National Cancer Institute®
Last Modified: October 1, 2002
UI - 11831641
AU - Regina A; Demeule M; Laplante A; Jodoin J; Dagenais C; Berthelet F;
TI - Moghrabi A; Beliveau R Multidrug resistance in brain tumors: roles of the blood-brain barrier.
SO - Cancer Metastasis Rev 2001;20(1-2):13-25
AD - Laboratoire de Medecine Moleculaire, Hopital Sainte-Justine-Universite du Quebec a Montreal, Canada.
Malignant brain tumors and brain metastases present a formidable clinical challenge against which no significant advances have been made over the last decade. Multidrug resistance (MDR) is one of the main factors in the failure of chemotherapy against central nervous system tumors. The MDR1 gene encoding P-glycoprotein (P-gp), a drug efflux pump which plays a significant role in modulating MDR in a wide variety of human cancers, is highly expressed in the blood-brain barrier (BBB). The BBB controls central nervous system exposure to many endogenous and exogenous substances. The exact molecular mechanisms by which the BBB is involved in the resistance of brain tumors to chemotherapy remain to be identified. The purpose of this review is to summarize reports demonstrating that P-gp, one of the most phenotypically important markers of the BBB, is present in primary brain tumors and thus plays a crucial role in their clinical resistance to chemotherapy.
UI - 12186465
AU - Duffau H; Denvil D; Capelle L
TI - Absence of movement disorders after surgical resection of glioma invading the right striatum.
SO - J Neurosurg 2002 Aug;97(2):363-9
AD - Department of Neurosurgery, Hopital de la Salpetriere, Paris, France. email@example.com
OBJECT: Despite the high frequency of striatal lesions, the rate of movement disorders reported in the literature is lower than expected (< 10%). To maximize the extent of resection in low-grade gliomas invading the right striatum, the authors performed a striatal resection in a series of 14 patients, observed the lack of movement disorders following these procedures, and discuss herein the mechanisms likely to explain these findings. METHODS: Fourteen patients harboring a low-grade glioma that was infiltrating the right nondominant striatum, and in whom the results of neurological examination were normal, underwent surgery in which intraoperative electrical mapping was used, allowing the identification of pyramidal pathways. The striatum was resected in all procedures, and corticospinal tracts were systematically detected and preserved. Ten patients presented with a transient postoperative motor deficit, and nine with a loss of interest and affect. These symptoms all resolved within 3 months, except for one case of persistent hemiparesis. No postoperative movement disorder was noted, even transitorily. All resections were categorized as either total or subtotal on control magnetic resonance images. CONCLUSIONS: These findings show that the nondominant striatum can be removed in cases of glioma invasion without inducing even transitory movement disorders. This phenomenon could be explained by the combined resection of the two classes of striatal neurons, an associated pallidal and thalamocortical resection, or a compensatory recruitment of parallel networks. Thus, these results may allow the surgeon to maximize the extent of removal of low-grade gliomas involving basal ganglia. Striatal resection may induce transient hemiparesis and "athymhormic syndrome," however, necessitating that the patient be clearly informed before surgery.
UI - 1646217
AU - Lamberts SW; Koper JW; de Jong FH
TI - The endocrine effects of long-term treatment with mifepristone (RU 486).
SO - J Clin Endocrinol Metab 1991 Jul;73(1):187-91
AD - Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.
UI - 11954761
AU - Bertalanffy H; Benes L; Miyazawa T; Alberti O; Siegel AM; Sure U
TI - Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients.
SO - Neurosurg Rev 2002 Mar;25(1-2):1-53; discussion 54-5
AD - Department of Neurosurgery, Philipps University of Marburg, Germany. firstname.lastname@example.org
The authors review the pertinent literature dealing with all aspects of cerebral cavernous malformations in the adult. Clinical, neuroradiological, pathological, and epidemiological aspects are presented. The clinical significance of bleeding from cavernous malformations and various hemorrhage patterns are discussed in relation to the factors that influence hemorrhage rates. Recent reports describing the genetic mechanisms of inheritance, de novo formation, and angiogenesis of cavernomas are reviewed as well. Brainstem cavernomas have received special attention, since their clinical management is controversial in the literature. Presently, microsurgical removal is favored by the majority of authors and stereotactic radiosurgery appears to be inappropriate for prevention of bleeding from a cavernoma. Our own case material consists of data of 72 patients operated upon during the past 5 years. Twenty-four patients harbored the lesion within the brainstem, 18 within the deep white matter of the hemispheres, 12 in the basal ganglia or thalamus, 11 in superficial areas of the hemisphere, and seven within the cerebellum. The perioperative morbidity rate was 29.2% (21/72) while the rate of long-term morbidity was 5.5% (4/72), with no mortality in this series. It is concluded that cerebral cavernous malformations, including lesions in critical regions of the brain, can be treated microsurgically with excellent results and an acceptable morbidity.
