Michael L Gruber, M.D.

Invasion is not an independent prognostic factor in high-grade glioma
Narayana, Ashwatha; Perretta, Donato; Kunnakkat, Saroj; Gruber, Deborah; Golfinos, John; Parker, Erik; Medabalmi, Praveen; Zagzag, David; Pat Eagan, R N; Gruber, Michael
2011 Jul;7(3):331-335, Journal of cancer research & therapeutics
Purpose: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti-angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. Materials and Methods: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. Results: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. Conclusions: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis
— id: 140539, year: 2011, vol: 7, page: 331, stat: Journal Article,

Involved-Field Radiation Therapy After Surgical Resection of Solitary Brain Metastases
Connolly, E; Parker, E; Golfino, J; Kunnakkat, S; Gruber, M; Narayana, A
2010 APR ;33(2):208-208, American journal of clinical oncology
— id: 109504, year: 2010, vol: 33, page: 208, stat: Journal Article,

INVASION IS AN IMPORTANT PROGNOSTIC FACTOR IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS
Kunnakkat, Saroj D.; Perretta, Donato; Medabalmi, Praveen; Gruber, Michael L.; Gruber, Deborah; Golfinos, John; Parker, Erik; Narayana, Ashwatha
2010 NOV ;12(2):5-5, Neuro-oncology
— id: 122728, year: 2010, vol: 12, page: 5, stat: Journal Article,

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma
Narayana A; Kunnakkat SD; Medabalmi P; Golfinos J; Parker E; Knopp E; Zagzag D; Eagan P; Gruber D; Gruber ML
2010 Jan 1;82(1):77-82, International journal of radiation oncology biology physics
PURPOSE: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. METHODS AND MATERIALS: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. RESULTS: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). CONCLUSION: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials
— id: 138155, year: 2010, vol: 82, page: 77, stat: Journal Article,

INVASION AS A DOMINANT FEATURE OF FAILURE PATTERN IN HIGH-GRADE GLIOMAS FOLLOWING BEVACIZUMAB THERAPY
Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Gruber, Deborah; Gruber, Michael L.
2010 NOV ;12(2):3-3, Neuro-oncology
— id: 122727, year: 2010, vol: 12, page: 3, stat: Journal Article,

Predictors of Multiple Sclerosis Following Clinically Isolated Syndrome with a Tumefactive Demyelinating Lesion
Graber, JJ; Kister, I; Gruber, MCL; Warren, FA; Weinberg, HJ; Neophytides, AN; Inglese, M; Zagzag, D; Herbert, J
2009 ;72(11):A78-A78, Neurology
— id: 111993, year: 2009, vol: 72, page: A78, stat: Journal Article,

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival
Narayana, Ashwatha; Kelly, Patrick; Golfinos, John; Parker, Erik; Johnson, Glyn; Knopp, Edmond; Zagzag, David; Fischer, Ingeborg; Raza, Shahzad; Medabalmi, Praveen; Eagan, Patricia; Gruber, Michael L
2009 Jan;110(1):173-180, Journal of neurosurgery
Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored
— id: 90721, year: 2009, vol: 110, page: 173, stat: Journal Article,

EXPRESSION OF PHOSPHORYLATED VEGFR2 RECEPTOR IN HIGH-GRADE GLIOMAS
Fischer, I; Raza, S; Medabalmi, P; Aldape, K; Gruber, M; Narayana, A
2008 OCT ;10(5):855-856, Neuro-oncology
— id: 91328, year: 2008, vol: 10, page: 855, stat: Journal Article,

High-grade glioma before and after treatment with radiation and Avastin: initial observations
Fischer, Ingeborg; Cunliffe, Clare H; Bollo, Robert J; Raza, Shahzad; Monoky, David; Chiriboga, Luis; Parker, Erik C; Golfinos, John G; Kelly, Patrick J; Knopp, Edmond A; Gruber, Michael L; Zagzag, David; Narayana, Ashwatha
2008 Oct;10(5):700-708, Neuro-oncology
We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers
— id: 91374, year: 2008, vol: 10, page: 700, stat: Journal Article,

Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging
Law, Meng; Young, Robert J; Babb, James S; Peccerelli, Nicole; Chheang, Sophie; Gruber, Michael L; Miller, Douglas C; Golfinos, John G; Zagzag, David; Johnson, Glyn
2008 May;247(2):490-498, Radiology
PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV
— id: 91375, year: 2008, vol: 247, page: 490, stat: Journal Article,

