Bio

Clinical Focus


  • Cancer > Neuro Oncology
  • Neurology
  • Glioma
  • Brain Metastasis
  • Carcinomatosis, Leptomeningeal
  • chemotherapy induced neuropathy
  • Paraneoplastic Syndromes

Academic Appointments


Honors & Awards


  • Who's Who in America, Marquis (2015)
  • Selected Participant, NINDs Clinical Trials Training Course (2011)

Boards, Advisory Committees, Professional Organizations


  • Member, American Society of Clinical Oncology (2010 - Present)
  • Member, Society of Neuro-Oncology (2010 - Present)
  • Member, American Academy of Neurology (2005 - Present)

Professional Education


  • Residency:University of California School of Medicine (2009) CA
  • Internship:University of California School of Medicine (2007) CA
  • Residency:University Of Iowa Hospitals and Clinics (2005) IA
  • Fellowship:Stanford University (2011) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2010)
  • Medical Education:University of Pennsylvania School of Medicine (2004) PA

Research & Scholarship

Current Research and Scholarly Interests


I'm a board certified neuro-oncologist who treats both primary brain tumors as well as metastatic disease to the brain and nervous system. My research concentrates on clinical trials for patients with late-stage central nervous system cancer. I have a special interest in leptomeningeal disease, a devastating complication of lung and breast cancers. I collaborate with Stanford scientists to detect this disease earlier, and with our breast and lung oncologists to improve outcomes for patients.

Clinical Trials


  • Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma Not Recruiting

    This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer. All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin. Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Vani Jain, 650-723-1005.

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  • Molecular Analysis of Thoracic Malignancies Recruiting

    A research study to learn about the biologic features of cancer development, growth, and spread. We are studying components of blood, tumor tissue, normal tissue, and other fluids, such as urine, cerebrospinal fluid, abdominal or chest fluid in patients with cancer. Our analyses of blood, tissue, and/or fluids may lead to improved diagnosis and treatment of cancer by the identification of markers that predict clinical outcome, markers that predict response to specific therapies, and the identification of targets for new therapies.

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  • Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With MF With Variable CD30 Expression Level Not Recruiting

    The purpose of this study is to learn the effects of an investigational medication, SGN 35, on patients with mycosis fungoides. Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kokil Bakshi, 650-421-6370.

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  • PI/II of Temozolomide & Hypofractionated Radiotherapy in Tx of Supratentorial Glioblastoma Multiform Not Recruiting

    The purpose of this study is to investigate the safety and effectiveness of a combination treatment for glioblastoma multiforme utilizing radiotherapy with the FDA approved chemotherapy drug temozolomide

    Stanford is currently not accepting patients for this trial. For more information, please contact Polly Young, 650-497-7499.

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  • Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases Recruiting

    This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

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  • A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE) Not Recruiting

    The purpose of this pivotal, phase 3, randomized, multicenter study is to compare VB-111 plus bevacizumab to bevacizumab in adult patients with recurrent Glioblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Phase 1b/2, Multicenter, Open-label Study of ACP-196 in Subjects With Recurrent Glioblastoma Multiforme (GBM) Not Recruiting

    A Phase 1b/2, multicenter, open-label study designed to evaluate the efficacy and safety of ACP-196 in subjects with recurrent GBM who have progressed after 1 or 2 prior systemic treatment regimens.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cathy Recht, 650-723-6095.

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  • Study of REGN2810 (Anti-PD-1) in Patients With Advanced Malignancies Recruiting

    This is a phase 1, open-label, multicenter, ascending-dose escalation study of REGN2810, alone and in combination with other anti-cancer therapies in patients with advanced malignancies.

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  • P2/3 Randomized Study of Toca 511 & Toca FC Versus SOC in Subjects Undergoing Surgery for Recurrent GBM/AA Recruiting

    This is a multicenter, randomized, open-label phase 2/3 study of Toca 511 and Toca FC versus standard of care that comprises Investigator's choice of single agent chemotherapy (lomustine or temozolomide) or bevacizumab administered to subjects undergoing resection for first or second recurrence (including this recurrence) of GBM or AA. Subjects meeting all of the inclusion and none of the exclusion criteria will be randomized prior to surgery in a 1:1 ratio to receive either Toca 511 and Toca FC (Experimental arm, Arm T) or control treatment with one option of standard of care (Arm SOC). Due to the prognostic influence of molecular subgroups such as isocitrate dehydrogenase mutation, the trial will be stratified based on this determination from the primary pathology or subsequent biopsy known locally or otherwise determined centrally. A second stratification factor is based on the patient's Karnofsky Performance Score (KPS) (70-80 vs 90-100). Further, to account for potential differences in treatment choices for the control arm in regions, the trial will be stratified by geographical region during the randomization process. The study will be conducted in 2 parts; enrollment in the phase 3 will begin after phase 2 results are available.