UI - 11949830
AU - Newton HB; Slivka MA; Stevens CL; Bourekas EC; Christoforidis GA; Baujan
TI - MA; Chakeres DW Intra-arterial carboplatin and intravenous etoposide for the treatment of recurrent and progressive non-GBM gliomas.
SO - J Neurooncol 2002 Jan;56(1):79-86
AD - Department of Neurology, The Ohio State University Medical Center and James Cancer Hospital and Solove Research Institute, Columbus 43210, USA. email@example.com
Recurrent and progressive non-GBM gliomas are a diverse group of brain tumors that often respond poorly to adjuvant chemotherapy treatment. Regional intra-arterial (IA) administration of chemotherapy may result in increased tumor uptake of drug, with improvement in response rates and time to progression (TTP). Twenty-five patients with recurrent or progressive non-GBM gliomas were treated with IA carboplatin (200 mg/m2/d) and intravenous (IV) etoposide (100 mg/m2/d) for 2 days every 4 weeks. Patients ranged in age from 22 to 68 years (mean 37.8). All but one patient had received standard irradiation, and eight patients had attempted prior chemotherapy. Five of 25 patients had objective responses (20%), while another 15 patients had stable disease (60%), receiving a total of 318 IA treatment procedures. There was one complete response (4.0%), three partial responses (12.0%), one minor response (4.0%), 15 stable diseases (60.0%), and five progressive diseases (20.0%). The median TTP was 24.2 weeks overall and 32 weeks in responders. Overall median survival was 34.2 weeks. Therapy was well tolerated, with mainly hematologic toxicity. Two patients had embolic complications. Although these are preliminary results, IA carboplatin and IV etoposide have modest activity against recurrent and progressive non-GBM gliomas and warrants further study.
UI - 11949831
AU - Oya N; Shibamoto Y; Nagata Y; Negoro Y; Hiraoka M
TI - Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure.
SO - J Neurooncol 2002 Jan;56(1):87-94
AD - Department of Radiology, Faculty of Medicine, Kyoto University, Japan. firstname.lastname@example.org
The long-term results of external beam radiotherapy following surgical resection in patients with intracranial ependymomas were evaluated to identify the prognostic factors and the pattern of recurrence. Between were treated with external beam irradiation with >40 Gy following surgery. Total doses of 40.5-63.4Gy were delivered to the tumor site in 22-46 fractions over 33-101 days. Six patients with spinal deposit or positive cerebrospinal fluid cytology received whole spinal axis irradiation, and 4 patients received prophylactic spinal irradiation. The median follow-up of surviving patients was 110 months. The 10-year overall and relapse-free survival rates were 47% and 42%, respectively. In multivariate analysis, female gender, lower tumor grade and total resection were found to be associated with better relapse-free survival. Twenty of 26 recurrences developed at the primary tumor site (inside the irradiation field), two at the unirradiated cerebellum and spinal cord, and four at the spinal cord without intracranial failure. Only one of 34 patients with supratentorial tumors developed isolated spinal metastasis, whereas 3 of 14 patients with infratentorial tumors did so. Regarding the late neurotoxicity of radiotherapy, one of the 15 long-term (>4 years) survivors whose psychosocial status could be evaluated showed marked cognitive impairment. It was suggested that the use of new treatment strategies to improve local control would be warranted, and that prophylactic whole spinal axis irradiation appeared to be of more benefit in patients with infratentorial tumors than in those with supratentorial tumors.
UI - 12042921
AU - Tomita T; Cortes RF
TI - Astrocytomas of the cerebral peduncle in children: surgical experience in seven patients.
