Intraoperative, interstitial brachytherapy in newly diagnosed brain metastases through cesium-131 collagen tile implant: A multi-institutional case series

Carlin Chuck; Mazen Taman; Trenton Kite; Alice Lin; Natalie Amaral-Nieves; Elaina Wang; Joseph Oldam; Abigail A Teshome; Hsien-Chung Chen; Rohil Shekher; Sabrina Zeller; Heinrich Elinzano; Sasmit Sarangi; Eric T Wong; Mark Rivard; Clara Ferreira; Simon Hanft; Clark C Chen

doi:10.1093/noajnl/vdag113

. 2026 May 26;8(1):vdag113. doi: 10.1093/noajnl/vdag113

Intraoperative, interstitial brachytherapy in newly diagnosed brain metastases through cesium-131 collagen tile implant: A multi-institutional case series

Carlin Chuck ¹, Mazen Taman ², Trenton Kite ³, Alice Lin ⁴, Natalie Amaral-Nieves ⁵, Elaina Wang ⁶, Joseph Oldam ⁷, Abigail A Teshome ⁸, Hsien-Chung Chen, Rohil Shekher ⁹, Sabrina Zeller ¹⁰, Heinrich Elinzano ¹¹, Sasmit Sarangi ¹², Eric T Wong ¹³, Mark Rivard ^14,¹⁵, Clara Ferreira ¹⁶, Simon Hanft ^17,^†, Clark C Chen ^18,^†,^✉

¹ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

² Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

³ Department of Neurosurgery, Allegheny Health Network Neuroscience Institute, Pittsburgh, PA, USA

⁴ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

⁵ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

⁶ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

⁷ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

⁸ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

⁹ Department of Radiation Oncology, Westchester Medical Center, Valhalla, NY, USA

¹⁰ Department of Neurosurgery, Westchester Medical Center, Valhalla, NY, USA

¹¹ Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA

¹² Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA

¹³ Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA

¹⁴ Department of Radiation Oncology, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

¹⁵ Division of Hematology/Oncology, Department of Medicine and Brown University Health Cancer Institute, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA

¹⁶ Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, USA

¹⁷ Department of Neurosurgery, Westchester Medical Center, Valhalla, NY, USA

¹⁸ Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA

^✉

Corresponding Author: Clark C. Chen, MD, PhD, FAANS, Warren Alpert Medical School of Brown University, APC 7593 Eddy St, Providence, RI 02903, USA (clark_chen@brown.edu).

^†

Simon Hanft and Clark C Chen These authors contributed equally to this work and share senior authorship.

PMCID: PMC13242292 PMID: 42254832

Abstract

Background

Cesium-131 collagen tile has gained traction as an intraoperative brachytherapy platform for recurrent intracranial tumors, but outcome data in newly diagnosed brain metastases (nBM) remain sparse, with fewer than ten cases reported. This study evaluates the safety and efficacy of cesium-131 collagen tiles in nBM patients.

Methods

Clinical information was collected for consecutive nBM patients treated at three neurosurgical centers. Local control and overall survival (OS) were calculated.

Results

The cohort comprised 36 patients (14 men, 22 women; mean age, 62.1 ± 8.9 years) with 39 nBM. Histologies included lung (n = 19), melanoma (n = 8), breast (n = 4), gastrointestinal (n = 3), and genitourinary (n = 5) metastases. The mean pre-operative tumor diameter was 3.29 ± 1.35 cm. Gross total resection was achieved in all but one case. Mean Karnofsky Performance Score (KPS) before resection/tile implant was 81 ± 11.1. The average hospital stay was 2.2 ± 1.6 days. Thirty-day and 90-day readmission rates were 25.0% and 19.4%, respectively; there were no unplanned returns to the operating room. With a median follow-up of 328 days, one-year actuarial local control was 100%, with one recurrence at two years. Median overall survival (OS) was 182 days. Radiation necrosis was observed in one patient (2.6%). KPS improved or remained stable in 28 patients (77.8%) and declined in 8 (22.2%). A decline in KPS at one month post-procedure was associated with shorter OS (65 vs. 211 days; P = .02).

Conclusion

This multi-institutional study provides the first dedicated evaluation of cesium-131 collagen tiles for the treatment of nBM, demonstrating excellent safety and local control.

Keywords: brain metastases, cesium-131, collagen tile implant, intraoperative brachytherapy, local control

Key Points.

First multi-institutional series of nBM treated with Cs-131 collagen tiles.
One-year local control 100% with 2.6% radionecrosis and no unplanned return to the operating room.
Shorter overall survival was seen in patients showing KPS decline one month post-procedure.

Importance of the Study

Evidence for intraoperative Cs-131 collagen tile brachytherapy in newly diagnosed brain metastases has been limited. This multi-institutional series of 39 lesions provides the first focused assessment, demonstrating excellent 1-year local control (100%) and a low incidence of radionecrosis (2.6%), despite enrichment of BMs with maximal diameters > 3 cm. Karnofsky Performance Status (KPS) was preserved in 73% of the treated patients. KPS decline at 1 month post-procedure was associated with shorter survival. These results support the feasibility, safety, and efficacy of intraoperative Cs-131 brachytherapy and lay the foundation for future studies.

