Publications by authors named "Paul L Moots"

13 Publications

  • Page 1 of 1

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

J Natl Compr Canc Netw 2017 11;15(11):1331-1345

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.
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http://dx.doi.org/10.6004/jnccn.2017.0166DOI Listing
November 2017

Preradiation Chemotherapy for Adult High-risk Medulloblastoma: A Trial of the ECOG-ACRIN Cancer Research Group (E4397).

Am J Clin Oncol 2018 06;41(6):588-594

University of Virginia Medical Center, Charlottesville, VA.

Objectives: To assess the long-term outcomes and objective response (OR) to preradiation chemotherapy and radiation in adult high-risk medulloblastoma.

Materials And Methods: In this prospective phase II trial, adults with high-risk medulloblastoma were treated with 3 cycles of preradiation cisplatin, etoposide, cyclophosphamide, and vincristine followed by craniospinal radiation (CSI). OR, progression-free survival (PFS), overall survival (OS), and toxicities were assessed.

Results: Eleven patients were enrolled over a 6-year period. Six (55%) had subarachnoid metastases. Two (18%) had an OR to preradiation chemotherapy. Two (18%) progressed while on chemotherapy. Completion of CSI was not compromised. The OR rate after chemotherapy and radiation was 45% (5/11). Nonevaluable patients at both time-points weakened the response data conclusions. Median PFS was 43.8 months. Five-year PFS was 27%. Five-year OS was 55%. Nonmetastatic (M0) and metastatic (M+) patients had similar outcomes.

Conclusions: The OR to this preradiation chemotherapy regimen is lower than anticipated from the adult and pediatric literature raising a question about comparative efficacy of chemotherapy in different age groups. The OS achieved is similar to retrospective adult series, but worse than pediatric outcomes. Although this regimen can be administered without compromising delivery of CSI, our results do not provide support for the use of this neoadjuvant chemotherapy for adult medulloblastoma.
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http://dx.doi.org/10.1097/COC.0000000000000326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352534PMC
June 2018

Valganciclovir and bevacizumab for recurrent glioblastoma: A single-institution experience.

Mol Clin Oncol 2016 Feb 4;4(2):154-158. Epub 2015 Dec 4.

Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Prolonged treatment with adjuvant valganciclovir has been shown in one retrospective study to exert a significant effect on overall survival (OS) in newly diagnosed patients with glioblastoma multiforme (GBM). However, studies evaluating the effectiveness of valganciclovir in the treatment of recurrent GBM have not been performed. We evaluated the effect of valganciclovir in the recurrent setting in combination with bevacizumab therapy. A retrospective analysis was performed on patients treated for recurrent GBM with off-label valganciclovir and bevacizumab at Vanderbilt University. We identified 13 patients who received valganciclovir plus bevacizumab at some point during their treatment, 8 of whom were started on valganciclovir and bevacizumab concurrently upon first recurrence, whereas 5 had valganciclovir added to their bevacizumab regimen prior to a second recurrence. of these patients, 12 were pathologically confirmed to have GBM, and 1 patient was diagnosed with gliosarcoma. We also identified an institutional cohort of 50 patients who had not been exposed to valganciclovir, but were treated with bevacizumab for first recurrence. The progression-free survival (PFS) at 6 months (PF6) and median OS (mOS) in the valganciclovir plus bevacizumab group was 62% and 13.1 months, respectively, for all 13 patients, and 50% and 11.3 months, respectively, for the 8 concurrently treated patients. In the institutional bevacizumab cohort, the PF6 and mOS were 34% and 8.7 months, respectively. In this retrospective analysis, valganciclovir in combination with bevacizumab exhibited a trend toward improved survival in patients with recurrent GBM. However, given the small sample size and the retrospective nature of this study, a larger prospective study is required to confirm these results.
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http://dx.doi.org/10.3892/mco.2015.692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734189PMC
February 2016

Central Nervous System Cancers, Version 1.2015.

