Biomedical subjects

W M Wara

Publications and source records attributed to W M Wara.

At least 37 records · Page 2Linked to original sources

PubMed1996

Gamma knife for glioma: selection factors and survival.

PURPOSE: To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS: We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. RESULTS CONCLUSION: The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS: Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.

Adolescent↗

PubMed1996

Reirradiation of primary CNS tumors.

PURPOSE: Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy. METHODS AND MATERIALS: We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas. RESULTS: Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment. CONCLUSIONS: Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.

Adolescent↗

PubMed1996

Radiosurgery for hemangioblastoma: results of a multiinstitutional experience.

PURPOSE: Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. METHODS AND MATERIALS: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy). RESULTS: Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR. CONCLUSIONS: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

Adrenal Cortex Hormones↗

PubMed1996

Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme.

PURPOSE: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. METHODS AND MATERIALS: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analysis of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. RESULTS: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. CONCLUSION: Although higher minimum tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost dose of 45-50 Gy in conjunction with conventional external beam radiotherapy, and reoperation for symptomatic necrosis.

Adolescent↗

PubMed1996

Toxicities of total-body irradiation for pediatric bone marrow transplantation.

PURPOSE: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone transplant (BMT) in children with immunodeficiency or hematologic disorders. METHODS AND MATERIALS: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. RESULTS: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of all patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts. Graft-vs.-host-disease (GVHD), pubertal development arrest, and delayed puberty were seen. One child developed papillary thyroid carcinoma, 49 months post-BMT. Similar neuropsychological testing decrements were also observed. CONCLUSION: Our experience suggests that intensive chemoradiotherapy, even at a young age, does not cause severe, acute, or late toxicities but does result in a small IQ decrement and the risk of secondary malignancy in children with long-term follow-up.

Adolescent↗

PubMed1996

Brainstem gliomas in children. A Children's Cancer Group review of 119 cases.

Brainstem gliomas (BSG) with intrinsic and extensive brainstem involvement continue to have a poor outlook despite current treatment approaches. Neuroimaging studies have aided in the differentiation of malignant brainstem tumors from more 'benign' subgroups. A Children's Cancer Group protocol evaluating outcome in children with BSG after treatment with hyperfractionated radiotherapy (7,200-7,800 cGy) was recently completed. The clinical aspects of 119 children entered into this study were reviewed in an attempt to determine risk groups and prognostic indicators. The overall survival of this group was very poor and there was no statistically significant correlation of survival with age, sex, clinical symptoms and signs, or tumor grade. Longer survival was only associated with prolonged duration of brainstem symptoms and signs greater than 1 month prior to diagnosis of the tumor. Improved outlook for children with BSG will require further research in tumor biology and newer therapeutic modalities.

Adolescent↗

PubMed1996

Gamma knife radiosurgery in children.

52 pediatric patients were treated with radiosurgery at the University of California, San Francisco. Arteriovenous malformations were treated in 27 patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2 years after radiosurgery. Arteriovenous malformation rebleed was noted in 1 patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of 14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three patients treated for neoplasms developed necrosis after radiosurgery.

Adolescent↗

PubMed1996

Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.

A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

Adolescent↗

PubMed1996

Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco.

PURPOSE: The purpose of our investigation was to correlate the extent and degree of organ involvement at presentation of Langerhans' cell histiocytosis (LCH) with subsequent disease course, survival, and late sequelae. MATERIALS AND METHODS: The medical records of 71 patients with a pathologic diagnosis of LCH, age 0 to 21 years, who presented between January 1, 1969 and June 30, 1994, were reviewed for organ involvement at diagnosis, treatment, disease course, and late sequelae. Supplementary data were obtained by mailed questionnaire. RESULTS: The median follow-up time from diagnosis for all patients was 8.1 years. Involvement at diagnosis included nine patients with skin-only disease, 22 with monostotic disease, 12 with polyostotic disease, and 28 with multisystem presentation. Treatment was surgery only in 17 and chemotherapy and/or radiotherapy in 54 patients. Recurrences were seen in 35 patients, with the highest rate in the polyostotic group. Ten patients died: seven with the multisystem presentation, two with monostotic disease, and one with skin-only disease. Causes included progressive LCH (n = 6) and late sequelae of either treatment (n = 3) or disease (n = 1). Late sequelae were seen in 64% of 51 patients with more than 3 years of follow-up data. The most common were skeletal defects in 42%, dental problems in 30%, diabetes insipidus in 25%, growth failure in 20%, sex hormone deficiency in 16%, hypothyroidism in 14%, hearing loss in 16%, and other CNS dysfunction in 14%. The overall estimated survival rates at 5, 15, and 20 years are 88%, 88%, and 77%, with an estimated event-free survival rate of only 30% at 15 years. CONCLUSION: Despite the favorable survival, more than half of LCH patients will have further dissemination of disease or late sequelae, including even some patients with single-system disease at diagnosis. Future treatment needs to be designed to prevent disease progression and late sequelae.

