Stuart A Grossman

Johns Hopkins Medicine, Baltimore, Maryland, United States

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Publications (213)1160.01 Total impact

  • Neuro-Oncology 11/2015; 17(suppl 5):v25-v25. DOI:10.1093/neuonc/nov204.33 · 5.56 Impact Factor

  • Neuro-Oncology 11/2015; 17(suppl 5):v198-v199. DOI:10.1093/neuonc/nov231.17 · 5.56 Impact Factor

  • Neuro-Oncology 11/2015; 17(suppl 5):v119-v120. DOI:10.1093/neuonc/nov217.30 · 5.56 Impact Factor
  • J. Campian · A. Piotrowski · F. Hakim · J. Rose · X.-Y. Yan · R. Gress · S. Grossman ·

    Neuro-Oncology 11/2015; 17(suppl 5):v111-v111. DOI:10.1093/neuonc/nov218.16 · 5.56 Impact Factor

  • Neuro-Oncology 11/2015; 17(suppl 5):v161-v161. DOI:10.1093/neuonc/nov225.35 · 5.56 Impact Factor
  • Prakash Ambady · Matthias Holdhoff · David Bonekamp · Fay Wong · Stuart A Grossman ·
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    ABSTRACT: Treatment of patients with newly diagnosed primary CNS lymphomas using high dose methotrexate regimens is reported to yield about 30% long term survivors with minimal neurotoxicity. As in other systemic large cell lymphomas, it is generally assumed that most relapses occur within 5 years of diagnosis. A retrospective review of the Johns Hopkins experience in 52 patients treated between 1995 and 2008 yielded 19 patients (37%) who achieved a complete response and were followed for over 5 years. Four of these patients remained progression-free for over 10 years. However, two of these long-term survivors have now relapsed over 10 years after their initial diagnosis. An analysis of progression and overall survival does not reveal a plateau suggesting that even patients who have not recurred for over 10 years remain at high risk for relapse after treatment with single agent high dose methotrexate.
    10/2015; DOI:10.2217/cns.15.34
  • Susannah Ellsworth · Xiaobu Ye · Stuart A Grossman ·
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    ABSTRACT: Purpose: Patients with glioblastoma (GBM) frequently deteriorate clinically and radiographically after chemoradiation and may require repeat surgical intervention. We attempted to correlate pathologic findings with preoperative clinical characteristics and survival in patients undergoing reoperation for GBM. Materials and methods: Patients eligible for this retrospective analysis had pathologically confirmed GBM diagnosed between 2005 and 2010, received standard radiation and temozolomide, and underwent repeat resection within 18 months of diagnosis. Results: Thirty-eight patients were identified. Median age was 56 years (range, 30 to 80 y), 55% were male, and 66% had baseline performance status ≥90%. Median survival was 16.3 months (95% confidence interval [CI], 13.3-19.8) from initial surgery. At reoperation, 21% of patients had no pathologically evident tumor. Median time from initial diagnosis to second surgery was similar in patients with and without evident tumor (8.5 vs. 8.8 mo, respectively). Patients without evident tumor tended to have a worse performance status. Median overall survival from second surgery was 7 months (95% CI, 4.2-10.1) and 9.1 months (95% CI, 2.1-25.3) for patients with and without evident tumor, respectively. Multivariate proportional hazards analysis showed a hazard ratio for death of 0.61 (95% CI, 0.25-1.49) for patients without evident tumor after adjusting for Karnofsky performance status and second surgical procedure. Conclusions: GBM patients with and without disease recurrence have similar clinical characteristics at the time of second surgical resection. Pathologic outcomes were not correlated with specific clinical or radiologic characteristics, including the time from diagnosis to reoperation. There was a trend toward improved overall survival among patients without evident tumor at reoperation.
