The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study

J Neurosurg 141:461–473, 2024

Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure.

METHODS This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value.

RESULTS The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5–95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6–156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I–IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy 2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness.

CONCLUSIONS BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases

https://doi.org/10.3171/2020.4.JNS201250

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.

METHODS A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.

RESULTS A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).

CONCLUSIONS The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.