Image Guided Intraoperative Radiation Therapy After Surgical Resection of Brain Metastases: A First In-Human Feasibility Report.

Purpose: A correct placement of the applicator during intraoperative radiation therapy for brain metastasis is of paramount importance, to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation because the applicator itself limits the visual range. No image guided verification is currently performed intracranially. We hypothesize that image guided intraoperative radiation therapy would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience. Methods and Materials: Phantom-based measurements were performed to reach the best cone beam computed tomography imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room cone beam computed tomography device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required. Results: An optimal image quality was achieved with 120-kV voltage, 20-mA current, and a tube current time product of 150 mAs. An additional 0.51 mSv patient exposure was calculated for the entire procedure. The wide dynamic range (-600 HU to +600 HU) of cone beam computed tomography and a 27 HU mean computed tomography values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact. Conclusions: This first in-human procedure confirmed the feasibility of kilovoltage image guided intraoperative radiation therapy in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis.

PURPOSE: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT. METHODS: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection. RESULTS: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively). CONCLUSION: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT.