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.     

Stereotactic Radiosurgery for Human Glioma: Treatment Parameters and Outcome for Low vs. High Grade

Stereotactic radiosurgery (SRS) offers the precise, local delivery of radiation for the treatment of recurrent gliomas. We examined the comparative characteristics, treatments, and outcome in a population having with low– and high–grade gliomas. Between September 1991 and December 1995, 20 patients (13 males, 7 females) had SRS for low-grade [9 patients: World Health Organization (WHO) grade II] vs. high-grade (11 patients: 9 WHO grade IV and 2 WHO grade III) gliomas. The patients with low-grade gliomas were younger (mean age ± SE, 39.6 ± 5.4 years; range, 11.4–61.0 years) than those with high-grade gliomas (51.3 ± 13.9 years; range, 32.9–78.5 years) (P = 0.09). Tumor locations were similar in the two groups: lobar for 7 of 9 low-grade vs. 9 of 11 high-grade gliomas (P = NS) and diencephalic or cerebellar for the remainder. The initial surgical treatments were biopsy, subtotal resection, and total resection for three, three, and three patients with low-grade gliomas, vs. three, seven, and one patients with high-grade gliomas, respectively (P = NS). Except for three patients with low-grade gliomas, all patients had conventional postoperative fractionated external-beam radiotherapy. The doses were 5583 ± 342 vs. 5345 ± 261 cGy (P = NS) for low- vs. high-grade gliomas, respectively. Intervals from surgery and conventional radiation (if given) to progression and SRS tended to be longer for low-grade gliomas: 37.5 ± 9.5 vs. 30.6 ± 11.1 months (P = NS) for low- vs. high-grade gliomas, respectively. High-grade gliomas were larger. The diameters of the collimators that allowed enclosure of the enhancing tumor volume within the specified treatment isodoses were 22.4 ± 2.0 mm for low-grade vs. 29.8 ± 2.8 mm for high-grade gliomas (P = 0.02, ANOVA). SRS doses and isodose percentiles were similar, however, for the two groups: 1650 ± 191 cGy and 79 ± 4.0% vs. 1932 ± 182 cGy and75 ± 3.5% for low- vs. high-grade gliomas, respectively (P = NS, dose and isodose). All patients with high-grade gliomas were followed until death. The mean survival after SRS was 11.6 ± 1.5 months (42 ± 12 months after surgery). Five of nine patients with low-grade gliomas expired 31.6 ± 6.0 months after SRS (P < 0.001, Kaplan–Meier log rank) (74.0 ± 16.0 months after surgery). The four survivors have been followed for 8, 13, 35, and 38 months after SRS, respectively. Multivariate analysis shows that the category of histologic grade correlates significantly with survival after radiosurgery (P = 0.01). SRS may be an important therapeutic option for patients with recurrent gliomas, regardless of their grade.     

Permanent Iodine-125 Implants in the Treatment of Low-Grade Gliomas

We report a retrospective study on the use of the permanent iodine-125 (¹²⁵I) implants in the management of low-grade gliomas. From July 1988 to July 1997, 16 patients with low-grade gliomas underwent permanent ¹²⁵I implants in the management of their lesions. There were 7 males and 9 females ranging in age from 4 to 48 years (mean 19). The location was in the cerebral hemisphere in 7 patients, brainstem in 5 patients and thalamus/basal ganglia in 4 patients. Prior to brachytherapy, 9 patients underwent surgical resection and 7 patients underwent stereotactic biopsy procedures. Fourteen patients were treated as part of the initial management and 2 were recurrent. The histological diagnosis was: 9 WHO grade II astrocytomas, 3 oligodendrogliomas, 2 gemistocytic astrocytomas, 1 pilocytic astrocytoma, and 1 ependymoma. The tumor volume ranged from 0.7 to 33.4 cc (mean 8.4). Stereotactic treatment planning was used to encompass the contrast-enhancing rim of the tumor visualized by computerized tomography with an initial dose rate of 0.05 Gy/hour with ¹²⁵I. The total activity ranged from 0.8 to 20.5 mCi. With a median follow-up period of 35 months (range, 4–105 months), the 2- and 5-year survival rates were 93.7% and 87.5%, respectively. Three patients underwent reoperation after implants, two of three had recurrent disease, and one had radiation necrosis. Permanent ¹²⁵I implants appear to be safe and effective as a part of the multimodality management of low-grade gliomas.     

