Publications by authors named "Katherine B Peters"

75 Publications

Utilizing a Palliative Care Screening Tool in Patients With Glioblastoma.

J Adv Pract Oncol 2020 Sep-Oct;11(7):684-692. Epub 2020 Sep 1.

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina.

Patients with glioblastoma have poor overall survival and experience significant burden from neurologic decline and adverse treatment effects. Despite the well-known benefits of early palliative care integration with oncology care, utilization of palliative care is low. The purpose of this quality improvement (QI) project is to investigate the feasibility, value, and effectiveness of using an adapted palliative care screening tool to improve outpatient palliative care screening and referral of glioblastoma patients. This QI project was conducted over a 10-week period. A glioma palliative care screening tool was developed and integrated into outpatient visits. Providers were required to use the screening tool during each patient visit. Patients 18 years or older who were diagnosed with a World Health Organization grade IV glioma and returning to the neuro-oncology clinic for a brain MRI evaluation were targeted. Screening, palliative care discussion, and referral rates were evaluated. Among 530 eligible patients who returned to the clinic over a 10-week period, the tool was available for 433 patients. Fifty-six percent (n = 294/530) of the patients were screened. Nine percent (n = 27) of screened patients were identified as candidates for a palliative care referral (score ≥ 5 on the screening tool). Of these 27 patients, the proportion of patients who had a palliative care discussion was 63% (n = 17). Overall, 71% (n = 12) of patients who had a palliative care discussion were referred to a palliative care provider. Integrating a glioma palliative care screening tool with outpatient visits can draw attention to palliative care needs and lead to a referral to palliative care.
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http://dx.doi.org/10.6004/jadpro.2020.11.7.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646633PMC
September 2020

A broad perspective on evaluating bias in the neuro-oncology workplace.

Neuro Oncol 2021 Feb 6. Epub 2021 Feb 6.

Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA.

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http://dx.doi.org/10.1093/neuonc/noaa286DOI Listing
February 2021

When tumefactive demyelination is truly a tumor: case report of a radiographic misdiagnosis.

CNS Oncol 2021 Jan 15:CNS69. Epub 2021 Jan 15.

Department of Neurosurgery, Duke University School of Medicine, The Preston Robert Tisch Brain Tumor Center, Durham, NC 27710, USA.

Oligodendrogliomas are slow-growing tumors that account for 15-20% of gliomas. This case report describes the case of an adult male patient diagnosed initially with tumefactive demyelination and multiple sclerosis, which was subsequently found to be a well-differentiated low-grade oligodendroglioma. This case emphasizes the importance of timely diagnosis in oligodendrogliomas and other brain tumors for the prompt initiation of appropriate therapy, to minimize the likelihood of disease progression, ensure symptom management and escalation of unnecessary treatments for multiple sclerosis.
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http://dx.doi.org/10.2217/cns-2020-0028DOI Listing
January 2021

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Nat Commun 2021 01 13;12(1):352. Epub 2021 Jan 13.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, 27710, USA.

Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.
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http://dx.doi.org/10.1038/s41467-020-20469-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806846PMC
January 2021

Health care resource utilization and treatment of leptomeningeal carcinomatosis in the United States.

Neurooncol Pract 2020 Dec 21;7(6):636-645. Epub 2020 Jul 21.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, US.

Background: The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges.

Methods: The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis.

Results: We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%).

Conclusions: LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.
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http://dx.doi.org/10.1093/nop/npaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716175PMC
December 2020

Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group.

Support Care Cancer 2020 Nov 24. Epub 2020 Nov 24.

The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.

Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management.
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http://dx.doi.org/10.1007/s00520-020-05860-9DOI Listing
November 2020

What is New in Neuro-oncology?

Neurol Clin 2021 02 7;39(1):163-179. Epub 2020 Nov 7.

Department of Neurology, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA; Lou & Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center.

Neuro-oncology is a rapidly developing field. A continuous evolution in the understanding of the molecular underpinnings of central nervous system tumors has helped reconfigure the classification of brain tumors. More importantly, it has laid the path forward for the development and investigation of new therapeutics. The authors discuss the classification of brain tumors and novel therapies in brain tumors as well as promising treatments underway.
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http://dx.doi.org/10.1016/j.ncl.2020.09.009DOI Listing
February 2021

RAF and MEK inhibitor therapy in adult patients with brain tumors: a case-based overview and practical management of adverse events.