J Natl Compr Canc Netw 2015 Oct;13(10):1191-202

From University of Alabama at Birmingham Comprehensive Cancer Center; City of Hope Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; Yale Cancer Center/Smilow Cancer Hospital; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; The University of Texas MD Anderson Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of Washington/Seattle Cancer Care Alliance; Roswell Park Cancer Institute; Duke Cancer Institute; UC San Diego Moores Cancer Center; University of Michigan Comprehensive Cancer Center; Memorial Sloan Kettering Cancer Center; St. Jude Children's Research Hospital/University of Tennessee Health Science Center; Massachusetts General Hospital Cancer Center; American Brain Tumor Association; Vanderbilt-Ingram Cancer Center; Mayo Clinic Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Stanford Cancer Institute; Fred & Pamela Buffet Cancer Center; Huntsman Cancer Institute at the University of Utah; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; Moffitt Cancer Center; Fox Chase Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; National Comprehensive Cancer Network.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.
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http://dx.doi.org/10.6004/jnccn.2015.0148DOI Listing
October 2015

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

J Natl Compr Canc Netw 2014 Nov;12(11):1517-23

From University of Alabama at Birmingham Comprehensive Cancer Center; City of Hope Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; The University of Texas MD Anderson Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of Washington/Seattle Cancer Care Alliance; Memorial Sloan Kettering Cancer Center; Roswell Park Cancer Institute; Duke Cancer Institute; UC San Diego Moores Cancer Center; American Brain Tumor Association; University of Michigan Comprehensive Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Massachusetts General Hospital Cancer Center; Vanderbilt-Ingram Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Stanford Comprehensive Cancer Center; Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; Huntsman Cancer Institute at the University of Utah; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; Moffitt Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; and National Comprehensive Cancer Network.

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337873PMC
http://dx.doi.org/10.6004/jnccn.2014.0151DOI Listing
November 2014

Central nervous system cancers.

J Natl Compr Canc Netw 2013 Sep;11(9):1114-51

Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN. org, contains recommendations on additional subtypes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124889PMC
http://dx.doi.org/10.6004/jnccn.2013.0132DOI Listing
September 2013

Cancer susceptibility variants and the risk of adult glioma in a US case-control study.

J Neurooncol 2011 Sep 4;104(2):535-42. Epub 2011 Jan 4.

Department of Cancer Epidemiology & Genetics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case-control study. Cases were identified from neurosurgical and neuro-oncology clinics at major academic centers in the Southeastern US. Controls were identified from the community or were friends or other associates of cases. We examined a total of 191 susceptibility variants in genes identified in published cancer GWAS including glioma. A total of 639 glioma cases and 649 controls, all Caucasian, were included in analysis. Cases were enrolled a median of 1 month following diagnosis. Among glioma GWAS-identified variants, we detected associations in CDKN2B, RTEL1, TERT and PHLDB1, whereas we did not find overall associations for CCDC26. Results showed clear heterogeneity according to histologic subtypes of glioma, with TERT and RTEL variants a feature of astrocytic tumors and glioblastoma (GBM), CCDC26 and PHLDB1 variants a feature of astrocytic and oligodendroglial tumors, and CDKN2B variants most prominent in GBM. No examined variant in other cancer GWAS was found to be related to risk after adjustment for multiple comparisons. These results suggest that GWAS-identified SNPs in glioma mark different molecular etiologies in glioma. Stratification by broad histological subgroups may shed light on molecular mechanisms and assist in the discovery of novel loci in future studies of genetic susceptibility variants in glioma.
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http://dx.doi.org/10.1007/s11060-010-0506-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138895PMC
September 2011

Molecular genetic analysis of a primitive neuroectodermal tumor arising after intracranial radiation and chemotherapy for leukemia.

