Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.
BACKGROUND AND OBJECTIVE
A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed.


METHODS
Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/β = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05.


RESULTS
There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location.


CONCLUSION
This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.
['Garimall|Sidyarth|S|http://orcid.org/0000-0002-3334-2328', 'Shanker|Mihir|M|', 'Johns|Erin|E|', 'Watkins|Trevor|T|', 'Olson|Sarah|S|', 'Huo|Michael|M|', 'Foote|Matthew C|MC|', 'Pinkham|Mark B|MB|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D001932:Brain Neoplasms D003131:Combined Modality Therapy D003399:Craniotomy D005260:Female D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D009364:Neoplasm Recurrence, Local D009369:Neoplasms D019635:Neurosurgical Procedures D010315:Particle Accelerators D011182:Postoperative Care D011379:Prognosis D000069473:Radiation Dose Hypofractionation D011880:Radiotherapy Planning, Computer-Assisted D018714:Radiotherapy, Adjuvant D012189:Retrospective Studies D015996:Survival Rate D055815:Young Adult
Hypofractionated stereotactic radiotherapy Cavity Surgery Brain metastases Postoperative Radiosurgery