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Background: Hearing preservation is a major concern in the management of acoustic neuroma (AN), whether treated by surgery or radiation or followed conservatively., Objective: To assess the change in hearing in patients who underwent radiotherapy for ANs and to compare it with data from conservatively managed patients., Design: Prospective case series., Setting: Neuro-otology, neurosurgery, and radiation oncology practices in tertiary care hospitals of the University Health Network, University of Toronto., Patients and Methods: Between 1991 and 1999, 32 patients who underwent radiotherapy were followed prospectively. Seventeen patients had pretreatment measurable hearing and a minimum 1-year follow-up. Twelve of these patients underwent Gamma Knife radiation and five had fractionated radiation therapy with a linear accelerator. Pre- and post-treatment hearing was classified according to the Gardner-Robertson (GR) classificatiom and according to the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium (AAO-HNS CHE)., Outcome Measure: Change in hearing post-treatment., Results: Mean follow-up was 48 months. Deterioration in the level of hearing was observed in 8 and 11 of the patients using the AAO-HNS CHE and the GR classifications, respectively. Forty-four to 70% of the patients had lost their pretreatment serviceable hearing, depending on the classification of hearing used and how serviceable hearing was defined. Compared with series of patients followed conservatively in our institution and in other studies, patients who receive stereotactic radiation appear to lose hearing at least at the same rate., Conclusion: Our data suggest that hearing loss continues to occur despite radiotherapy, and patients should be advised accordingly.

Capillary hemangiomas are rare benign vascular tumors that tend to occur in children. Whereas the majority of hemangiomas may regress spontaneously, those associated with functional sequelae or severe symptoms may require treatment. Two patients with capillary hemangiomas of the cavernous sinus that caused neurological symptoms were treated with fractionated stereotactic radiation therapy. Both hemangiomas had shown a progressive increase in size during observation before radiation therapy; both tumors regressed after radiotherapy. Up to the time of the last follow-up evaluation both patients experienced symptomatic relief after radiation. One patient's tumor remains in complete remission and the second tumor continues to demonstrate minor residual contrast enhancement without progression. The authors conclude that fractionated stereotactic radiation therapy is a useful treatment modality in the management of symptomatic capillary hemangiomas when these tumors arise in regions of the brain or skull base in which a complete resection cannot be accomplished.

Purpose: A systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma., Methods: MEDLINE, CANCERLIT, the Cochrane Library, and relevant conference proceedings were searched to identify randomized trials and meta-analyses., Results: Pooling of six randomized trials detected a significant survival benefit favouring post-operative radiotherapy compared with no radiotherapy (risk ratio, 0.81; 95% confidence interval, 0.74 to 0.88, P<0.00001). Two randomized trials demonstrated no significant difference in survival rates for whole brain radiation versus more local fields that encompass the enhancing primary plus a 2 cm margin. A randomized trial detected a small improvement in survival with 60 Gy in 30 fractions over 45 Gy in 20 fractions. Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50-60 Gy., Conclusions: Post-operative external beam radiotherapy is recommended as standard therapy for patients with malignant glioma. The high-dose volume should incorporate the enhancing tumour plus a limited margin (e.g. 2 cm) for the planning target volume, and the total dose delivered should be in the range of 50-60 Gy in fraction sizes of 1.8-2.0 Gy. Radiation dose intensification and radiation sensitizer approaches are not recommended as standard care. For patients older than age 70, preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy. Supportive care alone is a reasonable therapeutic option in patients older than age 70 with a poor performance status.

Whole brain radiotherapy (RT) is frequently used to palliate symptoms in patients with brain metastases, but the palliative benefit to patients has not been well documented. We conducted a longitudinal observational prospective study of patients receiving standard RT (20 Gray (Gy)/5 fractions) for symptomatic brain metastases. End-points were observer rating of neurological symptoms, patient-rated symptoms, performance status, neurological functional status, cognitive function and quality of life (QOL). Median survival for the 75 patients was 86 days (95% confidence interval (CI): 65-101 days). At 1 month, 19% of patients showed an improvement or resolution of presenting symptoms, 23% were stable and 55% had progressed or died. Patient-rated symptoms were increased at 1 month in comparison to baseline data. Only 4 patients had an improved performance status and 22 were stable. Many patients with brain metastases have a short life expectancy and may not benefit from even short duration radiation schedules. Further effort is needed to optimise patient selection and tailor treatment appropriately.