Brain metastases (BM) represent a severe and often debilitating sequalae of systemic malignancy, affecting 20%-40% of cancer patients.¹ BM can profoundly affect the quality of life through cognitive decline, neurologic deficits, seizures, and emotional distress.² Historically, clinical management of BM was shaped by a nihilistic outlook, driven by poor prognostication.³ However, advances in systemic therapy, including targeted therapies,⁴^,⁵ immunotherapies,⁶^,⁷ and antibody-drug conjugates,⁸ have significantly extended survival and improved systemic control.⁹ In the context of improved extracranial disease management, local control of BM has become increasingly vital, not only to improve survival but also to preserve quality of life for affected patients.¹⁰

For BMs presenting with mass effect or causing neurological deficit, surgical resection followed by radiosurgery of the resection cavity remains the cornerstone of oncologic management.¹¹ While local control achieved with this paradigm is excellent for BM < 2.5 cm, > 40% of lesions > 2.5 cm recur locally after treatment.¹²^,¹³ Additionally, up to a third of BM patients do not receive postoperative radiosurgery or undergo delayed radiosurgery—contributing to increased risk of local recurrence.¹⁴ Finally, post-operative radiation treatment of the resection cavity requires additional hospital visits, which impose emotional and physical stress on patients already navigating complex oncologic care.¹⁵^,¹⁶

Intraoperative placement of interstitial brachytherapy at the time of surgical resection offers a compelling solution to many of the limitations of the current care paradigm for BM, including avoiding delays associated with postoperative radiosurgery.¹⁷ GammaTile (GT, GT Medical Technologies, Tempe, AZ, USA) is a recently FDA-cleared intracranial brachytherapy platform consisting of a postage-stamp-sized collagen tile unit embedded with regularly spaced cesium-131 (Cs-131) seeds.¹⁸ The pliable collagen matrix mimics the properties of Gelfoam (Pfizer Inc., NY), a hemostatic agent familiar to most neurosurgeons.¹⁹^,²⁰ This familiarity reduces the learning curve and facilitates integration into standard neurosurgical procedures.¹⁹^,²⁰ Moreover, the collagen matrix maintains uniform seed spacing during the time of most intense radiation delivery,²¹^,²² thereby minimizing the risk of radiation necrosis. Finally, because of rapid dose fall-off, GT enables the safe delivery of a higher radiation dose to the resection cavity, surpassing what can be safely achieved with external radiation.^23-25

Since receiving FDA clearance in 2018 for the treatment of malignant brain tumors,²⁶ Cs-131 collagen tiles have undergone rapid clinical adoption.²⁰ However, there is limited data on its effectiveness in patients with newly diagnosed BM (nBM). The available literature comprised case series with a mix of nBMs and recurrent BMs, with < 10 nBMs reported.²²^,²⁷ We present this multi-institutional case series of 39 consecutive nBM (in 36 patients) treated with maximal safe resection and implanted with Cs-131 tiles to address this knowledge gap.

Methods

Study Population

The study was conducted under IRB 00010486 and Data Use Agreements between participating institutions. Data were retrospectively collected from consecutive newly diagnosed BM (nBM) patients who fulfilled the following eligibility criteria: (1) underwent maximal safe resection and Cs-131 tile implant between 2020 and 2024, (2) age ≥18 years old, and (3) final pathology confirmed diagnosis of BM. The decision to proceed with surgery and Cs-131 tile implant was reviewed by a multidisciplinary brain tumor board that included members of the neurosurgery, neuro-oncology, radiation oncology, neuroradiology, and neuropathology teams. Consideration for cesium brachytherapy during the multidisciplinary discussion included the poor control rates for tumors larger than 2.5 cm,²⁸ eliminating the need for hospital visits for post-operative radiosurgery,¹⁵^,¹⁶ and the shorter time to initiation of systemic therapy.¹⁴ The neurosurgeon consented for the surgical procedure, while consent for Cs-131 tile implant was obtained separately by the radiation oncologist. Data collected included: patient age, sex, diagnosis, Karnofsky Performance Score (KPS), symptoms at presentation, tumor location, length of hospital stay, extent of resection, procedural complications, duration of follow-up, 30-day readmission, overall survival (OS, measured from the time of Cs-131 tiles placement), and radiology findings. The primary endpoint of the study was actuarial local control. The secondary endpoints included: overall survival, radiation necrosis rate, hospital stay, peri-operative KPS, 30/90-day readmission, and return to the operating room during the study period. All data were de-identified before analysis.

Surgical Resection and Cs-131 Tiles Implant

The number of Cs-131 tiles required was calculated using a surface-area calculator that accounted for the metastasis dimensions, the percent surface area at risk, and the estimated cavity contraction after resection. Tile transfer, surgical technique, and Cs-131 tile implant followed a multidisciplinary workflow, as previously described.¹⁹^,²⁰ In brief, the medical physicist transported the Cs-131 tiles in radiation-shielded trays to the operating suite. With the assistance of the participating radiation oncologist, the tiles were unpacked, transferred into sterile metallic trays, and hydrated with normal saline. The neurosurgeon then positioned the hydrated tiles within the resection cavity. Radiation safety assessments were performed both before and after the implant to ensure regulatory compliance. Following cesium tile implantation, the patient completed a four-day dexamethasone taper and then discontinued the medication. No additional radiation therapy was administered to the resection cavity beyond cesium brachytherapy. Postoperative follow-up included a surgical visit at 2-4 weeks, with subsequent evaluations at 2-3 month intervals.

Clinical and Imaging Collection

MRIs were acquired on 1.5T or 3T scanners using T1, T2, fluid-attenuated inversion recovery (FLAIR), T1 with gadolinium sequences (1 mm slice), and dynamic susceptibility contrast (DSC). Gross versus subtotal resection was determined based on the clinical radiology report. The FLAIR sequence was used for evaluating surgical margins. Local failure was defined as new contrast enhancement within 1 cm of the treated cavity that exceeded expected postoperative changes. Radiation necrosis was defined as postoperative enhancement exceeding 1 cm³ or increased FLAIR signal intensity, no elevation in cerebral blood volume, and without radiographic evidence of viable tumor recurrence as determined by blinded neuroradiologist review. Cases of local failure or radiation necrosis were additionally reviewed by and confirmed by the co-senior authors (SH and CCC).