Neurooncol Pract 2020 Jul 27;7(4):369-375. Epub 2020 Feb 27.

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA.

Targeted therapy has gained mainstream attention with notable successes against specific genetic mutations in many cancers. One particular mutation, the V600E mutation, is present in a small subset of gliomas in adults. Although clinical experience and trial data of RAF-targeted therapy in adults with glioma are lacking at this time, the poor prognosis of adult high-grade glioma has led neuro-oncology practitioners to consider the use of targeted therapy in these patients. In this manuscript, we describe the use of RAF and MEK inhibitors in adults with recurrent glioma. We discuss the utility of these agents, describe their toxicities, and give examples of management strategies. Given the significant toxicities of RAF and MEK inhibitors, along with the long potential duration of treatment, neuro-oncology providers should counsel patients carefully before initiating therapy and monitor them closely while undergoing treatment with RAF-targeted therapy.
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http://dx.doi.org/10.1093/nop/npaa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393273PMC
July 2020

Volumetric analysis of IDH-mutant lower-grade glioma: a natural history study of tumor growth rates before and after treatment.

Neuro Oncol 2020 12;22(12):1822-1830

Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.

Background: Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials.

Methods: In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model.

Results: The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (-15.24% /180 days, 95% CI: [-21.37%, -8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108).

Conclusion: In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.
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http://dx.doi.org/10.1093/neuonc/noaa105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746936PMC
December 2020

Ibrutinib in primary central nervous system diffuse large B-cell lymphoma.

CNS Oncol 2020 03 6;9(1):CNS51. Epub 2020 Mar 6.

Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.

The standard regimen for the treatment of newly diagnosed primary CNS lymphoma (PCNSL) remains regimens that contain high-dose methotrexate (MTX). While these regimens can provide control for some patients, there is a dearth of options for the treatment of patients with PCNSL who cannot tolerate MTX-containing regimens, or whose cancers are refractory to MTX. In this article, we review a promising new option; ibrutinib, a Bruton tyrosine kinase inhibitor, for patients with relapsed and refractory PCNSL.
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http://dx.doi.org/10.2217/cns-2019-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163401PMC
March 2020

Patterns of relapse after successful completion of initial therapy in primary central nervous system lymphoma: a case series.

J Neurooncol 2020 Apr 5;147(2):477-483. Epub 2020 Mar 5.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.

Purpose: Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin's lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of systemic disease. This rare disease accounts for ~ 3% of all primary central nervous system (CNS) tumors. Methotrexate-based regimens are the standard of care for this disease with overall survival rates ranging from 14 to 55 months. Relapse after apparent complete remission can occur. We sought to understand the outcomes of patients who relapsed.

Methods: This is an IRB-approved investigation of patients treated at our institution between 12/31/2004 and 10/12/2016. We retrospectively identified all cases of PCNSL as part of a database registry and evaluated these cases for demographic information, absence or presence of relapse, location of relapse, treatment regimens, and median relapse-free survival.

Results: This analysis identified 44 patients with a pathologically confirmed diagnosis of PCNSL. Mean age at diagnosis was 63.1 years (range 20-86, SD = 13.2 years). Of the 44 patients, 28 patients successfully completed an initial treatment regimen without recurrence or toxicity that required a change in therapy. Relapse occurred in 11 patients with the location of relapse being in the CNS only (n = 5), vitreous fluid only (n = 1), outside CNS only (n = 3), or a combination of CNS and outside of the CNS (n = 2). Sites of relapse outside of the CNS included testes (n = 1), lung (n = 1), adrenal gland (n = 1), kidney/adrenal gland (n = 1), and retroperitoneum (n = 1). Median relapse-free survival after successful completion of therapy was 6.7 years (95% CI 1.1, 12.6).

Conclusion: After successful initial treatment, PCNSL has a propensity to relapse, and this relapse can occur both inside and outside of the CNS. Vigilant monitoring of off-treatment patients with a history of PCNSL is necessary to guide early diagnosis of relapse and to initiate aggressive treatment.
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http://dx.doi.org/10.1007/s11060-020-03446-3DOI Listing
April 2020

Recurrent Extradural Myxopapillary Ependymoma With Oligometastatic Spread.