Background and Purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT., Materials and Methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose., Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%)., Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT.

Purpose: To describe (1) the use of surgery and radiotherapy (RT) in the treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3) proportion of survival time spent in the hospital after diagnosis., Methods and Materials: We performed a population-based cohort study of all Ontario Cancer Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR records, hospital files containing surgical procedure codes from the Canadian Institute for Health Information, and province-wide RT records. We studied the odds of treatment using multivariate logistic regression. We expressed the time spent in the hospital as the mean number of days per case, and as a proportion of the interval between diagnosis and death, or 24 months following diagnosis, whichever came first. We used the life-table method and Cox proportional hazards regression to describe survival., Results: The proportion of patients with GBM undergoing any surgery directed at the tumor varied with age (p < 0.0001) and region of residence (p < 0.0001). The proportion undergoing RT varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among patients receiving RT and 3 months among those not receiving RT. The percentage of survival time spent in the hospital was similar among those who received from 49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted relative risk of death varied with age and region of residence., Conclusion: We observed practice variation in the treatment of patients with GBM according to age, region of residence, and year of diagnosis. Survival did not increase during the study period. The variation in RT dose between those receiving from 49.5 to < 53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival between regions where one or the other of the dose ranges predominated, nor was variation in dose ranges among the regions paralleled by variation in the proportion of survival time spent in the hospital.

Object: Until recently the assessment of outcome in patients treated for glioma has emphasized length of survival with the evaluation of quality of life (QOL) limited to unidimensional, mostly physical, measures. The authors report the multidimensional assessment of QOL as part of a randomized clinical trial of brachytherapy as a boost in the initial treatment of patients with glioblastoma multiforme., Methods: A questionnaire previously developed by the senior authors and psychometrically validated was completed by patients on randomized entry into the study and at follow-up review every 3 months thereafter. The questionnaire was presented in a linear-analog self-assessment format. Karnofsky Performance Scale (KPS) scores were also recorded on each occasion. No differences were found between patients in either arm of the study (conventional radiation therapy consisting of 50 Gy in 25 fractions or conventional radiation plus a brachytherapy boost of a minimum peripheral tumor dose of 60 Gy) in KPS and QOL scores during the 1st year of follow-up review. However, there was a statistically significant deterioration in patients' overall KPS scores during the 1st year of follow up compared with baseline scores. Of QOL items evaluated, statistically significant deteriorations were found in self care, speech, and concentration, and on subscale analyses, cognitive functioning and physical experience (symptoms) deteriorated significantly during the 1st year of follow up, compared with baseline values. The correlation between QOL and KPS scores was low., Conclusions: Future studies in patients harboring malignant gliomas must incorporate measures assessing QOL because traditional measures focusing on physical or neurological functioning give an incomplete assessment of the patient's experience.

Combined pleomorphic xanthoastrocytoma-ganglioma is a rare neoplasm, occurring in patients younger than 30 years. The clinical course of these tumors is difficult to predict because of their rarity. We report a case of combined pleomorphic xanthoastrocytoma-ganglioma that, in addition to the patient's age, is unusual in several respects. The lesion was located in the cerebellar vermis of a 60-year-old man and was radiographically solid. Histologically, there was an admixture of markedly pleomorphic astrocytic cells and neoplastic ganglion cells, with permeation of the overlying leptomeninges and surrounding cerebellum. In addition, there was focal capillary endothelial proliferation. There was no necrosis, and mitotic activity was rare at 1 mitotic figure per 40 high-power fields. The patient underwent a near gross total resection and postoperative radiotherapy and remains well through 16 months of follow-up.

