Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience.

PURPOSE: GammaTile® (GT) is a brachytherapy platform that received Federal Drug Administration (FDA) approval as brain tumor therapy in late 2018. Here, we reviewed our institutional experience with GT as treatment for recurrent glioblastomas and characterized dosimetric parameter and associated clinical outcome. METHODS AND MATERIALS: A total of 20 consecutive patients with 21 (n = 21) diagnosis of recurrent glioblastoma underwent resection followed by intraoperative GT implant between 01/2019 and 12/2020. Data on gross tumor volume (GTV), number of GT units implanted, dose coverage for the high-risk clinical target volume (HR-CTV), measured by D90 or dose received by 90% of the HR-CTV, dose to organs at risk, and six months local control were collected. RESULTS: The median D90 to HR-CTV was 56.0 Gy (31.7-98.7 Gy). The brainstem, optic chiasm, ipsilateral optic nerve, and ipsilateral hippocampus median Dmax were 11.2, 5.4, 6.4, and 10.0 Gy, respectively. None of the patients in this study cohort suffered from radiation necrosis or adverse events attributable to the GT. Correlation was found between pre-op GTV, the volume of the resection cavity, and the number of GT units implanted. Of the resection cavities, 7/21 (33%) of the cavity experienced shrinkage, 3/21 (14%) remained stable, and 11/21 (52%) of the cavities expanded on the 3-months post-resection/GT implant MRIs. D90 to HR-CTV was found to be associated with local recurrence at 6-month post GT implant, suggesting a dose response relationship (p = 0.026). The median local recurrence-free survival was 366.5 days (64-1,098 days), and a trend towards improved local recurrence-free survival was seen in patients with D90 to HR-CTV ≥ 56 Gy (p = 0.048). CONCLUSIONS: Our pilot, institutional experience provides clinical outcome, dosimetric considerations, and offer technical guidance in the clinical implementation of GT brachytherapy.

GammaTile® (GT) as a brachytherapy platform for rapidly proliferating glioblastomas: from case series to clinical trials.

PURPOSE: Radiation plays a central role in glioblastoma treatment. Logistics related to coordinating clinic visits, radiation planning, and surgical recovery necessitate delay in radiation delivery from the time of diagnosis. Unimpeded tumor growth occurs during this period, and is associated with poor clinical outcome. Here we provide a pilot experience of GammaTile ® (GT), a collagen tile-embedded Cesium-131 (131Cs) brachytherapy platform for such aggressive tumors. METHODS: We prospectively followed seven consecutive patients (2019-2023) with newly diagnosed (n = 3) or recurrent (n = 4) isocitrate dehydrogenase wild-type glioblastoma that grew > 100% in volume during the 30 days between the time of initial diagnosis/surgery and the radiation planning MRI. These patients underwent re-resection followed by GT placement. RESULTS: There were no surgical complications. One patient developed right hemiparesis prior to re-resection/GT placement and was discharged to rehabilitation, all others were discharged home-with a median hospital stay of 2 days (range: 1-5 days). There was no 30-day mortality and one 30-day readmission (hydrocephalus, requiring ventriculoperitoneal shunting (14%)). With a median follow-up of 347 days (11.6 months), median progression free survival of ≥ 320 days (10.6 months) was achieved for both newly and recurrent glioblastoma patients. The median overall survival (mOS) was 304 and 347 days (10 and 11.5 mo) for recurrent and newly diagnosed glioblastoma patients, respectively. CONCLUSION: Our pilot experience suggests that GT offers favorable local control and safety profile for patients afflicted with rapidly proliferating glioblastomas and lay the foundation for future clinical trial design.

First application of GammaTile cesium-131 brachytherapy with maximal safe resection of a glioma in a patient with limited scleroderma.

