 | Small-cell lung cancer | News

Twice-daily radiotherapy may increase brain metastasis risk in SCLC

medwireNews: Marginal survival gains among patients with small-cell lung cancer (SCLC) who receive twice- versus once-daily thoracic radiotherapy (RT) plus prophylactic cranial irradiation occur at the cost of an increased risk for brain metastases, research shows.

Jinming Yu (Shandong Cancer Hospital, China) and colleagues explain that twice daily RT was introduced to clinical practice “decades ago […] based on radiobiological principles.”

However, they believe that their findings indicate that it may now be “time to review real-world experiences and reconsider its value.”

The study included 778 patients (median age 55 years, 74% men) with SCLC who underwent thoracic RT, chemotherapy, and prophylactic cranial irradiation (25 Gy given in 10 fractions once daily) at eight hospitals in China between 2003 and 2016.

Of these, 609 received once-daily thoracic RT at a typical dose of 50–66 Gy delivered in 25–33 fractions, while 169 received twice-daily thoracic RT at a dose of 45 Gy given in 30 fractions.

At 3 years, patients who received twice-daily RT had a significantly higher rate of brain metastases than those who received once-daily treatment, at 26.0% versus 16.9%, resulting in a hazard ratio (HR) of 1.55.

Similar results were observed when the researchers used propensity-score matching to control for confounding by demographic and treatment-related variables.

Specifically, the 3-year rate of brain metastases was 26.0% among the 169 patients who received twice-daily RT and was 14.9% among the 169 matched patients who received once-daily RT, giving a significant HR of 1.71.

Furthermore, subgroup analyses suggested that the difference between the two groups was independent of disease stage and timing of prophylactic cranial irradiation.

In the matched cohort, both median progression-free survival (20.1 vs 18.8 months) and overall survival (47.2 vs 32.8 months) were statistically comparable with once-daily versus twice-daily RT, but the researchers note that the difference for overall survival was of borderline statistical significance.

Writing in JAMA Network Open, Yu and co-authors say their analysis “suggests that [once-daily] RT may be superior to [twice-daily] RT in controlling brain metastases in patients with small cell lung cancer, with multiple unverified, hypothesis-generating underlying mechanisms.”

Once such mechanism “may be related to the impairment of the blood–spinal cord barrier or the blood-brain barrier,” they write, noting that the shorter time interval between fractions with twice-daily RT results in less time for cellular sublethal radiation damage repair. This could then lead to “more severe disruption of the permeability of the thoracic blood–spinal cord barrier [followed by] more transmigration of residual tumor cells.”

The researchers conclude that the study “supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

JAMA Network Open 2019; 2: e190103​​​​​​​

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