Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases

Abstract

Object Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole brain radiotherapy (WBRT) remains the standard of care with the rate of local control >90%. However, WBRT is delivered over 10–15 days, which can delay other therapy and is associated with acute and long-term toxicities. Intra-operative permanent Cesium-131 (Cs-131) implants can be performed at the time of surgery, thereby avoiding any additional therapy. We evaluate the safety, feasibility and efficacy of a novel treatment approach of brain metastases with a permanent intra-operative Cs-131 brachytherapy. Methods After IRB approval, 24 patients with a newly diagnosed metastasis to the brain (n=24) were accrued on a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung (16), breast (2), kidney (2), melanoma (2), colon (1), and cervix (1). Cs-131 stranded seeds were placed as a permanent volume implant. Prescription dose was 80Gy at 5mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. Primary end point was resection cavity freedom from progression (FFP). Secondary end points included distant metastases FFP, median survival, overall survival (OS), and toxicity. Results Median follow-up was 19.3 months (range, 12.89 – 29.57 months). Median age was 65 years (range, 45–84 years). Median volume of resected tumor was 10.31 cc (range, 1.77 - 87.11 cc). Median number of seeds employed was 12 (range, 4–35) with median activity per seed of 3.82 mCi (range, 3.31–4.83 mCi) and total activity of 46.91 mCi (range, 15.31–130.70 mCi). Local recurrence FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI = 63.2%, 99.1%). Distant metastasis FFP was 48.4% (95% CI = 26.3%, 67.4%). Median OS was 9.9 months (95% CI = 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI = 29.1%, 67.8%). Complications included cerebrospinal fluid leak (1), seizure (1), infection (1). There was no radiation necrosis. Conclusions Cs-131 post-resection permanent brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment approach was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rates, and minimal toxicity. These results merit further study with a multicenter trial.

Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer

“…Clinical studies have shown that TISSEEL fibrin glue is biocompatible and biostable in the brain of human patients 18 . Importantly, these properties have led to the use of fibrin scaffolds for tissue engineering of adipose, skin, liver, and bone tissues 19 , delivery of therapeutic molecule for various diseases 19,20 , and brachytherapy treatment of brain tumors 21–23 .…”

Neurosurgical management of brain metastases

“…43 Local therapy with intraoperative radiation or brachytherapy may be a particularly attractive option for lesions that result in resection cavities too large to be treated safely with SRS such as those great than 15 ml in volume. 44,45 Local radiation to the resection cavity, either via SRS or intraoperative radiotherapy, has been associated with an increased rate of distant failure and leptomeningeal disease in comparison to adjuvant WBRT. 46 Leptomeningeal disease is associated with breast histology and infratentorial location.…”

Neurocognitive function and quality of life in patients with newly diagnosed brain metastasis after treatment with intra-operative cesium-131 brachytherapy: a prospective trial

“…Treatment technique has been previously described [23]. In short, patients underwent maximally safe neurosurgical resection of lesions.…”

“…However, the main criticism of these studies, the majority of which involved I-125 implants, was the high rate of radiation necrosis from 5 % up to 23 % in one series [19][20][21][22]. Intraoperative permanent Cesium-131 (Cs-131) implants may provide a viable alternative to WBRT with high response rates and minimal toxicity [23]. We have previously reported very promising results from our prospective series of 24 patients who received surgical resection with intraoperative Cs-131 brachytherapy achieving excellent local control and minimum toxicity.…”