TY - JOUR
T1 - Optimizing Whole Brain Radiation Therapy Dose and Fractionation
T2 - Results From a Prospective Phase 3 Trial (NCCTG N107C [Alliance]/CEC.3)
AU - Trifiletti, Daniel M.
AU - Ballman, Karla V.
AU - Brown, Paul D.
AU - Anderson, S. Keith
AU - Carrero, Xiomara W.
AU - Cerhan, Jane H.
AU - Whitton, Anthony C.
AU - Greenspoon, Jeffrey
AU - Parney, Ian F.
AU - Laack, Nadia N.
AU - Ashman, Jonathan B.
AU - Bahary, Jean Paul
AU - Hadjipanayis, Costas G.
AU - Urbanic, James J.
AU - Barker, Fred G.
AU - Farace, Elana
AU - Khuntia, Deepak
AU - Giannini, Caterina
AU - Buckner, Jan C.
AU - Galanis, Evanthia
AU - Roberge, David
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821, U10CA180882, and UG1CA189823 (to the Alliance for Clinical Trials in Oncology), U10CA180790, U10CA180867, U10CA180863, (CCTG), and U10CA180868 (NRG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Purpose: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. Methods and Materials: NCCTG N107C [Alliance]/CEC.3 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 in 10 fractions or 37.5 Gy in 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 in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P =.01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P =.66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P =.14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P =.09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P =.18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P =.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.
AB - Purpose: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. Methods and Materials: NCCTG N107C [Alliance]/CEC.3 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 in 10 fractions or 37.5 Gy in 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 in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P =.01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P =.66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P =.14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P =.09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P =.18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P =.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.
UR - http://www.scopus.com/inward/record.url?scp=85076574833&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2019.10.024
DO - 10.1016/j.ijrobp.2019.10.024
M3 - Article
C2 - 31654784
AN - SCOPUS:85076574833
SN - 0360-3016
VL - 106
SP - 255
EP - 260
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -