Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme

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>or=70, 125I seed activity>or=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.     

A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.     

Permanent I Interstitial Radiation Therapy in the Treatment of Non-GBM High-Grade Gliomas

This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent¹²⁵ iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with ¹²⁵I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan–Meier method for unvariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 31 patients received external radiation therapy (5000 to 6000 cGy) before the implant; 10 patients were implanted without additional external beam radiation, and 9 patients underwent external radiation therapy before implant placement. With a mean follow-up of 40.76 months (range 3.47–87 months); 1–, 3–, and 5-year survival were 78.5% (± .05%), 58.7% (± .07%), and 56.2% (± .07%) respectively. Since 56.2% of the patients were alive at 5 years, median survival has not been reached yet. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%), and brain abcess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky, and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location, and preoperative Karnofsky greater than 70. Surgical treatment of patients with non-GBM high grade gliomas combined with external beam radiation and permanent ¹²⁵I implants represent a valuable alternative for the treatment of patients with malignant gliomas, allowing patients good quality of life and long survival.     

Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas

The authors report the results of a randomized study conducted to evaluate the relative benefit of treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or the combination of procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine (PCV) administered after radiation therapy with hydroxyurea to 76 evaluable patients with glioblastoma multiforme and 72 patients with other anaplastic gliomas. The primary end-point of the study was time to tumor progression. For better-risk patients with Karnofsky performance scores of 70 to 100, results suggest that PCV was of greater benefit than BCNU (p = 0.15 for glioblastoma multiforme; p = 0.13 for other anaplastic gliomas). Median times to tumor progression were 31 and 32 weeks for patients with glioblastoma multiforme; 25th percentile times to progression were 70 and 40 weeks for patients treated with PCV and BCNU, respectively. For patients with other anaplastic gliomas treated with PCV and BCNU, median times to progression were 123 and 77 weeks, respectively. Multivariate analysis showed that the prognostic variables of age and Karnofsky scores were important for patients with glioblastoma multiforme and other anaplastic gliomas, and that the extent of surgical resection was important for those with other anaplastic gliomas.     

Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.     

Brachytherapy of brain tumors.

Temporary implants of high-activity 125iodine sources have been used in the treatment of brain tumors since December 1979 at the University of California, San Francisco. For previously untreated patients who underwent external beam radiation therapy followed by implant boost, median survival from the date of diagnosis was 88 weeks for 34 patients with glioblastoma multiforme (GM) and 157 weeks for 29 patients with nonglioblastoma gliomas (NGM). For recurrent tumors treated with brachytherapy only, median survival from the date of the implant was 54 weeks for 45 patients with GM and 81 weeks for 50 patients with NGM. Finally, in 48 patients with recurrent tumors treated with combined hyperthermia and brachytherapy, median survival from the date of the implant was 46 weeks for 25 patients with GM and 44 weeks for 7 patients with metastases; 18-month survival was 65% for 16 patients with NGM. Brachytherapy appears to be a useful technique for the treatment of selected recurrent brain tumors and selected primary glioblastomas.     

Permanent iodine-125 interstitial radiation therapy in the treatment of non-glioblastoma multiforme high-grade gliomas

BACKGROUND: This study evaluates prognostic factors influencing survival outcomes for 60 patients with permanent iodine-125 implants in the primary treatment of non-glioblastoma multiforme (GBM) high-grade gliomas. METHODS: Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/h with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan-Meier method for univariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 34 patients received external radiation therapy (5,000-6,000 cGy) before the implant; 13 patients were implanted without additional external beam radiation, and 13 patients underwent external radiation therapy before implant placement. RESULTS: With a mean follow-up of 77.6 months (range 3.5-164 months), 1-, 3-, 5- and 10-year survival were 86.7% (+/-0.05%), 60% (+/-0.07%), 50% (+/-0.07%) and 45.7% (+/-0.7%), respectively. The median survival time was 57 months. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%) and brain abscess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky score and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location and preoperative Karnofsky score greater than 70. RPA classification was used to define this group of patients. In RPA classes I and II (n = 43), 1-year survival was 93%, while 3-, 5- and 10-year survival was 67.4, 60.5 and 55.5%, respectively, and median survival time was 91 months. In RPA class III (n = 7), 1-year survival was 71.4%, while 3- and 5-year survival was 42.9 and 28.6%, respectively, and median survival time was 47 months. In RPA class IV (n = 10), 1-year survival was 60%, while 3-, 5- and 10-year survival was 50, 22.2 and 11.1%, respectively, and median survival time was 37 months. CONCLUSION: Brachytherapy with permanent implant of 125I appears promising in the treatment of primary non-GBM malignant gliomas. It improved survival time and reduced the incidence of complications and provided good quality of life. In order to further confirm these results, multicenter randomized prospective studies are needed. RPA analysis is a valid tool to define prognostically distinct survival groups. In this study, 2-year survival and median survival time were improved in all prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with 125I implants. Further randomized studies with effective stratification are needed.     

Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system

Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.     

