Samuel Trichter

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

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 a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local 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%). One-year distant 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 CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Cesium-131 permanent seed brachytherapy: Dosimetric evaluation and radiation exposure to surgeons, radiation oncologists, and staff

PURPOSE Cesium-131 ((131)Cs) radioactive seed is Food and Drug Administration approved for permanent seed implant for all cancers, including lung and head and neck (HN) cancers. We describe the first clinical report of (131)Cs dosimetry and exposure rates to treating physicians and staff. METHODS AND MATERIALS Twenty-eight patients received (131)Cs implant for early stage lung and recurrent HN cancers. A nomogram was developed to calculate the number of seeds needed to cover the wedge line with the prescription dose (80 Gy). Final dosimetry was obtained after CT planning a few days following the surgical procedure. Radiation exposure to the treating physicians and staff was measured at the completion of the procedure. RESULTS A nomogram was developed using the variseed software with source data from American Association of Physicists in Medicine TG-43 report. The total volume covered by the prescription isodose line of (131)Cs was measured and compared with (125)I. The prescription volume was smaller for (131)Cs. In addition, the exposure rate with (131)Cs was found to be acceptable. CONCLUSION Our preliminary experience with (131)Cs lung and HN brachytherapy has been very encouraging with excellent dosimetric coverage and acceptable exposure to the treating physicians and staff.

Limited resection followed by intraoperative seed implantation is comparable to stereotactic body radiotherapy for solitary lung cancer

The objective of this study was to compare the outcomes of patients who underwent wedge resection plus intraoperative brachytherapy versus patients who received stereotactic body radiotherapy (SBRT) for single malignant lung nodules.

Morphea as a Consequence of Accelerated Partial Breast Irradiation

Morphea is a localized form of scleroderma usually unaccompanied by the typical systemic stigmata that characterize progressive systemic scleroderma. It rarely manifests at the site of whole breast external-beam radiation therapy. We present an unusual case of radiation-induced morphea (RIM) that occurred after accelerated partial breast irradiation (APBI) using intracavitary Contura brachytherapy. A 65-year-old white woman was treated for stage IIA invasive ductal carcinoma of the left breast with APBI to a dose of 34 Gy in 3.4-Gy fractions twice daily over the course 5 days with intracavitary brachytherapy. At 1.5 years after completion of APBI, the patient developed an area of tenderness, erythema, and induration at the site of irradiation. A skin biopsy was consistent with morphea. To our knowledge, this is the first case of RIM confined to the area of APBI.

Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection.

PURPOSE To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS) tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. MATERIALS AND METHODS In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60%) patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT), 4/10 (40%) received radiotherapy (RT) for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy) was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. RESULTS Median follow-up was 38 months (range, 18 - 57 months). Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm). Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG), respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033). There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI) imaging did not identify radiation necrosis. CONCLUSIONS Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality.

The role of dose escalation with intracavitary brachytherapy in the treatment of localized CNS malignancies: Outcomes and toxicities of a prospective study

PURPOSE This single-institution prospective study was designed to investigate the feasibility and safety of dose escalation with GliaSite (Proxima Therapeutics Inc., Alpharetta, GA) brachytherapy for the treatment of patients with newly diagnosed and recurrent central nervous system (CNS) tumors after neurosurgical resection. We now report mature results of this trial, its outcomes, and a toxicity profile. METHODS AND MATERIALS Ten adult consecutive patients with recurrent and newly diagnosed CNS malignancies underwent GliaSite brachytherapy after maximally safe neurosurgical resection between 2004 and 2007. GliaSite balloon was placed intraoperatively, and the size was selected so as to conform to the surgical cavity. Low-dose-rate radiation was delivered with an aqueous solution of organically bound (125)I (Iotrex: sodium 3-((125)I)-iodo-4-hydroxybenzenesulfonate; Proxima Therapeutics Inc.), introduced into the balloon portion of the device via a subcutaneous port. Two to 3 weeks later, the device was filled with Iotrex for a median dwell time of 94.3 hours (range, 68.0-120.5 hours), after which the balloon was explanted. A commercial 3-D planning system was used for a detailed analysis of dosimetry. Median dose of 52.0 Gy (range, 45.0-60.0 Gy) was prescribed 0.5-1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG) criteria were used to assess acute and long-term toxicities associated with this technique. Followup was assessed with MRI scans and was available on all enrolled patients. RESULTS Median followup for surviving patients was 38 months (range, 18-57 months). Mean size of GliaSite balloon was 3.4 cm (range, 2.0-4.0 cm). Mean volume of filling was 19.0 cc (range, 4.0-35.0 cc). Median activity of Iotrex was 301.6 mCi (range, 95.0-515.4 mCi). Median survival was 14.0 months for the entire cohort after the treatment with the GliaSite device. Of our cohort, 6/10 (60%) patients sustained recurrence (20% local and 40% distant). Median time to recurrence after treatment with GliaSite was 8.0 months, and median time to death after recurrence was 7.5 months. There were no RTOG Grade 3 or 4 acute or late toxicities. Followup MRI imaging did not identify any evidence of radiation necrosis. CONCLUSIONS Our data indicate that treatment with GliaSite balloon brachytherapy is feasible and safe, while rendering acceptable local control and minimal acute and long-term toxicities for newly diagnosed and recurrent CNS malignancies. These encouraging results compel us to embark on testing larger numbers of patients with this treatment modality.