Statistical Analysis

Descriptive statistics for surgical parameters and cohort-level overall survival were computed in R (v4.1.2; R Core Team 2021), and survival curves were generated using the Kaplan-Meier method.

Results

Patient Characteristics

The demographics of the 36 nBM patients (with 39 nBM lesions) who underwent surgical resection and Cs-131 tile implant are shown in Table 1. Three patients in this cohort (patients 5, 10, and 15) underwent resection of two nBM, with Cs-131 tiles implanted at both resection sites. The male:female ratio was 0.63:1, including 14 men and 22 women. The mean cohort age was 62.1 years (± 8.9 years). The primary cancer histology included: 19 lung, 8 melanoma, 4 breast, 3 gastrointestinal, and 5 genitourinary cancers. The nBMs were predominantly supratentorial (n = 32, 88.9%), and the mean pre-operative diameter of the nBM was 3.29 cm (±1.35 cm). The size distribution of 39 nBM is shown in Figure 1A, binned into ≤ 1, ≤ 2, ≤ 3, ≤ 4, ≤ 5, and ≤ 6 cm. Figure 1B shows the size distribution for each patient. Of the 39 nBM, only 7 were ≤ 2 cm in maximal diameter, and the majority was larger than this threshold. >50% were 3 cm or greater in maximal diameter. Thus, the majority of resection cavities in this series are large and are less likely to achieve durable local control with post-operative SRS. The average KPS before resection/Cs-131 tile implant was 81 ± 11.1 (range: 60-100).

Table 1.

Basic demographics

	Total (N = 36)
Age, mean (SD), years	62.1 (8.9)
Female sex, n (%)	22 (61.1%)
Primary cancer diagnosis
- Breast	4 (11.1%)
- Colon	2 (5.6%)
- Esophageal	1 (2.8%)
- Lung	19 (52.8%)
- Melanoma	6 (16.7%)
- Renal	1 (2.8%)
- Urothelial	1 (2.8%)
- Vulvar SCC	1 (2.8%)
- Sex Cord-Stromal	1 (2.8%)
Intracranial metastasis burden
- Solitary	17 (47.2%)
- Dominant/oligometastatic	15 (41.7%)
- Diffuse metastatic disease	4 (11.1%)
Location
- Supratentorial	32 (88.9%)
- Infratentorial	4 (11.1%)
Maximum tumor diameter, median [IQR], cm	3, [2, 4]

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For image description, please refer to the figure legend and surrounding text. — (A) Size distribution of the nBM within the cohort, with each nBM on the x-axis (labeled 1-39) and largest diameter (in cm) on the y-axis. (B) Histogram with largest diameter (in cm) on the x-axis, going from 0-1 cm to 5-6 cm (the largest grouping of the cohort), and number of nBM on the y-axis.

Illustrative Case 1: Tumor Control

Patient 36 is a 59-year-old female who presented with a 6-week history of progressive confusion and mixed aphasia. CT of the brain showed a 4.7 × 4.4 × 6.5 cm left temporal mass with significant mass effect (Figure 2A). Chest CT showed a 1.9 × 1.8 cm left upper lobe spiculated lung mass. Because of a spinal cord stimulator implant, the patient was not cleared for an MRI. The patient underwent a gross total resection of the lesion and Cs-131 tile placement (Figure 2B and C), without complications. The patient’s neurologic examination showed significant improvement postoperatively. She was discharged to rehabilitation on post-operative day three. Final pathology revealed metastatic lung adenocarcinoma. The spinal cord stimulator was subsequently determined to be MRI safe. A brain MRI performed one year after the procedure showed excellent local control, with resolution of the peri-lesional FLAIR abnormality (Figure 2D).

MR Images of a patient with local control one year after cesium tile placement. — Illustrative example of local control achieved with Cesium-131 (Cs-131) collagen tile implant. (A) Presenting head CT (axial, sagittal, and coronal) of patient 36 with a left temporal brain metastasis. (B) Post-operative brain MRI (axial, sagittal, coronal, and FLAIR) after a gross total resection and Cs-131 tile implant. (C) Radiation dosimetry (color-coded numbers represent isodoses in gray = Gy). (D) One-year follow-up MRI (axial, sagittal, coronal, and FLAIR) without evidence of local recurrence.

Illustrative Case 2: Tumor Progression

Patient 26 is a 73-year-old female who presented with a brain MRI that showed a 4.2 × 5.7 × 6.7 cm right occipital mass with significant mass effect (Figure 3A). The patient underwent an uneventful gross total resection of the lesion and Cs-131 tile placement (Figure 3B and C). Final pathology revealed findings consistent with metastatic lung carcinoma. The patient’s neurologic examination remained stable post-procedure, and the patient was discharged to rehabilitation on post-operative day five. A surveillance brain MRI performed a year after the procedure showed excellent local control, with resolution of the peri-lesional FLAIR abnormality (Figure 3D). However, a surveillance MRI performed 24 months later revealed a new, contrast-enhancing mass within a centimeter of the previous resection cavity (Figure 3E), indicating local recurrence.

