Robert P. Dinapoli

Mayo Clinic - Rochester, Rochester, MN, United States

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Publications (48)265.53 Total impact

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    ABSTRACT: Anaplastic oligoastrocytomas (AOA) are relatively uncommon high-grade gliomas. While oligodendroglial elements are thought to be associated with better outcomes, the magnitude of the difference is not clear. Between 1980 and 1999, Mayo Clinic and the NCCTG conducted 10 trials of radiation therapy and chemotherapy in adults with newly-diagnosed high-grade gliomas. All pathology slides were reviewed by one of the authors (BWS or CG). We grouped patients by cell type and grade, compared survival distributions by the log-rank statistic, and performed multiple variable analyses. Of 1368 patients, 68 (5%) had AOA, including 21 Grade 3 (OA3) and 47 grade 4 (OA4), 153 (11%) had anaplastic astrocytoma (AA), and 1147 (84%) had glioblastoma multiforme (GBM). Patients with OA3 survived significantly longer than those with OA4 (P=0.0001) or AA (P=0.0044). Patients with OA4 lived significantly longer than those with GBM (P=0.0005). The same differences were noted for PFS. Prognostic factors for survival identified by multiple variable analysis were histology, age, ECOG performance score, and extent of surgical resection, but not treatment administered. Patients with anaplastic oligoastrocytoma have distinct outcomes based upon grade (OA3 vs. OA4) and in comparison with pure astrocytoma (AA or GBM). Future trials which include more than one histologic entity need to report results by cell type and grade and account for the varying prognoses in interpreting treatment outcomes.
    No preview · Article · Oct 2007 · Journal of Neuro-Oncology
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    ABSTRACT: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Therapy consisted of carmustine (40 mg/m(2)/d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m(2)/d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma.
    No preview · Article · Mar 2005 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: The outcome and cognitive performance data collected in a prospective, intergroup clinical trial were analyzed to assess the prognostic importance of the baseline (before radiotherapy) Mini-Mental State Examination (MMSE) score in patients with low-grade glioma. The patients studied were 203 adults with a supratentorial low-grade glioma randomly assigned to low-dose (50.4 Gy in 28 fractions) or high-dose (64.8 Gy in 36 fractions) localized radiotherapy. Folstein MMSE scores and neurologic function scores at baseline in combination with multiple other baseline variables were analyzed. The median follow-up was 7.4 years for the 101 patients still alive. Patients (n = 36) with an abnormal baseline MMSE score (< or =26) had a worse 5-year progression-free survival rate (27% vs. 60%; p <0.001) and overall survival rate (31% vs. 76%; p <0.001) compared with those with a normal score. On multivariate analysis, the baseline MMSE score was a statistically significant predictor of survival. Other factors associated with overall survival were age, tumor size, and tumor histologic type. The presence of an abnormal baseline MMSE score was a strong predictor of poorer progression-free and overall survival for patients with a low-grade glioma. The baseline MMSE should be considered in future prognostic scoring systems.
    No preview · Article · May 2004 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: Supratentorial pilocytic astrocytomas in adults are uncommon. A prospective clinical trial was conducted to obtain clinical and outcome data in these patients. Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. At the time of analysis (median follow-up, 10 years), 1 patient (5%) had died and 19 patients (95%) were alive. The 5-year progression-free and overall survival rates were 95%. The cause of death in the patient who died (2.1 years after enrollment) was unknown; a radiographic examination obtained shortly before the patient's demise revealed no signs of progression. Progression in 1 patient approximately 1 month after enrollment required injection of (32)P into an enlarging cyst. The patient required RT approximately 18 months later because of further progression. This patient was alive without evidence of progression 9 years after RT. No toxic effects had been recorded at the latest follow-up examinations. With follow-up comparable or superior to that in many retrospective studies, the results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. The vast majority of patients remained stable after gross or subtotal resection and no adjuvant therapy. RT need not be offered to adults with supratentorial pilocytic astrocytoma after gross or subtotal resection; instead, close observation is recommended. Because only 3 patients received RT after biopsy, it is difficult to comment on the effect of RT on their outcome as a group.
