Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

1990 ◽  
Vol 72 (5) ◽  
pp. 737-744 ◽  
Author(s):  
Edward H. Oldfield ◽  
Robert Friedman ◽  
Timothy Kinsella ◽  
Ross Moquin ◽  
Jeffrey J. Olson ◽  
...  
Keyword(s):  
Survival Rates ◽  
Cranial Irradiation ◽  
High Dose ◽  
Radiation Toxicity ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Brain Irradiation ◽  
Cns Neoplasms ◽  
Fine Print

✓ To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p < 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise “unsafe” doses of radiation in patients with CNS neoplasms.

Hypothalamic dysfunction following whole-brain irradiation

1986 ◽  
Vol 65 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Jeffrey I. Mechanick ◽  
Fred H. Hochberg ◽  
Alan LaRocque
Keyword(s):  
Computerized Tomography ◽  
Radiation Necrosis ◽  
Cortical Atrophy ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Hypothalamic Dysfunction ◽  
Brain Irradiation ◽  
X Irradiation ◽  
Fine Print

✓ The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage.

Medulloblastoma: freedom from relapse longer than 8 years — a therapeutic cure?

1991 ◽  
Vol 75 (4) ◽  
pp. 575-582 ◽  
Author(s):  
Mark G. Belza ◽  
Sarah S. Donaldson ◽  
Gary K. Steinberg ◽  
Richard S. Cox ◽  
Philip H. Cogen
Keyword(s):  
Medical Center ◽  
Survival Rates ◽  
Adjunctive Treatment ◽  
High Dose ◽  
Content Type ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Fine Print

✓ Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (≥ 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately.

Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
S. Issa ◽  
J. Hwang ◽  
J. Karch ◽  
J. Fridlyand ◽  
M. Prados ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Dose Methotrexate ◽  
Biomarker Analysis

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p<0.028) and OS (p<0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]

Stereotactic radiosurgery for cerebral metastatic melanoma

1993 ◽  
Vol 79 (5) ◽  
pp. 661-666 ◽  
Author(s):  
Salvador Somaza ◽  
Douglas Kondziolka ◽  
L. Dade Lunsford ◽  
John M. Kirkwood ◽  
John C. Flickinger
Keyword(s):  
Stereotactic Radiosurgery ◽  
Systemic Disease ◽  
Tumor Resection ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Tumor ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Fine Print

✓ To determine local tumor control rates and survival of patients with melanoma metastases to the brain, the authors reviewed the results of 23 consecutive patients with a total of 32 tumors (19 patients had a solitary tumor and four had multiple tumors) who underwent adjuvant stereotactic radiosurgery. Tumor locations included the cerebral hemisphere (24 cases), brain stem (four cases), basal ganglia (two cases), and cerebellum (two cases). Fifteen patients had associated cranial symptomatology and eight had incidental metastases. All patients had tumors of 3 cm or less in diameter (mean tumor volume 2.5 cu cm), and all received fractionated whole-brain radiation therapy (30 Gy) in addition to radiosurgery (mean tumor margin dose 16 Gy). Nineteen patients were managed with both modalities at the time of diagnosis; four underwent radiosurgery 3 to 12 months after fractionated whole-brain radiotherapy. The mean patient follow-up period was 12 months (range 3 to 38 months). After radiosurgery, eight patients improved, 13 remained stable, and two deteriorated. One patient subsequently required craniotomy because of intratumoral hemorrhage; this patient and three others are living 13 to 38 months after radiosurgery. Nineteen patients died, 18 from progression of their systemic disease and one from another hemorrhage into a new brain metastasis. The local tumor control rate was 97%. Only two patients subsequently developed new intracranial metastases. The median survival period after diagnosis was 9 months (range 3 to 38 months). The authors believe that stereotactic radiosurgery coupled with fractionated whole-brain irradiation is an effective management strategy for cerebral metastases from a melanoma. Multi-institutional trials are warranted to confirm that stereotactic radiosurgery results equal or surpass the outcome achieved with craniotomy and tumor resection.

Treatment of Primary CNS Lymphoma with Induction High-Dose Methotrexate, Temozolomide, Rituximab Followed by Consolidation Cytarabine/Etoposide: A Pilot Study with Biomarker Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1364-1364 ◽  
Author(s):  
Samar Issa ◽  
Arthur Shen ◽  
Jon Karch ◽  
Cigall Kadoch ◽  
Marc Shuman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Immunohistochemical Analysis ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Biomarker Analysis

Abstract Background: There is no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). The goals of this study were: to determine the safety and efficacy of a methotrexate (MTX)-based induction therapy followed by high-dose consolidation chemotherapy and the elimination or deferral of whole brain irradiation, to identify molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 23 newly diagnosed, CD20-positive, immunocompetent PCNSL patients were treated with combination high-dose intravenous MTX (8 gm/m2), temozolomide (150 mg/m2/day) and intravenous rituximab (375 mg/m2) (MTR). Patients in complete remission (CR) after eight courses of MTX were offered consolidation with high-dose cytarabine (2 g/m2 x 8 doses) and etoposide (40 mg/kg over 96 hours) (AE). Candidate markers of outcome in PCNSL were identified by gene expression profile analysis of an independent, multicenter dataset of PCNSL tumors. Immunohistochemical analysis of one of these markers, death-associated protein-1 (DAP-1), was performed on paraffin sections of tumors from 18 of the patients treated with the MTR regimen. Results: MTR induction followed by AE consolidation was well tolerated with no treatment-related mortality or evidence for neurotoxicity. Thirteen patients (56.5%) attained CR with induction; 8 received consolidation; 5 in CR refused AE. Median progression-free (PFS) and overall survival (OS) has not yet been reached with a median follow-up of 33 months. Karnovsky performance status (KPS) correlated with improved survival (p<0.0281). Expression by lymphoma cells of DAP-1, a regulator of apoptosis, was associated with improved progression-free survival (p<0.03) and overall survival (p<0.038). Conclusions: Combination MTR followed by AE is well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A multi-center study has been initiated to further evaluate this regimen. DAP-1 may be a tumor suppressor whose expression in PCNSL predicts a favorable response to MTX-based therapy.

Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia

1984 ◽  
Vol 61 (4) ◽  
pp. 772-776 ◽  
Author(s):  
Pascal Tiberin ◽  
Esther Maor ◽  
Rina Zaizov ◽  
Ian J. Cohen ◽  
Menachem Hirsch ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Childhood Leukemia ◽  
Multimodality Treatment ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
Whole Brain Irradiation ◽  
Content Type ◽  
Brain Irradiation ◽  
Low Dosage

✓ The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8½-year-old girl. This tumor occurred 6½ years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

Radiation therapy in the management of low-grade supratentorial astrocytomas

1989 ◽  
Vol 70 (6) ◽  
pp. 853-861 ◽  
Author(s):  
Edward G. Shaw ◽  
Catherine Daumas-Duport ◽  
Bernd W. Scheithauer ◽  
David T. Gilbertson ◽  
Judith R. O'Fallon ◽  
...  
Keyword(s):  
Low Dose ◽  
Survival Rates ◽  
High Dose ◽  
Survival Times ◽  
Low Dose Radiation ◽  
Tumor Removal ◽  
Content Type ◽  
Pilocytic Astrocytomas ◽  
Dose Radiation ◽  
Fine Print

✓ The records of 167 patients with grade 1 or 2 supratentorial pilocytic astrocytomas (41 patients), ordinary astrocytomas (91 patients), or mixed oligoastrocytomas (35 patients) diagnosed between 1960 and 1982 are retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 33 patients (20%) and subtotal or biopsy only in the remaining 134 patients (80%). Postoperative radiation therapy was given to 139 (83%) of the 167 patients, with a median dose of 5000 cGy (range 600 to 6500 cGy). Multivariate analysis revealed that a pilocytic histology was the most significant prognostic variable associated with a good survival. The 5- and 10-year survival rates were, respectively, 85% and 79% for the 41 patients with pilocytic astrocytomas compared to 51% and 23% for the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas. Postoperative irradiation did not appear to be associated with improved survival times in the patients with pilocytic astrocytomas; however, in the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas, those who received “high-dose” radiation (≥ 5300 cGy) had significantly better survival times than those who received “low-dose” radiation (< 5300 cGy) or surgery alone. The 5- and 10-year survival rates were, respectively, 68% and 39% for the 35 patients receiving high-dose radiation, 47% and 21% for the 67 receiving low-dose radiation, and 32% and 11% for the 19 treated with surgery alone. The survival rate was poor for the 23 patients with ordinary astrocytomas and oligoastrocytomas who underwent gross total or radical subtotal tumor removal (14 of whom were also irradiated): 52% at 5 years and 21% at 10 years, with 19 of 23 patients developing tumor progression and dying 1 to 12 years postoperatively. In contrast, all 10 patients with pilocytic astrocytomas who had gross total or radical subtotal tumor removal alone were long-term survivors, with follow-up periods of about 4 to 25 years.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors

2004 ◽  
Vol 14 (5) ◽  
pp. 966-971 ◽  
Author(s):  
F. Ghaemmaghami ◽  
N. Behtash ◽  
N. Memarpour ◽  
K. Soleimani ◽  
P. Hanjani ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Survival Rates ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Results Of Treatment ◽  
Trophoblastic Tumors ◽  
Multi Agent ◽  
Late Group ◽  
Tomography Scan

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996–2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17–53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.

Radiotherapy of glioblastoma multiforme

1973 ◽  
Vol 39 (2) ◽  
pp. 197-202 ◽  
Author(s):  
Ruth G. Ramsey ◽  
William N. Brand
Keyword(s):  
Overall Survival ◽  
Specific Treatment ◽  
Tumor Location ◽  
Whole Brain Irradiation ◽  
Efficient Treatment ◽  
Content Type ◽  
Treatment Groups ◽  
Brain Irradiation ◽  
Brain Scan ◽  
Fine Print

✓ A comparison is made between limited field and whole brain irradiation in the treatment of 60 patients with intracranial glioblastomas, 34 of whom were picked at random for either treatment and 26 who were selected for specific treatment. A significant increase in overall survival time and tumor-free period was found in the limited field treatment groups and this was especially significant in those patients selected for limited field treatment. The improved results are felt to be due to the higher dose permissible because of avoidance of more sensitive brain-stem structures. Tumor location in the frontal lobe also appears significant in the longer survival of those patients selected for limited field treatment. More exact localization of the lesion by brain scan, surgery, and angiography also contribute to more efficient treatment and consequently better survival.

Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.

1992 ◽  
Vol 10 (9) ◽  
pp. 1390-1396 ◽  
Author(s):  
J H Silber ◽  
J Radcliffe ◽  
V Peckham ◽  
G Perilongo ◽  
P Kishnani ◽  
...  
Keyword(s):  
Multiple Linear Regression Model ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Iq Testing ◽  
Brain Irradiation ◽  
Significant Difference ◽  
Appropriate Therapy ◽  
The Impact

PURPOSE Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.

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