MR images of a patient who suffered local progression two years after cesium tile placement. — Illustrative example of local recurrence that occurred two years after Cesium-131 (Cs-131) collagen tile implant. (A) Presenting head MRI (axial and sagittal) of patient 26 with a right occipital brain metastasis. (B) Post-operative brain MRI (axial and sagittal) after a gross total resection and Cs-131 tile implant. (C) Radiation dosimetry (color-coded numbers represent isodoses in centigray = cGy). (D) One-year follow-up MRI (axial and sagittal) without evidence of local recurrence. (E) Two-year follow-up MRI (axial and sagittal) revealed a new, contrast-enhancing mass within a centimeter of the previous resection cavity.

Illustrative Case 3: Adverse Radiation Effect

A 62-year-old female whose past medical history is notable for sex cord stromal tumor presented with a two-week history of progressive expressive aphasia. MRI of the brain showed a 4.7 × 3.7 × 4.6 cm left temporal mass with significant mass effect (Figure 4A). The patient underwent a gross total resection of the lesion and Cs-131 tile placement (Figure 4B). The patient’s neurologic examination showed significant improvement postoperatively, and the patient was discharged home on postoperative day 3. Final pathology revealed metastatic carcinoma, consistent with sex cord stromal tumor metastasis. The patient presented 3 months post-procedure with a new-onset seizure and recurrent aphasia. The brain MRI during this presentation revealed a new FLAIR abnormality involving approximately a quarter of the cerebrum, without any new contrast enhancement (Figure 4C).²⁹ Perfusion imaging was used to evaluate the MR changes and demonstrated no increase in perfusion. The patient was treated with corticosteroids without a definitive tissue diagnosis after review at the multidisciplinary tumor board. The patient’s symptoms improved, and an MRI obtained one month after corticosteroid treatment showed a significant reduction in FLAIR volume (Figure 4D), with sustained clinical and radiographic stability following steroid discontinuation.

MR images of a patient who suffered adverse radiation effect after cesium tile placement. — Illustrative example of radiation necrosis that occurred after Cesium-131 (Cs-131) collagen tile implant. (A) Presenting head MRI (axial and sagittal) of patient 25 with a left temporal brain metastasis. (B) Post-operative brain MRI (axial and sagittal) after a gross total resection and Cs-131 tile implant and radiation dosimetry (color-coded). (C) MRI (axial and sagittal) taken three months after implant as workup for new-onset seizure and recurrent aphasia. (D) MRI (axial and sagittal) taken a month after initiation of corticosteroid treatment.

Surgical Outcome, Hospital Course, and Readmission

Gross total resection was achieved in 35 of the 36 patients in this cohort (97.2%) (Table 2). Despite a subtotal resection in subject 29, the residual tumor was fully covered by the 60‑Gy isodose, and brachytherapy achieved sustained local control through 216 days, when the patient ultimately passed from systemic disease progression. The median hospital length of stay was 2.2 days (± 1.6 days). There was no 30-day mortality. There were nine 30-day readmissions (25.0%), including wound infection (n = 1), seizure (n = 4), neurologic decline (n = 2), medical decline (n = 1), and fall (n = 1). There were seven 90-day readmissions (19.4%) due to seizure (n = 1), fall (n = 2), pneumothorax from a lung biopsy (n = 1), and medical decline (n = 3). There were no other hospital-acquired conditions (HACs). There were no unplanned returns to the operating room during the study period. The one case of wound infection was successfully treated with systemic antibiotics.

Table 2.

Surgical characteristics

	Total (N = 36)
Gross total or subtotal resection
- GTR	35 (97.2%)
- STR	1 (2.8%)
Preoperative KPS, median [IQR]	80 [70, 90]
Postoperative KPS, median [IQR]	85 [70, 90]
KPS change from Surgery median [IQR]	0 [0, 2.5]
3-month KPS (among survivors) median [IQR]	70 [55, 90]
30-day readmission	9 (25%)
90-day readmission	7 (19.4%)
Follow-up duration, mean (SD), days	328 (320)
Radiation necrosis, n (%)	1 (2.8%)
Overall survival, median [IQR]	182 [82, 285]
Survival at follow-up, n (%)	12 (33%)

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In terms of functional status, the mean preoperative KPS was 81.1 (± 11.0, range: 60-100, Table 2). At the one-month follow-up, the mean KPS was 81.1 (± 13.5, range 60-100). KPS improved in 10 patients (27.7%), remained stable in 19 patients (52.7%), and declined in 8 patients (22.2%). KPS at 3 months after Cs-131 tile implant was available for 26 patients. The mean 3-month KPS was 82.2 (± 13.7, range: 60-100, Table 2). Compared with the pre-resection/Cs-131 tile implant, KPS improved in 9 patients (34.6%), remained stable in 10 patients (38.5%), and declined in 7 patients (26.9%).

Local Control and Overall Survival

At a median follow-up of 328 days, the 1-year actuarial local control rate was 100%, with one local failure two years post-Cs-131 tile implant. The median OS for the cohort was 182 days [inter-quartile range (IQR): 83-285], with 12 patients (33%) alive at the time of last follow-up (Figure 5). The median OS was less than the actuarial local control, as many deaths were attributable to systemic disease progression. Preoperative KPS was not significantly associated with OS (77 vs. 199 days, P = .232).

Kaplan-Meier survival of cesium tile treated brain metastasis patients. — Kaplan-Meier curve of overall survival of brain metastasis cohort.

Association Between Overall Survival and KPS

Although KPS is not typically used to represent a patient’s overall clinical condition, it serves as a reasonable proxy, as it reliably reflects functional status and has demonstrated prognostic value in cancer patients.³⁰ In our analysis, KPS was dichotomized at 70 because this threshold marks the point at which patients remain functionally independent, distinguishing them from those who require assistance.³¹ This cutoff is commonly used in oncology studies to stratify patients by clinical performance and prognosis.