Front Oncol 2019 28;9:1322. Epub 2019 Nov 28.

The Preston Robert Tisch Brain Tumor Center, Duke University Health System, Durham, NC, United States.

Myxopapillary ependymomas are a slow-growing, grade I type glial tumor in the lumbosacral region. More rarely, they can present as extradural, subcutaneous sacrococcygeal, or perisacral masses, and it is under these circumstances that they are more likely to spread. Here, we report the presentation of a sacrococcygeal mass in patient that was initially resected confirming extradural myxopapillary ependymoma. At initial resection, multiple small pulmonary nodules were detected. This mass recurred 2 years later at the resection site with an interval increase in the previously imaged pulmonary nodules. Resection of both the post-sacral mass and largest lung metastasis confirmed recurrent myxopapillary ependymoma with oligometastatic spread. Because these tumors are rare, with extradural presentation being even more infrequent, to this date there are no definitive therapeutic guidelines for initial treatment and continued surveillance. For myxopapillary ependymoma, current standard of care is first-line maximal surgical resection with or without postoperative radiotherapy depending on the extent of disease and extent of resection. However, there remains insufficient evidence on the role of radiotherapy to oligometastatic foci in providing any further survival benefit or extending time to recurrence. Thus, prospective studies assessing the role of upfront treatment of oligometastases with local resection and adjuvant radiotherapy are needed for improved understanding of extradural myxopapillary ependymoma.
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http://dx.doi.org/10.3389/fonc.2019.01322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892774PMC
November 2019

Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

Neuro Oncol 2020 05;22(5):694-704

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Background: VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).

Methods: Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).

Results: VB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.

Conclusions: Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.
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http://dx.doi.org/10.1093/neuonc/noz231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229257PMC
May 2020

The role of chemotherapy in the treatment of central neurocytoma.

CNS Oncol 2019 11 5;8(3):CNS41. Epub 2019 Nov 5.

Department of Neurosurgery, Duke University Hospital, Durham, NC 27710, USA.

Central neurocytoma (CN) is a rare WHO grade II central nervous system (CNS) tumor. This is an update on chemotherapeutic agents used in its treatment. An institutional review board-approved, chart review of patients seen at our institution resulted in a single case treated with chemotherapy and is herein included. We proceeded with a comprehensive literature review. We identified 18 citations, representing 39 cases of adult and pediatric CN treated with chemotherapy. With the addition of our single case, the total number of recurrent CN patients treated with temozolomide (TMZ) is nine. There exists marked heterogeneity in chemotherapy used to treat CN. TMZ is incorporated into treatment regimens in the setting of tumor recurrence: its role merits further study.
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http://dx.doi.org/10.2217/cns-2019-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880304PMC
November 2019

Second primary cancers in long-term survivors of glioblastoma.

Neurooncol Pract 2019 Sep 4;6(5):386-391. Epub 2019 Feb 4.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.

Background: Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM.

Methods: Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis.

Results: We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1).

Conclusions: Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.
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http://dx.doi.org/10.1093/nop/npz001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753354PMC
September 2019

Randomized open-label phase II trial of 5-day aprepitant plus ondansetron compared to ondansetron alone in the prevention of chemotherapy-induced nausea-vomiting (CINV) in glioma patients receiving adjuvant temozolomide.

Support Care Cancer 2020 May 22;28(5):2229-2238. Epub 2019 Aug 22.

Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.

Purpose: CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated.

Methods: One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150-200 mg/m/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL).

Results: Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity.

Conclusions: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.
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http://dx.doi.org/10.1007/s00520-019-05039-xDOI Listing
May 2020

Complementary and integrative health interventions and their association with health-related quality of life in the primary brain tumor population.

Complement Ther Clin Pract 2019 Aug 18;36:43-48. Epub 2019 May 18.

Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, DUMC Box 3624, Durham, NC, 27710, USA. Electronic address:

Background And Purpose: Little is known about complementary and integrative health intervention usage in the primary brain tumor population. We aimed to identify the percentage of patients using these practices and explore the impact on quality of life.