SO - Childs Nerv Syst 2002 May;18(5):225-30
AD - Division of Pediatric Neurosurgery, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA. email@example.com
OBJECTS: Cerebral peduncle tumors are rare in childhood but often consist of benign astrocytomas. Surgical resection, however, is considered to be detrimental because of the highly sensitive neural structures. These tumors are often treated by radiation therapy (RT). We resected such tumors in seven patients, whom we then followed up without adjuvant therapy. The surgical approach and postoperative course are analyzed.METHODS: Seven children, ranging in age from 4 to 16 years, were treated from 1993 to 2000. Tumors showed extension in various directions to the thalamus, pons and neighboring cisterns. All were treated by surgical resection through a subtemporal approach: total resection was achieved in three and subtotal resection in four. Operative complications were minimal. Two patients were worse after surgery, albeit temporarily, in motor, oculomotor or memory functions. All the tumors were benign astrocytomas. None of the patients received postoperative RT. Only one patient had a recurrence during the follow-up period, which ranged from 1 year to 8.5 years in duration.CONCLUSIONS: Benign astrocytomas of the cerebral peduncle are amenable to radical tumor resection by an appropriate surgical approach and with microsurgical techniques. Even following subtotal resection, these tumors frequently remain stable or involute. These children can be spared RT.
UI - 11696117
AU - Orliaguet GA; Hanafi M; Meyer PG; Blanot S; Jarreau MM; Bresson D; Zerah
TI - M; Carli PA Is the sitting or the prone position best for surgery for posterior fossa tumours in children?
SO - Paediatr Anaesth 2001;11(5):541-7
AD - Departement d'Anesthesie Reanimation, CHU Necker-Enfants Malades, Paris, France. firstname.lastname@example.org
BACKGROUND: The aim of this study was to compare complications in children operated for posterior fossa tumours in the sitting position with those in the prone position. METHODS: We retrospectively assessed the perioperative course of posterior fossa tumour (PFT) surgery according to the operating position. Sixty children were operated in the sitting position (SP) and 19 in the prone position (PP). Preoperative data were not different between groups. RESULTS: Patients in the PP group received a larger median (95% confidence interval) volume of intraoperative blood transfusion than patients in the SP group [200 (20-325) versus 0 (0-80) ml, P=0.04]. Intraoperative complications, as well as severe perioperative complications were more frequent in the PP group (P=0.01). The median duration of tracheal intubation [20 (18-24) versus 36 (18-72) h, P=0.037], of ICU stay [2 (2-3) versus 4 (2-5) days, P=0.02] and of hospital stay [11 (9-12) versus 14 (10-20) days, P=0.02] was longer in the PP group compared with the SP group. CONCLUSIONS: PFT surgery in the sitting position in children is not associated with an increased number or severity of perioperative complications, while the postoperative course appears better in this position.
UI - 12182772
AU - Selker RG; Shapiro WR; Burger P; Blackwood MS; Arena VC; Gilder JC;
TI - Malkin MG; Mealey JJ Jr; Neal JH; Olson J; Robertson JT; Barnett GH; Bloomfield S; Albright R; Hochberg FH; Hiesiger E; Green S; Brain Tumor Cooperative Group 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.
SO - Neurosurgery 2002 Aug;51(2):343-55; discussion 355-7
AD - email@example.com
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 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.
UI - 12145515
AU - Due-Tonnessen BJ; Helseth E; Scheie D; Skullerud K; Aamodt G; Lundar T
TI - Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): report of 110 consecutive cases.
SO - Pediatr Neurosurg 2002 Aug;37(2):71-80
AD - Department of Neurosurgery, National Hospital, Rikshospitalet, N-0027 Oslo, Norway.
The objective of this retrospective study was to present long-term follow-up data for 110 consecutive children and young adults treated for a benign cerebellar astrocytoma at our institution between 1960 and 2001. Mean age at presentation was 8.9 years. The total surgical mortality was 9%, but declined from 16% in 1960-1977 to 0% in 1988-2001. At the close of the study 97/110 patients were still alive. Nine deaths were surgery related, 2 patients died of shunt-related causes and 2 patients died due to tumor recurrence. Five-, 10- and 25-year survival were 90, 89 and 85%, respectively. Multiple Cox regression analysis showed that tumor infiltration of the brain stem and the time period of surgery were the only explanatory variables significantly associated with survival. Five-year survival improved from 79% in the time period of 1960-1977 to 100% in the time period of 1988-2001. Tumor recurrence after total tumor resection was observed in 5 of 76 (7%) evaluable patients. Growth of residual tumor after subtotal tumor resection was observed in 7 of 26 (27%) evaluable patients. Recent followup MR revealed regression of residual tumor in 14 of 16 patients. Only 5 of these patients had received radiotherapy. Thus, spontaneous regression of residual tumor is a more frequent event than growth of residual tumor. The functional outcome was favorable in 82% of the patients [Karnofsky performance index (KPI) > or = 90]. Eighteen percent of the patients had moderate to severe disabilities (KPI 50-80). CONCLUSIONS: Benign cerebellar astrocytoma is a surgical disease where the prognosis with respect to both survival and functional outcome is favorable. Spontaneous regression of residual tumor is frequently encountered, allowing for observation of residual tumors instead of performing a second resection in cases where a second resection carries a high risk of neurological sequelae. Copyright 2002 S. Karger AG, Basel
UI - 12297119
AU - Gaya A; Rees J; Greenstein A; Stebbing J
TI - The use of temozolomide in recurrent malignant gliomas.