When divided into patients with KPS ≥70 versus <70, there were no differences in OS of the nBM patient based on pre-operative KPS (median [IQR] 192 [100.5, 427] vs. 82.5 [66, 131.8], P = .33, Figure 6A), 1-month post-surgery/Cs-131 tile implant KPS (median [IQR] 205 [158, 547] vs. 67.5, [56, 85], P = .082, Figure 6B), or three-month post-surgery/Cs-131 tile implant KPS (median [IQR] 263 [205, 723] vs. 146.5 [130, 165], P = .17, Figure 6C). However, a KPS decline of 20 points one month after resection/Cs-131 tile implant was associated with shorter OS. The OS for nBM patients with stable or improved KPS one month post-resection/Cs-131 tiles implant was 210.5 days [IQR: 162-343]. In contrast, the OS for nBM patients whose KPS declined 20 points one month post-procedure was 68 days [IQR: 58-70] (P = .018) (Figure 6D).

Discussion

By permitting radiation to commence intraoperatively and eliminating the standard postoperative delay associated with post-operative resection cavity radiosurgery, cesium brachytherapy offers a distinct therapeutic advantage. However, there is limited data available for Cs‑131 tiles in nBM, our study provides the first estimates of their safety and efficacy in this context. In this cohort of 39 nBM managed with maximal safe resection followed by Cs-131 tile implantation, the treatment demonstrated a highly favorable safety profile and excellent local control, the study’s primary endpoint. With a median follow-up of 328 days, the actuarial one-year local control was 100%, with one case of radiation necrosis (2.6%). This local control is noteworthy in the context of the larger BM treated in this study, with a mean diameter of 3.29 cm (±1.35 cm). For the study’s secondary endpoints, the mean hospital stay was 2.2 ± 1.6 days. The 30-day readmission rate of 22% was comparable to that reported in published literature for craniotomy alone for tumor resection (without Cs-131 tile implant).³² There were no unplanned returns to the operating room. The median OS of the cohort was 182 days.

To evaluate the findings of Cs-131 tiles relative to prior studies of suture-stranded Cs-131 seed implants, we reviewed the literature and identified seven relevant articles, though only two specifically addressed nBM—both articles authored by the same group of investigators. Wernicke et al initially reported the outcomes of a phase I/II study of 24 newly diagnosed BM patients who underwent resection and suture-stranded Cs-131 seed implants.³³ Subsequently, the authors enrolled additional patients and reported clinical outcomes for a total cohort of 42 patients.³⁴ The mean pre-operative diameter of BM was 3.0 cm (range 2.0-6.8 cm). With a median follow-up of 11.9 months, the local control and radiation necrosis rate remained 100% and 0%, respectively. There were three superficial wound infections and one intracranial abscess. These suture-stranded Cs-131 seed implant findings are comparable to our results for Cs-131 tiles.

To assess the efficacy and safety profile of Cs-131 tiles in nBM relative to those reported in the recurrent BM, we compared our findings to the three peer-reviewed articles identified in the literature. Imber et al reported 24 patients with BM that recurred after radiosurgery who underwent surgical resection and Cs-131 tile implant.²⁴ There was one postoperative wound dehiscence. With a median follow-up of 1.6 years, one-year local control was 91.6% (which is comparable to that reported in the current study). The symptomatic radiation necrosis rate was 17%. A second study by Kutuk et al reported 100% one-year local control and 8.3% radiation necrosis in a series of 12 patients with BM that recurred after radiosurgery who underwent resection and Cs-131 tile implant (median follow-up of 14.5 months).³⁵ A third study by Beckham et al reported on 31 patients with recurrent BM who underwent resection and Cs-131 tile implantation.³⁶ The series reported an 87% 1-year local control rate and an 8% risk of radionecrosis, with a median follow-up of 11.8 months. Collectively, these studies suggest excellent local control and acceptable risks of radiation necrosis; patient-specific outcomes with Cs-131 tiles in BM that recurred after radiosurgery likely depend on a complex interplay of tumor biology, cumulative radiation exposure, and extent of surgical resection.³⁷^,³⁸

Given the large nBMs treated in this study (mean maximal diameter of 3.29 cm, with 75% > 2.5 cm), the one-year actuarial local control of 100% compares quite favorably to local recurrence rates up to 40% following resection and radiosurgery to the resection cavity of nBM.³⁹ This finding is consistent with a matched-pair analysis of clinical outcomes after suture-stranded Cs-131 seed versus radiosurgery for resected BM.⁴⁰ The study compared the clinical outcome of 30 BM patients who underwent Cs-131 brachytherapy relative to 60 retrospectively identified control patients who underwent radiosurgery, selected to match brachytherapy-treated patients in a 2:1 ratio according to tumor histology, size, patient performance status, and recursive partitioning analysis class. The local control rates for the brachytherapy and radiosurgery cohorts were 90% and 71.7%, respectively (P = .049). Radiation necrosis rates (3.3% and 10%) and surgical complication rates (6.6% and 8.4%) were comparable between groups. These findings support the general principle that brachytherapy, relative to post-resection cavity radiosurgery, circumvents delays in radiation initiation and permits intensified radiation dosing directly to the tumor bed.