Change in pattern of relapse following anti-angiogenic therapy in high grade glioma
Narayana, A; Golfinos, JG; Raza, S; Knopp, E; Medabalmi, P; Parker, E; Kelly, P; Zagzag, D; Gruber, M
2008 AUG ;72(1):S11-S11, International journal of radiation oncology biology physics
— id: 86794, year: 2008, vol: 72, page: S11, stat: Journal Article,

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma
Narayana, Ashwatha; Golfinos, John G; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick; Parker, Erik; Knopp, Edmond A; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L
2008 Oct 1;72(2):383-389, International journal of radiation oncology biology physics
INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely
— id: 91373, year: 2008, vol: 72, page: 383, stat: Journal Article,

High cerebral blood volume in human gliomas predicts deletion of chromosome 1p: Preliminary results of molecular studies in gliomas with elevated perfusion
Law, Meng; Brodsky, Jennie E; Babb, James; Rosenblum, Marc; Miller, Douglas C; Zagzag, David; Gruber, Michael L; Johnson, Glyn
2007 Jun;25(6):1113-1119, Journal of magnetic resonance imaging
PURPOSE: To determine if increased perfusion using dynamic susceptibility contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions. Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to chemotherapy improving survival in gliomas. MATERIALS AND METHODS: We retrospectively reviewed 16 patients who had DSC MRI and molecular studies of their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of heterozygosity using polymerase chain reaction (PCR). DNA was extracted from paraffin curls of brain tumor sections and nail clippings. Relative cerebral blood volume (rCBV) measurements were then statistically compared with the presence of 1p and 19q deletions. RESULTS: Patients with 1p19q deletions (N = 7) demonstrated rCBV values of 10.54 +/- 2.93. Patients without 1p deletions (N = 9) had rCBV values of 4.84 +/- 2.4 (P = 0.012). Logistic regression demonstrated that rCBV was able to predict the presence of a 1p deletion to significance levels of 0.038 and 0.044, adjusted and not adjusted for age and sex, respectively. The kappa coefficient for the agreement between predicted deletion status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions of 19q alone, or together with 1p deletions, were not associated with high rCBV. CONCLUSION: Histopathologic, molecular, and imaging evidence supports increased neovascularity in gliomas with 1p deletions in this preliminary study. We propose a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high rCBV.
— id: 73001, year: 2007, vol: 25, page: 1113, stat: Journal Article,

Predicting time to progression/survival in gliomas with cerebral blood volume measurements using dynamic susceptibility contrast perfusion MR imaging
Law, M; Babb, J; Peccerelli, N; Young, R; Chheang, S; Gruber, M; Golfinos, J; Miller, D; Zagzag, D; Johnson, G
2006 OCT ;8(4):494-495, Neuro-oncology
— id: 70330, year: 2006, vol: 8, page: 494, stat: Journal Article,

Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas
Chen, B; Ahmed, T; Mannancheril, A; Gruber, M; Benzil, DL
2004 MAY 15 ;100(10):2201-2207, Cancer
BACKGROUND. Malignant astrocytomas are among the most resistant tumors to curative treatments. Mean survival without treatment is measured in weeks, and even with maximal surgery and radiation, the mean reported survival is < 1 year. The advent of supportive treatments and newer agents has resulted in benefits for many patients with cancer. The authors investigated the safety and effect on survival of a high-dose thiotepa and carboplatin regimen with autologous stem cell transplantation (ASCT) in patients with malignant astrocytomas who were enrolled in a prospective trial approved by an institutional review board (IRB). METHODS. Twenty-one patients were enrolled in an IRB-approved, prospective trial. After baseline testing was completed, patients underwent peripheral stem cell mobilization with cyclophosphamide (4 g/m(2)) and etoposide (450 mg/m(2)) fol- lowed by granulocyte-colony-stimulating factor (10 mug/kg). Peripheral stem cells were harvested when leukocyte counts recovered. Patients received 2 cycles of thiotepa (750 mg/m(2)) and carboplatin (1600 mg/m(2)) followed by infusion of the preserved stem cells. The cycles were administered 6-10 weeks apart. Primary outcome measures were patient survival (Kaplan-Meier analysis) and treatment toxicity (using National Cancer Institute common toxicity criteria). RESULTS. Autologous stem cells were harvested effectively and transfused in all patients. Kaplan-Meier survival analysis demonstrated a survival time of 34.3 +/- 5.5 months (range, 9-94 months). Despite significant myelosuppression, only three patients experienced Grade 4 complications and eight experienced Grade 3 complications. CONCLUSIONS. High-dose chemotherapy with thiotepa and carboplatin with concomitant ASCT was used safely to treat patients with malignant astrocytomas and may provide a survival advantage. Cancer 2004; 100:2201-7. (C) 2004 American Cancer Society
— id: 98210, year: 2004, vol: 100, page: 2201, stat: Journal Article,

