Optimizing whole brain radiotherapy dose and fractionation: Results from a prospective phase III trial (NCCTG N107C (Alliance)/CEC.3)

Daniel M Trifiletti, Karla V Ballman, Paul D Brown, S Keith Anderson, Xiomara W Carrero, Jane H Cerhan, Anthony C Whitton, Jeffrey Greenspoon, Ian F Parney, Nadia N Laack, Jonathan B Ashman, Jean-Paul Bahary, Costas G Hadjipanayis, James J Urbanic, Fred G Barker, Elana Farace, Deepak Khuntia, Caterina Giannini, Jan C Buckner, Evanthia Galanis, David Roberge
International Journal of Radiation Oncology, Biology, Physics 2019 October 22

PURPOSE: Whole brain radiotherapy (WBRT) remains a commonly employed cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits.

METHODS: XXXXX randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy/10 fractions, or 37.5 Gy/15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher's exact tests.

RESULTS: Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy/10 fractions (53%), and 43 were treated with 37.5 Gy/15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology more frequent with protracted WBRT, 72% vs. 45%, p=0.01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy/15 fractions) did not significantly impact time to cognitive failure (hazard ratio, HR=0.91[95%CI: 0.6, 1.39], p=0.66), surgical bed control (HR=0.52 [95%CI: 0.22, 1.25], p=0.14), intracranial tumor control (HR=0.56 [95%CI: 0.28, 1.12], p=0.09), or OS (HR=0.72 [95%CI: 0.45, 1.16], p=0.18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least one grade ≥3 adverse event with 37.5 Gy/15 fractions vs. 30 Gy/10 fractions (54% vs. 31%, respectively, p=0.03).

CONCLUSIONS: This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.


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