    No preview · Article · Apr 2004 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: To assess the neurocognitive effects of cranial radiotherapy on patients with low-grade gliomas, we analyzed cognitive performance data collected in a prospective, intergroup clinical trial. Patients included 203 adults with supratentorial low-grade gliomas randomly assigned to a lower dose (50.4 Gy in 28 fractions) or a higher dose (64.8 Gy in 36 fractions) of localized radiotherapy. Folstein Mini-Mental State Examination (MMSE) scores and neurologic function scores (NFS) at baseline and key evaluations were analyzed. Median follow-up was 7.4 years in 101 patients still alive. A change of more than three MMSE points was considered clinically significant. In patients without tumor progression, significant deterioration from baseline occurred at years 1, 2, and 5 in 8.2%, 4.6%, and 5.3% of patients, respectively. Most patients with an abnormal baseline MMSE score (< 27) experienced significant increases. Baseline variables such as radiation dose, conformal versus conventional radiotherapy, number of radiation fields, age, sex, tumor size, NFS, seizures, and seizure medications did not predict cognitive function changes. In this population, most low-grade glioma patients maintained a stable neurocognitive status after focal radiotherapy as measured by the MMSE. Patients with an abnormal baseline MMSE were more likely to have an improvement in cognitive abilities than deterioration after receiving radiotherapy. Only a small percentage of patients had cognitive deterioration after radiotherapy. However, more discriminating neurocognitive assessment tools may identify cognitive decline not apparent with the use of the MMSE.
    No preview · Article · Aug 2003 · Journal of Clinical Oncology
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    ABSTRACT: To investigate the safety of thrice-daily hyperfractionated radiotherapy (RT) given in conjunction with BCNU (carmustine) in high-grade gliomas. Patients >18 years old with newly diagnosed high-grade gliomas were eligible. The dose of radiation was 5040 cGy, with a 1440-cGy boost in 180 cGy fractions delivered thrice daily in two 6-day periods with a 2-week interval. BCNU (200 mg/m(2)) was administered on the first day of radiation, then every 7 weeks for 1 year and every 10 weeks for another year. Eighteen patients were enrolled. The mean age was 49.6 years. Sixteen patients had astrocytomas (Grade 3 or 4 in 5 and 11 patients, respectively) and 2 had oligoastrocytomas (Grade 3 and 4 in 1 patient each). One underwent total resection, 9 subtotal resection, and 8 biopsy only. Thirteen patients had stable disease, 4 regression, and 1 progression. The median time to progression was 37.8 weeks. The median overall survival was 44.4 weeks. Nine patients had neurologic toxicities, including 2 deaths at 69 and 139 weeks. This regimen is unacceptably toxic. Factors that could have contributed to the toxicity may include the total radiation dose, thrice-daily hyperfractionation, and the concurrent use of i.v. BCNU.
    No preview · Article · Jul 2002 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. From 1986 to 1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102 to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2 tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with astrocytoma dominant) in 32% of patients and oligodendroglioma (or oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast enhancement. Extent of resection was gross total in 14% of patients, subtotal in 35%, and biopsy only in 51%. At the time of the present analysis, 83 patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and 85% and 64%, respectively, with high-dose RT (log rank P =.48). Multivariate analysis identified histologic subtype, tumor size, and age as the most significant prognostic factors. Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed in seven patients, with one fatality in each treatment arm. The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5% with high-dose RT. This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.
    No preview · Article · Jun 2002 · Journal of Clinical Oncology