Interstitial 125-iodine radiosurgery of low-grade gliomas of the insula of Reil

Summary Between 1979 and 1991 67 patients with low-grade gliomas of the insula (of Reil) were treated with 125-iodine interstitial radiosurgery. Retrospective analysis with a median follow-up of 55 months demonstrated a 5- and 10-year survival rate of 54% and 47%, respectively, for all low-grade gliomas treated and a 5- and 10-year survival rate of 57% for 49 patients with astrocytomas WHO grade II analysed separately. The median Karnofsky performance status of survivors was 90%. Malignant change was the cause of death in 85%, failure to control tumour growth in the remaining cases. Multivariate analysis with a Cox proportional hazard model identified solely the pre-operative Karnofsky performance score of 70–80 vs. 90% as a prognostic factor for outcome (p=0.001, risk ratio 3. 62), but not age, gender, tumour volume, length of disease before treatment, mode of implantation, or major vs. moderate or no shrinkage of tumour volume after interstitial radiosurgery.Thus, 125-iodine radiosurgery yielded survival rates in these deep-seated insular gliomas comparable to those reported after surgery and radiation therapy of lobar tumours. This was achieved with a low peri-operative mortality and morbidity and at low costs.     

Intra-operative radiation therapy for malignant brain tumours: Rationale,method, and treatment results of cerebral glioblastomas

Summary In radiation therapy for malignant brain tumours, the dose of radiation that can be safely delivered to a tumour is limited by the radiation tolerance of the adjacent normal brain tissue. Among various radiation modalities to produce local tumour eradication without unacceptable complications, we chose a large, single irradiation dose during the operation (intra-operative radiation therapy, IORT). In contrast to X-ray or Cobalt-60 gamma ray irradiation, IORT with a high-energy electron beam delivered by the Shimadzu 20 MeV betatron provides acceptable dose homogeneity with rapid fall-off of the radiation dose beyond the treatment volume. Thus, IORT has the advantage of precise demarcation of the target volume, minimum damage to surrounding normal tissues, and a high absorbed target dose (15–25 Gy in 5–10 min).On the basis of our experience with 170 patients treated by IORT, we established the treatment indications and method in patients with malignant brain tumours. IORT with a dose of 15–25 Gy was delivered to widely resected tumours followed by external radiation therapy. No acute or subacute complications were observed. Treatment results of 30 patients with glioblastoma treated by IORT (mean 18.3 Gy) combined with external radiation therapy (mean 58.5 Gy) resulted in a median survival of 119 weeks and a 2-year survival rate of 61%.Supported by a Research Grant for Cancer (3–46, 4–23) from the Ministry of Health and Welfare, and by a Grant-in-Aid for Scientific Research (03454343) from the Ministry of Education, Science and Culture of Japan.     

Long-Term Follow-Up of Brachytherapy in Untreated Malignant Glioma

Objective: Long-term follow-up of patients with malignant glioma randomized to treatment with and without brachytherapy. Methods: Twenty-six patients were randomized to brachytherapy and external radiation, and 23 to external radiation alone. There were 19 and 17 glioblastomas, and 3 and 8 anaplastic astrocytomas, in the nonimplant and implant groups, respectively, and 1 malignant oligodendroglioma in each group. For brachytherapy, iodine- 125 seeds were implanted to deliver a homogeneous dose of 40 cGy/hr for a maximum of 6000 cGy to the enhancing tumor margin. All patients received external radiation for a total of 6020 cGy delivered to the tumor plus 3 cm margin over 7 weeks, followed by BCNU chemotherapy. Conclusions: The median survival was 78 and 66 weeks in the implant and nonimplant groups respectively, and their survival curves were not different (log rank, p=0.394). A significant multivariate relationship did exist between survival and age (p=0.0092), tumor grade (p=0.0001), and Karnofsky (p=0.021). Treatment with brachytherapy is subject to selection bias, which does exclude a large proportion of patients.     

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.     