SO - Cancer Treat Rev 2002 Apr;28(2):115-20
AD - Department of Radiotherapy, Hammersmith Hospitals NHS Trust, Fulham Palace Road, London W6 8RF, UK. firstname.lastname@example.org
Gliomas are the most common primary intracerebral tumours and over 60% of these are malignant. Standard treatment in the UK for patients with a good performance status consists of surgery and postoperative radiotherapy, however, recurrence is almost inevitable. Treatment of recurrent malignant gliomas (MG) is limited to further surgery, chemotherapy and novel biological therapies. The response rate to standard chemotherapy protocols for recurrent MG is less than 30%. Temozolomide (Temodar-US, Temodal-Rest of World) is an oral alkylating agent with a similar chemical structure to dacarbazine, and has recently been licensed in the UK for second line treatment of recurrent MG. Several phase II studies and one randomised trial suggest that Temozolomide improves time to progression and quality of life but not overall survival. The drug is well tolerated with dose limiting myelosuppression and thrombocytopenia occurring in less than 10% of patients at current dosage schedules. A randomised trial comparing Temozolomide with best first line adjuvant chemotherapy (PCV) is about to start recruiting patients. Further clinical studies investigating its role in neoadjuvant treatment or in combination with radiotherapy or other chemotherapeutic approaches are ongoing.
UI - 12365113
AU - Sur RK; Nayler S; Ahmed SN; Donde B; Uijs RR; Cooper K; Giraud A
TI - Angiosarcomas--clinical profile, pathology and management.
SO - S Afr J Surg 2000 May;38(1):13-6
AD - Department of Radiation Oncology and Anatomical Pathology, University of the Witwatersrand, South African Institute for Medical Research, Johannesburg.
Files of 8 patients with primary angiosarcomas treated in the Department of Radiation Oncology at the University of the Witwatersrand from 1982 to 1995 were identified. None of these patients had received prior radiotherapy or chemotherapy which would have predisposed them to the formation of an angiosarcoma. Slides of 6 patients were reviewed. Five of the 6 were confirmed as having angiosarcomas, while 1 patient was found to have a peripheral neuro-epithelial tumour. Four patients had angiosarcomas of the breast, while there was 1 patient each with angiosarcoma of the skin, intestine and brain. Complete excision was the primary modality of management whenever possible. Postoperative radiotherapy was given in cases of incomplete excision, patient refusal of radical surgery or gross tumour. Four patients died within 4 months of diagnosis. Three patients are alive (2 with no evidence of disease) 22-96 months after diagnosis. In 1 patient follow-up details were not available as he did not return for treatment. Angiosarcomas are aggressive malignant tumours arising from the endothelial cells. Complete surgical excision is the treatment of choice in the management of this aggressive disease, which has a poor prognosis.
UI - 11334274
AU - Zhou HH; Kelly PJ
TI - Transcranial electrical motor evoked potential monitoring for brain tumor resection.
SO - Neurosurgery 2001 May;48(5):1075-80; discussion 1080-1
AD - Department of Anesthesiology, New York University Medical Center, New York 10016, USA.