    American journal of clinical oncology 10/2015; DOI:10.1097/COC.0000000000000136 · 3.06 Impact Factor
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    ABSTRACT: Background: The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival. Materials and Methods: Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non-small cell lung cancer (N=47). Results: Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13-2.87; resected pancreas: HR, 2.2; 95% CI, 1.17-4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53-5.42; and lung: HR, 1.7; 95% CI, 0.8-3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54-2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression. Conclusions: Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors.
  • Susannah Ellsworth · Stuart A Grossman ·
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    ABSTRACT: The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
    British Journal of Cancer 09/2015; DOI:10.1038/bjc.2015.317 · 4.84 Impact Factor
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    ABSTRACT: Iniparib is a prodrug that converts to highly reactive cytotoxic metabolites intracellularly with activity in preclinical glioma models. We investigated the maximum tolerated dose (MTD) of iniparib with monthly (m) and continuous (c) temozolomide (TMZ) dosing schedules in patients with malignant gliomas (MG). Adults with newly diagnosed MG who had successfully completed ≥80 % of radiation (RT) and TMZ without toxicity received mTMZ dosing (150-200 mg/m(2) days 1-5/28 days) or cTMZ dosing (75 mg/m(2)/days × 6 weeks) in conjunction with iniparib (i.v. 2 days/week) in the adjuvant setting. Iniparib was dose escalated using a modified continual reassessment method (mCRM). 43 patients (32 male; 34 GBM, 8 AA, 1 gliosarcoma; median age 54 years; median KPS 90) were enrolled across 4 dose levels. In the mTMZ group, 2/4 patients had dose limiting toxicities (DLT) at 19 mg/kg/week (rash/hypersensitivity). At 17.2 mg/kg/week, 1/9 patients had a DLT (grade 3 fatigue). Additional grade 3 toxicities were neutropenia, lymphopenia, and nausea. In the cTMZ group, one DLT (thromboembolic event) occurred at 10.2 mg/kg/week. Dose escalation stopped at 16 mg/kg/week based on mCRM. The mean maximum plasma concentration of iniparib increased with dose. Concentration of the two major circulating metabolites, 4-iodo-3-aminobenzamide and 4-iodo-3-aminobenzoic acid, was ≤5 % of the corresponding iniparib concentration. Iniparib is well tolerated, at doses higher than previously investigated, in combination with TMZ after completion of RT + TMZ in patients with MG. Recommended phase 2 dosing of iniparib based on mCRM is 17.2 mg/kg/week with mTMZ and 16 mg/kg/week with cTMZ. An efficacy study of TMZ/RT + iniparib followed by TMZ + iniparib in newly diagnosed GBM using these doses has completed enrollment. Survival assessment is ongoing.
    Journal of Neuro-Oncology 08/2015; 125(1). DOI:10.1007/s11060-015-1876-0 · 3.07 Impact Factor
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    ABSTRACT: Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n = 5) and cytotoxic (n = 3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, < one to 56 cycles), and 96% were evaluable for primary end points. During cycle 1, grade ≥ 3 nonhematologic and grade ≥ 4 hematologic toxicities were 5% (28 of 565 adverse events) and 0.9% (five of 565 adverse events), respectively, and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (complete and partial response) was 5.5%. Median progression-free and overall survival times were 1.8 and 6 months, respectively. Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties in this population. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 08/2015; 33(28). DOI:10.1200/JCO.2015.61.1525 · 18.43 Impact Factor