While KPS is not generally considered a comprehensive measure of a patient’s clinical state, it remains a practical surrogate, as it consistently captures functional capacity and has proven prognostic relevance in neuro-oncology.³⁰ The observed association between survival and KPS offers insights into patient selection and surgical considerations. A KPS of 60 is a reasonable selection cutoff for bBM, as all patients in this series had KPS >60 and demonstrated reasonable survival and clinical outcomes. The observation that 34.6% of the nBM patients in this case series showed improved KPS after surgical resection suggests that the initial KPS may be confounded by mass effect or deficits attributable to the BM.⁴¹ The finding that patients whose KPS declined after the resection showed shorter OS (P = .018) underscores the importance of the “safe” in maximal safe resection. The finding further underscores the vulnerability of this patient population, as deterioration in functional status may preclude eligibility for subsequent systemic therapy.

The observation that local control was achieved with Cs-131 tile implant in patient three, despite subtotal resection, merits further discussion. A similar observation was previously reported in a case where gross total resection was precluded due to firm adherence of the BM to a prominent cortical vein.¹⁹ Nevertheless, this patient achieved 1-year local control with the placement of Cs-131 tiles adjacent to the residual tumor. These two examples suggest that Cs-131 tiles offer a sound strategy for enhancing local control in subtotally resected BM. Of note, Cs-131 tiles are unlikely to be effective against residual tumor burden extending beyond their dosimetric reach,²⁶ underscoring the need to pursue maximal safe resection even when brachytherapy is considered.

While our study offers a glimpse into the safety and efficacy of Cs-131 brachytherapy as a therapeutic platform for nBM, the study suffers from inherent limitations associated with a retrospective case series, including selection bias, temporal bias, observer bias, lack of control populations, and influence of uncontrolled confounding variables (e.g. intra- and inter-tumoral heterogeneity).⁴² For example, the study cohort is enriched for nBM lesions exceeding 2.5 cm in maximal diameter, thereby selecting for tumors with a higher likelihood of recurrence. The actuarial 1-year control of 100% is impressive in this context. The inclusion of 39 nBM of different tumor histologies also limits our study. However, our sample size remains within the accepted standards for early-phase safety and efficacy assessments. Moreover, the results reported are consistent with those reported for suture-stranded Cs-131 implants.^43–45 The inclusion of clinical experience from highly specialized practices across three academic centers also limits the generalizability of the study’s results. Additionally, the median follow-up of 328 days is likely insufficient to evaluate late radiation effects. That said, the follow-up duration aligns with the expected survival of nBM patients across the histologies included in this study.⁴⁶ Finally, the absence of a definitive tissue diagnosis in one case of radiation necrosis limits interpretation of the data; however, the clinical course strongly supports the diagnosis of radiation necrosis. While our findings require validation in larger, prospective cohorts, this study establishes a foundational framework to inform the design and methodology of these future confirmatory trials.

Conclusions

In this first dedicated multi-institutional series of newly diagnosed brain metastases managed with maximal safe resection and Cs-131 collagen tile implant, we observed excellent local control, a low incidence of adverse radiation effects, and excellent functional preservation.

Contributor Information

Carlin Chuck, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Mazen Taman, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Trenton Kite, Department of Neurosurgery, Allegheny Health Network Neuroscience Institute, Pittsburgh, PA, USA.

Alice Lin, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Natalie Amaral-Nieves, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Elaina Wang, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Joseph Oldam, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Abigail A Teshome, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Rohil Shekher, Department of Radiation Oncology, Westchester Medical Center, Valhalla, NY, USA.

Sabrina Zeller, Department of Neurosurgery, Westchester Medical Center, Valhalla, NY, USA.

Heinrich Elinzano, Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Sasmit Sarangi, Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Eric T Wong, Department of Neurology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Mark Rivard, Department of Radiation Oncology, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA; Division of Hematology/Oncology, Department of Medicine and Brown University Health Cancer Institute, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Clara Ferreira, Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, USA.

Simon Hanft, Department of Neurosurgery, Westchester Medical Center, Valhalla, NY, USA.

Clark C Chen, Department of Neurosurgery, Warren Alpert School of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.

Conflict of Interest Statement

Clara Ferreira, Clark C. Chen, and Simon Hanft are consultants for GT Medical Technologies (GammaTile). All other authors declare no conflicts of interest.

Author Contributions

Conceptualization: CC, SH, CCC, CF; Methodology: CC, MT, MR, CF, SH, CCC; Formal analysis: CC, MT, AAT; Investigation: CC, MT, TK, AL, NAN, EW, JO, AAT, HCC, RS, SZ, HE, SS, ETW, MR, CF, SH, CCC; Data curation: MT, CC, TK, AL, NAN, EW, JO, AAT, HCC, RS, SZ; Writing—original draft: CC, MT, AAT; Writing—review & editing: CC, MT, TK, AL, NAN, EW, JO, AAT, HCC, RS, SZ, HE, SS, ETW, MR, CF, SH, CCC; Visualization: MT, CC, SH, CCC; Supervision: HE, SS, ETW, MR, CF, SH, CCC; Project administration: CC, SH, CCC.

Funding

None declared.

Ethics Approval Statement

This study was approved by the Institutional Review Boards of all participating institutions under protocol IRB 00010486, with data-sharing governed by executed Data Use Agreements. All patient data were retrospectively collected and de-identified prior to analysis. For all prospectively treated patients, informed consent for surgical resection and for cesium-131 tile implantation was obtained separately in accordance with the Declaration of Helsinki.

Data Availability

De-identified data underlying this study are available from the corresponding author upon reasonable request, in accordance with institutional data-sharing policies and IRB requirements.

References

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26. Zhang S, Patel K, Dusenbery K, et al. Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience. J Neurooncol. 2024;169:11-23. 10.1007/s11060-024-04631-4 [DOI] [PubMed] [Google Scholar]
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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

De-identified data underlying this study are available from the corresponding author upon reasonable request, in accordance with institutional data-sharing policies and IRB requirements.