OBJECTIVE: This study was designed to examine whether transcranial electrical motor evoked potential (MEP) monitoring is safe, feasible, and valuable for brain tumor surgery. METHODS: Fifty consecutive patients undergoing brain tumor resection were studied, using nitrous oxide/propofol anesthesia. MEPs were continuously recorded throughout surgery, using a Sentinel 4 evoked potential system (Axon Systems, Inc., Hauppauge, NY). The MEPs were elicited by transcranial electrical stimulation (train of 5; stimulation rate, 0.5-2 Hz; square wave pulse with a time constant of 0.5 ms; stimulation intensity, 40-160 mA) through spiral electrodes placed over the primary motor cortex and were recorded by needle electrodes inserted into the contralateral orbicularis oris, biceps, abductor pollicis brevis, and anterior tibialis muscles. When MEP amplitudes decreased by more than 50%, MEP stimulation was repeated, with increased stimulation intensity, and MEP changes were reported to the surgeon. The motor function of each patient was examined before and after surgery, using a reproducible scale. The relationship between MEP amplitude decreases and worsening motor status was analyzed using linear regression. RESULTS: Preoperative neurological examinations revealed mild to moderate motor deficits (2/5 to 4/5) for 38% of patients (19 of 50 patients). Most of the patients (96%) exhibited recordable baseline MEPs. Persistent MEP decreases of more than 50% were noted for eight patients (16%) (11 muscles). The MEPs were completely abolished in two patients (three muscles). The degree of postoperative worsening of motor status was correlated with the degree of intraoperative MEP amplitude reduction (r = -0.864; P < 0.001). CONCLUSION: Persistent intraoperative MEP reductions of more than 50% were associated with postoperative motor deficits. The degree of MEP amplitude reduction was correlated with postoperative worsening of motor status. Transcranial electrical MEP monitoring is feasible, safe, and valuable for brain tumor surgery.
UI - 11821471
AU - Aoyama H; Shirato H; Ikeda J; Fujieda K; Miyasaka K; Sawamura Y
TI - Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors.
SO - J Clin Oncol 2002 Feb 1;20(3):857-65
AD - Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-beta)-secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-beta-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-beta-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the last follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas.
UI - 12065573
AU - Paulino AC
TI - Induction chemotherapy and involved-field radiotherapy for intracranial germinoma.
SO - J Clin Oncol 2002 Jun 15;20(12):2911; discussion 2911-2
UI - 12361645
AU - Ioffe V; Hudes RS; Shepard D; Simard JM; Chin LS; Yu C
TI - Fetal and ovarian radiation dose in patients undergoing gamma knife radiosurgery.
SO - Surg Neurol 2002 Jul;58(1):32-41; discussion 41
AD - Department of Radiation Oncology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21229, USA.
BACKGROUND: It is difficult to estimate the fetal or ovarian radiation dosage for female patients undergoing Gamma Knife radiosurgery. Our goals are to determine the fetal and ovarian radiation dose at various distances from a cranial isocenter, to provide a reference for practitioners to estimate the fetal dose with respect to gestational age, and to identify the components of pelvic extracranial radiation. METHODS: An anthropomorphic phantom and ion chamber were used to measure the dose at 50, 60, and 70 cm from a cranial isocenter and at three points within the transverse plane for the supine position. Each measurement consisted of a 5-minute exposure. Additional measurements were taken for four collimator sizes, the prone position, off-axis, and with one-half of all collimator holes plugged. RESULTS: The values of the fetal and ovarian dose rates ranged from 0.27 cGy/min to 0.05 cGy/min based on distance from the isocenter. The fetal and ovarian dose can be up to 8.1 cGy for a 30-minute Gamma Knife treatment. The dose fell off more rapidly than predicted by the inverse square law. There was no dependence of fetal dose rate on collimator size. No advantage to the prone position could be shown. Leakage and collimator scatter are the main components of extracranial dose 50 to 70 cm from the isocenter. CONCLUSIONS: The fetal and ovarian dose is a function of treatment time and distance from the isocenter. We recommend pregnancy status assessment in women of reproductive age and treatment plan design using large volume shots in order to minimize treatment time.
UI - 12234394
AU - Kondziolka D; Hadjipanayis CG; Flickinger JC; Lunsford LD
TI - The role of radiosurgery for the treatment of pineal parenchymal tumors.
SO - Neurosurgery 2002 Oct;51(4):880-9
AD - Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA.