The purpose of this report is to present the first documented application of GammaTile to an intra-cranial tumor of a patient with a symptomatic radiosensitive connective tissue disorder, a case where there were significant concerns with standard oncologic strategies. We hypothesized that GammaTile® (GT Medical Technologies, Tempe, Arizona, USA) would also be advantageous in the application of intra-cranial tumors in patients with conditions of increased radiosensitivity. We generated a standard external beam radiation therapy (EBRT) plan consisting of an overall 1.5 cm expansion to 59.4 Gy in 1.8 Gy fractions. Also, we developed a CyberKnife (Accuray, Sunnyvale, CA, USA) plan with a 5 mm expansion on the surgical cavity prescribed to 60 Gy in 30 fractions, to make an EBRT comparison using the same prescription volume as GammaTile. We report the first published application of GammaTile® brachytherapy to an intra-cranial malignancy in a patient with limited scleroderma. The dose delivered by GammaTile was compared to the dose that would be delivered with both typical volumes and small volumes of EBRT. The maximum dose delivered to the scar and scalp by GammaTile was reduced to half of that from other external beam techniques (~25 Gy vs. ~55 Gy). MRI imaging at 6 months and 12 months post-resection demonstrated no evidence of disease recurrence nor radiation necrosis. At the 12-month follow-up visit, the surgical scar was well-healed with no skin changes to the surrounding scalp. Dosimetrically and clinically, this report highlights the successful application of GammaTile to an intra-cranial tumor bed in a patient with scleroderma.

Novel combination of GammaTile cesium-131 brachytherapy with 5-aminolevulinic acid fluorescence-guided resection in the re-irradiation of pediatric recurrent high-grade glioma: illustrative case.

BACKGROUND: Herein, the authors describe the successful utilization of 5-aminolevulinic acid (5-ALA) and the first case of GammaTile cesium-131 therapy in a pediatric patient with recurrent high-grade glioma. 5-ALA was utilized to optimize gross-total resection prior to GammaTile implantation. After conversion to an equivalent dose in 2-Gy fractions (EQD2), a composite was made of the GammaTile dose with the initial external beam radiotherapy. Two hypothetical plans consisting of a standard hypofractionated strategy for glioma reirradiation and a CyberKnife plan using GammaTile's planning target volume were developed and likewise underwent EQD2 conversion and composite plan generation with the initial radiotherapy. OBSERVATIONS: 5-ALA was useful in achieving gross-total resection with no acute toxicity from the surgery or GammaTile irradiation. When compared with the hypothetical composite doses, GammaTile's composite, axium point dose (D0.03cc) to the brainstem was 32.9 Gy less than the hypofractionated and the CyberKnife composite plans at 38.7 Gy and 40.2 Gy, respectively. The right hippocampus demonstrated a substantially reduced composite plan dose with GammaTile with a D0.03cc of 62.4 Gy versus 71.7 and 80.7 Gy for the hypofractionated and CyberKnife composite plans, respectively. LESSONS: Utilization of 5-ALA and GammaTile therapy yielded clinically superior tumor debulking and effective radiotherapy dose localization with sparing of organs at risk, respectively.

GammaTile® (GT) as a brachytherapy platform for rapidly growing brain metastasis.

Background: A subset of brain metastasis (BM) shows rapid recurrence post-initial resection or aggressive tumor growth between interval scans. Here we provide a pilot experience in the treatment of these BM with GammaTile® (GT), a collagen tile-embedded Cesium 131 (131Cs) brachytherapy platform. Methods: We identified ten consecutive patients (2019-2023) with BM that showed either (1) symptomatic recurrence while awaiting post-resection radiosurgery or (2) enlarged by >25% of tumor volume on serial imaging and underwent surgical resection followed by GT placement. Procedural complication, 30-day readmission, local control, and overall survival were assessed. Results: For this cohort of ten BM patients, 3 patients suffered tumor progression while awaiting radiosurgery and 7 showed >25% tumor growth prior to surgery and GT placement. There were no procedural complications or 30-day mortality. All patients were discharged home, with a median hospital stay of 2 days (range: 1-9 days). 4/10 patients experienced symptomatic improvement while the remaining patients showed stable neurologic conditions. With a median follow-up of 186 days (6.2 months, range: 69-452 days), no local recurrence was detected. The median overall survival (mOS) for the newly diagnosed BM was 265 days from the time of GT placement. No patients suffered from adverse radiation effects. Conclusion: Our pilot experience suggests that GT offers favorable local control and safety profile in patients suffering from brain metastases that exhibit aggressive growth patterns and support the future investigation of this treatment paradigm.