Ann Clin Lab Sci 2009 ;39(3):295-302

Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Primitive neuroectodermal tumors are aggressive tumors of the central nervous system (CNS), yet their etiology remains unclear. We report a case of a primitive neuroectodermal tumor (PNET) arising in the cerebellum and pons 7 yr after intracranial radiation and chemotherapy for leukemia involving the CNS. This case suggests a possible link between radiation, chemotherapy, and the formation of these tumors, with a potential new pathogenetic role for somatic inactivation of the protooncogene RET.
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December 2009

Differential responsiveness among "high risk" pediatric brain tumors in a pilot study of dose-intensive induction chemotherapy.

Pediatr Blood Cancer 2004 Jul;43(1):46-54

Department of Neurology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.

Background: These factors have been predictive for progressive disease on therapy (PDOT) among pediatric brain tumors: >1.5 cm(2) unresectable tumor, glioblastoma, supratentorial primitive neuroectodermal tumor, and metastatic medulloblastoma (MBL). This pilot study sought to correlate cytoreductive response with progression free survival.

Procedures: Four courses of cisplatinum, cyclophosphamide, etoposide, and vincristine preceded hyperfractionated radiotherapy (RT). Maintenance chemotherapy consisted of eight cycles of carboplatin, etoposide, and vincristine. Biopsy specimens were immunohistochemically studied for labeling index, hypoxia, and multidrug resistance proteins.

Results: Twenty newly diagnosed patients [nine primitive neuroectodermal tumors/MBL, one choroid plexus carcinoma, eight malignant gliomas, and two anaplastic ependymomas] were treated. Ten patients, who required neuraxis irradiation, constituted the "PNET" group. These demonstrated five complete and one partial response (PR), with an estimated median progression free survival of 44 months and median survival in excess of 53 months. Patients treated with involved field irradiation were designated the "Glioma" group. Induction chemotherapy produced partial and minor responses (MRs) among 5/10. Their estimated median progression free survival was 6.9 months (P = 0.035 relative to the PNET) with a median survival of 10.7 months (P = 0.04). Age, labeling index, the presence of hypoxia, and Pgp/MDR1 expression failed to discriminate between the two groups.

Conclusions: This induction regimen produced a cytoreductive response in 6/10 and achieved a significant improvement in progression free survival among 7/10 in the PNET group. Unfortunately, responses among Glioma patients did not translate into durable control. Expression of the biologic factors was similar between both groups and did not correlate with diagnosis or response.
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http://dx.doi.org/10.1002/pbc.20043DOI Listing
July 2004

Pathologic quiz case: cerebellar hemorrhage in an octogenarian. Gliosarcoma.

Arch Pathol Lab Med 2003 Aug;127(8):e345-6

Department of Pathology, Division of Neuropathology, Vanderbilt University Medical Center, Nashville, Tenn, USA.

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http://dx.doi.org/10.5858/2003-127-e345-PQCCHIDOI Listing
August 2003

Dural lesions mimicking meningiomas.

Hum Pathol 2002 Dec;33(12):1211-26

Department of Pathology, Vanderbilt Medical School, Nashville, TN 37232, USA.

Recently, a number of neoplastic and nonneoplastic entities have been reported that radiographically and clinically mimic meningiomas. Because these lesions occur infrequently and may resemble a meningioma during intraoperative analysis, they may not be considered in the differential diagnosis. This review (and case illustrations) considers some of the newly recognized and notable lesions that can mimic meningiomas, including solitary fibrous tumors, gliosarcomas, leiomyosarcomas, hemangiopericytomas, melanocytomas, Hodgkin's disease, plasmacytomas, inflammatory pseudotumors, neurosarcoidosis, plasma cell granulomas, Rosai-Dorfman disease, Castleman's disease, xanthomas, rheumatoid nodules, and tuberculomas. Awareness that these lesions involve the dura may facilitate intraoperative recognition and, in some cases, preclude unnecessary additional surgery.
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http://dx.doi.org/10.1053/hupa.2002.129200DOI Listing
December 2002
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