  • No preview · Article · Nov 2001 · International Journal of Radiation OncologyBiologyPhysics
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    Scott D.Z. Eggers · Diva R. Salomao · Robert P. Dinapoli · Steven Vernino
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    ABSTRACT: Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is locally aggressive and frequently accompanied by distant metastases. Neurologic complications of Merkel cell carcinoma are rare. We describe a 69-year-old man who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel cell carcinoma. The paraneoplastic syndrome improved with initial treatment of the malignancy. He subsequently developed a solitary brain metastasis and died of leptomeningeal carcinomatosis.
    Preview · Article · Apr 2001 · Mayo Clinic Proceedings
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    ABSTRACT: It is standard practice for the oncological follow-up of patients with brain tumors (especially in the setting of clinical trials) to include neurological examination and neuroradiological studies such as computerized tomography (CT) or magnetic resonance (MR) imaging in addition to evaluation of the patients' symptomatology and performance score. The validity of this practice and its impact on the welfare of patients with high-grade gliomas has not been adequately assessed. The purpose of this study is to provide such an assessment. The authors studied 231 similarly treated patients who were participating in three prospective North Central Cancer Treatment Group or Mayo Clinic trials who developed progressive disease during follow up. According to the protocol, the symptom status, performance score, results of neurological examination, and CT or MR status were recorded prospectively in each patient at each evaluation (every 6-8 weeks). At progression, 177 (77%) of 231 patients experienced worsening of their baseline symptoms or they developed new ones. In the remaining 54 asymptomatic patients (23%), neuroradiological imaging revealed the progression. Asymptomatic progression was more likely to be detected on MR imaging compared with CT studies (p < 0.01). In no asymptomatic patient was progression detected on neurological examination alone. The median survival time after tumor recurrence was 13.3 weeks in symptomatic patients compared with 41.7 weeks in the asymptomatic group (p < 0.0001). Asymptomatic patients were more aggressively treated, with surgery (p < 0.0001) and second-line chemotherapy (p < 0.0002). Multivariate analysis of survival time following first progression by using both classification and regression trees and Cox models showed that treatment at recurrence was the most important prognostic variable. Symptoms are the most frequent indicators of progression in patients with high-grade gliomas (77%). All asymptomatic progressions were detected on neuroradiological studies; MR imaging was more likely than CT scanning to reveal asymptomatic recurrences. Survival after disease progression was significantly longer in asymptomatic patients and could be related both to treatment following progression and to other favorable prognostic factors such as performance score.
    No preview · Article · Aug 2000 · Journal of Neurosurgery
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    ABSTRACT: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. Adults with cerebral or cerebellar solitary non-brainstem tumors </= 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors </= 20 mm, 15 Gy for those 21-30 mm, and 12 Gy for those 31-40 mm in maximum diameter. Dose was prescribed to the 50-90% isodose line. Doses were escalated in 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Oncology Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS toxicity) was < 20% within 3 months of radiosurgery. Chronic CNS toxicity was also assessed. Between 1990-1994, 156 analyzable patients were entered, 36% of whom had recurrent primary brain tumors (median prior dose 60 Gy) and 64% recurrent brain metastases (median prior dose 30 Gy). The maximum tolerated doses were 24 Gy, 18 Gy, and 15 Gy for tumors </= 20 mm, 21-30 mm, and 31-40 mm in maximum diameter, respectively. However, for tumors < 20 mm, investigators' reluctance to escalate to 27 Gy, rather than excessive toxicity, determined the maximum tolerated dose. In a multivariate analysis, maximum tumor diameter was one variable associated with a significantly increased risk of grade 3, 4, or 5 neurotoxicity. Tumors 21-40 mm were 7.3 to 16 times more likely to develop grade 3-5 neurotoxicity compared to tumors < 20 mm. Other variables significantly associated with grade 3-5 neurotoxicity were tumor dose and Karnofsky Performance Status. The actuarial incidence of radionecrosis was 5%, 8%, 9%, and 11% at 6, 12, 18, and 24 months following radiosurgery, respectively. Forty-eight percent of patients developed tumor progression within the radiosurgical target volume. A multivariate analysis revealed two variables that were significantly associated with an increased risk of local progression, i.e. progression in the radiosurgical target volume. Patients with primary brain tumors (versus brain metastases) had a 2.85 greater risk of local progression. Those treated on a linear accelerator (versus the Gamma Knife) had a 2.84 greater risk of local progression. Of note, 61 % of Gamma Knife treated patients had recurrent primary brain tumors compared to 30% of patients treated with a linear accelerator. The maximum tolerated doses of single fraction radiosurgery were defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for tumors </= 20 mm, 21-30 mm, and 31-40 mm in maximum diameter. Unacceptable CNS toxicity was more likely in patients with larger tumors, whereas local tumor control was most dependent on the type of recurrent tumor and the treatment unit.
    No preview · Article · May 2000 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: Neurologic involvement occurs in 10% to 20% of patients with disseminated histoplasmosis. We describe a 20-year-old woman who had headache and diplopia but no evidence of systemic infection. Magnetic resonance imaging showed an enhancing mass in the thalamomesencephalic and third ventricular region. After subtotal resection of what was presumed to be a glioma, the patient had symptoms and signs of meningitis. Subsequent pathological review demonstrated noncaseating granulomas, and serologic tests and cultures confirmed the diagnosis of histoplasmosis. Initiation of antifungal therapy and removal of an infected shunt system resulted in clinical improvement. Clinicians should maintain a high index of suspicion in patients who are from any area endemic for histoplasmosis.
    Full-text · Article · Sep 1999 · Mayo Clinic Proceedings
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    ABSTRACT: There is no standard treatment for patients with recurrent gliomas, and their prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has significant activity in many low-grade lymphoproliferative disorders. The authors conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in patients with recurrent gliomas. Patients with a histologically confirmed primary brain tumor with evidence of progression after radiation therapy were eligible. Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on days 1 through 5 every 28 days. For those with a history of prior nitrosourea therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1 through 5. Treatment was continued until progression or a maximum of 12 cycles. Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades were entered in the study. Treatment was well tolerated. Major toxicities were myelosuppression and neurotoxicity. No responses were seen. The authors conclude that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity in patients with recurrent gliomas was established.
    No preview · Article · May 1999 · American Journal of Clinical Oncology
  • E. Shaw · C. Scott · L. Souhami · R. Dinapoli · R. Kline · J. Loeffler · N. Farnan