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  • Phase II Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer Recruiting

    This phase II trial studies how well pegylated irinotecan NKTR 102 works in treating patients with non-small cell lung cancer, small cell lung cancer, or breast cancer that has spread to the brain and does not respond to treatment. Pegylated irinotecan NKTR 102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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  • A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors Not Recruiting

    To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cathy Kahn Recht, 650725863.

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Publications

All Publications


  • Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases JOURNAL OF NEURO-ONCOLOGY Li, Y., Pan, W., Connolly, I. D., Reddy, S., Nagpal, S., Quake, S., Gephart, M. H. 2016; 128 (1): 93-100

    Abstract

    Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAF (V600E) mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient's clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTEN (R130*) at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD.

    View details for DOI 10.1007/s11060-016-2081-5

    View details for Web of Science ID 000376095600011

    View details for PubMedID 26961773

  • The "Liquid Biopsy": the Role of Circulating DNA and RNA in Central Nervous System Tumors CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Connolly, I. D., Li, Y., Gephart, M. H., Nagpal, S. 2016; 16 (3)

    Abstract

    The detection of tumor-derived circulating nucleic acids in patients with cancer, known as the "liquid biopsy," has expanded from use in plasma to other bodily fluids in an increasing number of malignancies. Circulating nucleic acids could be of particular use in central nervous system tumors as biopsy carries a 5-7 % risk of major morbidity. This application presents unique challenges that have limited the use of cell-free DNA and RNA in the diagnosis and monitoring of CNS tumors. Recent work suggests that cerebrospinal fluid may be a useful source of CNS tumor-derived circulating nucleic acids. In this review, we discuss the available data and future outlook on the use of the liquid biopsy for CNS tumors.

    View details for DOI 10.1007/s11910-016-0629-6

    View details for Web of Science ID 000371174000005

    View details for PubMedID 26838352

  • Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. Journal of clinical oncology Kim, Y. H., Tavallaee, M., Sundram, U., Salva, K. A., Wood, G. S., Li, S., Rozati, S., Nagpal, S., Krathen, M., Reddy, S., Hoppe, R. T., Nguyen-Lin, A., Weng, W., Armstrong, R., Pulitzer, M., Advani, R. H., Horwitz, S. M. 2015; 33 (32): 3750-3758

    Abstract

    In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored.In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety.Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event.Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.

    View details for DOI 10.1200/JCO.2014.60.3969

    View details for PubMedID 26195720

  • Glioblastoma Multiforme Recurrence: An Exploratory Study of F-18 FPPRGD(2) PET/CT1 RADIOLOGY Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2015; 277 (2): 497-506

    Abstract

    Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (©) RSNA, 2015 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2015141550

    View details for Web of Science ID 000368435100026

    View details for PubMedID 25965900

  • Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma JOURNAL OF NEURO-ONCOLOGY Nagpal, S., Recht, C. K., Bertrand, S., Thomas, R. P., Ajlan, A., Pena, J., Gershon, M., Coffey, G., Kunz, P. L., Li, G., Recht, L. D. 2015; 123 (2): 277-282

    Abstract

    Patients with recurrence of high-grade glioma (HGG) after bevacizumab (BEV) have an extremely poor prognosis. Etirinotecan pegol (EP) is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Here we report results of a Phase 2, single arm, open-label trial evaluating EP in HGG patients who progressed after BEV. Patients age >18 with histologically proven anaplastic astrocytoma or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy >6 weeks and KPS ≥ 50 were required. The primary endpoint was PFS at 6-weeks. Secondary endpoint was overall survival from first EP infusion. Response was assessed by RANO criteria. Single agent EP was administered IV every 3 weeks at 145 mg/m2. Patients did not receive BEV while on EP. 20 patients (90 % GB) were enrolled with a median age of 50 and median KPS of 70. Three patients with GB (16.7 % of GB) had partial MRI responses. 6-week PFS was 55 %. Median and 6-month PFS were 2.2 months (95 % CI 1.4-3.4 months) and 11.2 % (95 % CI 1.9-28.9 %) respectively. Median overall survival from first EP infusion was 4.5 months (95 % CI 2.4-5.9). Only one patient had grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Three patients had confirmed partial responses according to RANO criteria. These clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in HGG.