OBJECTIVE: Radiosurgery is an appealing alternative management strategy for selected patients with biopsy-proved pineal parenchymal tumors. The purpose of this report was to clarify its role in conjunction with other surgical, radiation, and medical approaches. METHODS: We retrospectively evaluated 16 patients who had undergone radiosurgery as the primary or adjuvant treatment for pineal parenchymal tumors. Ten patients (62.5%) had pineocytomas, two (12.5%) had mixed pineocytoma and pineoblastoma, and four (25%) had pineoblastomas. The mean marginal dose was 15 Gy, and the mean tumor volume was 5.0 cm(3). The mean follow-up periods from the time of diagnosis or the time of radiosurgery were 61 and 52 months, respectively. RESULTS: The overall actuarial 2- and 5-year survival rates after diagnosis were 75.0 and 66.7%, respectively. In 14 patients who were evaluated with imaging, 4 (29%) demonstrated complete remission, 8 (57%) had partial remission, 2 (14%) had no change, and no patient had local progression. The local tumor control rate (complete remission, partial remission, or no change) was 100%. Five patients died during follow-up. One patient with a pineocytoma and three patients with pineoblastomas died secondary to leptomeningeal or extracranial spread tumor. No cause of death was established for one patient. Two patients developed adverse radiation effects after radiosurgery. CONCLUSION: Our initial experience suggests that stereotactic radiosurgery is a valuable primary management modality for patients with pineocytomas. As adjuvant therapy, radiosurgery may be used to boost local tumor dose during multimodality management of malignant pineal parenchymal tumors.
UI - 12234397
AU - Rock JP; Hearshen D; Scarpace L; Croteau D; Gutierrez J; Fisher JL;
TI - Rosenblum ML; Mikkelsen T Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis.
SO - Neurosurgery 2002 Oct;51(4):912-9; discussion 919-20
AD - Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, Michigan 48202, USA. email@example.com
OBJECTIVE: The differentiation of tumor recurrence from radiation necrosis in patients with malignant gliomas who have been treated previously remains a challenge. Magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography cannot provide definitive histopathological insight. Multivoxel proton magnetic resonance spectroscopic imaging ((1)H MRSI) may be reliable in guiding the clinical management of untreated patients; however, its value in managing previously treated patients remains unclear. METHODS: Twenty-seven patients who had been treated previously with surgery, radiotherapy, and chemotherapy and reoperated for clinical and/or radiographic signs that caused suspicion for recurrent disease were studied. Tissues were categorized into four groups: spectroscopically normal, pure tumor, mixed tumor and radiation necrosis, and pure radiation necrosis. Spectral data for choline (Cho), lipid-lactate (Lip-Lac), N-acetylaspartate, and creatine (Cr) were analyzed as Cho/normal Cr (nCr), Lip-Lac/Cho, Lip-Lac/nCr, N-acetylaspartate/Cho, N-acetylaspartate/nCr, and Cho/normal Cho (nCho). Stereotactic biopsies were obtained within 48 hours of (1)H MRSI and were directly correlated digitally with (1)H MRSI data. Logistic regression analysis was performed on the basis of data obtained from 99 (1)H MRSI observations to determine whether the (1)H MRSI ratios varied according to tissue category. RESULTS: (1)H MRSI ratios were found to distinguish pure tumor from pure necrosis. The odds of a biopsy's being pure tumor and having either a Cho/nCr value greater than 1.79 or a Lip-Lac/Cho value less than 0.75 are seven times the odds of that biopsy's being pure necrosis (odds ratio, 7.00; P = 0.0136). The odds of a biopsy's being pure necrosis and having either a Cho/nCr value less than 0.89 or a Cho/nCho value less than 0.66 are six times the odds of that biopsy's being pure tumor (odds ratio, 5.71; P = 0.0329). The odds of a biopsy's being pure necrosis and having either a Lip-Lac/Cho value greater than 1.36 or a Lip-Lac/nCr value greater than 2.84 are more than five times the odds of the biopsy's being pure tumor (odds ratio, 5.25; P = 0.0322). In addition, although only marginally significant, Lip-Lac/Cho and Lip-Lac/nCr ratios distinguish pure tumor from pure necrosis. No values suggested that mixed specimens could be distinguished in a statistically significant way from either pure tumor or pure necrosis. CONCLUSION: The data that we gathered suggest that metabolite ratios derived on the basis of (1)H MRSI spectral patterns do allow reliable differential diagnostic statements to be made when the tissues are composed of either pure tumor or pure necrosis, but the spectral patterns are less definitive when tissues composed of varying degrees of mixed tumor and necrosis are examined.
UI - 12368625
AU - Kasperbauer JL; Orvidas LJ; Atkinson JL; Abboud CF
TI - Rathke cleft cyst: diagnostic and therapeutic considerations.