Focal irradiation has emerged as a useful modality in the management of malignant brain tumors. Its main limitation is radiation necrosis. We report on the radiation dose distribution in the cerebellum of a patient who developed imaging and autopsy diagnosis of radiation necrosis after permanent iodine-125 implants for a solitary osseous plasmacytoma of her left occipital condyle. A 55-year-old woman initially presented with neck and occipital pain and a lytic lesion of her left occipital condyle. A cytological diagnosis of solitary osseous plasmacytoma was made by transpharyngeal needle biopsy. After an initial course of external beam radiation, the patient required further treatment with systemic chemotherapy 21 months later for clinical and radiographic progression of her disease. She ultimately required subtotal surgical resection of an anaplastic plasmacytoma with intracranial extension. Permanent low-activity iodine-125 seeds were implanted in the tumor cavity. Satisfactory local control was achieved. However, clinical and imaging signs of radiation damage appeared 28 months after iodine-125 seed implantation. Progressive systemic myeloma led to her death 11 years after presentation and 9 years after seed implantation. Radiation dose distribution is described, with a discussion of toxicity from focal radiation dose escalation.

Purpose: [corrected] In women treated with supradiaphragmatic irradiation for Hodgkin's disease (HD) the relative risk (RR) of breast cancer (BC) has been reported to be elevated, particularly in younger women. A retrospective chart review was conducted to investigate the incidence of BC and to describe the characteristics of these cases. Based on these results, predictions were made regarding the future incidence of breast cancer in this patient population, and surveillance strategies are outlined., Patients and Methods: Charts from 1965 through 1990 were reviewed at the Princess Margaret Hospital to include women

Primary central nervous system lymphoma (PCNSL) is a relatively uncommon disease in which spontaneous remission is exceedingly rare. We are reporting three cases of primary CNS lymphoma with spontaneous regression in two to eight weeks, from the time of the initial diagnosis. The remission lasted for four years in the first case, two years in the second, and one year in the third case. Tissue diagnosis was made in the first two cases after relapse, and in the third case a biopsy was done at the initial presentation. The literature and the possible pathophysiological mechanisms of this interesting phenomenon are discussed.

The diagnosis of cancer of the central nervous system (CNS) is often the diagnosis of an incurable, progressive disease with devastating effects on the physical, psychosocial, and cognitive functioning of patients. Because many of the treatment options are noncurative in nature, issues related to quality and quantity of life become paramount. The purpose of the authors' research was to explore the prevalence of psychosocial needs in this cancer population and to determine whether these needs and their resolution impact on quality of life (QOL). Telephone interviews were conducted with 75 patients in whom primary CNS cancer was diagnosed and who were able to pass the Mini-Mental Health Status Examination. Analysis of results indicated that the majority of patients (97.3%) had at least one concern; concerns over treatment side effects, controlling uncertainty, having a meaningful existence, self and body image, and family concerns were among the five most frequently cited need domains. Most patients (91.8%) received help. However, 75.3% reported needing additional help. The number of needs reported and the severity of fatigue most significantly impacted QOL. The study identified the needs and experiences of the patient with CNS cancer. Quality of life and needs assessment information can be used to screen patients for distress and to measure the outcome of medical and psychosocial care and ultimately to ease the burden of illness.

Objective: To determine the effect of initial therapy (surgery and external beam radiation) on the proliferative capacity of glioblastoma and whether adjunctive high focused doses of radiation therapy can further reduce the proliferative capacity of the tumor. This would provide a rationale for attempting to further control local tumor growth with the different forms of high-dose focused radiation available., Methods: Patients with glioblastoma were initially treated within a randomized, controlled study with or without iodine-125 (125 I) brachytherapy after initial surgical resection and external beam radiation (50 Gy in 25 fractions). Specimens from 24 consecutive patients later reoperated for "recurrence" were used to determine the effects of 125 I brachytherapy on the histological features and proliferating cell nuclear antigen index of the tumor tissue., Results: 125 I brachytherapy reduced histological features prognostic for tumor progression, i.e., cellularity, pleomorphism, vessel hyperplasia, and degree of mitosis (P < 0.05). The degree of mitosis (marker for the mitotic or "M" phase) and proliferating cell nuclear antigen index (market for the late G1 and S phase) provide complementary data on the cell kinetics of the tumor. Proliferating cell nuclear antigen immunostaining was lower in the 125 I brachytherapy group (34.6 +/- 8.2%, mean +/- standard error) compared with the control nonimplant group (68.2 +/- 3.5%). 125 I brachytherapy produced a dramatic reduction in mitotic figures (mean histological score = 0.0 +/- 0.0)., Conclusion: Adjunctive treatment of glioblastoma with discrete high doses of radiation therapy delivered by 125 I brachytherapy allows further control of the proliferative capacity of the tumor.