Adolescent↗

PubMed1996

Radiation response and survival time in patients with glioblastoma multiforme.

The determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external- beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p< 0.001 for radiation response and p=0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

Adolescent↗

PubMed1996

Radiotherapy for cerebral metastases.

Whole brain radiotherapy (WBRT) for patients with unresected brain metastases results in symptomatic response in about 50% of patients and improvement in median survival to 3 to 6 months. Most patients with brain metastases are appropriately treated with a conventional palliative course of 30 Gy in 10 fractions over 2 weeks, although accelerated hyperfractionation with 32 Gy to the whole brain plus a boost to at least 54.4 Gy at 1.6 Gy twice daily yields better results for patients with solitary metastases. Patients with a life-expectancy of greater than 6 months should receive at most that or equal to 2.0 Gy per fraction to minimize the risk of radiation-induced leukoencephalopathy and dementia. Patients with good performance status, absent or controlled primary tumor, and no extracranial metastases might benefit from surgical resection or radiosurgery (with or without adjunctive WBRT) to improve local control.

Brain Neoplasms↗

PubMed1995

Medulloblastoma in adults.

PURPOSE: To examine the relationship between extent of disease and outcome in adults with medulloblastoma. METHODS AND MATERIALS: We reviewed the records of all patients over 15 years old with newly diagnosed or recurrent medulloblastoma treated by or referred to the University of California, San Francisco, and recorded demographic characteristics, clinical symptoms, radiographic findings, extent of resection, staging, myelography, computerized tomography (CT) scans or magnetic resonance (MR) images of the spine, histopathological assessment, treatment received, treatment response, recurrence patterns, and survival duration. RESULTS: A total of 47 patients were identified, 26 of whom were designated "poor-risk" because they had < 75% removal of tumor, metastatic disease, or brain-stem or leptomeningeal invasion. All patients had radiation therapy; 32 had adjuvant chemotherapy. Twenty-two patients (47%) died of tumor progression, 19 are progression-free, and 6 are alive with disease. The median survival time was 282 weeks in poor-risk patients and has not been reached in good-risk patients. Overall and disease-free 5-year survival rates differed significantly between the two groups (81% vs. 54%, p = 0.03 and 58% vs. 38%, p = 0.05, respectively). Tumors most often recurred in the posterior fossa. The median survival time from recurrence was 77 weeks (range 44 to 89 weeks). CONCLUSION: These findings are similar to those reported for children. Therefore, staging and treatment in adults should be approached the same way as in children: staging should include cerebrospinal fluid assessment and spinal imaging. Treatment should be based on staging, and should include craniospinal irradiation; additional chemotherapy should probably be reserved for poor-risk patients.

Adolescent↗

PubMed1995

Radiation therapy for primary intracranial germ-cell tumors.

PURPOSE: To evaluate the diagnosis, therapy, and survival of patients with intracranial germ-cell tumors. To define the role of prophylactic craniospinal irradiation and chemotherapy necessary to impact on survival. METHODS AND MATERIALS: Forty-eight patients with surgically confirmed or suspected primary intracranial germ-cell tumors treated at UCSF between 1968-1990 were reviewed. Thirty-four patients had a pathologic diagnosis, including 24 germinomas, 3 malignant teratomas, 2 choriocarcinomas, 1 embryonal carcinoma, 1 endodermal sinus tumor, and 3 mixed tumors. Information obtained included histology, location, cerebrospinal fluid (CSF) cytology, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (B-HCG), metastatic evaluation, radiation details, survival, and sites of failure. Minimum follow-up time was 2 years and ranged to a maximum of 24 years, with a median of 8 years. RESULTS: Median age at diagnosis was 16 years with 36 males and 12 females. Ten of 32 patients had elevated B-HCG at diagnosis; 6 of 29 had elevations of AFP. Cerebrospinal fluid cytology was negative in 35 of 36 patients evaluated; myelography or spinal MRI was positive in only 1 of 31 patients studied. Five-year actuarial disease-free survival after irradiation was 91% for germinomas, 63% for unbiopsied tumors, and 60% for nongerminoma germ-cell tumors with doses of 50-54 Gy to the local tumor site with or without whole-brain or whole-ventricular irradiation. Routine prophylactic cranio-spinal axis irradiation was not given with a spinal only failure rate of 2%. Eleven of 48 patients have expired, with an actuarial 5-year survival rate of 100% for germinomas, 79% for nonbiopsied tumors, and 80% for nongerminoma germ-cell tumors. CONCLUSION: With complete diagnostic craniospinal evaluation, spinal irradiation is not necessary. Cure rates for germinomas are excellent with irradiation alone. Multidrug chemotherapy is necessary with irradiation for nongerminoma germ-cell tumors. Histology is the most important prognostic factor; therefore, all patients should have surgical conformation of their diagnosis so that appropriate treatment can be given.