SO - Laryngoscope 2002 Oct;112(10):1836-9
AD - Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA. Kasperbauer.firstname.lastname@example.org
OBJECTIVE: To highlight diagnostic and therapeutic issues about Rathke cleft cysts for otorhinolaryngologists. STUDY DESIGN: Retrospective. METHODS: We retrospectively reviewed data collected on Rathke cleft cysts between 1978 and 1998: presenting symptoms, visual acuity, surgical treatment, complications, recurrences, and effect on daily activity. RESULTS: Twenty-nine patients were diagnosed with a Rathke cleft cyst (11 male and 18 female patients; mean age, 46 y). The most common presenting symptom was head pain (55%). The majority (59%) of cases demonstrated suprasellar extension on preoperative imaging, with pituitary dysfunction identified in 66%. Recurrence occurred in eight patients (28%). Postoperative visual function improved or remained stable in all patients. Persistent pituitary dysfunction required hormonal supplementation in seven patients (24%). Only one patient with an astrocytoma in addition to a Rathke cleft cyst did not maintain the ability to perform normally on an assessment of activities of daily living, a striking contrast to patients with craniopharyngioma. CONCLUSIONS: Conclusions were as follows: 1) Rathke cleft cysts must be considered as sources of head pain and pituitary dysfunction. 2) Persistent or recurrent cyst formation occurs in approximately one-third of the patients. Recurrence may take many years, and follow-up imaging is recommended for at least a decade. 3) Maintenance of the ability to perform the activities of normal daily living can be expected after surgical management. 4) Most Rathke cleft cysts can be managed through transnasal exposure of the sella. 5) Packing the sella may result in predisposition to recurrent cyst formation.
UI - 11914886
AU - Schumacher T; Hofer S; Eichhorn K; Wasner M; Zimmerer S; Freitag P;
TI - Probst A; Gratzl O; Reubi JC; Maecke R; Mueller-Brand J; Merlo A Local injection of the 90Y-labelled peptidic vector DOTATOC to control gliomas of WHO grades II and III: an extended pilot study.
SO - Eur J Nucl Med Mol Imaging 2002 Apr;29(4):486-93
AD - Institute of Nuclear Medicine, University Hospitals, Basel, Switzerland.
We have previously presented preliminary observations on targeting somatostatin receptor-positive malignant gliomas of all grades by local injection of the radiolabelled peptidic vector 90Y-DOTATOC. We now report on our more thorough clinical experience with this novel compound, focussing on low-grade and anaplastic gliomas. Small peptidic vectors have the potential to target invisible infiltrative disease within normal surrounding brain tissue, thereby opening a window of opportunity for early intervention. Five progressive gliomas of WHO grades II and III and five extensively debulked low-grade gliomas were treated with varying fractions of 90Y-DOTATOC. The vectors were locally injected into the resection cavity or into solid tumour. The activity per single injection ranged from 555 to 1,875 MBq, and the cumulative activity from 555 to 7,030 MBq, according to tumour volumes and eloquence of the affected brain area, yielding dose estimates from 76+/-15 to 312+/-62 Gy. Response was assessed by the clinical status, by steroid dependence and, every 4-6 months, by magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography. In the five progressive gliomas, lasting responses were obtained for at least 13-45 months without the need for steroids. Radiopeptide brachytherapy had been the only modality applied to counter tumour progression. Interestingly, we observed the slow transformation of a solid, primarily inoperable anaplastic astrocytoma into a resectable multi-cystic lesion 2 years after radiopeptide brachytherapy. Based on these observations, we also assessed the feasibility of local radiotherapy following extensive debulking, which was well tolerated. Targeted beta-particle irradiation based on diffusible small peptidic vectors appears to be a promising modality for the treatment of malignant gliomas.
UI - 10870063
AU - Koot RW; Maarouf M; Hulshof MC; Voges J; Treuer H; Koedooder C; Sturm V;
TI - Bosch DA Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme.
SO - Cancer 2000 Jun 15;88(12):2796-802
AD - Department of Neurosurgery, Academic Medical Center, Amsterdam, The Netherlands.
BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM. Copyright 2000 American Cancer Society.
UI - 10728209
AU - Packer RJ
TI - Childhood brain tumours: new directions in management.
SO - Eur J Paediatr Neurol 1997;1(5-6):133-8
AD - Department of Neurology, Children's National Medical Center, Washington, DC 20010, USA.
UI - 12217793
AU - Gupta T; Sarin R
TI - Poor-prognosis high-grade gliomas: evolving an evidence-based standard of care.
SO - Lancet Oncol 2002 Sep;3(9):557-64
AD - Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.