Purpose: To retrospectively analyze the long term results of treatment and the patterns of failure for patients with chordoma of the sacrum, base of skull and mobile spine treated predominantly with postoperative photon irradiation., Materials and Methods: Forty-eight adult patients with chordoma of the sacrum (23), base of skull (20) or mobile spine (5), were seen between 1958-1992. Forty-four were referred post operatively with overt disease and 31 of these were irradiated with conventionally fractionated radiation to a median dose of 50 Gy/25 fractions/5 weeks (range 25-60 Gy). Eight received a hyperfractionation protocol of 1 Gy, 4 hourly, 4 times a day (median 40 Gy/44 fractions/14 days), two sacral patients were treated with a hypofractionation protocol and three cases with skull base tumours were referred elsewhere for proton therapy. Endpoints measured were survival from diagnosis, objective response rate, symptomatic response rate and clinical or radiological progression-free survival from radiotherapy., Results: Median survival was 62 months (range 4-240 month) from diagnosis with no difference between clival and non-clival presentations. One complete and no partial responses were identified in 23 assessable patients. A subjective response was recorded for 12/14 (85%) with pain and 10/23 (45%) with neurological signs or symptoms, and the median time to progression for those with overt disease was 35 months (range 5-220 months). There was no survival advantage to patients receiving radiation doses > 50 Gy (median 60 Gy) compared to doses < 50 Gy (median 40 Gy). There was no difference between the conventional or hyperfractionation regimens with respect to the degree or duration of symptomatic response, or in progression-free survival. Fourteen patients who progressed after irradiation were retreated with surgery (6), irradiation (7) or both modalities (1). Median survival after retreatment was 18 months, and the only two symptomatic responses seen were with reirradiation, and after failure of relatively low dose initial therapy. At last follow-up, 35 were dead of or with disease, seven are alive with disease, and two are disease-free. Thirty-eight had local disease persistence as the sole site of failure, and four developed distant metastases initially or subsequently., Discussion: Overt residual chordoma is rarely cured with conventional external beam irradiation, but treatment does provide useful and prolonged palliation of pain for most patients. Chordoma is a disease with low metastatic potential, and better local control may improve survival. Complete resection rates may be improved for patients with sacral disease by using planned excisions in centres experienced in treating this rare disease. Because radiation therapy may prove to be more successful in controlling microscopic disease, it should be considered as a pre- or postoperative adjuvant to a macroscopically complete resection. Patients with skull base disease should also be resected in centres specializing in this surgery, but complete excision is unlikely. These patients will not obtain local control with conventional photon irradiation, and suitable patients should be considered for irradiation with stereotactic photon or particle beam therapy. For patients who progress after irradiation, there is limited symptomatic benefit to retreatment with surgery or reirradiation, and this should be limited to treating life-threatening complications.

Of 112 stereotactic high-activity iodine-125 implants for malignant brain tumors done as of July 1, 1994, ten have been done for recurrent single brain metastasis and constitute the study group described herein. All patients had initially undergone craniotomy for tumor resection followed by fractionated external beam whole brain radiation and recurred at the same site in the brain. The interval between initial cancer therapy and occurrence of the brain metastasis was 13-156 weeks (median: 63 weeks). The interval between initial treatment of the brain metastasis and its recurrence treated with brachytherapy was 13-69 weeks (median: 35 weeks). Minimum brachytherapy dose administered was 70 Gy at a median dose rate of 67 cGy/hour. Eight patients have died. Two died suddenly at 2 and 13 weeks post-implant of presumed pulmonary embolus. Five died of recurrence of the brain metastasis at 20, 39, 52, 103, and 143 weeks post-implant, and one died of systemic metastases at 40 weeks post-implant. Two patients remain alive 183 and 324 weeks post-implant. High-activity iodine-125 brachytherapy appears to be of benefit for selected patients with recurrent single brain metastasis but larger, and preferably randomized studies are needed.