Materials And Methods: Clinical records from patients seen in clinic between December 16, 2013 and February 28, 2014 were reviewed retrospectively. The questionnaires used were a modified version of the International Complementary and Alternative Medicine Questionnaire, the Functional Assessment of Cancer Therapy- Brain Cancer and the Functional Assessment of Chronic Illness Therapy- Fatigue.

Results: 76% of patients utilized a complementary and integrative health modality. The most frequently reported modalities used were vitamins, massage, and spiritual healing, prayer, diet and meditation.

Conclusion: These results confirm the usage of complementary and integrative health practices within the primary brain tumor population; however, there was no evidence of association between use and quality of life.
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http://dx.doi.org/10.1016/j.ctcp.2019.05.002DOI Listing
August 2019

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Support Care Cancer 2019 Oct 30;27(10):3729-3737. Epub 2019 Jul 30.

The Ohio State University Comprehensive Cancer Center, Columbus, USA.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.
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http://dx.doi.org/10.1007/s00520-019-04987-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728179PMC
October 2019

Single-institution retrospective review of patients with recurrent glioblastoma treated with bevacizumab in clinical practice.

Health Sci Rep 2019 Apr 13;2(4):e114. Epub 2019 Feb 13.

The Preston Robert Tisch Brain Tumor Center Duke University Medical Center Durham North Carolina.

Background And Aims: This retrospective review of patients with recurrent glioblastoma treated at the Preston Robert Tisch Brain Tumor Center investigated treatment patterns, survival, and safety with bevacizumab in a real-world setting.

Methods: Adult patients with glioblastoma who initiated bevacizumab at disease progression between January 1, 2009, and May 14, 2012, were included. A Kaplan-Meier estimator was used to describe overall survival (OS), progression-free survival (PFS), and time to greater than or equal to 20% reduction in Karnofsky Performance Status (KPS). The effect of baseline demographic and clinical factors on survival was examined using a Cox proportional hazards model. Adverse event (AE) data were collected.

Results: Seventy-four patients, with a median age of 59 years, were included in this cohort. Between bevacizumab initiation and first failure, defined as the first disease progression after bevacizumab initiation, biweekly bevacizumab and bevacizumab/irinotecan were the most frequently prescribed regimens. Median duration of bevacizumab treatment until failure was 6.4 months (range, 0.5-58.7). Median OS and PFS from bevacizumab initiation were 11.1 months (95% confidence interval [CI], 7.3-13.4) and 6.4 months (95% CI, 3.9-8.5), respectively. Median time to greater than or equal to 20% reduction in KPS was 29.3 months (95% CI, 13.8-∞). Lack of corticosteroid usage at the start of bevacizumab therapy was associated with both longer OS and PFS, with a median OS of 13.2 months (95% CI, 8.6-16.6) in patients who did not initially require corticosteroids versus 7.2 months (95% CI, 4.8-12.5) in those who did ( = 0.0382, log-rank), while median PFS values were 8.6 months (95% CI, 4.6-9.7) and 3.7 months (95% CI, 2.7-6.6), respectively ( = 0.0243, log-rank). Treatment failure occurred in 70 patients; 47 of whom received salvage therapy, and most frequently bevacizumab/carboplatin (7/47; 14.9%). Thirteen patients (18%) experienced a grade 3 AE of special interest for bevacizumab.

Conclusions: Treatment patterns and outcomes for patients with recurrent glioblastoma receiving bevacizumab in a real-world setting were comparable with those reported in prospective clinical trials.
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http://dx.doi.org/10.1002/hsr2.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482327PMC
April 2019

"Neuro-oncology research in Nigeria: a great untapped potential".

World Neurosurg 2019 Jan 16. Epub 2019 Jan 16.

Division of Neurosurgery, Department of Surgery, College of Medicine, Duke University, Durham, USA. Electronic address:

Background: Nigeria has the largest population in Africa and has sub-optimal access to neuro-oncology care. It has been estimated that there is approximately 1 neurosurgeon to 2.4 million people in the country, with only few of these trained in the neuro-oncology sub-specialty and no dedicated medical or radiation neurooncologists. There is a paucity of information on the field of neuro-oncology in Nigeria. This manuscript aims to provide an overview of the current state of neuro-oncology literature in Nigeria.