    No preview · Article · Dec 1998 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.
    No preview · Article · Oct 1998 · Journal of Neurosurgery
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    ABSTRACT: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.
    No preview · Article · Oct 1998 · Journal of Clinical Oncology
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    ABSTRACT: The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.
    No preview · Article · Jul 1998 · Journal of Clinical Oncology
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    ABSTRACT: A Phase I study to determine the safety, toxicity, and maximum tolerated dose (MTD) of carmustine (BCNU) and interferon alpha-2a (IFN-a) when combined with radiation as initial therapy in high-grade glioma. Patients with newly diagnosed Grade 3 or 4 astrocytoma, oligoastrocytoma, or gliosarcoma were enrolled after surgery. All received radiation therapy to the brain (64.8 Gy/36 fractions), combined with a single dose of BCNU (200 mg/m2) at the start of radiation. Chemotherapy after completing radiation consisted of BCNU 150 mg/m2 once every 7 weeks, and IFN-a 12 x 10(6) units/m2 subcutaneously Days 1-3 each week of a 7-week cycle. Subsequent dose modification was based on constitutional symptoms for IFN-a and on myelosuppression for BCNU. Fifteen patients were entered on the study. Four were excluded because they did not receive IFN-a (3 refused treatment and 1 patient left the study due to multiple medical problems). Eleven were evaluable for toxicity and efficacy. Nonhematological toxicity, mainly lethargy and flu-like symptoms, were dose-limiting for IFN-a. After the first 6 patients were treated per the initial protocol, the frequency of IFN-a administration was decreased to Days 1-3 on weeks 1, 3, and 5 of the 7-week cycle for 5 additional patients. Lethargy, fever, chills, myalgias, alopecia, and anorexia occurred in all patients. Other toxicities included nausea and vomiting (91%), central-nervous-system depression or mood changes (64%), headaches (55%), and elevation of liver enzymes (36%). Grade 3-4 leukopenia occurred in 4 (45%) of 11 patients, and Grade 3-4 thrombocytopenia in 3 (27%) of 11 patients. Due to myelosuppressive effects, BCNU dose was not escalated. Median survival of the cohort was 44 months. Objective responses occurred in 5 (56%) of 9 patients and median duration of response was 33 months. The MTD of this combination after radiation therapy is IFN-a 12 x 10(6) units/m2 Days 1-3, on Weeks 1, 3, and 5 of a 7-week cycle and BCNU 150 mg/m2 Day 1, every 7 weeks. Treatment with radiation, IFN-a, and BCNU is feasible and effective in patients with high-grade gliomas, although constitutional symptoms from IFN-a are substantial.
    No preview · Article · Feb 1998 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: Purpose: We performed a randomized trial to comparesurvival distributions and toxicity of radiation therapy (RT)and DBD with RT and BCNU in patientswith high-grade astrocytoma. Methods: A total of 238patients with supratentorial grade 3 and grade 4astrocytoma were studied. Patients were stratified by age,extent of surgery, tumor grade, and performance scoreand randomly assigned to receive RT 55-60 Gyand either DBD, 200 mg/m2 orally on Days1–10 every five weeks or BCNU, 200 mg/m2intravenously every seven weeks. Median age was 60years; 62% were 55 years or older. Eighty-threepercent had subtotal resection, 58% had grade 4tumors, and 83% had performance scores of 0–2.Results: Survival distributions for all patients in thetwo arms were similar, with median survival of41 weeks in each arm. Time to progressiondistributions were virtually identical, with medians of 22weeks. BCNU produced significantly greater hematologic toxicity; medianleukocyte and platelet nadirs on the first cyclewere 3.6 vs. 4.7 (P=0.0001) and117 vs. 162 (P < 0.0001),="" and="" overallplatelet="" nadirs="" were="" 80.5="" vs.="" 114="" (p="0.0019)." non-hematologic="" toxicities="" were="" also="" significantly="" greater="" withbcnu,="" including="" nausea="" (57%="" vs.="" 31%;="" p="">
    No preview · Article · Jun 1997 · Journal of Neuro-Oncology
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    ABSTRACT: To determine factors associated with survival differences in patients treated with radiosurgery for glioma. We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. 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. 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.
    No preview · Article · Jan 1997 · International Journal of Radiation OncologyBiologyPhysics

Publication Stats

3k Citations
265.53 Total Impact Points


  • 1987-2007
    • Mayo Clinic - Rochester
      • • Department of Neurology
      • • Department of Oncology
      Rochester, MN, United States
  • 2003
    • Wake Forest University
      Winston-Salem, North Carolina, United States
  • 1989
    • George Washington University
      Washington, Washington, D.C., United States
  • 1982
    • Mayo Foundation for Medical Education and Research
      Rochester, Michigan, United States