Temozolomide in combination with irinotecan for treatment of recurrent malignant glioma
Gruber, Michael L; Buster, Ward P
2004 Feb;27(1):33-38, American journal of clinical oncology
The prognosis for patients with recurrent malignant glioma is poor. Both temozolomide and irinotecan have been shown to be active in this disease. A study was performed combining temozolomide 200 mg/m2 daily for 5 days and irinotecan 125 mg/m2 on days 6, 13, and 20 initially (Schedule A) and then changed to (Schedule B) temozolomide 200 mg/m2 daily for 5 days and irinotecan 350 mg/m2 on day 6. Each cycle was 28 days. All patients with recurrent tumor had to complete two cycles of therapy to be evaluable. Six cycles of treatment were provided for all responders. Thirty-two patients were treated, 6 with schedule A, 24 with schedule B, and 2 initially schedule A and then switched to schedule B. Eighteen patients (56%) had glioblastoma and 14 patients and anaplastic glioma (AOA 8, anaplastic astrocytoma 4, AO 2). Eighty-three percent (15/18) of patients with glioblastoma responded (complete response [CR] 2, partial response [PR] 3, stable disease [SD] 10). Median duration of response was 24 weeks, and 6-month progression-free survival (PFS) was 39% (7/18). Fourteen patients with anaplastic glioma were treated and all responded (CR 3, PR 2, SD 9). Median duration of response was 29 weeks and 6-month PFS was 71% (10/14). Grade IV leukopenia occurred in one patient and grade IV thrombocytopenia in two patients. Two patients were admitted to the hospital for neutropenic fever. Nonhematologic toxicity was mild and mostly gastrointestinal. These results demonstrate a favorable response and low toxicity with combined irinotecan and temozolomide therapy and warrant further clinical evaluation
— id: 44922, year: 2004, vol: 27, page: 33, stat: Journal Article,

Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin
Cha S; Knopp EA; Johnson G; Litt A; Glass J; Gruber ML; Lu S; Zagzag D
2000 May;21(5):881-890, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Dynamic, contrast-enhanced MR imaging has allowed quantitative assessment of cerebral blood volume (CBV) in brain tumors. The purpose of our study was to compare postcontrast T1-weighted imaging with dynamic, contrast-enhanced T2*-weighted echo-planar imaging in the evaluation of the response of recurrent malignant gliomas to thalidomide and carboplatin. METHODS: Serial MR imaging was performed in 18 consecutive patients with recurrent malignant gliomas receiving both thalidomide and carboplatin for 12-month periods. Six patients undergoing carboplatin therapy alone were chosen as control subjects. Conventional postcontrast T1-weighted images were compared with relative CBV (rCBV) maps calculated on a pixel-by-pixel basis from dynamic echo-planar imaging data. Tumor progression was evaluated clinically using established criteria for malignant gliomas. Studies were performed at 2- to 3-month intervals, and imaging and clinical findings were compared. RESULTS: Tumor response to treatment, based on clinical findings, did not correlate well with conventional imaging findings. The rCBV values decreased significantly in all patients between the start of therapy and the first follow-up in the study group, but not in the control group. The difference in rCBV values between the clinically stable and the progressive group at 12-month follow-up was statistically significant, with the progressive group having higher values. CONCLUSION: Dynamic, contrast-enhanced MR imaging is a valuable adjunct to conventional imaging in assessing tumor activity during antiangiogenic therapy, and correlates better than conventional studies with clinical status and response to therapy
— id: 9344, year: 2000, vol: 21, page: 881, stat: Journal Article,

Phase I/II study of carboplatin and thalidomide in recurrent glioblastoma multiforme
Gruber, Michael L; Glass, Jon
2000 Nov 03-06;18(SUPPL. 1):41-42, Cancer investigation
— id: 15833, year: 2000, vol: 18, page: 41, stat: Journal Article,

Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme
Rosenthal MA; Gruber ML; Glass J; Nirenberg A; Finlay J; Hochster H; Muggia FM
2000 Mar;47(1):59-63, Journal of neuro-oncology
Taxol has activity in the treatment of high grade gliomas but estramustine phosphate (EMP) has not been used in this setting. In vitro data demonstrates that EMP is cytotoxic to glioma cell lines and estramustine binding proteins are expressed by glioma cells. The combination of Taxol and EMP is reported to be active in the treatment of hormone-refractory prostate cancer and in taxane-resistant breast and ovarian cancer. We therefore performed a phase II study to assess the activity and toxicity of this combination in high grade gliomas. Taxol was given at a dose of 225 mg/m2 intravenously over three hours on day 1 and EMP was given at a dose of 900 mg/m2 orally on days 1 through 3. Cycles were repeated every three weeks. Twenty patients with recurrent glioblastoma multiforme (GBM) were enrolled: 11 male, median age 45 years. All patients received anti-epileptic medications and 17 (80%) had received prior chemotherapy. Of 18 evaluable patients, two had partial responses (11) and six had stable disease (33%) for a minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia occurring in only three patients. There were no other grade 3 or 4 toxicities. The median time to progression for the cohort was only six weeks (range 3-60+ weeks). The median overall survival was 12 weeks (range 3-60+ weeks). In conclusion, the combination of Taxol and EMP is well tolerated and has modest activity in the treatment of recurrent GBM
— id: 36034, year: 2000, vol: 47, page: 59, stat: Journal Article,

Lobular capillary hemangioma of the cauda equina. Case report
Holtzman RN; Brisson PM; Pearl RE; Gruber ML
1999 Apr;90(4 Suppl):239-241, Journal of neurosurgery
This 56-year-old woman presented with a 1-year history of low-back pain, sciatica, and paresthesias in the right S-1 dermatome. On examination the patient was shown to have a right-sided Lasegue's sign, normal strength, hypalgesia in the right S-1 dermatome, and a slight diminution of the right Achilles tendon reflex. Magnetic resonance imaging revealed a 2-cm intradural enhancing lesion at the level of the L-4 vertebra. Laminectomy of L3-L5 vertebrae was performed, and intradural exploration disclosed a blueberry-appearing tumor that was surrounded by an intense arachnoiditis and attached to the right S-1 nerve root. A cystic collection of cerebrospinal fluid was seen caudal to the tumor. Complete removal required transection of the adherent nerve root fascicles. Histological analyses indicate that the lesion was a lobular capillary hemangioma, which, to the authors' knowledge, appears to be one of the first recorded examples of such a case
— id: 36035, year: 1999, vol: 90, page: 239, stat: Journal Article,

Carboplatin chemotherapy before irradiation in newly diagnosed glioblastoma multiforme
Gruber ML; Glass J; Choudhri H; Nirenberg A
1998 Aug;21(4):338-340, American journal of clinical oncology
The authors evaluated the efficacy of neoadjuvant carboplatin chemotherapy before external-beam irradiation in patients who had histologically proven glioblastoma multiforme. Twenty-five patients were treated with carboplatin, 600 mg/m2, intravenously once every 4 weeks for a total of 4 planned cycles. External-beam irradiation (60 Gy involved field) was planned after carboplatin. Of 15 patients who had residual tumor assessable for response, seven had stable disease, six had partial responses, one had a complete response, and one had progressive disease. Two of the patients who had partial responses progressed before radiotherapy. Of 10 who had gross total resections, two progressed after 3 to 4 cycles. The median time to tumor progression was 8.4 months. Median survival was 19.2 months. Myelotoxicity and other side effects of treatment were modest. Carboplatin chemotherapy after biopsy or resection of glioblastoma multiforme before irradiation is feasible. These results warrant further clinical investigation of the role that carboplatin chemotherapy may have in the treatment of patients who have newly diagnosed glioblastoma multiforme
— id: 7586, year: 1998, vol: 21, page: 338, stat: Journal Article,

Electrodermal responses to implied versus actual violence on television
Kalamas AD; Gruber ML
1998 Jan;125(1):31-37, Journal of general psychology
The electrodermal response (EDR) of children watching a violent show was measured. Particular attention was paid to the type of violence (actual or implied) that prompted an EDR. In addition, the impact of the auditory component (sounds associated with violence) of the show was evaluated. Implied violent stimuli, such as the villain's face, elicited the strongest EDR. The elements that elicited the weakest responses were the actual violent stimuli, such as stabbing. The background noise and voices of the sound track enhanced the total number of EDRs. The results suggest that implied violence may elicit more fear (as measured by EDRs) than actual violence does and that sounds alone contribute significantly to the emotional response to television violence. One should not, therefore, categorically assume that a show with mostly actual violence evokes less fear than one with mostly implied violence
— id: 36036, year: 1998, vol: 125, page: 31, stat: Journal Article,