Recurrent Malignant Gliomas Treated with Radiosurgery

The inability to control malignant glioma results in a high incidence of local failure and poor survival. Focal therapy such as radiosurgery permits delivery of a high dose of radiation with moderate toxicity. This report summarizes the outcome of patients with recurrent malignant glioma treated with radiosurgery at University of Wisconsin Hospital, between January 1989 and December 1997, when 30 patients were treated radiosurgically. All patients had undergone and failed external beam radiotherapy (median dose of 59.4 Gy) prior to radiosurgery. All recurrences were detected by clinical deterioration and confirmed by radiographic progression. No patient was treated for radiographic progression only in the context of a screening protocol. Eight out of 30 patients underwent subtotal resection prior to radiosurgery and 3 received chemotherapy along with radiosurgery. Radiosurgery was delivered in a single fraction using a modified linear accelerator. The median tumor volume was 7.2 cm³ (range 0.42–35.1 cm³) and the median minimal tumor dose was 12 Gy at the 50–80% isodose line. Median follow-up is 70 months. The median overall survival is 8 months; the 1- and 2-year survival rates are 20% and 9%, respectively. For patients with an initial diagnosis of non-glioblastoma, the median survival is 11 months and for those with glioblastoma the median survival is 7 months. The median progression-free survival is 4 months for the entire cohort, 5 months for nonglioblastoma, and 3 months for glioblastoma. The 1-year actuarial reoperation rate after radio-surgery is 7.6%. Radiosurgery for recurrent malignant glioma may improve short-term survival for selected patients with a lower reoperation rate than brachytherapy.     

The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery,external radiotherapy,and carmustine versus surgery,interstitial radiotherapy boost,external radiation therapy,and carmustine

OBJECTIVE: The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas. METHODS: The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. (125)I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the (125)I implantation plus external beam radiation and BCNU therapy. RESULTS: The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of (125)I was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups. CONCLUSION: We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.     

Interstitial brachytherapy for low-grade cerebral gliomas: Analysis of results in a series of 36 cases

Summary The results obtained with interstitial brachytherapy in thirty-six low-grade cerebral gliomas (2 pilocytic astrocytomas, 23 astrocytomas and 11 oligodendrogliomas) are reported (mean follow-up: 75 months, range 37–159). All tumours were situated in locations which did not call for surgical removal as the treatment of choice. Their volume ranged from 4 to 82 cc (m=32); the Karnofsky performance status (KPS) of the treated patients lay between 0.60 and 0.90.The sources utilized (Iridium-192 in 32 cases and Iodine-125 in 4) were implanted permanently in 22 patients and temporarily in 14, using the Talairach stereotactic apparatus. The mean peripheral dose was 89.7 Gy for the permanent implants and and 42.8 Gy with a rate of 32.05 cGy/h for the temporary implants. External beam irradiation was added for tumour volumes greater than 35 cc (19 cases) on a second target volume extending 2 cm beyond the tumoural borders treated with interstitial irradiation.The survival estimates for the entire group showed a probability of 82.9% at 60 months, of 56.8% at 96, 39.4% at 120 (m.s.t.: 112 months). The quality of life in the treated patients was satisfactory, KPS never falling below a mean score of 0.70. The extent of the target volume turned out to be the most significant factor influencing survival at the multivariate analysis. Severe neurological impairment due to radionecrosis occurred in 4 patients (11%), three of them requiring surgical decompression. Target volume and radiation dose showed a direct correlation with the risk of radionecrosis at the regression analysis, the critical values being 35 cc and 100 Gy (permanent implants) or 50 Gy (42 cGy/h, temporary implants) respectively. The analysis of the results indicates that, even though many questions still remain open, brachytherapy can represent a valid alternative to surgery for tumours not suitable for surgical removal.Study partially supported by a grant from the Italian Ministry of University and of Scientific and Technological Research.     

Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m² and cisplatin 30 mg/m² on days 1, 8, 22, and 29; concurrent radiation (45—50 Gy) was applied to the tumor and regional lymph nodes (1.8—2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m²) and cisplatin (50 mg/m²) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7—38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2—9.4 months). The median survival amounted to 10.7 months (range 8.4—13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8—41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.     

Efficacy of Post Operative Adjuvant Therapy with Human Interferon Beta, MCNU and Radiation (IMR) for Malignant Glioma: Comparison Among Three Protocols

Summary  In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-β), MCNU and radiation).  In protocol 1 (n=45: AA=13, GM=32), 1 ×10⁶ IU of HuIFN-β was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n=19: AA=11, GM=8) was comparable with protocol 1 except HuIFN-β was administrated twice a day at a dose of 1×10⁶ IU each. Protocol 3 (n=13: AA=5, GM=8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1, 63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5% of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols.  In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We conclude that twice a day administrations of HuIFN-β in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.     

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.     

