Surgically Targeted Radiation Therapy: Safety Profile of Collagen Tile Brachytherapy in 79 Recurrent, Previously Irradiated Intracranial Neoplasms on a Prospective Clinical Trial

Abstract

Purpose: Resection alone is typically insufficient treatment for recurrent previously irradiated intracranial neoplasms yet repeat external beam radiation (EBR)is often not given a second time to avoid causing radiation brain injury (RBE). The clinical impact of not having an effective adjuvant treatment is that practitioners are often reluctant to recommend reoperation, even when potentially beneficial. Combining resection (R)with adjuvant brachytherapy (BT)represents a theoretically attractive therapeutic option for several reasons. However, two of the main concerns hampering the routine use of brain brachytherapy have been a)the high rates of adverse effects (AE), including RBE and wound healing, and b)the added operating room time necessary to implant sources. To overcome these shortcomings, we designed and then prospectively trialed a permanently implanted device that optimizes inter-seed spacing and prevents deleterious direct source-to-brain contact while also functioning as a multi-seed carrier thereby speeding the implant process. Materials and Methods: From 2/13 to 2/18 recurrent previously irradiated intracranial neoplasms were treated on a prospective, single arm, multi-histology study (ClinicalTrials.gov, NCT#03088579). At the completion of maximum safe resection, biocompatible collagen squares (Suturable DuraGen, Integra LifeSciences Corp., Plainsboro, NJ)were imbedded (GammaTile Loader, GT Medical Technologies, Tempe, AZ USA)with Cs 131 sources (Proxcelan, IsoRay Medical, Inc., Richmond, WA)and the Resulting tile brachytherapy (TBT)constructs (see top figure)were permanently implanted in the operative bed under direct visualization. The collagen tiles offset sources 3 mm from brain surface and 10 mm from each other, and were configured to deliver a dose of 120-150 Gy at the resection surface and 60-80 Gy 5 mm deep to the operative bed. No additional local therapy was given without progression. Results: 79 recurrent previously irradiated tumors in 74 patients were treated: 40 high grade gliomas (HGG)(10 grade 3, 30 grade 4), 23 meningiomas (1 grade 1, 20 grade 2, 2 grade 3), 12 metastases (Mets), and 4 “other”. Median age 61 years; 31 females/43 males. Median prior RT dose at implant site 70 Gy, range 16-110 Gy. Average prior same site surgeries were 2, range 0-4. Average seed sources implanted was 22, range 4-72; average mCi per seed 3.5. Median implant D90 was 63Gy, range 54-80 Gy. Average implantation time was 5 minutes. At a median follow-up of 13.4 months (range 1-54.6 mo.), surgical AE’s were wound infection in 2/79 (2.5%), dural closure breakdown requiring surgery in 2/79 (2.5%), and 1 each (1.3%)procedure related hematoma, shunt placement, and coma (full autopsy negative). Symptomatic radiation brain changes at any time during follow up occurred in 6/79 (8%), all treated medically. Ten consented patients had only necrosis at frozen section and were not implanted; this 11% rate of preexisting symptomatic radiation necrosis (10/89)from prior EBR was higher than that seen after R+TBT. The figure below shows examples of collagen tiles (upper)and the observed AE’s by histology (lower). Conclusion: The safety profile observed with R+TBT was excellent, with AE’s at a similar or lower rate than expected. Recently published initial outcomes data from this trial1 and the recently granted FDA clearance suggest this therapy (GammaTileTM)could help expand the treatment options for this difficult cohort of patients. [Figure presented]References: 1. Brachman DG et al. J Neurosurg. 2018 Dec 21:1-10. [Epub ahead of print]