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)
Glass J; Shustik C; Hochberg FH; Cher L; Gruber ML
1996 Dec;30(3):257-265, Journal of neuro-oncology
Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [2 mg maximum] on day 1; dexamethasone 10 mg/m2 days 1-5), and MTX (3.5 gm/m2) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT. Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity
— id: 36037, year: 1996, vol: 30, page: 257, stat: Journal Article,

Echo-planar MR cerebral blood volume mapping of gliomas. Clinical utility
Aronen HJ; Glass J; Pardo FS; Belliveau JW; Gruber ML; Buchbinder BR; Gazit IE; Linggood RM; Fischman AJ; Rosen BR; et al.
1995 Sep;36(5):520-528, Acta radiologica (Stockholm)
Neovascularization is a common phenomenon in gliomas. MR imaging cerebral blood volume (CBV) mapping utilizes ultrasfast echo-planar imaging and simultaneous use of gadolinium-based contrast material. To determine the utility of MR CBV mapping in the clinical evaluation of gliomas, we followed 15 patients with serial studies. This technique provided functional information that was not evident with conventional CT or MR imaging. Low-grade tumors demonstrated homogeneously low CBV, while high-grade tumors often showed areas of both high and low CBV. The maximum tumor CBV/white matter ratio was compared between low- (n = 3) and high-grade gliomas (n = 5) in patients without previous treatment and with histologic verification (n = 8) and was significantly higher in high-grade gliomas (p < 0.01). High CBV foci in nonenhancing tumor areas were present in 2 cases. The distinction between radiation necrosis and active tumor could be made correctly in 3 of 4 cases. The information provided by MR CBV mapping has the potential to be an adjunct in the clinical care of glioma patients
— id: 36038, year: 1995, vol: 36, page: 520, stat: Journal Article,

Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome
Glass J; Gruber ML; Cher L; Hochberg FH
1994 Aug;81(2):188-195, Journal of neurosurgery
The treatment of primary central nervous system lymphoma with chemotherapy prior to whole-brain radiation therapy (WBRT) has improved outcome considerably in this previously fatal disease. Complete or partial responses to intravenous methotrexate (3.5 gm/sq m with leucovorin rescue every 3 weeks for two to four cycles) were seen in 12 of 13 patients originally treated. A total of 25 patients (including the original 13) have now been treated with one to six cycles of methotrexate every 10 to 21 days prior to WBRT. Twenty-two had partial or complete responses, with a median duration of response of 32 months. Median survival time was 33 months (42.5 months in those responding to therapy). Nine patients are alive and without evidence of disease 9 to 122 months following therapy. Acute and long-term toxicities were minimal. Systemic methotrexate administration prior to WBRT is well tolerated and produces long-term survival
— id: 36039, year: 1994, vol: 81, page: 188, stat: Journal Article,

Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989
Miller DC; Hochberg FH; Harris NL; Gruber ML; Louis DN; Cohen H
1994 Aug 15;74(4):1383-1397, Cancer
BACKGROUND. Primary central nervous system non-Hodgkin's lymphoma (NHL-CNS) is an enigmatic disease of uncertain origin. At the Massachusetts General Hospital, 104 patients with NHL-CNS were seen from 1958 through 1989. An impression of changes in the frequency of diagnosis, character of the tumors, and therapy for this disease prompted this study of the pathologic features, clinical data, and natural history of this tumor in these 104 patients. METHODS. Histologic slides (neurosurgical specimens and autopsy tissues) were available for 99 patients. The tumors were classified by the Working Formulation classification. Immunostaining data and all clinical data were retrieved from the relevant offices and hospital charts. RESULTS. Primary central nervous system non-Hodgkin's lymphoma tripled in frequency (5.66 cases per year in 1978-89 versus 1.75 cases per year in 1958-77) and now represents 6.6% of all primary brain neoplasms (versus 3.3% before 1978; chi 2 = 17.52, P < 0.01). For the 99 tumors histologically classified, 89% were high grade. Intermediate grade lymphomas, once the second most common subtype, have disappeared since 1983. All tumors had diffuse architecture; 77% (including all 11 patients with acquired immune deficiency syndrome) were large cell subtypes. Two cases were intravascular lymphoma. With one exception, all of the 41 tumors evaluated were B-cell types; 32 of 40 had monotypic surface immunoglobulin. There was 1 T-cell lymphoma. Of 64 tumor recurrences, 29 were at the initially defined site; 12 were in the leptomeninges, 29 were in other sites in the neuraxis, and 8 were in systemic sites. Systemic metastases have not occurred since 1984. Median survival for the 68 patients who survived after diagnostic surgery and for whom follow-up information could be obtained was 19 months; 9 months for those with high grade tumors and 30.5 months for those with intermediate grade tumors. This difference was not significant (P = 0.13). A separate set of seven patients had focal tumorlike lymphoid infiltrates composed of benign-appearing lymphocytes, which were associated with good long term survival. The differential histologic diagnosis of NHL-CNS was occasionally difficult, and the spectrum of this differential was broader than generally stated. CONCLUSIONS. Primary central nervous system non-Hodgkin's lymphoma has increased in frequency even in nonimunocompromised patient populations. This increase has been accompanied by the disappearance of intermediate grade histologic types, suggesting a fundamental shift in the biology of the neoplasms. The introduction of chemotherapeutic regimens appears to have altered the natural history such that systemic metastases outside the central nervous system no longer occur, and there are now some long term survivors of this formerly uniformly fatal disease
— id: 12918, year: 1994, vol: 74, page: 1383, stat: Journal Article,