Dosimetric Impact of Source Displacement in GammaTile Surgically Targeted Radiation Therapy for Gliomas.

Background This study aims to evaluate dosimetric changes that happened during the first month after GammaTile surgically targeted radiation therapy (STaRT) for gliomas due to Cesium-131 (Cs-131) seed displacement caused by cavity shrinkage in brain brachytherapy. Methodology In this study, 10 glioma patients had 4-11 GammaTiles placed along the resection bed after maximal safe resection during craniotomy. Each GammaTile is composed of four Cs-131 seeds embedded in a biodegradable collagen sponge to minimize seed movement and maintain seed-to-cavity surface distance. The Cs-131 seed positions were identified using VariSeed on day one. On day 30, post-implant computed tomography (CT) images and dosimetry parameters were calculated. An iterative closest point (ICP) algorithm was used to compute rigid transformation between the day one and day 30 seed clouds. The seed displacement was calculated after registration. The volume receiving 100% of the prescription dose (V100), the dose received by 90% of the planning target volume (D90_PTV), the planning target volume receiving 100% of the prescription dose (V100_PTV), and the dose to organs at risk (OARs) were calculated for both CT images to determine the dosimetric changes from any seed displacement. Results The mean seed displacement of 1.8 ± 1.0 mm for all patients was observed between day one and day 30. The maximum seed displacement for each patient ranged from 2.3 mm to 7.3 mm. The mean V100 difference between day one and day 30 was 2.5 cc (range = 0.5-6.5 cc). The mean D90_PTVs were 95.5% (range = 69.0%-131.0%) and 98.1% (range = 19.9%-149.0%) on day one and day 30, respectively. The mean V100_PTVs were 88.4% (range = 81.3%-99.1%) and 87.9% (range = 47.0%-99.7%) on day one and day 30, respectively. On day one, the brainstem dose was 63.5 Gy for one case and 28.1 Gy for another case; while on day 30, the brainstem dose was 55.8 Gy and 20.6 Gy for the same patients, contributing to 7.7 Gy (12.8%) and 7.5 Gy (12.5%) dose reductions to brainstem for these patients, respectively. Only two patients received a dose to the optic nerves (34.1 Gy and 5.2 Gy). There were small changes (1.8 Gy and 0.5 Gy, respectively) in the dose to optic nerves when comparing the dose calculated on day one and the dose calculated on day 30 CT images. The same two patients received 30.4 Gy and 6.8 Gy to the chiasm, respectively. Small changes in the dose to the chiasm (≤1.1 Gy) were noted between day one and day 30. Conclusions A maximum seed displacement of up to 7.3 mm and a mean seed displacement of 1.8 mm caused by cavity shrinkage were observed during the first month after GammaTile STaRT for gliomas. There were noticeable changes in dosimetry parameters. Changes in the doses to OARs, particularly the brainstem, were large (up to 12.8% of the prescription dose). These changes in dosimetry should be considered when evaluating treatment outcomes and planning future GammaTile treatments.

GammaTile: Comprehensive Review of a Novel Radioactive Intraoperative Seed-Loading Device for the Treatment of Brain Tumors.