Over the last several decades in Europe and 15 years in North America, numerous centers have used stereotactic high-activity brachytherapy for patients with malignant brain tumors. A number of nonrandomized series have contributed information regarding the efficacy compared to historical controls for patients with de novo and recurrent malignant gliomas and metastases. Two randomized studies for patients with de novo malignant astrocytoma and glioblastoma are nearing completion. Based on the author's personal experience with 115 patients and the reported literature, we conclude that brachytherapy is appropriate for a minority of patients with malignant brain tumors, that reoperation is frequently required, and complications of therapy can be significant. However, a proportion of highly selected patients benefit significantly from this therapy.

We report the case of a 58 year old woman with an epidermoid cyst of the right cerebello-pontine angle that was subtotally excised. She recurred 2 years later and received radiotherapy with resolution of symptoms and shrinkage of the cyst. The natural history of epidermoid cysts and the role of radiotherapy in their management is discussed.

Purpose: To assess the efficacy of interstitial brachytherapy in the treatment of patients with recurrent malignant astrocytoma., Methods and Materials: Forty-six patients with recurrent malignant astrocytoma were treated with stereotactic high-activity temporary iodine-125 implants between September, 1986 and October, 1992. All patients had been initially treated for malignant astrocytoma (44) or low-grade astrocytoma (2) with surgery and external fractionated radiation. The median time between initial diagnosis and recurrence treated with brachytherapy was 12.5 months. Twenty-five patients received chemotherapy prior to brachytherapy., Results: All but four patients have died; median survival time following brachytherapy is 46 weeks. Twelve patients underwent reoperation for radiation necrosis at a median interval of 6.5 months after treatment (26%). Five patients incurred complications directly due to brachytherapy (11%). Forty-four patients are evaluable regarding pattern of failure following brachytherapy. Six of these 44 patients (13.6%) recurred at a distance from the treatment volume (4 in brain and 2 in spinal subarachnoid space)., Conclusion: Brachytherapy confers modest but meaningful prolongation of survival in selected patients with recurrent malignant astrocytoma, but complications are significant, reoperation frequently required, and recurrence outside the treatment volume common.

We describe two patients who developed devastating strokes due to intracranial arterial occlusion 15 weeks and 97 weeks following high dose stereotactic iodine-125 brachytherapy for glioblastoma multiforme. In both cases the occlusion was within the implant volume at points receiving 110-281 Gy and there was no other evidence of significant atherosclerosis in the patients. We therefore conclude that these complications were a direct result of the brachytherapy. The phenomenon of radiation-induced occlusion of large cerebral arteries is reviewed.

The pattern of tumor recurrence was studied in a series of 68 patients who were treated with interstitial brachytherapy for malignant astrocytoma. Thirty-six patients had newly diagnosed tumors and were treated following surgery and external beam therapy, while 32 were treated for recurrent tumors. Recurrence pattern was determined using computed tomography at the time of clinical deterioration. Thirty-eight percent of tumor recurrence occurred within the original tumor margin and 50% occurred at the original site but extended beyond the initial margin. In all, 88.0% recurred at the initial tumor site, 71.4% being confined to within 2 cm of the pretreatment tumor borders while 6.0% recurred intracranially outside of the initial tumor margin. One patient recurred with spinal metastasis while two patients developed systemic metastases. The significance of these findings is discussed.

Except for isolated case reports, blastomycosis has not been identified as a significant problem in immunosuppressed patients. We describe an unusual case with blastomycotic infection of a cerebral glioma in a 56-year-old man who underwent radiotherapy for his tumor and died of fulminant blastomycotic pneumonia. This is believed to be the first reported case of Blastomyces dermatitidis infection of a cerebral glioma. The light microscopic and ultrastructural features of B. dermatitidis, the giant forms of which were encountered in our patient, are described, and thr role of immunosuppression due to steroid therapy in the pathogenesis of this fulminant infection are reviewed.

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)