    View details for DOI 10.1007/s11060-015-1795-0

    View details for Web of Science ID 000355632800010

  • Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain. The neuroradiology journal Andre, J. B., Nagpal, S., Hippe, D. S., Ravanpay, A. C., Schmiedeskamp, H., Bammer, R., Palagallo, G. J., Recht, L., Zaharchuk, G. 2015; 28 (2): 112-119

    Abstract

    Bevacizumab (BEV) is increasingly used to treat recurrent glioblastoma (GBM) with some reported improvement in neurocognitive function despite potential neurotoxicities. We examined the effects of BEV on cerebral blood flow (CBF) within recurrent GBM tumor and in the contralateral middle cerebral artery (MCA) territory.Post-chemoradiation patients with histologically confirmed GBM were treated with BEV and underwent routine, serial tumor imaging with additional pseudocontinuous arterial spin labeling (pcASL) following informed consent. Circular regions-of-interest were placed on pcASL images directly over the recurrent tumor and in the contralateral MCA territory. CBF changes before and during BEV treatment were evaluated in tumor and normal tissue. Linear mixed models were used to assess statistical significance.Fifty-three pcASL studies in 18 patients were acquired. Evaluation yielded lower mean tumoral CBF during BEV treatment compared with pre-treatment (45 ± 27 vs. 65 ± 27 ml/100 g/min, p = 0.002), and in the contralateral MCA territory during, compared with pre-BEV treatment (35 ± 8.4 vs. 41 ± 8.4 ml/100 g/min, p = 0.03). The decrease in mean CBF tended to be greater in the tumoral region than in the contralateral MCA, though the difference did not reach statistical significance (31% vs. 13%; p = 0.082).BEV administration results in statistically significant global CBF decrease with a potentially preferential decrease in tumor perfusion compared with normal brain tissue.

    View details for DOI 10.1177/1971400915576641

    View details for PubMedID 25923677

  • Brain Tumor Mutations Detected in Cerebral Spinal Fluid CLINICAL CHEMISTRY Pan, W., Gu, W., Nagpal, S., Gephart, M. H., Quake, S. R. 2015; 61 (3): 514-522

    Abstract

    Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood-brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative "liquid biopsy" of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined.We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease.We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from <5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations from the CSF of a patient with leptomeningeal disease by use of cancer panel sequencing, and the result was concordant with genetic testing on the primary tumor biopsy.Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care.

    View details for DOI 10.1373/clinchem.2014.235457

    View details for Web of Science ID 000352161300013

  • Prolonged Survival of Patients With Non-Small-Cell Lung Cancer With Leptomeningeal Carcinomatosis in the Modern Treatment Era CLINICAL LUNG CANCER Riess, J. W., Nagpal, S., Iv, M., Zeineh, M., Gubens, M. A., Ramchandran, K., Neal, J. W., Wakelee, H. A. 2014; 15 (3): 202-206

    Abstract

    Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM.Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3.LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007).In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication.

    View details for DOI 10.1016/j.cllc.2013.12.009

    View details for Web of Science ID 000334315100008

    View details for PubMedID 24524822

  • Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

    Abstract

    We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

    View details for DOI 10.1016/j.ijrobp.2013.07.034

    View details for Web of Science ID 000325763300022

  • Simultaneous perfusion and permeability measurements using combined spin- and gradient-echo MRI JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Schmiedeskamp, H., Andre, J. B., Straka, M., Christen, T., Nagpal, S., Recht, L., Thomas, R. P., Zaharchuk, G., Bammer, R. 2013; 33 (5): 732-743

    Abstract

    The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T1-, T2-, and -related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.