GammaTile is a Food and Drug Administration (FDA)-licensed device consisting of four cesium-131 (Cs-131) radiation-emitting seeds in the collagen tile about the postage stamp size. The tiles are utilized to line the brain cavity immediately after tumor resection. GammaTile therapy is a surgically targeted radiation therapy (STaRT) that helps provide instant, dose-intense treatment after the completion of resection. The objective of this study is to explore the safety and efficacy of GammaTile surgically targeted radiation therapy for brain tumors. This study also reviews the differences between GammaTile surgically targeted radiation therapy (STaRT) and other traditional treatment options for brain tumors. The electronic database searches utilized in this study include PubMed, Google Scholar, and ScienceDirect. A total of 4,150 articles were identified based on the search strategy. Out of these articles, 900 articles were retrieved. A total of 650 articles were excluded for various reasons, thus retrieving 250 citations. We applied the exclusion and inclusion criteria to these retrieved articles by screening their full text and excluding 180 articles. Therefore, 70 citations were retrieved and included in this comprehensive literature review, as outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram. Based on the findings of this study, GammaTile surgically targeted radiation therapy (STaRT) is safe and effective for treating brain tumors. Similarly, the findings have also shown that the efficacy of GammaTile therapy can be enhanced by combining it with other standard-of-care treatment options/external beam radiation therapy (EBRT). Also, the results show that patients diagnosed with recurrent glioblastoma (GBM) exhibit poor median overall survival because of the possibility of the tumor returning. Therefore, combining STaRT with other standard-of-care treatment options/EBRT can improve the patient's overall survival (OS). GammaTile therapy enhances access to care, guarantees 100% compliance, and eliminates patients' need to travel regularly to hospitals for radiation treatments. Its implementation requires collaboration from various specialties, such as radiation oncology, medical physics, and neurosurgery.

GammaTile® brachytherapy in the treatment of recurrent glioblastomas.

BACKGROUND: GammaTile® (GT) is a recent U.S. Food and Drug Administration (FDA) cleared brachytherapy platform. Here, we report clinical outcomes for recurrent glioblastoma patients after GT treatment following maximal safe resection. METHODS: We prospectively followed twenty-two consecutive Isocitrate Dehydrogenase (IDH) wild-type glioblastoma patients (6 O6-Methylguanine-DNA methyltransferase methylated (MGMTm); sixteen MGMT unmethylated (MGMTu)) who underwent maximal safe resection of recurrent tumor followed by GT placement. RESULTS: The cohort consisted of 14 second and eight third recurrences. In terms of procedural safety, there was one 30-day re-admission (4.5%) for an incisional cerebrospinal fluid leak, which resolved with lumbar drainage. No other wound complications were observed. Six patients (27.2%) declined in Karnofsky Performance Score (KPS) after surgery due to worsening existing deficits. One patient suffered a new-onset seizure postsurgery (4.5%). There was one (4.5%) 30-day mortality from intracranial hemorrhage secondary to heparinization for an ischemic limb. The mean follow-up was 733 days (range 279-1775) from the time of initial diagnosis. Six-month local control (LC6) and twelve-month local control (LC12) were 86 and 81%, respectively. Median progression-free survival (PFS) was comparable for MGMTu and MGMTm patients (~8.0 months). Median overall survival (OS) was 20.0 months for the MGMTu patients and 37.4 months for MGMTm patients. These outcomes compared favorably to data in the published literature and an independent glioblastoma cohort of comparable patients without GT treatment. CONCLUSIONS: This clinical experience supports GT brachytherapy as a treatment option in a multi-modality treatment strategy for recurrent glioblastomas.

Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles.

The prognosis for patients diagnosed with recurrent glioblastoma (GBM) remains poor, with no clear standard of care regarding salvage therapy. Common approaches include chemotherapy, re-resection, tumor treating fields, and reirradiation. However, most studies have shown these to have limited benefits. Reirradiation is particularly difficult due to concern for increased risk of toxicity to surrounding normal brain tissue. A novel intracranial brachytherapy system called GammaTile® (GT Medical Technologies, Tempe, Arizona) involves the placement of Cesium-131 radioactive tiles in the tumor cavity following maximal safe resection. This allows for a highly conformal dose distribution with rapid fall-off to minimize overlap with prior radiation fields and for the application of radiation directly to the high-risk tumor bed. This case report highlights a patient with GBM who survived 11.5 years through multiple recurrences and discusses the many salvage treatments he received, including bevacizumab, irinotecan, and stereotactic radiosurgery (SRS). This case exemplifies that aggressive systemic and local therapies can work well in select patients allowing for long-term survival with a good quality of life. Further efforts should be made to identify which patients may benefit from these therapies. The case study additionally reports on the use of GammaTile therapy. Due to prior external beam radiation therapy and SRS to the treatment site, further external beam radiation options were limited, and the patient was offered GammaTile as local therapy. Although it did not provide a survival benefit in this case due to progressive disease outside of the field of treatment, GammaTile serves as a valuable option in providing local therapy to patients who can no longer receive further radiation. It should be used with careful consideration in lesions characterized by aggressive local invasion.