Interstitial brachytherapy for malignant brain tumors: preliminary results

The authors report their experience with interstitial brachytherapy in 46 patients with malignant brain tumors. Twenty-three patients received implants after external radiation for newly diagnosed malignant astrocytoma, as part of a randomized study (Group I). Eighteen patients received implants for recurrent malignant astrocytoma (Group II) and 3 for recurrent solitary cerebral metastasis from adenocarcinoma of the lung (Group III). Two additional patients received implants as part of their initial therapy for a radiation-induced malignant astrocytoma and a malignant fibrous histiocytoma. In all patients high-activity iodine-125 sources were implanted temporarily by a stereotactic technique. To date 50 patients have been entered in the randomized study with a maximum follow-up of 31 months. The small numbers and short follow-up preclude any conclusions regarding the efficacy of brachytherapy used as part of initial therapy. The median survival to date in the 23 patients in this group who received implants is 60 weeks. The median survival to date for the 18 patients who received implants for recurrent malignant astrocytoma is 44 weeks postimplant. Two of the three patients who received implants for recurrent solitary metastasis are alive at 41 and 49 weeks postimplant; a third died at 39 weeks postimplant. Significant complications attributable to interstitial brachytherapy have been observed in 10 of 46 patients (21.7%). A second operation for clinical and radiological deterioration was performed in 12 patients (26.1%) 8 to 105 weeks after brachytherapy. The authors conclude that interstitial brachytherapy is beneficial for selected patients with recurrent malignant astrocytoma and solitary recurrent metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)     

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m²/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59?±?10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.     

Synergism between BCNU and irradiation in the treatment of anaplastic gliomas. An in vivo study using the avian sarcoma virus-induced glioma model.

The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.     

Intravenous administration of high doses of carboplatin in multimodal treatment of high grade gliomas: a phase II study

Summary The object of this study is to evaluate the efficacy of a high dose of carboplatin in 20 patients operated on for high grade glioma (Group A) compared with a matched control (Group B) treated with BCNU administered after radiotherapy. The toxicity profile has been evaluated during the therapy. The survival of patients entering this study was measured in terms of months: the mean survival time was 10.45 months and the median 11.0 months in the — group treated with carboplatin (8 patients are still alive); the 18-month survival rate was 10%. The mean survival time of the control group was 9.85 months and the median 10.5 months; no patients are still alive and the 18-month survival rate was 0%. On the basis of our phase II clinical study, we could conclude that i.v. administration of high-doses of carboplatin in high grade gliomas is generally well tolerated and the results are better than those of a matched control treated with 1–2 courses of BCNU (low-dose). The adjuvant treatment and the role of carboplatin in the therapy of high grade gliomas is discussed.     

Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine

Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.     

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.     

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.     

Iodine-125-seed implantation combined with external radiotherapy under potentially curative intention in patients with advanced stage-C prostatic cancer

We report on 18 patients, aged 43-77 years, with clinical stage-C adenocarcinoma of the prostate, primarily treated by pelvic lymphadenectomy and 125I-seed implantation. After lymphadenectomy, the staging assessment differed from the preoperative diagnosis as follows: 4 patients were classified as stage C; 6 as D1, and 8 as D2 (distant nodal metastases). The 4 patients, classified postoperatively as stage C, received no further treatment. 11 patients with a postoperative classification of stage D had additional external beam radiation to the pelvic and paraaortic lymph nodes with shielding of the implanted prostatic region. In addition, 8 of these 11 patients had hormonal therapy. The remaining 3 patients have been treated by combining interstitial irradiation with preoperative external beam radiotherapy; postoperative irradiation was supplemented when the lymph nodes were positive.     

Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources

The authors report survival data for the first 41 patients treated for recurrent malignant gliomas with interstitial brachytherapy at the University of California, San Francisco (1980-1984). Iodine-125 (125I) sources were temporarily implanted using stereotaxic techniques. The median survival period for 18 patients with recurrent glioblastomas was 52 weeks after brachytherapy; two patients are alive more than 5 years after brachytherapy. The median survival period for 23 patients with recurrent anaplastic astrocytomas is 153 weeks after brachytherapy, with 10 patients alive more than 3 years and four patients alive more than 4 years after brachytherapy. Both groups did significantly better (p less than 0.01) than groups of patients with the same diagnoses and similar general characteristics who were treated at recurrence with chemotherapy alone. Because of deterioration of their clinical condition and evidence of recurrence from computerized tomographic scans, 17 (41%) of 41 patients required reoperation 20 to 72 weeks after brachytherapy. Despite the invariable presence of apparently viable tumor cells mixed with necrotic tissue in the resected specimen, nine patients have survived more than 2 years after reoperation and two of the nine are still alive 4 years after reoperation. The authors conclude that brachytherapy with temporarily implanted 125I sources for well-circumscribed, hemispheric, recurrent malignant gliomas is effective and offers a chance for long-term survival even though focal radiation necrosis can seriously degrade the quality of survival in a minority of patients.     

