Johnson, Derek R.

Abstract Diffuse midline glioma (DMG) of the pons remains the leading cause of death among pediatric patients with brain tumors, despite numerous attempts to intensify treatment. While standard treatment includes 54Gy in 30 fractions of radiation over six weeks of time, nearly all patients progress within the treatment field, and many experience symptomatic radionecrosis with steroid dependence. Symptom improvement typically begins after 20Gy to the tumor. Both hypofractionation and reirradiation after recurrence have been found to be safe for patients with DMG. Our study aims to enroll patients with newly diagnosed pontine DMG aged >1 year (no maximum age), and collect molecular information about DMG via stereotactic biopsy, followed by a short 2 week course of 25Gy in 10 fractions of radiation, with volumes guided by MRI with tractography reconstruction and FDOPA PET radiotracer uptake. Patients are followed closely and can complete the 25Gy in 10 fraction radiation course up to 3 times total for meeting radiographic and clinical progression criteria. Our primary endpoint is to estimate the time to progression from diagnosis to after receiving the second 25Gy course, and to compare this to the historical 7 month standard from diagnosis to progression after one 54Gy course. We aim to improve the time interval where patients are asymptomatic at home while minimizing time receiving daily treatments. Other endpoints will include the patient quality of life, caregiver quality of life, PFS intervals after each course, overall survival, and toxicity.

Abstract PET imaging plays an essential role in achieving earlier and more specific diagnoses of dementia syndromes, important for clinical prognostication and optimal medical management. This has become especially vital with the recent development of pathology-specific disease-modifying therapy for Alzheimer disease, which will continue to evolve and require methods to select appropriate treatment candidates. Techniques that began as research tools such as amyloid and tau PET have now entered clinical use, making nuclear medicine physicians and radiologists essential members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice. Within this framework, multiple cases will be shown to illustrate a systematic approach of FDG PET interpretation and integration of PET imaging of specific molecular pathology including dopamine transporters, amyloid, and tau. The approach presented here incorporates contemporary understanding of both common and uncommon dementia syndromes, intended as an updated practical guide to assist with the sophisticated interpretation of nuclear medicine examinations in the context of this rapidly and continually developing area of imaging.

Background and purpose Radiation therapy is an important component of treatment in patients with malignancies of the head, neck, and spine. However, radiation to these regions has well-known potential side effects, many of which can be encountered on imaging. In this manuscript, we review selected radiographic manifestations of therapeutic radiation to the head, neck, and spine that may be encountered in the practice of radiology. Methods We conducted an extensive literature review of known complications of radiation therapy in the head, neck, and spine. We excluded intracranial and pulmonary radiation effects from our search. We selected complications that had salient, recognizable imaging findings. We searched our imaging database for illustrative examples of these complications. Results Based on our initial literature search and imaging database review, we selected cases of radiation-induced tumors, radiation tissue necrosis (osteoradionecrosis and soft tissue necrosis), carotid stenosis and blowout secondary to radiation, enlarging thyroglossal duct cysts, radiation myelopathy, and radiation-induced vertebral compression fractures. Conclusions We describe the clinical and imaging features of selected sequelae of radiation therapy to the head, neck, and spine, with a focus on those with characteristic imaging findings that can be instrumental in helping to make the diagnosis. Knowledge of these entities and their imaging findings is crucial for accurate diagnosis. Not only do radiologists play a key role in early detection of these entities, but many of these entities can be misinterpreted if one is not familiar with them.

BACKGROUND: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM). OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012. METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived. RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided. CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis. https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma

Metastatic neuroendocrine tumour (NET) to brain has been reported in 1.5–5% of patients with NETs. Differentiation between intracranial NET metastasis and meningiomas can cause a diagnostic dilemma. We present a symptomatic case of a 66-year-old male with a history of left-sided skull base mass. The diagnosis of a meningioma was made based on the MRI findings and clinical presentation. The patient received radiation and the mass remained stable on serial MRI images at follow-up visits. Five years after his initial presentation, the patient’s mass showed further growth. He also complained of worsening of his recent diagnosis of irritable bowel syndrome and fluctuations in his blood pressure. Surgical resection was performed, and histopathological features were consistent with moderately differentiated neuroendocrine tumour. Further evaluation with 68 Gallium-DOTATATE positron emission-computed tomography (Ga-68 PET/CT) showed metastatic disease involving the bones, lymph nodes, and liver without convincing evidence of the location of primary malignancy within the bowel loops or the pancreas. The patient was started on combination of capecitabine and temozolomide with partial response and significant improvement of his symptoms. This case highlights the clinical and radiological behaviour of intracranial NET that can mimic the diagnosis of meningioma.