    View details for DOI 10.1038/jcbfm.2013.10

    View details for Web of Science ID 000318394400013

  • A Patient With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer With Development of Leptomeningeal Carcinomatosis While on Targeted Treatment With Crizotinib JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Riess, J. W., Nagpal, S., Neal, J. W., Wake, H. A. 2013; 11 (4): 389-394

    Abstract

    Leptomeningeal carcinomatosis (LM) is an infrequent yet morbid and often fatal complication of non-small cell lung cancer (NSCLC). Management of LM is multimodal, often involving systemic chemotherapy, radiotherapy, and a variety of symptom management maneuvers to address elevated intracranial pressure, pain, and mood changes that can accompany the disease. It is increasingly recognized that tumors with actionable mutations in NSCLC, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, respond well to systemic therapy with tyrosine kinase inhibitors yet often progress in the central nervous system. More information is needed regarding the natural history and optimal management of LM in specific molecular subtypes of NSCLC. This case report summarizes the management of a patient with ALK-positive NSCLC who developed LM while on targeted treatment with crizotinib within the context of current NCCN Clinical Practice Guidelines in Oncology and recently published studies.

    View details for Web of Science ID 000317543800006

  • ETIRINOTECAN PEGOL DNA Topoisomerase 1 Inhibitor Oncolytic DRUGS OF THE FUTURE Nagpal, S., Recht, L. D. 2013; 38 (4): 227-233
  • The incidence and significance of multiple lesions in glioblastoma JOURNAL OF NEURO-ONCOLOGY Thomas, R. P., Xu, L. W., Lober, R. M., Li, G., Nagpal, S. 2013; 112 (1): 91-97

    Abstract

    The location and distribution of glioblastoma (GBM) within the brain parenchyma plays an important role in surgical and radiation planning. Prior studies have reported incidences of multiple lesions at the time of diagnosis ranging from 0.5 to 20 %. Multiple lesions can be further categorized as multifocal (multiple areas involved, but with a clear path of spread from one lesion to another) or multicentric (multiple lesions, no clear path of spread). In this retrospective study, we reviewed our experience with GBM and found the incidence of multiple lesions at time of diagnosis was 35 %, much higher than previously suggested in the literature. Patients with single lesions had an improved overall survival when compared to patients with multiple lesions (18 vs. 10 months). Patients with multicentric lesions fared the worst, with average survival of 3 months. However, the difference between single and multiple lesions (multifocal or multicentric) was no longer significant when taking into consideration age, Karnofsky performance score (KPS) and extent of resection by multivariate analysis. Age, KPS, gross total resection, and MGMT status were independent predictors of outcome. Multiple lesions did not independently confer a worse outcome, but were associated with lower KPS scores and inability to perform gross total resection. These findings suggest that single, multiple and multicentric imaging exams represent a spectrum of presentations of a single disease. The rate of multiple lesions reported here may be the result of improved imaging technology, suggesting that incidence of multiple lesions will continue to increase as imaging technology advances.

    View details for DOI 10.1007/s11060-012-1030-1

    View details for Web of Science ID 000315487900011

  • A case series of NSCLC patients with different molecular characteristics and choroidal metastases: improvement in vision with treatment including pemetrexed and bevacizumab. Journal of thoracic oncology Riess, J. W., Nagpal, S., Das, M., Neal, J. W., Kim, J. W., Wakelee, H. A. 2013; 8 (2): e17-8

    View details for DOI 10.1097/JTO.0b013e31827690da

    View details for PubMedID 23328555

  • A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab JOURNAL OF THORACIC ONCOLOGY Riess, J. W., Nagpal, S., Das, M., Neal, J. W., Kim, J. W., Wakelee, H. A. 2013; 8 (2): E17-E18
  • EGFR mutation status and brain metastases in non-small cell lung cancer: an understudied problem TRANSLATIONAL CANCER RESEARCH Riess, J. W., Nagpal, S. 2013; 2 (1): 54-56
  • Advances in the management of glioblastoma: the role of temozolomide and MGMT testing. Clinical pharmacology : advances and applications Thomas, R. P., Recht, L., Nagpal, S. 2013; 5: 1-9

    Abstract

    Glioblastoma (GB) is one of the most lethal forms of cancer, with an invasive growth pattern that requires the use of adjuvant therapies, including chemotherapy and radiation, to prolong survival. Temozolomide (TMZ) is an oral chemotherapy with a limited side effect profile that has become the standard of care in GB treatment. While TMZ has made an impact on survival, tumor recurrence and TMZ resistance remain major challenges. Molecular markers, such as O6-methylguanine-DNA methyltransferase methylation status, can be helpful in predicting tumor response to TMZ, and therefore guides clinical decision making. This review will discuss the epidemiology and possible genetic underpinnings of GB, how TMZ became the standard of care for GB patients, the pharmacology of TMZ, the practical aspects of using TMZ in clinic, and how molecular diagnostics - particularly the use of O6-methylguanine-DNA methyltransferase status - affect clinical management.