GammaTile Brachytherapy Combined With External Beam Radiation Therapy for the Treatment of a Partially Resected Secondary Glioblastoma (WHO Grade 4 IDH-Mutant Astrocytoma): Matching External Beam Dose Gradient to Brachytherapy Dose Fall-Off.

Reirradiation of recurrent glioblastomas is most commonly managed with hypofractionated external beam radiation with a modest overall effect. GammaTile, which is a Cesium-131 source embedded in collagen mesh, is an approach that allows the surgical bed of resectable intracranial tumors to receive a greater biological dose than is possible with any form of external beam radiation therapy (EBRT). In this case report, a 28-year-old male presents with a WHO grade 4 isocitrate dehydrogenase (IDH)-mutant astrocytoma (formerly secondary glioblastoma) of the left occipital/parietal lobe after receiving 45 Gy and two cycles of adjuvant temozolomide four years prior for a grade 3 IDH-mutant astrocytoma. The patient proceeded to undergo craniotomy with maximal safe resection and application of GammaTile to a dose of 60 Gy at 5mm depth. Shortly afterward, he developed symptomatic progression of disease in the bilateral splenium and left thalamus/basal ganglia. We irradiated the undertreated residual disease with EBRT to a dose of 35 Gy in 10 fractions without introducing excessive dose to the GammaTile irradiated volume. This was achieved by creating one portion of the planning target volume with a homogeneous dose and another part where the delivered dose decreased with the GammaTile dose buildup. Treatment planning utilized the Gradient Optimization feathering technique with non-coplanar volumetric modulated arc therapy. The resulting composite between the hypofractionated EBRT and GammaTile dose distribution created an approximate dose equivalent of 50 Gy in 2 Gy fractions to the residual disease with no hot spots or areas of under coverage. This is the first report showing the feasibility of combining GammaTile with dose-matched EBRT volumes in a reproducible manner to sub-totally resected, recurrent intracranial neoplasms.

Treating Recurrent Brain Metastases Using GammaTile Brachytherapy: A Case Report and Dosimetric Modeling Method.

One of the treatment options for recurrent brain metastases is surgical resection combined with intracranial brachytherapy. GammaTile® (GT) (GT Medical Technologies, Tempe, Arizona) is a tile-shaped permanent brachytherapy device with cesium 131 (131Cs) seeds embedded within a collagen carrier. We report a case of treating a patient with recurrent brain metastases with GT and demonstrate a dosimetric modeling method.

Surgical Outcomes of Novel Collagen Tile Cesium Brachytherapy for Recurrent Intracranial Tumors at a Tertiary Referral Center.

Treatment for recurrent intracranial neoplasms is often difficult and less standardized. Since its approval by the Food & Drug Administration (FDA), GammaTileTM (GT, GT Medical Technologies, Tempe, AZ), a novel collagen tile cesium brachytherapy, has been investigated for use in this population. This study presents the initial experience with the use of GT for patients with recurrent intracranial neoplasms at a tertiary referral center. A retrospective analysis of all patients with GT implantation from November 2019 to July 2021 was performed. Information regarding demographics, clinical history, imaging data, prior tumor treatment, dosing, surgical complications, and outcomes was collected. Twelve patients were included in this study. Pathologies included gliomas (five patients), meningiomas (five patients), and metastatic tumors (two patients). The median tumor volume treated was 24 cc (IQR: 21.2 - 31.3 cc), and patients had a median of 7.5 tiles implanted (IQR: 5.4 - 10.3). One patient had a delayed epidural hematoma requiring reoperation, which was unrelated to GT implantation. Median follow-up was seven months (IQR: 3 -10), with the longest follow-up time of 20 months. Two patients have had local disease recurrence and three patients have had systemic progression of their disease. Three patients are deceased with survivals of 2.9, 4.8, and 5.8 months. Collagen tile brachytherapy is a safe and viable option for patients with recurrent intracranial tumors. Our data are consistent with early results seen at other institutions. Long-term data with larger patient populations are required to assess efficacy, safety, and indications for the use of this novel technology.