Methods: A systematic literature review was performed, utilizing Google Scholar, PubMed, and African Journals Online, to search for articles related to neuro-oncology in Nigeria, from 1963-2018. Articles were reviewed and categorized.

Results: Sixty-three relevant articles were identified. They comprised original research in basic science (N= 1), clinical science (N = 59), and reviews (n=3). Retrospective case series were the most common type of publication. Categorizing according to histology, articles focused on meningioma (N=12), pituitary tumors (N=10), glioma (N=7), CNS metastases (N=6), multiple histologic types (N=25) and other types of tumors (N=3). Eight pediatric neuro-oncology publications were amongst these. Two manuscripts, focusing on surgical subjects, specifically addressed issues on neuro-oncology clinical practice in Nigeria. Of the total manuscripts, 26 were published in Nigerian based journals, and 37 in journals outside Nigeria. The majority of the journals were low impact factor journals. An increasing number of publications over time was noted.

Conclusions: There is a small but growing scholarly literature in neuro-oncology from Nigeria. However, there continues to be room for growth in neuro-oncology research output. With Nigeria's large patient population, there is potential to learn and add to the academic literature. While there are logistical obstacles to both patient care and research in neuro-oncology in Nigeria, there is promise for favorable advancement.
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http://dx.doi.org/10.1016/j.wneu.2018.12.192DOI Listing
January 2019

Pilot Study to Describe the Trajectory of Symptoms and Adaptive Strategies of Adults Living with Low-grade Glioma.

Semin Oncol Nurs 2018 12 6;34(5):472-485. Epub 2018 Nov 6.

Objectives: To describe the adaptability to the patterns in symptoms and quality of life (QoL) during 6 months post low-grade glioma diagnosis by valid and reliable tools; to identify through qualitative interviews patient/provider adaptive techniques and strategies; and to assess associations among patient characteristics, symptoms and QoL, and adaptive techniques or strategies.

Data Sources: Demographic, clinical and pathologic data from medical records. Validated instruments that assess QoL, fatigue, depression, and distress were completed at 2, 4, and 6 months post diagnosis. Qualitative interviews identifying the symptoms, challenges, adaptive techniques and strategies were conducted at 4 and 6 months.

Conclusion: The most frequently used adaptive strategies included: obtaining community support (87%), managing expectations (73%) and support systems (67%), and seeking out knowledge about physical (67%) and behavioral symptoms (53%). Seizures were reported with IDH1 (11%) but not IDH1. Patients with either IDH1 or TERT consistently reported lower QoL and higher distress, depression, and fatigue scores. IDH1/TERT may be related to lower QoL because of IDH1-related seizures.

Implications For Nursing Practice: Findings provide a list of adaptive strategies and characteristics to address the problems and symptoms that may improve overall QoL in patients with low-grade glioma.
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http://dx.doi.org/10.1016/j.soncn.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612906PMC
December 2018

Evidence-based Treatment for Low-grade Glioma.

Semin Oncol Nurs 2018 12 2;34(5):465-471. Epub 2018 Nov 2.

Objectives: To identify the tumors included in the WHO classification of low-grade gliomas, and review the importance of molecular biomarkers and their implication for treatment, prognosis, and outcomes.

Data Sources: Published research, clinical guidelines, educational articles in oncology journals, and Web-based resources.

Conclusion: Molecular neuropathology has influenced the reclassification of low-grade gliomas and, as such, has provided patient-specific treatments with improving outcomes.

Implications For Nursing Practice: Nurses play a key role in patient education and communication with the patient's interdisciplinary care team. Understanding the molecular neuropathology that determine treatment recommendations and in turn recognizing and identifying complications provides improved patient/caregiver satisfaction and outcomes.
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http://dx.doi.org/10.1016/j.soncn.2018.10.008DOI Listing
December 2018

Adjunctive perampanel for glioma-associated epilepsy.

Epilepsy Behav Case Rep 2018 9;10:114-117. Epub 2018 Oct 9.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States of America.

