Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur

Abstract

Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose

“…In addition, caution should be taken when interpreting Mohammadi et al results due to the potential impact of WBRT and the short median duration of imaging follow-up, which makes a true assessment of LF and RN definition difficult, as RN and LF events usually occur 9-12 months after SRS. 20,[23][24][25] In our study, we analyzed a larger cohort with longer imaging follow-up, and found that pre-WBRT was associated with a lower rate of LF. This is likely due to the fact that the majority of patients received WBRT in combination with SRS (previously the standard of care), meaning that a higher radiation dose was delivered to targeted lesions.…”

“…In the study by Mohammadi et al, 896 patients with 3034 BM ≤2 cm were treated with Gamma Knife SRS with or without WBRT (38%); PD was 24 Gy for 2410 tumors (80%), 19-23 Gy for 408 tumors (13%), and 15-18 Gy for 216 tumors (7%). 18 With 6.2 months of median follow-up, PD 24 Gy to the median isodose line of 56% resulted in significantly decreased rates of LF compared with lower doses (15)(16)(17)(18)(19)(20)(21)(22)(23). Multivariate analysis showed that lesion size >1 cm (P < 0.001), PD <24 Gy (P = 0.01), and no additional radiation (WBRT) (P = 0.001) were independently associated with higher rates of LF.…”

Effect of setup error in the single‐isocenter technique on stereotactic radiosurgery for multiple brain metastases

“…In SRS for brain metastases, the clinical PTV margin has frequently been set by adding 0.1 cm to the GTV diameter to concentrate the high dose on the GTV and minimize the doses to surrounding normal tissue. 8,[23][24][25][26] Herein, the coverage-based margin greater than 0.1 cm is necessary in many of the conditions in this study. In brain SRS on multiple isocenters, a high dose to the brain could cause necrosis by extending the PTV margin.…”

Pseudoprogression of brain tumors

“…This may occur after a median interval of 7 to 11 months, but sometimes after more than 5 years. Radiation necrosis may explain up to half of the lesions that progress radiologically after SRS …”