Background: Survival of patients with glioblastoma (GBM) increased in the 2000s, most prominently after the addition of temozolomide to the standard-of-care treatment protocol. The reason for subsequent improvements in survival in the late 2000s and early 2010s was less clear, with explanations including the introduction of bevacizumab, better surgical methods, and advances in supportive care. It is uncertain whether the trend of improving population-level survival has continued. Materials and Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed comparing survival of adult GBM patients diagnosed in consecutive 3-year periods from 2000 to 2017. Kaplan-Meier survival analysis and Cox proportional hazards models were used. Results: A total of 38,352 patients diagnosed with GBM between 2000 and 2017 met inclusion criteria. Median survival and percent survival to 12 and 24 months all progressively increased between 2000 and 2011. There were no significant differences in survival comparing 2009-2011 with 2012-2014 or 2015-2017. During the 2015-2017 period, median survival was 11 months, with 12 and 24-month survival proportions of 45.7% (95% confidence interval, 44.5-47.0) and 19.0% (95% confidence interval, 18.6-21.2), respectively. Conclusions: After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued. Subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017.

Abstract H3 K27M-mutant diffuse gliomas without midline involvement are extremely rare and their clinical behavior remains elusive due to limited reported follow-up data. We describe an H3 K27M-mutant diffuse non-midline glioma patient with extended follow-up. A 34-year-old woman presented with headache, memory loss, periods of changes in taste and smell, and confusion. Imaging studies revealed an 2.3 cm expansile T2/flair hyperintensity with patchy postcontrast enhancement centered in the left amygdala without associated restricted diffusion and no involvement of the midline structures. The tumor was debulked and consisted of a mitotically active infiltrating astrocytic glioma without tumor necrosis or microvascular proliferation, consistent with anaplastic astrocytoma. Targeted 187-gene neuro-oncology NGS testing detected an H3F3A K27M mutation along with a PTPN11 and a PPM1D mutation. FISH 1p/19q-codeletion testing was negative. MGMT promoter was unmethylated. The patient was treated with chemoradiation with temozolomide for 6 weeks followed by 12 cycles of temozolomide. Four years after initial resection, an area of increased post-contrast enhancement indicating tumor recurrence/progression was noted. Partial resection of the recurrent tumor revealed a mitotically active infiltrating astrocytic glioma with tumor necrosis consistent with glioblastoma. Molecular profiling of the recurrent tumor by the neuro-oncology NGS panel detected similar mutational profile (identical H3F3A K27M and PTPN11 mutation; different PPM1D mutation) with an additional SOS1 mutation. The patient completed 4 cycles of Lomustine and although clinically stable, imaging studies showed slight increase in residual tumor size concerning for tumor progression. Lomustine was discontinued, Bevacizumab therapy was initiated and patient was enrolled in clinical trial (NCT02525692). Despite tumor progression, this patient has had a relatively long disease course (5 years) suggesting that H3 K27M-mutant non-midline diffuse gliomas although molecularly similar, may follow a more favorable clinical course than their midline counterparts possibly due to the hemispheric location, which is more amenable for surgical resection.

Abstract BACKGROUND Somatostatin receptor (SSTR) PET/CT is utilized with increasing frequency in the clinical treatment of neuroendocrine tumors. Incidental CNS lesions are commonly noted and presumed to be meningiomas, however 68Gallium (Ga-68)-DOTATATE radionuclide use lacks specificity for meningioma identification. Currently there is no established SSTR-based imaging criteria for classification of incidental CNS lesions. METHODS We retrospectively analyzed patients across clinical and radiological databases at Mayo Clinic who had undergone both Ga-68-DOTATATE PET/CT and brain MR imaging who had an incidental CNS lesion identified with clinical or radiographic prediction of meningioma. Known meningioma diagnoses prior to imaging were excluded. Imaging indication, semi-quantitative measures, and corresponding clinical history were analyzed to identify metrics impacting both the predictive and descriptive utility of SSTR-based imaging as compared to corresponding MRI prediction in incidental CNS lesions. RESULTS Among 59 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (71%). Cases with concordant lesion type prediction of meningioma between imaging modalities (N = 25) displayed a higher median SUV max and Krenning score on Ga-68-DOTATATE PET compared to cases with concordant prediction of other lesions (N=10) or discordant prediction of meningioma (N=24). Ga-68-DOTATATE was more likely to discordantly predict meningioma as compared to the corresponding patient MRI in cases with lower SUV max values. The addition of Qclear technology was significantly associated with diagnostic clarification in cases of imaging discordant tumor type prediction. Prior cranial radiation or use of a somatostatin mimetic did not affect quantitative radiographic measures in lesion characterization, and MRI-based tumor size was similar across groups. CONCLUSION The continued development of SSTR-based imaging biomarker signatures across incidental CNS lesion subtypes will further define the role of this imaging modality in the clinical diagnosis and management of presumed meningiomas.

Abstract Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.