[vdag113-B1] 1. Xu K, Wang H, Zou YX, et al. Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer. Clin Transl Med. 2024;14:e1605. 10.1002/ctm2.1605 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B2] 2. Walbert T, Stec NE. Palliative care in brain tumors. Handb Clin Neurol. 2023;191:69-80. 10.1016/B978-0-12-824535-4.00011-2 [DOI] [PubMed] [Google Scholar]

[vdag113-B3] 3. Ivanova M, Porta FM, Giugliano F, et al. Breast cancer with brain metastasis: molecular insights and clinical management. Genes (Basel). 2023;14:1160. 10.3390/genes14061160 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B4] 4. Raghavendra AS, Ibrahim NK. Breast cancer brain metastasis: a comprehensive review. JCO Oncol Pract. 2024;20:1348-1359. 10.1200/OP.23.00794 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B5] 5. Bailleux C, Eberst L, Bachelot T. Treatment strategies for breast cancer brain metastases. Br J Cancer. 2021;124:142-155. 10.1038/s41416-020-01175-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B6] 6. Rodriguez-Baena FJ, Marquez-Galera A, Ballesteros-Martinez P, et al. Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases. Cancer Cell. 2025;43:413-427.e9. 10.1016/j.ccell.2025.01.008 [DOI] [PubMed] [Google Scholar]

[vdag113-B7] 7. Rishi A, Yu HHM. Current treatment of melanoma brain metastasis. Curr Treat Options Oncol. 2020;21:45. 10.1007/s11864-020-00733-z [DOI] [PubMed] [Google Scholar]

[vdag113-B8] 8. Mair MJ, Bartsch R, Le Rhun E, et al. Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours. Nat Rev Clin Oncol. 2023;20:372-389. 10.1038/s41571-023-00756-z [DOI] [PubMed] [Google Scholar]

[vdag113-B9] 9. Valiente M, Ahluwalia MS, Boire A, et al. The evolving landscape of brain metastasis. Trends Cancer. 2018;4:176-196. 10.1016/j.trecan.2018.01.003 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B10] 10. Hatiboglu MA, Akdur K, Sawaya R. Neurosurgical management of patients with brain metastasis. Neurosurg Rev. 2020;43:483-495. 10.1007/s10143-018-1013-6 [DOI] [PubMed] [Google Scholar]

[vdag113-B11] 11. Soffietti R, Abacioglu U, Baumert B, et al. Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro Oncol. 2017;19:162-174. 10.1093/neuonc/now241 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B12] 12. Suh JH, Kotecha R, Chao ST, Ahluwalia MS, Sahgal A, Chang EL. Current approaches to the management of brain metastases. Nat Rev Clin Oncol. 2020;17:279-299. 10.1038/s41571-019-0320-3 [DOI] [PubMed] [Google Scholar]

[vdag113-B13] 13. Redmond KJ, De Salles AAF, Fariselli L, et al. Stereotactic radiosurgery for postoperative metastatic surgical cavities: a critical review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines. Int J Radiat Oncol Biol Phys. 2021;111:68-80. 10.1016/j.ijrobp.2021.04.016 [DOI] [PubMed] [Google Scholar]

[vdag113-B14] 14. Roth O’Brien DA, Kaye SM, Poppas PJ, et al. Time to administration of stereotactic radiosurgery to the cavity after surgery for brain metastases: a real-world analysis. J Neurosurg. 2021;135:1695-1705. 10.3171/2020.10.JNS201934 [DOI] [PubMed] [Google Scholar]

[vdag113-B15] 15. Cordes MC, Scherwath A, Ahmad T, et al. Distress, anxiety and depression in patients with brain metastases before and after radiotherapy. BMC Cancer. 2014;14:731. 10.1186/1471-2407-14-731 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B16] 16. Araceli T, Fischl A, Haj A, et al. Psycho-oncological burden in patients with brain metastases undergoing neurological surgery. Front Oncol. 2024;14:1463467. 10.3389/fonc.2024.1463467 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B17] 17. Bellur S, Khosla AA, Ozair A, Kotecha R, McDermott MW, Ahluwalia MS. Management of brain metastases: a review of novel therapies. Semin Neurol. 2023;43:845-858. 10.1055/s-0043-1776782 [DOI] [PubMed] [Google Scholar]

[vdag113-B18] 18. Ekhator C, Nwankwo I, Rak E, Homayoonfar A, Fonkem E, Rak R. GammaTile: comprehensive review of a novel radioactive intraoperative seed-loading device for the treatment of brain tumors. Cureus. 2022;14:e29970. 10.7759/cureus.29970 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B19] 19. Dharnipragada R, Ferreira C, Shah R, Reynolds M, Dusenbery K, Chen CC. GammaTile^® (GT) as a brachytherapy platform for rapidly growing brain metastasis. Neurooncol Adv. 2023;5:vdad062. 10.1093/noajnl/vdad062 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B20] 20. Gessler DJ, Neil EC, Shah R, et al. GammaTile^® brachytherapy in the treatment of recurrent glioblastomas. Neurooncol Adv. 2022;4:vdab185. 10.1093/noajnl/vdab185 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B21] 21. Wernicke AG, Cavallaro J, Ablyazova F, et al. Placement of cesium-131 permanent brachytherapy seeds in periventricular high-grade gliomas: case report highlighting a novel technique to prevent seed migration. Illustrative cases. J Neurosurg Case Lessons. 2025;10:CASE25176. 10.3171/CASE25176 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B22] 22. Yekula A, Gessler DJ, Ferreira C, et al. GammaTile^® (GT) as a brachytherapy platform for rapidly proliferating glioblastomas: from case series to clinical trials. J Neurooncol. 2024;166:441-450. 10.1007/s11060-023-04545-7 [DOI] [PubMed] [Google Scholar]