Role of Isotope Selection in Long-term Outcomes in Patients With Intermediate-risk Prostate Cancer Treated With a Combination of External Beam Radiotherapy and Low-dose-rate Interstitial Brachytherapy

OBJECTIVE To examine the rates of long-term biochemical recurrence-free survival (BRFS) with respect to isotope in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) and brachytherapy. METHODS A total of 242 consecutive patients with intermediate-risk prostate cancer were treated with iodine-125 ((125)I) or palladium-103 ((103)Pd) implants after EBRT (range 45.0-50.4 Gy) from 1996 to 2002. Of the 242 patients, 119 (49.2%) were treated with (125)I and 123 (50.8%) with (103)Pd. Multivariate Cox regression analysis was used to analyze BRFS, defined according to the Phoenix definition (prostate-specific antigen nadir plus 2 ng/mL) with respect to Gleason score, stage, pretreatment prostate-specific antigen level, and source selection. Late genitourinary/gastrointestinal toxicities were assessed using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. RESULTS At a median follow-up of 10 years, the BRFS rate was 77.3%. A statistically significant difference was found in the 10-year BRFS rate between the (125)I- and (103)Pd-treated groups (82.7% and 70.6%, respectively; P = .001). The addition of hormonal therapy did not improve the 10-year BRFS rate (77.6%) compared with RT alone (77.1%; P = .22). However, a statistically significant difference in the BRFS rate was found with the addition of hormonal therapy to (103)Pd, improving the 10-year BRFS rate for (73.8%) compared with (103)Pd alone (69.1%; P = .008). On multivariate analysis, isotope type ((103)Pd vs (125)I), pretreatment prostate-specific antigen level >10 ng/mL, and greater tumor stage increased the risk of recurrence by 2.6-fold (P = .007), 5.9-fold (P < .0001), and 1.7-fold (P = .14), respectively. CONCLUSION (125)I renders a superior rate of BRFS compared with (103)Pd when used with EBRT. Hormonal therapy does not provide additional benefit in patients with intermediate-risk prostate cancer treated with a combination of EBRT and brachytherapy, except for the addition of hormonal therapy to (103)Pd.

Phase I/II Study of Neurosurgical Resection and Intra-operative Cesium-131 Radio-isotope Brachytherapy in Patients with Newly Diagnosed Brain Metastases

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 a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local 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%). One-year distant 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 CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Radiation Exposure and Safety Precautions Following 131Cs Brachytherapy in Patients with Brain Tumors

Abstract Cesium‐131 (131Cs) brachytherapy is a safe and convenient treatment option for patients with resected brain tumors. This study prospectively analyzes radiation exposure in the patient population who were treated with a maximally safe neurosurgical resection and 131Cs brachytherapy. Following implantation, radiation dose rate measurements were taken at the surface, 35 cm, and 100 cm distances. Using the half-life of 131Cs (9.69 d), the dose rates were extrapolated at these distances over a period of time (t = 30 d). Data from dosimetry badges and rings worn by surgeons and radiation oncologists were collected and analyzed. Postoperatively, median dose rate was 0.2475 mSv h−1, 0.01 mSv h−1, and 0.001 mSv h−1 and at 30 d post-implant, 0.0298 mSv h−1, 0.0012 mSv h−1, and 0.0001 mSv h−1 at the surface, 35 cm, and 100 cm, respectively. All but one badge and ring measured a dose equivalent corresponding to ~0 mSv h−1, while 1 badge measured 0.02/0.02/0.02 mSv h−1. There was a significant correlation between the number of seeds implanted and dose rate at the surface (p = 0.0169). When stratified by the number of seeds: 4–15 seeds (n = 14) and 20–50 seeds (n = 4) had median dose rates of 0.1475 mSv h−1 and 0.5565 mSv h−1, respectively (p = 0.0015). Using National Council on Radiation Protection guidelines, this study shows that dose equivalent from permanent 131Cs brachytherapy for the treatment of brain tumors is limited, and it maintains safe levels of exposure to family and medical personnel. Such information is critical knowledge for the neurosurgeons, radiation oncologists, nurses, hospital staff, and family as this method is gaining nationwide popularity.

Cesium-131 brachytherapy in high risk and recurrent head and neck cancers: first report of long-term outcomes

Purpose The feasibility and efficacy of re-irradiation using contemporary radiation techniques to treat recurrent head and neck cancer has been demonstrated but the role of brachytherapy is unclear. Here we describe the use of 131Cs brachytherapy with concurrent salvage surgery in 18 patients. Material and methods Eligible patients underwent maximal gross resection of the tumor with implantation of brachytherapy seeds delivering a minimum dose of 80 Gy to the tumor bed. Rates of overall survival, locoregional progression free survival, disease-free survival, and radiation-induced toxicity were analyzed. Results Retrospective Kaplan-Meier analysis shows median overall survival was 15 months and disease free survival was 12 months. Two patients developed grade 3 toxicity; all other complications were grade 1-2 with no grade 4 or 5 complications. Conclusions Compared to prior literature, our study shows comparable rates of survival with a decreased rate of radiation-induced toxicity.