What is your preferred fSRS dose/fractionation for large brain metastases?

For large intact brain metastases, my preferred fSRS dose/fractionation would be 27 Gy in 3 daily fractions. There are retrospective studies showing 1-yr local control rates of 91% using 27 Gy in 3 daily fractions vs 77% using single fraction SRS for large intact brain metastases > 2 cm (Minniti et al., PMID 27209508); and a large, international meta-analysis of 24 trials showed that treatment for large brain metastases with multifraction SRS had similar or better 1-year LC rates compared to sin...

Noting that "large" can be reasonably defined (and is variably reported) by maximal tumor diameter >2 to >3 cm or volume >4 to >15cc, based upon poor LC for current dose single-fx recommendations at these size/volumes (1y LC <50% as per historic RTOG 90-05), as well as subsequent reports demonstrating additional substratification; representative examples:

- MDACC: intact SRS vol </>2cc 1y LC 96% vs 87% (sole RF by MV; HR 4.56)
- Virginia: rsxn cavity </>15 cc 0% vs 27% LF

For large brain metastasis...

Answer from Rupesh Kotecha, MD, and Minesh Mehta MD, Miami Cancer Institute:

For intact brain metastasis, our current prescription approach is based on the maximum tumor diameter (Kotecha & Mehta, PMID 31162052):

a. For lesions < 2.0 cm in size: 24 Gy in 1 fraction

b. For lesions 2.1 – 3.0 cm in size*: 27 Gy in 3 fractions or 15 Gy x 2 fractions with a 4-week inter-fraction interval (18 Gy and 12 Gy is also acceptable)

c. For lesions 3.1 – 4.0 cm in size*: 30 Gy in 5 fractions or 15 Gy x 2 fractions...

In contrast to dosing for single-fraction SRS, there is not consensus for the optimal dosing for multi-fraction SRT. The two most common dose regimens are 9 Gy x 3 or 6 Gy x 5. Retrospective data does seem to indicate a dose-response relationship. For example, the University of Alabama showed better local control for a 5 fraction regimen of 30 Gy vs 25 Gy. An analysis from our institution (University of Maryland) showed a strong trend towards improved local control with a BED10 ≥ 50Gy (Remick et...

This is relatively rare, as most brain mets can be treated with 1-2 sessions to 20 or 25 Gy. With proton fSRS, I have used 3 x 9 Gy as well, and occasionally 4 x 6 Gy for posterior fossa/brain stem metastases, prescribed to the 80% isodose line, and applied without additional range uncertainty for protons beams.