# Two-Week Interval Hypofractionated Stereotactic Radiosurgery for Benign Intracranial Tumors: Volumetric Kinetics and Radiobiological Rationale

## TL;DR

A two-week interval hypofractionated radiosurgery approach for benign brain tumors shows effective tumor control with minimal side effects.

## Contribution

The study demonstrates that fixed two-week intervals in hypofractionated radiosurgery influence tumor response patterns without compromising outcomes.

## Key findings

- The treatment achieved a 98.4% tumor control rate with acceptable toxicity.
- Tumors showed a median monthly volume reduction of −0.64%.
- Hypofractionated treatment led to earlier and greater volumetric reduction in certain tumor types.

## Abstract

Benign brain tumors often grow slowly but can cause serious problems when they are located near critical structures such as the optic nerves, brainstem, or hearing pathways. Stereotactic radiosurgery is a common non-surgical treatment, but delivering the full radiation dose in a single session may increase the risk of side effects in these sensitive areas. Dividing the treatment into several sessions, called hypofractionated radiosurgery, is therefore increasingly used, yet the best timing between sessions remains unclear. In this study, we evaluated a treatment approach in which radiation was delivered at fixed two-week intervals. We analyzed tumor size changes over time and clinical outcomes in patients with common benign brain tumors. Our findings show that this schedule achieved excellent tumor control with acceptable side effects and produced distinct but predictable patterns of tumor response. These results suggest that the interval between treatment sessions itself is an important factor in optimizing radiosurgery for benign brain tumors.

Background/Objectives: Hypofractionated stereotactic radiosurgery (hfSRS) is increasingly used for benign intracranial tumors that are large or located near critical neural structures to reduce treatment-related toxicity. However, the optimal interval between fractions remains poorly defined, particularly for slowly proliferating benign tumors. This study evaluated clinical outcomes and longitudinal volumetric response patterns following Gamma Knife hfSRS delivered at fixed two-week intervals, with particular attention to the biological relevance of fraction timing. Methods: We retrospectively analyzed 126 patients with benign intracranial tumors, including meningioma, non-functioning pituitary neuroendocrine tumor (PitNET), vestibular schwannoma, and craniopharyngioma, treated between 2016 and 2022. Treatment was delivered in 2–5 fractions at fixed two-week intervals using Gamma Knife radiosurgery. Radiological outcomes included tumor control rate and longitudinal volumetric changes, while clinical outcomes included visual, auditory, and endocrine function. Propensity score matching was performed in PitNET and vestibular schwannoma cohorts to compare hfSRS with single-fraction stereotactic radiosurgery while minimizing baseline imbalances. Results: The overall tumor control rate was 98.4%. Across the entire cohort, tumors demonstrated a median volume reduction of −0.64% per month. In the propensity score–matched PitNET cohort, tumor control was comparable between treatment groups, whereas hfSRS was associated with earlier and greater volumetric reduction over time compared with single-fraction treatment. In the matched vestibular schwannoma cohort, long-term tumor control was similar between groups; however, transient tumor enlargement occurred more frequently after hfSRS without adversely affecting long-term tumor control or functional hearing outcomes. Conclusions: Hypofractionated stereotactic radiosurgery delivered at fixed two-week intervals achieved excellent tumor control with acceptable toxicity in selected benign intracranial tumors. These findings support the clinical feasibility of a fixed two-week inter-fraction interval and suggest that fraction timing may represent a biologically relevant treatment parameter influencing early volumetric response patterns without compromising long-term outcomes.