An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy and brachytherapy iodine implantation as monotherapies for localized prostate cancer

PURPOSE: Monotherapy with radical prostatectomy, high dose external beam radiotherapy or a (125)I implant is reported to produce equivalent outcomes. We assessed the health related quality of life associated with these 3 treatment approaches. MATERIALS AND METHODS: Extended Prostate Index Composite surveys were mailed to all 960 patients treated with a (125)I implant, high dose external beam radiotherapy or radical prostatectomy with or without hormonal therapy at our institution from 1998 to 2000. A total of 625 patients (65%) completed the surveys. Nerve sparing radical prostatectomy was performed when appropriate. The (125)I implant consisted of 145 Gy and high dose external beam radiotherapy consisted of 78 Gy. For urinary, rectal and sexual domains mean scores were calculated, compared by treatment modality and compared to normative values. RESULTS: A total of 234 patients with radical prostatectomy, 135 with external beam radiotherapy and 74 with a (125)I implant were treated with a monotherapy approach. Median age was 61 years in the radical prostatectomy group, 68 years in the high dose external beam radiotherapy group and 64 years in the (125)I implant group (p <0.001). Of the patients 97% [corrected] had cT1-2 disease and Gleason score 7 or less [corrected] Median time from treatment was 4.0 years for radical prostatectomy, 4.7 years for high dose external beam radiotherapy and 3.5 years for (125)I implantation. Radiation caused significantly worse bowel bother and bowel function than radical prostatectomy (p < or =0.018). Patients with high dose external beam radiotherapy had significantly better urinary function than patients with radical prostatectomy (p <0.001). While patients with radical prostatectomy had significantly worse urinary incontinence than those with a (125)I implant or high dose external beam radiotherapy (p <0.0001), patients with a (125)I implant had more urinary irritation than those with high dose external beam radiotherapy and radical prostatectomy (p <0.01 and <0.0001, respectively). Patients with a (125)I implant had significantly better sexual function than those with high dose external beam radiotherapy and radical prostatectomy (p = 0.01 and 0.0003, respectively). CONCLUSIONS: Of patients with prostate cancer treated with a monotherapy approach we noted better urinary continence in those who underwent radiation based therapies, and better bowel function and less urinary irritation in those who underwent surgery. Sexual function was impaired across all monotherapies but higher scores were seen in men who selected brachytherapy.     

Permanent iodine-125 implant and external beam radiation therapy for the treatment of malignant brain tumors.

Survival data of 114 patients treated for malignant brain tumors with 125I interstitial radiation therapy at Henry Ford Hospital, Detroit, Mich. (1986-1990), are presented. The first 64 patients were treated with temporary 125I implants with a total prescribed dose of 60 Gy at a dose rate of 40 cGy/h. In order to reduce the risk of injury to the surrounding normal tissue associated with high-dose brachytherapy, a new approach was initiated using permanent implants with a lower dose rate; 50 patients were treated after surgical resection with permanent implantation of 125I seeds at a lower dose rate of 4-7 cGy/h, with a total dose of 10,000-12,000 cGy, and concurrent external radiation therapy of 5,000 cGy. The rationale of this protocol was to increase the effectiveness of the low-dose-rate implant by a concurrent 'daily' boost of external radiation, thus inhibiting the proliferation of tumor cells during the protracted low-dose radiation treatment. Survival was compared between groups with permanent and temporary implants in terms of effectiveness in tumor control as well as impact on clinical condition. Low-dose-rate implant with concurrent external radiation therapy seems to offer the best chance for long-term survival without deterioration in the clinical condition.     

CyberKnife stereotactic radiotherapy for patients with malignant glioma.

OBJECTIVE: The CyberKnife is a new frameless image-guided radiosurgical modality. The authors report on their experience using the CyberKnife in 25 patients with malignant gliomas. METHODS: Twenty-five patients with histologically proven malignant gliomas (18 glioblastoma: GB, 7 anaplastic astrocytoma: AA) were treated with the CyberKnife at Konan St. Hill Hospital between June 1998 and November 2002. CyberKnife therapy was performed on 44 lesions (31 GB lesions, 13 AA lesions) in the 25 patients. The median target volume was 19.1 mL (range: 0.3 - 90.2). The median prescribed dose was 20.3 Gy (range: 13.9 - 26.4). Patient-, tumor-, and treatment-related variables were analyzed by univariate analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: In the 18 GB patients, the median survival after diagnosis was 20.7 months (82.6 weeks) with a mean follow-up of 85.7 weeks. Of the 7 AA patients, 6 were alive at the time of analysis with follow-up periods ranging from 11.4 to 52.8 months. Patients younger than 70 years had a median survival after diagnosis of 37.1 months, compared to 12.4 months for older patients (p = 0.003). Similarly, patients with well-controlled lesions had a median survival after diagnosis of 39.8 months compared to 16.0 months for those with uncontrolled lesions (p = 0.031). Late delayed radiation necrosis was seen in 1 GB patient. No other patient suffered acute or delayed neurological morbidity after CyberKnife therapy. CONCLUSION: This is the first report of CyberKnife stereotactic radiotherapy applied to the treatment of malignant gliomas. The frameless and painless CyberKnife stereotactic radiotherapy has the potential to be as useful for treatment of malignant glioma as other radiosurgical modalities.