Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs.
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ABSTRACT: Background
Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals.Objectives
To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT.Animals
Eight dogs with presumptive PNST.Methods
This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy.Results
Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy.Conclusions and clinical importance
This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.
SUBMITTER: Hansen KS
PROVIDER: S-EPMC5089643 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe incidence of malignant peripheral nerve sheath tumors (MPNSTs) is low in the general population, although individuals with Neurofibromatosis Type I (NF1) are particularly susceptible. These tumors generally have a high probability of metastasis. The rate and types of second malignancies (SMNs) after a primary diagnosis of MPNST are not well characterized. We aimed to quantify the rate of SMNs among individuals with a first primary MPNST using population-based data.MethodsWe estimated age-standardized incidence rates (SIRs) for SMNs among 1,579 primary MPNST cases between ages 0-85+ using SEER 18 (2000-2015). We estimated incidence rate ratios (IRRs) and 95% confidence intervals (95% CI) for SMNs in MPNST cases compared with general population rates. We conducted sex-stratified and age-restricted analyses (< 30 years at diagnosis).ResultsSeven percent (108/1579) of MPNST cases developed a SMN (SIR of 4635 cases/million). Compared to the general population, MPNST cases were more likely to develop SMNs (IRR: 29.3; 95% CI 23.8-34.8) and had a much higher rate of second MPNSTs (IRR: 15,992.9; 95% CI 9594.5-22,391.3). Aside from a second MPNST, second cancers were frequently diagnosed in the breast, lung, skin, and soft tissue in females and were myeloid and skin malignancies in males. When restricted to < 30 years of age, second MPNSTs were the most common cancers diagnosed.ConclusionsThe rate of SMNs among MPNST cases is tremendously higher than that observed among individuals with other cancers, particularly for second MPNSTs. These findings suggest rates of SMNs may also be higher in NF1 individuals.
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Project description:BackgroundPeripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location.Hypothesis/objectivesIdentify magnetic resonance imaging (MRI) features predictive of PNST histologic grade.AnimalsForty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation.MethodsA multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis.ResultsForty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade.Conclusions and clinical importanceGrade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement.
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Project description:PurposeBET bromodomain inhibitors have emerged as a promising therapy for numerous cancer types in preclinical studies, including neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (MPNST). However, potential mechanisms underlying resistance to these inhibitors in different cancers are not completely understood. In this study, we explore new strategy to overcome BET inhibitor resistance in MPNST.Experimental Design: Through modeling tumor evolution by studying genetic changes underlying the development of MPNST, a lethal sarcoma with no effective medical treatment, we identified a targetable addiction to BET bromodomain family member BRD4 in MPNST. This served as a controlled model system to delineate mechanisms of sensitivity and resistance to BET bromodomain inhibitors in this disease.ResultsHere, we show that a malignant progression-associated increase in BRD4 protein levels corresponds to partial sensitivity to BET inhibition in MPNST. Strikingly, genetic depletion of BRD4 protein levels synergistically sensitized MPNST cells to diverse BET inhibitors in culture and in vivo.ConclusionsCollectively, MPNST sensitivity to combination genetic and pharmacologic inhibition of BRD4 revealed the presence of a unique addiction to BRD4 in MPNST. Our discovery that a synthetic lethality exists between BET inhibition and reduced BRD4 protein levels nominates MPNST for the investigation of emerging therapeutic interventions such as proteolysis-targeting chimeras (PROTACs) that simultaneously target bromodomain activity and BET protein abundance.
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Project description:ObjectiveTo compare the symptoms and magnetic resonance imaging (MRI) findings between digital peripheral nerve sheath tumor (PNST) and major-nerve PNST.MethodsA total 36 cases with benign PNSTs (16 digital, 20 major-nerve) were enrolled. Chief complaint and Tinel sign were reviewed. Five classic MRI features of PNST, the signal intensity (SI), the enhancement, and the shape of tumor were evaluated on MRI.ResultsHalf of each group showed tenderness. Tinel sign was less frequent in digital PNST (12.5%) than major-nerve PNST (95.0%, P < 0.001). Split fat sign, entering and exiting nerve, target sign, and thin hyperintense rim were only observed in major-nerve PNST (P = <0.001, <0.001, 0.492, and 0.002, respectively). Fascicular sign was found in digital PNSTs (31.3%), but more frequent in major-nerve PNST (P < 0.001). In digital PNSTs, mild hyperintense SIs (56.2%) on T1-weighted images (T1-WI) was noted, but none in major-nerve PNST (P < 0.001). Both groups showed hyperintense SIs on T2-WI (P = 0.371). Homogeneity on T2-WI was noted in 43.8% of digital PNSTs, but none in major-nerve PNSTs (P = 0.004). Both groups showed heterogeneous enhancement (P = 0.066), but four (25%) digital PNSTs showed homogeneous enhancement. Lobulated shape was noted in 50% of digital PNSTs but none of major-nerve PNSTs (P = 0.001). Digital nerve was involved at 81.3% of digital PNSTs. Three foot cases showed unusual manifestations: bone destruction, skin thickening, and subungual location.ConclusionIn digital PNSTs, Tinel sign is not commonly found and classic MRI findings is insufficient. In addition, some digital PNSTs show different SI and enhancement from major-nerve PNSTs. However, digital soft tissue tumor involving digital neurovascular bundle and especially representing a fascicular sign should be considered the possibility of a digital PNST.
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