The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy
Glass J; Hochberg FH; Gruber ML; Louis DN; Smith D; Rattner B
1992 May;76(5):741-745, Journal of neurosurgery
Malignant oligodendrogliomas have been shown to be responsive to chemotherapy. The authors administered systemic chemotherapy to seven patients with oligodendroglioma or anaplastic oligodendroglioma, and to 14 with mixed oligodendroglioma-astrocytoma. Fourteen patients underwent chemotherapy before and seven after irradiation. The PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) chemotherapy was administered every 6 weeks (42-day cycles) for two to five cycles as follows: CCNU, 110 mg/sq m on Day 1; procarbazine, 60 mg/sq m/day on Days 8 to 21; and vincristine, 1.4 mg/sq m/day on Days 8 and 29. Complete or partial (greater than 50% reduction in tumor mass) responses at 20 to 100+ weeks after treatment were noted in 11 (79%) of the 14 patients treated before irradiation, including two with anaplastic oligodendroglioma and nine with mixed tumors. Complete responses were seen in two patients, one with anaplastic oligodendroglioma and one with a mixed tumor. Partial responses were seen in three of seven patients treated after radiotherapy. Stabilization of tumor growth followed PCV chemotherapy in four patients (two treated before and two after radiotherapy). Tumor growth progressed in two patients during therapy despite an initial response and in two patients despite therapy. The authors conclude that mixed oligodendroglial tumors as well as anaplastic oligodendrogliomas are responsive to PCV chemotherapy
— id: 36040, year: 1992, vol: 76, page: 741, stat: Journal Article,

In and out of the rabbit hole with Alice: assessing the consequences of efficiency prescriptions
Gruber ML
1991 ;15(1-2):175-192, Administration in social work
— id: 36043, year: 1991, vol: 15, page: 175, stat: Journal Article,

Visual scotomata resulting from lupus anticoagulant in a patient with lymphoma in remission
Gruber ML; Hochberg FH
1991 Dec;11(3):255-257, Journal of neuro-oncology
Episodic cerebro or retinovascular ischemic events without apparent cause occur in patients with cancer. We report a patient in remission from lymphoma whose multiple episodes of presumed ocular ischemia occurred in the setting of a circulating lupus anticoagulant. Symptoms resolved following therapy with Warfarin
— id: 36041, year: 1991, vol: 11, page: 255, stat: Journal Article,

Visual scotomata resulting from lupus anticoagulant in a patient with lymphoma in remission
Gruber ML; Hochberg FH
1991 Aug;11(1):77-79, Journal of neuro-oncology
Episodic cerebro or retinovascular ischemic events without apparent cause occur in patients with cancer. We report a patient in remission from lymphoma whose multiple episodes of presumed ocular ischemia occurred in the setting of a circulating lupus anticoagulant. Symptoms resolved following therapy with Warfarin
— id: 36042, year: 1991, vol: 11, page: 77, stat: Journal Article,

Systematic evaluation of primary brain tumors
Gruber ML; Hochberg FH
1990 Jun;31(6):969-971, Journal of nuclear medicine
— id: 36044, year: 1990, vol: 31, page: 969, stat: Journal Article,