  • 08/2015; 4(3). DOI:10.1007/s13566-015-0210-y
  • Roy E Strowd · Stuart A Grossman ·
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    ABSTRACT: Opinion statement: Central nervous system gliomas are the most common primary brain tumor, and these are most often high-grade gliomas. Standard therapy includes a combination of surgery, radiation, and chemotherapy which provides a modest increase in survival, but virtually, no patients are cured, the overall prognosis remains poor, and new therapies are desperately needed. Tumor metabolism is a well-recognized but understudied therapeutic approach to treating cancers. Dietary and nondietary modulation of glucose homeostasis and the incorporation of dietary supplements and other natural substances are potentially important interventions to affect cancer cell growth, palliate symptoms, reduce treatment-associated side effects, and improve the quality and quantity of life in patients with cancer. These approaches are highly desired by patients. However, they can be financially burdensome, associated with toxicities, and have, on occasion, reduced the efficacy of proven therapies and negatively impacted patient outcomes. The lack of rigorous scientific data evaluating almost all diet and supplement-based therapies currently limits their incorporation into standard oncologic practice. Rigorous studies are needed to document and improve these potentially useful approaches in patients with brain and other malignancies.
    Current Treatment Options in Oncology 08/2015; 16(8):356. DOI:10.1007/s11864-015-0356-2 · 3.24 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29-85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17-34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3-126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.
    Journal of Neuro-Oncology 06/2015; 124(2). DOI:10.1007/s11060-015-1840-z · 3.07 Impact Factor
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    ABSTRACT: Radiation (RT), temozolomide (TMZ), and dexamethasone in newly diagnosed high grade gliomas (HGG) produces severe treatment-related lymphopenia (TRL) that is associated with early cancer-related deaths. This TRL may result from inadvertent radiation to circulating lymphocytes. This study reinfused lymphocytes, harvested before chemo-radiation, and assessed safety, feasibility, and trends in lymphocyte counts. Patients with newly diagnosed HGG and total lymphocyte counts (TLC) ≥ 1000 cells/mm(3) underwent apheresis. Cryopreserved autologous lymphocytes were reinfused once radiation was completed. Safety, feasibility, and trends in TLC, T cell subsets and cytokines were studied. Serial TLC were also compared with an unreinfused matched control group. Ten patients were harvested (median values: age 56 years, dexamethasone 3 mg/day, TLC/CD4 1980/772 cells/mm(3)). After 6 weeks of RT/TMZ, TLC fell 69 % (p < 0.0001) with similar reductions in CD4, CD8 and NK cells but not Tregs. Eight patients received lymphocyte reinfusions (median = 7.0 × 10(7) lymphocytes/kg) without adverse events. A post-reinfusion TLC rise of ≥300 cells/mm(3) was noted in 3/8 patients at 4 weeks and 7/8 at 14 weeks which was similar to 23 matched controls. The reduced CD4/CD8 ratio was not restored by lymphocyte reinfusion. Severe lymphopenia was not accompanied by elevated serum interleukin-7 (IL-7) levels. This study confirms that severe TRL is common in HGG and is not associated with high plasma IL-7 levels. Although lymphocyte harvesting/reinfusion is feasible and safe, serial lymphocyte counts are similar to unreinfused matched controls. Studies administering higher lymphocyte doses and/or IL-7 should be considered to restore severe treatment-related lymphopenia in HGG.
    Journal of Neuro-Oncology 06/2015; 124(2). DOI:10.1007/s11060-015-1841-y · 3.07 Impact Factor
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    ABSTRACT: Background: Despite being a highly vascularized tumor, glioblastoma response to anti-vascular endothelial growth factor (VEGF) therapy is transient, possibly because of tumor co-option of preexisting blood vessels and infiltration into surrounding brain. Integrins, which are upregulated after VEGF inhibition, may play a critical role in this resistance mechanism. We designed a study of cediranib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, combined with cilengitide, an integrin inhibitor. Methods: This phase I study was conducted through the Adult Brain Tumor Consortium in patients with recurrent glioblastoma. Once the maximum tolerated dose was determined, 40 patients enrolled in a dose expansion cohort with 20 being exposed to anti-VEGF therapy and 20 being naive. The primary endpoint was safety. Secondary endpoints included overall survival, proportion of participants alive and progression free at 6 months, radiographic response, and exploratory analyses of physiological imaging and blood biomarkers. Results: Forty-five patients enrolled, and no dose toxicities were observed at a dose of cediranib 30 mg daily and cilengitide 2000 mg twice weekly. Complete response was seen in 2 participants, partial response in 2, stable disease in 13, and progression in 21; 7 participants were not evaluable. Median overall survival was 6.5 months, median progression-free survival was 1.9 months, and progression-free survival at 6 months was 4.4%. Plasma-soluble VEGFR2 decreased with treatment and placental growth factor, carbonic anhydrase IX, and SDF1α, and cerebral blood flow increased. Conclusions: The combination of cediranib with cilengitide was well tolerated and associated with changes in pharmacodynamic blood and imaging biomarkers. However, the survival and response rates do not warrant further development of this combination.
    Neuro-Oncology 05/2015; 17(10). DOI:10.1093/neuonc/nov085 · 5.56 Impact Factor
  • Roy E Strowd · Inas A Abuali · Stuart A Grossman ·
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    ABSTRACT: SUMMARY Indolent CNS lymphomas (CNSLs) are rare and no guidelines exist for management. Recent literature highlights the potential for safe and tolerable intrathecal (IT) delivery of rituximab, a large anti-CD20 monoclonal antibody, for aggressive CNSL. We report a patient with relapsed indolent CNSL who failed systemic rituximab and could not tolerate IT chemotherapies, but had an objective response of 6 months duration to IT rituximab.
    04/2015; 4(3):1-5. DOI:10.2217/cns.15.3
  • Carmen Kut · Stuart A Grossman · Jaishri Blakeley ·