KB-R9032, newly developed Na<Superscript>+</Superscript>/H<Superscript>+</Superscript> exchange inhibitor,attenuates reperfusion-induced arrhythmias in isolated perfused rat heart

Purpose This study was conducted to elucidate the effects of KB-R9032, a newly developed Na⁺-H⁺ exchange inhibitor, on reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart.Methods Male Wistar rat hearts (n = 48; 12 for each group) were perfused with modified Krebs-Ringers solution equilibrated with 5% carbon dioxide in oxygen by means of the Langendorff technique. An occluder was placed around the left anterior descending coronary artery (LAD). Heart rate, coronary flow, and ECG were monitored. Drug-free perfusate was used for 10min before switching to a perfusate containing various concentrations of KB-R9032. The added concentrations of KB-R9032 varied in the range of 0 (control) to 1 × 10^–5mol·l^–1. Each heart was subjected to regional ischemia (occlusion of LAD for 11min) and to 3min of reperfusion (release of the ligation).Results In the control group, reperfusion-induced ventricular fibrillation (VF) occurred in 91.7%, and the duration was 158.2 ± 14.4s (mean ± SEM); however, 1 × 10^–7, 1 × 10^–6, and 1 × 10^–5mol·l^–1 KB-R9032 reduced the incidence of VF to 75.0%, 42.9%, and 6.7%, respectively (P < 0.05 at 1 × 10^–5mol·l^–1 of KB-R9032) and reduced the duration of VF to 64.8 ± 22.1, 16.8 ± 10.1, and 1.2 ± 1.2s, respectively (P < 0.05 at 1 × 10^–6 and 1 × 10^–5mol·l^–1 of KB-R9032).Conclusion It was shown in this study that the Na⁺/H⁺ exchange inhibitor KB-R9032 suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.     

Single-Fraction Radiosurgery for Primary and Recurrent Malignant Gliomas

From November 1990 to May 1993, 37 patients with malignant gliomas were treated with single-fraction radiosurgery. Nineteen patients had newly diagnosed tumors. Twelve of these were gliob-lastoma multiforme (GBM) and 7 were anaplastic astrocytoma (AA). Tumors were recurrent after standard radiotherapy in 18 patients. Twelve were GBM and 6 were AA. Median ages were 56 years for those with primary tumors and 52 years for those with recurrent tumors. Strict neuroimaging criteria were not used to select patients for radiosurgery. Median tumor volumes for primary GBM and AA were 15 cc and 9.4 cc, respectively. Median volumes for recurrent GBM and AA were 22.6 cc and 19.6 cc, respectively. Karnofsky Performance Status was above 60% in all patients. Median tumor minimum doses were 30 Gy for primary tumors and 27 Gy for recurrent tumors. Median tumor maximum doses were 50 Gy and 55 Gy, respectively. Median follow-up was 14 months for primary glioma patients and 7.5 months for those with recurrent tumors. Survival analysis was performed using the Kaplan–Meier method. Comparison of prognostic factors was performed using the log-rank and Wilcoxon tests No patient in this series remains alive. Median survivals of those with primary GBM and AA were 13 and 12 months, respectively, from diagnosis. Median survivals of those with recurrent GBM and AA were 7 and 8 months, respectively, from the date of radio-surgery. Thirty-three of 37 patient deaths were due to tumor progression within the radiosurgery treatment volume. Tumor recurred outside the high-dose volume of radiosurgery in 3 patients. Acute complications necessitating hospitalization occurred in 3 patients. Fourteen patients (38%) became dependent on corticosteroids after radiosurgery. Six patients (16%) were resected after radiosurgery. Coagulative necrosis and morphologically intact tumor cells were identified in all resected patients. There was no significant influence of the following factors on actuarial survival of primary or recurrent tumors: age, gender, tumor volume, tumor location, duration from conventional radiotherapy, or radiosurgery dose. Tumor volume was a predictor of reoperation for AA. Indiscriminate application of radiosurgery in this series did not increase the survival of patients with primary or recurrent GBM. Central recurrence represents the predominant form of relapse when patients with malignant gliomas receive radiosurgery in the absence of imaging selection criteria. These criteria include tumor volume and evidence for a discreet lesion. Radiosurgery planning should provide a margin of normal brain parenchyma. Advances in tumor imaging and radiosurgery techniques may improve results of this unique modality for patients with malignant gliomas.     