Glioma-associated epilepsy is associated with excessive glutamate signaling. We hypothesized that perampanel, an amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, would treat glioma-related epilepsy. We conducted a single-arm study of adjunctive perampanel for patients with focal-onset glioma-associated seizures. The most common related adverse events were fatigue and dizziness. Three out of 8 participants had self-reported seizure reduction and an additional 3 reported improved control. Of these 6, 5 had isocitrate dehydrogenase 1 mutant gliomas. We conclude that perampanel is safe for patients with glioma-related focal-onset epilepsy. Further study into the association between AMPA signaling, IDH1 status and seizures is warranted.
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http://dx.doi.org/10.1016/j.ebcr.2018.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202665PMC
October 2018

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

N Engl J Med 2018 07 26;379(2):150-161. Epub 2018 Jun 26.

From the Departments of Neurosurgery (A.D., M.G., A.H.F., H.S.F., K.B.P., D.R., J.H.S., G.V., D.A., D.D.B.), Biostatistics (J.E.H., F.M.), Surgery (D.P.B., S.N.), and Pathology (W.T.H., R.E.M.) and the Preston Robert Tisch Brain Tumor Center (A.D., M.G., J.E.H., D.P.B., A.H.F., H.S.F., F.M., S.N., K.B.P., D.R., J.H.S., G.V., W.T.H., R.E.M., D.A., D.D.B.), Duke University Medical Center, and Istari Oncology (D.P.B.) - all in Durham, NC; Tempus Labs, Chicago (N.B.); and the School of Medicine, Deakin University, Geelong, VIC, Australia (A.M.M.).

Background: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.

Methods: We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast-enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 10 and 10 50% tissue-culture infectious doses (TCID), first in a dose-escalation phase and then in a dose-expansion phase.

Results: From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0×10 TCID) was identified as the phase 2 dose. One dose-limiting toxic effect was observed; a patient in whom dose level 5 (10 TCID) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months.

Conclusions: Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893 .).
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http://dx.doi.org/10.1056/NEJMoa1716435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065102PMC
July 2018

A Diffuse Leptomeningeal Glioneuronal Tumor Without Diffuse Leptomeningeal Involvement: Detailed Molecular and Clinical Characterization.

J Neuropathol Exp Neurol 2018 09;77(9):751-756

Department of Neurology, Duke University Medical Center, Durham, North Carolina.

Prior to their provisional WHO classification as a distinct entity in 2016, diffuse leptomeningeal glioneuronal tumors (DLGNT) were often regarded as diffuse leptomeningeal presentations of oligodendrogliomas or extraventricular neurocytomas. Their classification as a distinct entity partly relies on their pattern of growth, but DLGNTs without radiological leptomeningeal involvement have been described. In a patient with a DLGNT of the spinal cord without evidence of leptomeningeal involvement, we review in depth the clinical course and the histologic and molecular features of the neoplasm, in the context of other reported cases without diffuse leptomeningeal involvement. Our findings highlight the advantages of molecular analysis in making accurate diagnoses on small spinal tissue samples and underline the need for more long-term clinical follow-up of these rare neoplasms to inform treatment decisions.
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http://dx.doi.org/10.1093/jnen/nly053DOI Listing
September 2018

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma.

Oncologist 2018 08 17;23(8):889-e98. Epub 2018 Apr 17.

Duke University Medical Center, Durham, North Carolina, USA

Lessons Learned: Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis.

Background: Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3-11 months with bevacizumab (BEV)-containing regimens. BEV in rMG has 6-month progression free survival (PFS-6) of ∼40% and an objective response rate of 21.2%. BEV-containing regimens improve PFS-6 to 42.6%-50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor [VEGF]) by c-Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth.

Methods: Thirty-six BEV-naïve rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro-Oncology [RANO] criteria), PFS-6, overall survival (OS), and toxicity.

Results: Median patient follow-up was 65.0 months. Objective response rate was 27.8% (95% confidence interval [CI]: 15.7%-44.1%). Median OS was 11.2 months (95% CI: 7-17.5). PFS-6 was 41.7% (95% CI: 25.6%-57.0%). Most frequent treatment-related grade ≤2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ≥3 events included venous thromboembolism (four patients), including one death from pulmonary embolism.

Conclusion: Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.
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http://dx.doi.org/10.1634/theoncologist.2018-0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156179PMC
August 2018

Phase I/II trial of vorinostat, bevacizumab, and daily temozolomide for recurrent malignant gliomas.

J Neurooncol 2018 Apr 21;137(2):349-356. Epub 2017 Dec 21.

Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.

Prognosis of recurrent glioblastoma (GBM) is poor with 6-month progression-free survival (PFS6) ranging from 9 to 48% depending on the treatment regimen and use of anti-angiogenic therapies. We sought to study vorinostat (VOR), a histone deacetylase inhibitor, in combination with bevacizumab (BEV) and daily metronomic temozolomide (TMZ) in a Phase I/II trial in recurrent high-grade gliomas (HGGs). This was a Phase I/II open-label, single-arm study in recurrent HGG patients. Phase I primary endpoint was to determine the maximum tolerated dose (MTD) of VOR with BEV and daily TMZ. Phase II primary endpoint was PFS6. Regimen was BEV 10 mg/kg iv every 2 weeks, TMZ 50 mg/m po daily, and VOR 200 or 400 mg po alternating 7 days on then 7 days off throughout a 28-day cycle. Phase I portion enrolled nine subjects with three receiving VOR 200 mg and 6 receiving VOR 400 mg. With no dose-limiting toxicities (DLTs) at 200 mg and one DLT (thrombocytopenia, Grade 3) at 400 mg, the MTD was 400 mg. Phase II portion enrolled 39 GBM subjects, and PFS6 was 53.8% (95% CI 37.2-67.9%). Of note, 14 subjects had received prior BEV and all had received prior 5-day TMZ. Combination therapy with VOR, BEV, and daily TMZ was well tolerated and safe. While PFS6 was not statistically improved beyond historical controls, it is important to note that this was a heavily pretreated GBM population and further consideration is warranted in a less pretreated group.
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http://dx.doi.org/10.1007/s11060-017-2724-1DOI Listing
April 2018

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma.

Oncologist 2018 02 13;23(2):157-e21. Epub 2017 Nov 13.

Duke University Medical Center, Durham, North Carolina, USA

Lessons Learned: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression-free survival and overall survival with BEV-containing regimens.

Background: Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression-free survival (PFS) in recurrent GBM and is approved by the U.S. Food and Drug Administration for the treatment of recurrent GBM. Combination regimens have been explored, and in this phase II nonrandomized trial, we evaluated the efficacy of BEV combined with histone deacetylase inhibitor vorinostat (VOR) in recurrent GBM.

Materials And Methods: In this phase II, single-center, nonrandomized study, subjects with recurrent GBM received BEV 10 mg/kg intravenously (IV) every 2 weeks combined with VOR 400 mg p.o. daily for 7 days on, 7 days off, in a 28-day cycle. The primary endpoint was 6-month PFS (PFS6).

Results: Forty patients with recurrent GBM were enrolled and evaluated. PFS6 was 30.0% (95% confidence interval [CI] 16.8%-44.4%). Median overall survival (OS) was 10.4 months (95% CI 7.6-12.8 months). Overall radiographic response rate was 22.5% based on 9 partial responses. The most common grade 2 and above treatment-related adverse events were lymphopenia (55%), leukopenia (45%), neutropenia (35%), and hypertension (33%). Grade 4 adverse events were leukopenia (3%), neutropenia (3%), sinus bradycardia (3%), and venous thromboembolism (3%). Two deaths occurred in this study, with one due to tumor progression and another possibly related as death not otherwise specified.

Conclusion: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy.
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http://dx.doi.org/10.1634/theoncologist.2017-0501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813746PMC
February 2018

Management of glioblastoma in elderly patients.

J Neurol Sci 2017 Sep 1;380:250-255. Epub 2017 Aug 1.

Department of Neurology, Northwestern University, United States. Electronic address:

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults over 55years of age. The median age of diagnosis for patients with GBM is 64years old, with the incidence of patients between 75 and 85 increasing. The optimal treatment paradigm for elderly GBM patients continues to evolve due to the higher frequency of age-related and/or medical co-morbidities. Geriatric GBM patients have historically been excluded from larger, controlled clinical trials due to their presumed decreased likelihood of a sustained treatment response and/or a prolonged good outcome. Here, we highlight current treatment considerations of elderly GBM patients with respect to surgical, radiotherapeutic and systemic modalities, with considerations for improving future clinical outcomes for this patient population.
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http://dx.doi.org/10.1016/j.jns.2017.07.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328157PMC
September 2017