Patients with high-grade glioma (HGG) can be classified as having a favourable prognosis (younger or with good performance status) or a poor prognosis (older or with poor performance status) with median survival of 12-24 months and 6-9 months, respectively. The standard management for the favourable subgroup is maximum safe resection followed by adjuvant conventionally fractionated radio therapy, with or without chemotherapy. However, most patients with HGG have a poor prognosis and their optimum management has yet to be defined. In the poor-prognosis HGG subgroup, short-course radiotherapy is equivalent to conventional radiotherapy in terms of survival and palliation (level II evidence), but chemotherapy is not recommend ed (level II evidence). The problems with the existing systems of prognosis are discussed and a pragmatic system proposed. Owing to lack of any level I evidence, the need to conduct prospective randomised trials with quality of life and palliative effect as primary endpoints is emphasised. Until such time, maximum safe resection followed by a short course of focal radiotherapy is recommended as the standard of care in poor prognosis HGG.
UI - 11939089
AU - Arismendi G; Bohorquez M; Romero de Amaro Z; Cardozo D; Luzardo G;
TI - Molina O; Cardozo J [Epidemiologic studies of cerebellopontine angle tumors surgically treated in Maracaibo, Venezuela, in 1985-1999]
SO - Neurocirugia (Astur) 2002 Feb;13(1):22-6
AD - Departamento de Patologia, Hospital General del Sur, Maracaibo.
OBJECTIVE: To analyze the epidemiological, clinical and neuropathological data of cases of cerebellopontine angle (CPA) tumors. MATERIAL AND METHODS: The clinical records, neuroimaging and neuropathological studies of 50 patients with diagnosis of CPA tumor operated in different hospitals of Maracaibo, Venezuela, during the lapse January 1st, 1985-December 31, 1999 were reviewed. The variables age, gender, side of the lesion and neuropathological diagnosis were analyzed. RESULTS: A 2:1 female to male ratio was observed. Median age was 48 +/- 12.7 years. Acoustic neuromas (AN) represented 48% of the cases, whereas nonacoustic neuroma tumors (NANT) made up for the rest (52%). Meningiomas were the second more commonly diagnosed lesions, they constituted 32% of the cases. Meningiomas and AN were more frequent in women, their ratios being 7:1 and 1.6:1, respectively. In 60% of the cases the signs and symptoms became eloquent in patients of the fourth and fifth decades of life. CONCLUSIONS: The difference between our results and the ones previously reported in the medical literature are due in part to the predominance of female patients in our series. Endocrinologic, genetic and biochemical factors could also be responsible; nevertheless, this does not constitute the objective of the present study.
UI - 11995820
AU - Chamberlain MC
TI - Salvage chemotherapy with CPT-11 for recurrent glioblastoma multiforme.
SO - J Neurooncol 2002 Jan;56(2):183-8
AD - University of Southern California, Norris Comprehensive Cancer Hospital, Department of Neurology, Los Angeles 90033-0804, USA. email@example.com
BACKGROUND: A prospective Phase II study of CPT-11 in adult patients with recurrent supratentorial glioblastoma multiforme (GBM). METHODS: Forty patients (25 men, 15 women) ages 32-71 years (median 59), with recurrent GBM were treated. All patients had previously been treated with surgery and involved field radiotherapy (median dose 60 Gy; range 59-60). Additionally, all patients were treated with adjuvant chemotherapy (BCNU in 20, PCV in 18, Procarbazine in 2). Twenty-five patients (62%) were on anticonvulsants (phenytoin in 15, carbamazepine in 10) and 26 patients (65%) were on dexamethasone. Recurrent disease was defined by neuroradiographic disease progression (>25% increase in tumor dimensions) using gadolinium-enhanced MR imaging. The starting dose of CPT-11 was 400 mg/m2 followed in three weeks by 500 mg/m2, operationally defined as one cycle. At week 6, all patients were evaluated with MRI and neurological examination. RESULTS: All patients were evaluable. Two doses (one cycle) of CPT-11 were administered to all patients. CPT-11-related toxicity included: diarrhea (16 patients, 40%); thrombocytopenia (9 patients, 23%); and neutropenia (6 patients, 15%). No patient required transfusion nor was treatment for neutropenic fever required. No treatment-related deaths were observed. All patients demonstrated progressive disease following one cycle of CPT-11. CONCLUSIONS: The lack of response to CPT-11 in this patient group with recurrent GBM suggests either CPT-11 has minimal activity or CPT-11 doses/schedule utilized in this study were sub-optimal. The latter is supported by the modest toxicity seen in this study and the previously documented enhanced clearance of CPT-11 in patients on anticonvulsants and dexamethasone.
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