The Role of Stereotactic Radiosurgery in the Management of Benign, Atypical, and Malignant Meningiomas

Stereotactic radiosurgery and fractionated Stereotactic radiotherapy (SR) offer precise localization of radiation dose (Gy) for the treatment of meningioma (M). For the multimodal treatment with preservation of function, SR is complementary to both microsurgery (S) and conventional external beam radiotherapy (XRT). The role of SR in the management of atypical and malignant meningiomas, however, remains unexplored. Fifty consecutive patients with meningioma: 18 males (60.1 +/– 2.3 years) and 32 females (56.9 +/– 2.2 years) (p = NS) received SR. Thirty-one patients had surgery 69.6 +/– 13.9 months (95% CI: 53.3–98.0) prior to SR. For patients having S, the incidence of atypical or malignant versus benign meningiomas (14 versus 17 patients) increased with age (p = 0.03). Twenty patients had XRT approximately 18 months prior to SR. For antecedent XRT, the range of doses was 3600–6400 cGy (median: 5040 cGy). Following failure of S and/or XRT, patients had SR. Compared to other series, the mean tumor volumes for SR were comparatively large: 9.8 +/– 1.3 cm³ (range 0.3–37.1 cm³). The median SR dose was 3500 cGy (range 540–5400 cGy) administered in seven fractions (range 1–30). Linear regression analysis showed a consistent method for fractionation: the number of administered fractions increased (p = 0.053) and the total dose increased (p = 0.054) with tumor size. During the interval for follow–up (17.9 +/– 2.9 months), one patient with malignant meningioma required surgery for progression 8 months after SR. In the remaining patients, post-SR MRIs showed control (unchanged or smaller tumor volume) regardless of histology. These results show that SR may provide control of M regardless of grade.     

Is iodine-125 seed strand brachytherapy suitable for ureteral carcinoma?

BackgroundLong-term conventional high-dose radiation therapy can lead to retroperitoneal fibrosis and nerve damage in patients with advanced ureteral carcinoma (UC). The purpose of this study is to evaluate the safety and efficacy of nephrostomy combined with iodine-125 seed strand (ISS) brachytherapy for the treatment of UC.Materials and methodsTwenty-one patients with UC were treated with nephrostomy combined with ISS brachytherapy. The following parameters were recorded: technical success rate, procedure time, complications, mean D90 (dose delivered to the 90% gross tumor volume), organ at risk (OAR) dose, local control rate (LCR), ureteral patency (UP), local tumor progression (LTP), and overall survival (OS). The hydronephrosis score (HS), visual analog score (VAS), Karnofsky score and maximum diameter (MD) were compared before and 8 weeks after the operation.ResultsThe technical success rate was 100%, with a mean procedure time of 54.6 min. Three cases (14.5%) had bladder implant metastasis but no other major complications, such as ureteral perforation, infection, or severe bleeding, occurred. The mean D90 and OAR doses were 50.7 and 3.8 Gy, respectively. LCR was 100% with 28.6% UP at the 8-week evaluation. During the mean follow-up of 16.6 months, LTP occurred in 4 cases (19.1%), and the median OS was 25.0 months (95% CI 21.3–28.5). The HS, VAS, Karnofsky score and MD showed significant changes (all P < 0.01).ConclusionUC can be safely and effectively treated by nephrostomy combined with ISS brachytherapy, a viable option for patients who cannot undergo or refuse surgical resection.     

Spinal chordomas — results of treatment over a 17-year period

Summary Among a series of 511 spinal tumours treated in the Department of Neurosurgery at the Nordstadt Hospital in Hannover, Germany, between September 1977 and August 1994, 23 operations for spinal chordomas in 9 patients (3 females, 6 males) were performed. After an average period of 7±12 months (2 weeks to 5 years) patients presented at an average age of 45±17 years with pain (68%), gait ataxia (14%), motor weakness (9%) or sphincter disturbances (9%). A complete resection was achieved in 11 operations and a subtotal tumour removal in 12 instances. After subtotal removal, 5 tumours were treated postoperatively using local high dose radiotherapy (60–70 Gy). Overall, every chordoma recurred with the passage of time unless en-bloc resection of the tumour had been performed. The recurrence-free interval tended to be longer after radiotherapy. Analysis of postoperative results revealed a significant positive effect of radiotherapy for motor function, pain, Karnofsky score, and survival.In conclusion, en-bloc resection should be performed whenever localization and extension of the tumour allow one to do so. Surgery should be followed by local high dose radiotherapy.     

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.     

Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on stunned myocardium in anesthetized dogs

Purpose The present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na⁺/Ca²⁺ exchanger (NCX), on stunned myocardium in anesthetized dogs.Methods The dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5mg·kg^–1 i.v.) (group L) or high-dose KBR (10mg·kg^–1 i.v.) (group H) at 15min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).Results Recovery of %SS at 90min after reperfusion was significantly improved in group H (70.8% ± 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% ± 2.8% and 36.4% ± 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.Conclusion The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.