[vdag113-B23] 23. Pasli M, Cowles S, Jo J, et al. First application of GammaTile cesium-131 brachytherapy with maximal safe resection of a glioma in a patient with limited scleroderma. J Contemp Brachytherapy. 2023;15:365-371. 10.5114/jcb.2023.132083 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B24] 24. Imber BS, Young RJ, Beal K, et al. Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases. J Neurooncol. 2022;159:609-618. 10.1007/s11060-022-04101-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B25] 25. Kutuk T, Kotecha R, Herrera R, et al. Surgically targeted radiation therapy versus stereotactic radiation therapy: a dosimetric comparison for brain metastasis resection cavities. Brachytherapy. 2024;23:751-760. 10.1016/j.brachy.2024.06.007 [DOI] [PubMed] [Google Scholar]

[vdag113-B26] 26. Zhang S, Patel K, Dusenbery K, et al. Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience. J Neurooncol. 2024;169:11-23. 10.1007/s11060-024-04631-4 [DOI] [PubMed] [Google Scholar]

[vdag113-B27] 27. Budnick HC, Richardson AM, Shiue K, et al. GammaTile for gliomas: a single-center case series. Cureus. 2021;13:e19390. 10.7759/cureus.19390 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B28] 28. Ene CI, Abi Faraj C, Beckham TH, et al. Response of treatment-naive brain metastases to stereotactic radiosurgery. Nat Commun. 2024;15:3728. 10.1038/s41467-024-47998-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B29] 29. Alattar AA, Bartek J, Chuck C, et al. FLAIR extending beyond a quadrant (FEQ) of the cerebrum as a qualitative imaging biomarker: a conceptual proposition and proof-of-principle. Clin Exp Metastasis. 2025;42:53. 10.1007/s10585-025-10370-1 [DOI] [PubMed] [Google Scholar]

[vdag113-B30] 30. Freeman M, Ennis M, Jerzak KJ. Karnofsky performance status (KPS) ≤60 is strongly associated with shorter brain-specific progression-free survival among patients with metastatic breast cancer with brain metastases. Front Oncol. 2022;12:867462. 10.3389/fonc.2022.867462 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B31] 31. Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol. 1984;2:187-193. 10.1200/JCO.1984.2.3.187 [DOI] [PubMed] [Google Scholar]

[vdag113-B32] 32. Senders JT, Muskens IS, Cote DJ, et al. Thirty-day outcomes after craniotomy for primary malignant brain tumors: a national surgical quality improvement program analysis. Neurosurgery. 2018;83:1249-1259. 10.1093/neuros/nyy001 [DOI] [PubMed] [Google Scholar]

[vdag113-B33] 33. Wernicke AG, Yondorf MZ, Peng L, et al. Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases. J Neurosurg. 2014;121:338-348. 10.3171/2014.3.JNS131140 [DOI] [PMC free article] [PubMed] [Google Scholar]

[vdag113-B34] 34. Wernicke AG, Hirschfeld CB, Smith AW, et al. Clinical outcomes of large brain metastases treated with neurosurgical resection and intraoperative cesium-131 brachytherapy: results of a prospective trial. Int J Radiat Oncol Biol Phys. 2017;98:1059-1068. 10.1016/j.ijrobp.2017.03.044 [DOI] [PubMed] [Google Scholar]

[vdag113-B35] 35. Kutuk T, Tolakanahalli R, Chaswal V, et al. Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: initial clinical experience. Brachytherapy. 2023;22:872-881. 10.1016/j.brachy.2023.08.002 [DOI] [PubMed] [Google Scholar]

[vdag113-B36] 36. Beckham TH, Cha EE, Rooney MK, et al. Cesium-131 collagen tile brachytherapy for salvage of recurrent intracranial metastases. J Neurooncol. 2025;175:165-174. 10.1007/s11060-025-05113-x [DOI] [PubMed] [Google Scholar]

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PERMALINK

Intraoperative, interstitial brachytherapy in newly diagnosed brain metastases through cesium-131 collagen tile implant: A multi-institutional case series

Carlin Chuck

Mazen Taman

Trenton Kite

Alice Lin

Natalie Amaral-Nieves

Elaina Wang

Joseph Oldam

Abigail A Teshome

Hsien-Chung Chen

Rohil Shekher

Sabrina Zeller

Heinrich Elinzano

Sasmit Sarangi

Eric T Wong

Mark Rivard

Clara Ferreira

Simon Hanft

Clark C Chen

Abstract

Background

Methods

Results

Conclusion

Key Points.

Methods

Study Population

Surgical Resection and Cs-131 Tiles Implant

Clinical and Imaging Collection

Statistical Analysis

Results

Patient Characteristics

Table 1.

Figure 1.

Illustrative Case 1: Tumor Control

Figure 2.

Illustrative Case 2: Tumor Progression

Figure 3.

Illustrative Case 3: Adverse Radiation Effect

Figure 4.

Surgical Outcome, Hospital Course, and Readmission

Table 2.

Local Control and Overall Survival

Figure 5.

Association Between Overall Survival and KPS

Figure 6.

Discussion

Conclusions

Contributor Information

Conflict of Interest Statement

Author Contributions

Funding

Ethics Approval Statement

Data Availability

References

Associated Data

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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