Adolescent↗

PubMed1995

Fetal dose estimates for radiotherapy of brain tumors during pregnancy.

PURPOSE: To determine clinically the fetal dose from irradiation of brain tumors during pregnancy and to quantitate the components of fetal dose using phantom measurements. METHODS AND MATERIALS: Two patients received radiotherapy during pregnancy for malignant brain tumors. Case 1 was treated with opposed lateral blocked 10 x 15 cm fields and case 2 with 6 x 6 cm bicoronal wedged arcs, using 6 MV photons. Fetal dose was measured clinically and confirmed with phantom measurements using thermoluminescent dosimeters (TLDs). Further phantom measurements quantitated the components of scattered dose. RESULTS: For case 1, both clinical and phantom measurements estimated fetal dose to be 0.09% of the tumor dose, corresponding to a total fetal dose of 0.06 Gy for a tumor dose of 68.0 Gy. Phantom measurements estimated that internal scatter contributed 20% of the fetal dose, leakage 20%, collimator scatter 33%, and block scatter 27%. For case 2, clinical and phantom measurements estimated fetal dose to be 0.04% of the tumor dose, corresponding to a total fetal dose of 0.03 Gy for a tumor dose of 78.0 Gy. Leakage contributed 74% of the fetal dose, internal scatter 13%, collimator scatter 9%, and wedge scatter 4%. CONCLUSIONS: When indicated, brain tumors may be irradiated to high dose during pregnancy resulting in fetal exposure < 0.10 Gy, conferring an increased but acceptable risk of leukemia in the child, but no other deleterious effects to the fetus after the fourth week of gestation. For our particular field arrangements and linear accelerators, internal scatter contributed a small component of fetal dose compared to leakage and scatter from the collimators and blocks, and 18 MV photons resulted in a higher estimated fetal dose than 6 MV photons due to increased leakage and collimator scatter. These findings are not universal, but clinical and phantom TLD measurements estimate fetal dose accurately for energies < 10 MV and should be taken for each pregnant patient considered for treatment to confirm and document acceptable dose.

Adult↗

PubMed1995

Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.

PURPOSE: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. METHODS AND MATERIALS: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%. CONCLUSION: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.

Adolescent↗

PubMed1995

The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy.

PURPOSE: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors. METHODS: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival. RESULTS: Of 81 evaluable patients, 68 received > or = 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms < or = 2 months and a diffuse lesion were each associated with shorter survival and progression times. CONCLUSIONS: For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed.

Adolescent↗

PubMed1995

Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors.

PURPOSE: To identify factors associated with radiation pneumonitis (RP) resulting from combined modality therapy (CMT) for lung cancer. MATERIALS AND METHODS: Series published before 1994 that used CMT for the treatment of lung cancer and explicitly reported the incidence of RP are the basis for this analysis. Factors evaluated included the radiation dose per fraction (Fx), total radiation dose, fractionation scheme (split v continuous), type of chemotherapy and intended dose-intensity, overall treatment time, histology (small-cell lung cancer [SCLC] v non-small-cell lung cancer [NSCLC]), and treatment schedule (concurrent v induction, sequential, or alternating CMT). RESULTS: Twenty-four series, including 27 treatment groups and 1,911 assessable patients, met our criteria for inclusion in this analysis. The median total dose of radiation used in the trials analyzed was 50 Gy (range, 25 to 63 Gy). The median daily Fx used was 2.0 Gy (range, 1.5 to 4.0 Gy). Nineteen series included 22 treatment groups and 1,745 patients treated with single daily fractions. Among these patients, 136 received a daily Fx greater than 2.67 Gy. Five series used twice-daily radiotherapy and included 166 patients (Fx, 1.5 to 1.7 Gy). The incidence of RP was 7.8%. In a multivariate analysis, only daily Fx, number of daily fractions, and total dose were associated with the risk of RP (P < .0001, P < .018, and P < .003, respectively). CONCLUSION: In this analysis, the use of Fx greater than 2.67 Gy was the most significant factor associated with an increased risk of RP. High total dose also appears to be associated with an increased risk, but twice-daily irradiation seems to reduce the risk expected if the same total daily dose is given as a single fraction. High-Fx radiotherapy should be avoided in patients who receive CMT with curative intent.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost.

A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow-up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