    View details for DOI 10.2147/CPAA.S26586

    View details for PubMedID 23293540

  • Treatment of Leptomeningeal Spread of NSCLC: A Continuing Challenge CURRENT TREATMENT OPTIONS IN ONCOLOGY Nagpal, S., Riess, J., Wakelee, H. 2012; 13 (4): 491-504

    Abstract

    OPINION STATEMENT: Leptomeningeal metastasis is a serious and frequently fatal complication of non-small cell lung cancer. Curative treatment remains elusive, but careful use of radiation, systemic chemotherapy, intrathecal chemotherapy, and symptoms management can greatly improve quality of life and survival. For most patients, we recommend a combination of skull-based radiation with focal radiation to any symptomatic spinal segments followed by systemic chemotherapy. For patients with EGFR mutations, erlotinib may be used as first-line therapy in a daily or high-dose regimen. Pemetrexed has promise for use in patients with brain and leptomeningeal metastases. Patients with multiple comorbidities or low performance status may tolerate intrathecal therapy better than systemic chemotherapy. The most commonly used intrathecal chemotherapies are methotrexate and liposomal cytarabine, although newer agents, such as topotecan and mafosfamide, may be more effective. Elevated intracranial pressure, which causes headaches, vertigo, nausea, and vomiting, should be treated with dexamethasone and acetazolamide. In select patients, cerebrospinal fluid shunting may be considered. The use of antidepressants, central nervous system stimulants, benzodiazepines, antiemetics, and pain medications can increase quality of life in patients with leptomeningeal metastases.

    View details for DOI 10.1007/s11864-012-0206-4

    View details for Web of Science ID 000311292500006

    View details for PubMedID 22836285

  • Polymer Wafers (Gliadel) in the Treatment of Malignant Glioma NEUROSURGERY CLINICS OF NORTH AMERICA Nagpal, S. 2012; 23 (2): 289-?

    Abstract

    The 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU; carmustine) polymer wafer (Gliadel) was developed for use in malignant glioma to deliver higher doses of chemotherapy directly to tumor tissue while bypassing systemic side effects. Phase III clinical trials for patients with newly diagnosed malignant gliomas demonstrated a small, but statistically significant, improvement in survival. However, the rate of complications, including an increase in cerebrospinal fluid leaks and intracranial hypertension, has limited their use. This article reviews the current data for use of BCNU wafers in malignant gliomas.

    View details for DOI 10.1016/j.nec.2012.01.004

    View details for Web of Science ID 000303282100011

    View details for PubMedID 22440872

  • Neoplastic Myelopathy SEMINARS IN NEUROLOGY Nagpal, S., Clarke, J. L. 2012; 32 (2): 137-145

    Abstract

    Neoplastic myelopathy may be due to external compression or to direct intraparenchymal involvement of the spinal cord. In this review, the authors discuss the most common cause for compressive neoplastic myelopathy, metastatic disease. They also review other compressive lesions and discuss primary intramedullary spinal tumors. In the acute setting, compressive metastatic disease should be treated with high-dose steroids when clinically necessary; surgery should be considered for selected patients, followed by radiation therapy. For most primary intramedullary spinal tumors, surgical resection remains the standard initial therapy. Patients with incomplete resection of infiltrative tumors, high-grade pathology, or recurrent tumors may benefit from radiation, but most spinal tumors are relatively insensitive to traditional chemotherapy. Neoplastic myelopathy from either compressive or intraparenchymal causes remains a diagnostic and therapeutic challenge. In complex cases, referral to a specialty center with access to neurosurgeons, neuroradiologists, neuropathologists, and neurooncologists is recommended.