    JAMA Neurology 02/2015; 72(4). DOI:10.1001/jamaneurol.2014.3736 · 7.42 Impact Factor
  • Roy E Strowd · Matthias Holdhoff · Stuart A Grossman ·
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    ABSTRACT: Gliomas classified as grade II by the World Health Organization (WHO) include astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. This heterogeneous group of conditions is associated with a more favorable prognosis and longer-term survival than high-grade gliomas (HGGs). Neurosurgical resection and radiation therapy improve survival in symptomatic, progressive, or high-risk grade II gliomas. Until recently, the role of chemotherapy has been less clear. This review draws on insights from the management of HGGs and emerging data on the addition of PCV (procarbazine, lomustine [CCNU], and vincristine) to radiation for these neoplasms. Specifically, this review focuses on the current status of chemotherapeutic management of grade II gliomas, including optimal timing of treatment, and management of 1p19q codeleted and non-codeleted tumors.
    Oncology (Williston Park, N.Y.) 12/2014; 28(12). · 2.32 Impact Factor
  • Jian L. Campian · Guneet Sarai · Xiaobu Ye · Shanthi Marur · Stuart A Grossman ·
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    ABSTRACT: Background Severe treatment-related lymphopenia occurs commonly in many cancers and is associated with early tumor progression. Data are lacking as to whether this occurs in squamous cell head and neck cancer. Methods Serial total lymphocyte counts were retrospectively reviewed in patients with newly diagnosed squamous head and neck cancer undergoing chemoradiation and associated with treatment outcomes. ResultsThe median baseline total lymphocyte count in 56 patients was 1660 cells/mm(3), which fell by 73% to 445 cells/mm(3) 2 months after initiating chemoradiation (p < .0001). Human papillomavirus negative (HPV-) patients with a total lymphocyte count <500 cells/mm(3) at 2 months had significantly earlier disease progression than those with higher total lymphocyte counts (hazard ratio [HR], 5.75; p = .045). Conclusion Baseline total lymphocyte counts were normal, but at 2 months approximately 60% of patients had severe treatment-related lymphopenia regardless of HPV status. Severe treatment-related lymphopenia in HPV- patients is independently associated with earlier disease progression. Prospective studies are needed to confirm these findings, which suggest that immune preservation is important in this cancer. (c) 2014 Wiley Periodicals, Inc. Head Neck 36: 1747-1753, 2014
    Head & Neck 12/2014; 36(12). DOI:10.1002/hed.23535 · 2.64 Impact Factor

Publication Stats

6k Citations
1,160.01 Total Impact Points


  • 1987-2015
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Department of Neurology
      • • Johns Hopkins Oncology Center
      Baltimore, Maryland, United States
  • 2014
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
  • 1992-2014
    • Johns Hopkins University
      • Department of Radiation Oncology and Molecular Radiation Sciences
      Baltimore, Maryland, United States
  • 2002-2013
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2012
    • Harvard Medical School
      Boston, Massachusetts, United States
    • University of California, Irvine
      • Division of Hematology/Oncology
      Irvine, CA, United States
  • 2010
    • University of Pennsylvania
      • Department of Neurology
      Philadelphia, PA, United States
  • 2005
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 2004
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 2003
    • The Ohio State University
      Columbus, Ohio, United States
    • Wake Forest University
      • Department of Neurosurgery
      Winston-Salem, North Carolina, United States
    • City of Hope National Medical Center
      Duarte, California, United States
  • 1999
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
  • 1997
    • Columbia University
      • Department of Neurology
      New York, New York, United States