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  • Author or Editor: Ronald E. Warnick x
  • By Author: Breneman, John C. x
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Borimir J. Darakchiev, Robert E. Albright, John C. Breneman and Ronald E. Warnick

Object

Effective treatment options are limited for patients with recurrent glioblastoma multiforme (GBM), and survival is usually <1 year. Novel treatment approaches are needed. Localized adjunct treatment with carmustine (BCNU) wafers or permanent, low-activity 125I seed implants has been shown to be effective for GBM. This study assessed the efficacy and safety of these therapies in combination following tumor resection.

Methods

Thirty-four patients with recurrent GBM were treated with maximal tumor resection followed by implantation of BCNU wafers and permanent 125I seeds into the tumor cavity. Patients were followed up with clinical evaluations and magnetic resonance imaging studies once every 3 months. Survival and progression-free survival (PFS) were evaluated.

Results

During follow-up, local disease progression was observed in 27 patients, and 23 of them died. The median survival period was 69 weeks, and the median PFS was 47 weeks. The 12-month survival and PFS rates were 66 and 32%, respectively. Baseline factors associated with prolonged survival included Karnofsky Performance Scale score ≥ 70, 125I seed activity ≥ 0.8 mCi/cm3 of tumor cavity, and age < 60 years. Brain necrosis developed in 8 patients (24%) and was successfully treated with surgery or hyperbaric oxygen therapy.

Conclusions

The use of adjunct therapy combining BCNU wafers and permanent 125I seeds resulted in survival that compares favorably with data from similar studies performed in patients with recurrent GBM. The incidence of brain necrosis appeared to be higher than that expected with either treatment alone, although the necrosis was manageable and did not affect survival. This novel approach warrants further investigation in recurrent and newly diagnosed GBM.

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Bledi Brahimaj, Michael Lamba, John C. Breneman and Ronald E. Warnick

This case report documents the migration of 3 iodine-125 (125I) seeds from the tumor resection cavity into brain parenchyma over a 7-year period. A 66-year-old woman had a history of metastatic ovarian carcinoma, nickel allergy, and reaction to a titanium hip implant that required reoperation for hardware removal. In this unique case of parenchymal migration, the seed paths seemed to follow white matter tracts, traveling between 18.5 and 35.5 mm from the initial implant site. The patient's initial neurological decline, which was thought to be related to radiation necrosis, appeared to stabilize with medical therapy. She subsequently developed progressive right hemispheric edema that resulted in neurological deterioration and death. Considering her previous reactions to nickel and titanium, the authors now speculate that her later clinical course reflected an allergic reaction to the titanium casing of the 125I seeds. Containing a trace amount of nickel, 125I seeds can elicit a delayed hypersensitivity reaction in patients with a history of nickel dermatitis. Preoperative patch testing is recommended in these patients, and 125I seed implantation should be avoided in those who test positive.

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Elias Dagnew, Jeffrey Kanski, Michael W. McDermott, Penny K. Sneed, Christopher McPherson, John C. Breneman and Ronald E. Warnick

Object

Whole-brain radiotherapy (WBRT) after resection of a single brain metastasis can cause long-term radiation toxicity. The authors evaluated the efficacy of resection and placement of 125I seeds (without concomitant WBRT) for newly diagnosed single brain metastases.

Methods

In a retrospective review from two institutions (1997–2003), 15 women and 11 men (mean age 55 years) with single brain metastasis underwent gross-total resection and placement of permanent low-activity 125I seeds. Primary systemic cancer sites varied. Patients were monitored clinically and radiographically. With neuroimaging evidence of local recurrence or new distant metastasis, further treatment was administered at the physician's discretion. By the median follow-up evaluation (12 months), the local tumor control rate was 96%. Distant metastases occurred in three patients within 3 months, suggesting synchronous metastasis, and in six patients more than 3 months after treatment, indicating metachronous metastasis. Treatment in these cases included radio-surgery in seven patients, WBRT in two, and resection together with 125I seed placement in one. Two patients who suffered radiation necrosis required operative intervention (lesion diameter > 3 cm, total activity > 40 mCi). All 26 patients who had been treated using resection and placement of 125I seeds had a stable or an improved Karnofsky Performance Scale score. At the last review, nine of 16 living patients showed no evidence of treatment failure. The median actuarial survival rate was 17.8 months (Kaplan–Meier method).

Conclusions

Permanent 125I brachytherapy applied at the initial operation without WBRT provided excellent local tumor control. Local control and patient survival rates were at least as good as those reported for resection combined with WBRT. Although the authors noted a higher incidence of distant metastases compared with that reported in other studies of initial WBRT, these metastases were generally well controlled with a combination of surgery, stereotactic radiosurgery, and, less often, WBRT. Twenty-four patients (92%) never required WBRT, thus avoiding potential long-term radiation-induced neurotoxicity.