    View details for DOI 10.1055/s-0032-1322584

    View details for Web of Science ID 000307423200005

    View details for PubMedID 22961188

  • Treatment and Prophylaxis of Hematologic Malignancy in the Central Nervous System CURRENT TREATMENT OPTIONS IN NEUROLOGY Nagpal, S., Recht, L. 2011; 13 (4): 400-412

    Abstract

    OPINION STATEMENT: Central nervous system (CNS) involvement is a serious, and frequently fatal, complication of acute leukemias and very aggressive lymphomas. In patients with no evidence of CNS involvement at the time of diagnosis, the decision to include CNS prophylaxis in the treatment regimen should be based on cytologic diagnosis and other risk factors. Patients with a risk of CNS relapse greater than 10% should receive CNS prophylaxis with high-dose systemic chemotherapy, intrathecal therapy, radiation, or a combination thereof. The most commonly used systemic and intrathecal chemotherapies are methotrexate and cytarabine. Liposomal cytarabine, which increases CNS bioavailability and decreases the number of lumbar punctures needed, is our preference for intrathecal therapy. We usually reserve radiation therapy for patients who may not tolerate other forms of CNS prophylaxis. Patients with evidence of CNS involvement, either at diagnosis or relapse, should be treated until CNS disease clearance or dose-limiting toxicity is reached. Recent studies suggest that autologous stem cell transplantation may offer longer survivals for patients with CNS involvement and should be considered for patients who can tolerate the procedure. The use of rituximab in CNS prophylaxis and treatment has not yet been clearly delineated, but initial reports indicate that this agent and others may soon be available as an effective and tolerable CNS-directed therapy for lymphomas.

    View details for DOI 10.1007/s11940-011-0128-7

    View details for Web of Science ID 000292402500007

    View details for PubMedID 21484261

  • Bevacizumab improves quality of life in patients with recurrent glioblastoma. Chemotherapy research and practice Nagpal, S., Harsh, G., Recht, L. 2011; 2011: 602812-?

    Abstract

    Objective. To quantify the benefits in survival and quality of life in patients receiving bevacizumab (BEV) for recurrent glioblastoma (GBM). Methods. This is a retrospective study of 40 adult patients with recurrent GBM treated between 2005 and 2009 at a single institution. All patients had initial treatment with surgery, radiation, and concurrent temozolomide, then monthly temozolomide. Over 250 charts were screened. Sufficient data was available for 20 patients treated with BEV and 20 patients who did not receive BEV at the time of recurrence. The independent living score (ILS), designed to reward long-term independent survival, was calculated for each patient. Results. The mean ILS was nearly double in the BEV group compared to the No-BEV group (15.0 versus 8.2, P = 0.002, t-test). Two months after initiation of therapy, the median steroid dose dropped by over 90% in patients treated with BEV, but doubled in the NoBEV group. Median survival from the time of recurrence was significantly affected: 10.6 months in the BEV group versus 4.2 months (P < 0.001, log rank survival) in the NoBEV group. Conclusions. BEV increases independent living and lengthens overall survival after GBM recurrence. Reduction in steroid dose may contribute to prolonged independence.

    View details for DOI 10.1155/2011/602812

    View details for PubMedID 22312554

  • Cardiac Rupture After Intravenous t-PA Administration in Acute Ischemic Stroke NEUROCRITICAL CARE Dhand, A., Nakagawa, K., Nagpal, S., Gelfand, J. M., Kim, A. S., Smith, W. S., Tihan, T. 2010; 13 (2): 261-262

    Abstract

    Ventricular free wall rupture is a fatal complication of myocardial infarction (MI). Although described in MI patients who receive thrombolytic therapy, this complication is not well known in ischemic stroke patients who receive intravenous (IV) t-PA.Case report.We present a 93-year-old woman with an acute onset of a right middle cerebral artery syndrome in the setting of subacute MI. IV t-PA was administered and she subsequently developed asystolic arrest and died. Autopsy showed subacute MI, hemopericardium, and rupture of the left ventricle.This case illustrates a fatal cardiac complication of IV thrombolytic therapy for stroke. The speculated mechanism is hemorrhage into the infarcted myocardium.

