title: Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis.
abstract: OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3(range 0.21-76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of125I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.
authors.affiliation: Departments of 1 Radiation Oncology and.
authors.forename: David R
authors.initials: DR
authors.lastname: Raleigh
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Seymour
authors.affiliation: Department of Economics, California State University Chanel Islands, Camarillo; and.
authors.forename: Bryan
authors.initials: B
authors.lastname: Tomlin
authors.affiliation: Neurological Surgery, University of California San Francisco.
authors.forename: Philip V
authors.initials: PV
authors.lastname: Theodosopoulos
authors.affiliation: Neurological Surgery, University of California San Francisco.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: Neurological Surgery, University of California San Francisco.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
authors.affiliation: Department of Therapeutic Radiology, Yale University, New Haven, Connecticut.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Geneser
authors.affiliation: Departments of 1 Radiation Oncology and.
authors.forename: Devan
authors.initials: D
authors.lastname: Krishnamurthy
authors.affiliation: Departments of 1 Radiation Oncology and.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Fogh
authors.affiliation: Departments of 1 Radiation Oncology and.
authors.forename: Penny K
authors.initials: PK
authors.lastname: Sneed
authors.affiliation: Neurological Surgery, University of California San Francisco.
authors.forename: Michael W
authors.initials: MW
authors.lastname: McDermott
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D001921:Brain / Q000473:pathology* / Q000601:surgery; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007457:Iodine Radioisotopes
keywords: 125I = iodine-125; FFN = freedom from necrosis; GTR = gross-total resection; LFFP = local freedom from progression; MRI-1, first postoperative MRI; OS = overall survival; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; UCSF = University of California, San Francisco; WBRT = whole-brain radiotherapy; brachytherapy; brain metastasis; iodine-125; oncology; radiotherapy