Publications by authors named "Dina Randazzo"

14 Publications

  • Page 1 of 1

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20469-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806846PMC
January 2021

Performance of a nomogram for IDH-wild-type glioblastoma patient survival in an elderly cohort.

Neurooncol Adv 2019 May-Dec;1(1):vdz036. Epub 2019 Dec 20.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdz036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212897PMC
December 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03446-3DOI Listing
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/cns-2019-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880304PMC
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctcp.2019.05.002DOI Listing
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hsr2.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482327PMC
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soncn.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612906PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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 .).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1716435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065102PMC
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2017-0501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813746PMC
February 2018

A cross sectional analysis from a single institution's experience of psychosocial distress and health-related quality of life in the primary brain tumor population.

J Neurooncol 2017 Sep 1;134(2):363-369. Epub 2017 Jul 1.

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

Primary brain tumor patients experience high levels of distress. The purpose of this cross-sectional, retrospective study is to evaluate the level and different sources of psychosocial distress and how these pertain to health-related quality of life (HRQoL). The Primary and Recurrent Glioma registry at Duke's The Preston Robert Tisch Brain Tumor Center was queried retrospectively for demographic and clinical information on patients seen between December 2013 and February 2014. Data also included the National Comprehensive Cancer Network's Distress Thermometer (NCCN-DT), Functional Assessment of Cancer Therapy-Brain Cancer (FACT-Br), and Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F). 829 subjects completed questionnaires. 54% were male; 96% completed the NCCN-DT; 33.3% had a DT score ≥4 (moderate/severe distress). Women reported DT ≥ 4 more often than men (38.6 vs 29.0%; p = 0.005). Patients within 1 year of diagnosis reported DT ≥ 4 more often than those 1+ years after diagnosis (38.8 vs 30.9%; p = 0.034). 73.0% reported physical problems; the most frequent being fatigue (43.2%) and memory/concentration (40.9%). 42.0% complained of emotional problems with worry (29.4%) and nervousness (22.4%) being the most common. Patients who reported at least one practical, family, emotional or physical problem had significantly lower HRQoL scores (p < 0.001). Primary brain tumor patients experience memory dysfunction, fatigue, nervousness, worry, and financial concerns, which have a negative effect on the patient's HRQoL. By identifying and addressing these stressors, it may be possible to improve patient HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-017-2535-4DOI Listing
September 2017

Pineal Region Glioblastoma, a Case Report and Literature Review.

Front Oncol 2017 12;7:123. Epub 2017 Jun 12.

Department of Radiation Oncology, Brody School of Medicine, Greenville, NC, United States.

Introduction: Pineal region glioblastoma multiforme (GBM) is a rare disease entity with a generally poor prognosis. We present a case of a patient with an unresectable pineal region GBM treated with chemoradiation with favorable outcome.

Case Background: A 65-year-old patient who was presented with visual symptoms was found to have a pineal region tumor on imaging. A stereotactic biopsy showed a World Health Organization Grade IV GBM, -6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, isocitrate dehydrogenase 1 and 2 wild type. The patient was treated with radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide. Disease progression occurred at 58 weeks post-biopsy, which prompted the initiation of bevacizumab. The patient was alive and functioning well as of his last follow up, 166 weeks from the initial biopsy.

Discussion: On our review of the literature, 24 cases of pineal region GBM have been reported. The median reported survival for these previously reported cases was 6 months (range, 2-24 months). This patient has the longest overall survival reported to date for a patient with this diagnosis. This is the first patient in the literature with pineal region GBM who has been reported to have MGMT promoter methylation.

Concluding Remarks: Although pineal region GBM is a rare disease entity with a generally poor prognosis, long-term survival is achievable for select patients. MGMT promoter methylation may potentially have prognostic value. Favorable control of recurrent disease with the use of bevacizumab is possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2017.00123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466962PMC
June 2017

Psychosocial distress and its effects on the health-related quality of life of primary brain tumor patients.

CNS Oncol 2016 Oct 11;5(4):241-9. Epub 2016 Jul 11.

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

All cancer patients experience distress from the diagnosis, the effects of the disease or the treatment. Clinically significant distress decreases overall quality of life and the recognition of distress with prompt intervention is essential. The National Comprehensive Cancer Network distress thermometer (NCCN-DT) is a validated measuring tool that has been utilized in the primary brain tumor population to detect psychologic distress thereby provoking a referral process to the appropriate support system. Brain tumor patients commonly reported emotional and physical distress encompassing: fatigue, fears, memory and concentration and worry. More research is needed to identify the stressors of all primary brain tumor patients and their caretakers and integrate appropriate interventions to improve health-related quality of life in both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/cns-2016-0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040083PMC
October 2016