First clinical implementation of GammaTile permanent brain implants after FDA clearance.

PURPOSE: GammaTile cesium-131 (131Cs) permanent brain implant has received Food and Drug Administration (FDA) clearance as a promising treatment for certain brain tumors. Our center was the first institution in the United States after FDA clearance to offer the clinical use of GammaTile brachytherapy outside of a clinical trial. The purpose of this work is to aid the medical physicist and radiation oncologist in implementing this collagen carrier tile brachytherapy (CTBT) program in their practice. METHODS: A total of 23 patients have been treated with GammaTile to date at our center. Treatment planning system (TPS) commissioning was performed by configuring the parameters for the 131Cs (IsoRay Model CS-1, Rev2) source, and doses were validated with the consensus data from the American Association of Physicists in Medicine TG-43U1S2. Implant procedures, dosimetry, postimplant planning, and target delineations were established based on our clinical experience. Radiation safety aspects were evaluated based on exposure rate measurements of implanted patients, as well as body and ring badge measurements. RESULTS: An estimated timeframe of the GammaTile clinical responsibilities for the medical physicist, radiation oncologist, and neurosurgeon is presented. TPS doses were validated with published dose to water for 131Cs. Clinical aspects, including estimation of the number of tiles, treatment planning, dosimetry, and radiation safety considerations, are presented. CONCLUSION: The implementation of the GammaTile program requires collaboration from multiple specialties, including medical physics, radiation oncology, and neurosurgery. This manuscript provides a roadmap for the implementation of this therapy.

Innovation in Brain Tumor Treatment: A Nurse Perspective.

GammaTile is a newer development in brain tumor treatment providing surgically targeted treatment for patients suffering from both primary and recurrent tumors. This article addresses the implementation of this new treatment. The article provides an overview of brain tumors, their diagnosis, and more traditional, widely used treatments. The article discusses implementing a new treatment and the processes involved. It discusses the first patient case for the Columbus, OH area and makes recommendations for future uses of this innovative treatment in other areas of the body.

GammaTile®: Surgically targeted radiation therapy for glioblastomas.

Glioblastoma is the most common primary malignant neoplasm of the central nervous system in adults. Standard of care is resection followed by chemo-radiation therapy. Despite this aggressive approach, >80% of glioblastomas recur in proximity to the resection cavity. Brachytherapy is an attractive strategy for improving local control. GammaTile® is a newly US FDA-cleared device which incorporates 131Cs radiation emitting seeds in a resorbable collagen-based carrier tile for surgically targeted radiation therapy to achieve highly conformal radiation at the time of surgery. Embedding encapsulated 131Cs radiation emitter seeds in collagen-based tiles significantly lowers the technical barriers associated with traditional brachytherapy. In this review, we highlight the potential of surgically targeted radiation therapy and the currently available data for this novel approach.

Evolving Strategies to Potentially Further Optimize Surgical Interventions in Brain Cancer.

PURPOSE OF REVIEW: Provide an overview, the indications for use, and a synopsis of current literature regarding two evolving neurosurgical interventions-GammaTile therapy (GTT) and laser interstitial thermal therapy (LITT). RECENT FINDINGS: GTT delivers immediate, uniform, high-dose radiation with avoidance of direct brain-to-seed contact. Innate properties of the novel carrier system and cesium-131 source may explain lower observed rate of radiation-induced necrosis (RIN) and support use in larger and previously irradiated lesions. LITT delivers focal laser energy to cause heat-generated necrosis. Case series suggest use in difficult-to-access lesions and treatment of RIN. Collaboration among subspecialties and remaining up-to-date on evolving technology is critical in developing individualized treatment plans for patients with brain cancer. While patients should be thoroughly counseled that these interventions are not standard of care, in optimal clinical scenarios, GTT and LITT could extend quantity and quality of life for patients with few remaining options. Prospective studies are needed to establish specific treatment parameters.