    View details for DOI 10.1007/s12028-010-9384-8

    View details for Web of Science ID 000282093500018

    View details for PubMedID 20697837

  • Treatment and Prevention of Secondary CNS Lymphoma SEMINARS IN NEUROLOGY Nagpal, S., Glantz, M. J., Recht, L. 2010; 30 (3): 263-272

    Abstract

    Central nervous system (CNS) involvement in non-Hodgkin lymphoma is a serious, potentially preventable complication that can occur in 5 to 10% of patients. Its occurrence is directly correlated with pathologic aggressiveness and ranges from less than 3% in the indolent, less-aggressive histologies to as high as 50% in the very aggressive ones such as Burkitt lymphoma. Aggressive treatment once detected can improve neurologic outcome, but because it is often associated with contemporaneous systemic relapse, is rarely associated with long-term survival. Preventing its occurrence, therefore, remains an important goal of initial treatment. Despite there being some suggestive evidence that the addition of systemic rituximab and several intracerebrospinal fluid chemotherapy regimens may have decreased the incidence of CNS involvement, both optimal selection of those patients who should receive prophylaxis as well as the best prophylactic regimen remain active areas of investigation.

    View details for DOI 10.1055/s-0030-1255222

    View details for Web of Science ID 000279572600007

    View details for PubMedID 20577933

  • Decompressive laparotomy to treat intractable cerebral hypoxia. journal of trauma Nagpal, S., Halpern, C. H., Sims, C., Calland, J. F., Gracias, V. H., Schuster, J. M., LeRoux, P. D., Levine, J. M. 2009; 67 (5): E152-5

    View details for DOI 10.1097/TA.0b013e3180593657

    View details for PubMedID 19088554

  • Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence? Neurosurgical focus Stein, S. C., Levine, J. M., Nagpal, S., LeRoux, P. D. 2006; 21 (3): E2-?

    Abstract

    The authors review literature that challenges the view that vasospasm involving large arteries is the exclusive cause of delayed ischemic neurological deficits (DINDs) following subarachnoid hemorrhage. They discuss alternative mechanisms and review the evidence supporting a potential role for thromboembolism. They conclude that vasospasm and thromboembolism play interrelated and additive roles in the development of DINDs, and that this interaction provides opportunities for novel therapeutic approaches.

    View details for PubMedID 17029341

  • Management of patients with Schwan nomatosis: Report of six cases and review of the literature SURGICAL NEUROLOGY Huang, J. H., Simon, S. L., Nagpal, S., Nelson, P. T., Zager, E. L. 2004; 62 (4): 353-361

    Abstract

    Schwannomatosis is a rare tumor syndrome characterized by the presence of multiple schwannomas without the stigmata of neurofibromatosis (NF) Type 1 or 2. To better understand the natural history and clinical management of the syndrome, a retrospective review was conducted of patients diagnosed with schwannomatosis over an 11-year period at the University of Pennsylvania Medical Center (UPMC).Between 1990 and 2001, 131 patients underwent surgery for resection of spinal or peripheral nerve schwannomas in the Department of Neurosurgery at the University of Pennsylvania Medical Center. Among the 131 patients, there were 6 who had two or more pathologically proven schwannomas without radiographic or clinical evidence of vestibular schwannomas. The hospital charts, clinic notes, radiology films, operative reports, pathology slides, and reports from all 6 patients were retrospectively reviewed.The patient population consisted of 6 patients with a mean age of 48.7 (3 male: 3 female). All patients had enhanced brain magnetic resonance imaging (MRI) scans that were negative for vestibular schwannomas. Ophthalmological and general physical examinations did not reveal any findings suggestive of NF. There was no family history of NF or schwannomatosis. The locations of the schwannomas included intraspinal (multiple sites), paraspinal, brachial plexus, femoral nerve, sciatic nerve, calf, forearm, retroperitoneum, and middle cranial/infratemporal fossa region. The common presenting symptoms included paresthesias, palpable mass, pain, or weakness. All 6 patients underwent surgical resection of symptomatic lesions.For patients with schwannomatosis, surgery is indicated for symptomatic lesions, while asymptomatic tumors are followed conservatively. Because these patients are at increased risk for developing multiple schwannomas, we recommend regular surveillance and offer genetic counseling even though the pattern of inheritance is unknown.

    View details for DOI 10.1016/j.surneu.2003.11.020

    View details for Web of Science ID 000224263300013

    View details for PubMedID 15451291