Enhancing Brain Lesions Research Articles

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

Bilateral delayed non-ischemic enhancing brain lesions after treatment with flow-diverter.

Bilateral delayed non-ischemic enhancing brain lesions after treatment with flow-diverter.

Role of Contrast Enhanced MRI to Differentiate Between Neoplastic from Non-Neoplastic Ring Enhancing Brain Lesions

Introduction: Ring enhancing lesions in MRI of the brain can be caused by different pathological conditions. The common lesions are being some primary brain tumours, abscess, granuloma, resolving haematoma and infarct. Gadolinium compounds, which are paramagnetic IV contrast media for brain imaging, are especially helpful for identification of extra-axial tumours and intra-axial lesions associated with disrupted blood-brain barrier. The enhancing ring of an abscess is usually thinner and more uniform than that found in the neoplasm. Granulomatous abscesses tend to have a thicker ring than pyogenic abscesses and have less surrounding edema. Demyelinating disorders revealed nodular pattern and incomplete ring-enhancing pattern. Infarcts often show gyral enhancement. Enhancement is uniform in immune competent patients while ring-like in immunocompromised patients. Tuberculomas on contrast administration appear as nodular or ring-like enhancing lesions. Aims: To evaluate the role of magnetic resonance imaging in distinguishing neoplastic from non-neoplastic ring enhancing brain lesions. Material and methods: Forty patients with various ring enhancing lesions in the brain were detected by MRI. The age range of the patients was 13 to 63 years. Routine sequences of T1, T2 and FLAIR spin echo sequences with IV contrast were carried out. Signal intensities on unenhanced T1- and T2- weighted images for enhanced and unenhanced solid portions, enhancement patterns, margins, cortical involvement, mass effect, and presence of vasogenic edema were studied. Result : MRI showed 20% of cases were non-neoplastic ring enhancing brain lesions in comparison with 25% revealed by histopathology.65% cases diagnosed by MRI as neoplastic ring enhancing brain lesions in comparison with =75% cases revealed by histopathology. Sensitivity of MRI in the detection of secondary neoplastic ring enhancing brain lesions was 80% and specificity was 81.8%. Percentage of primary brain tumor revealed .....

Role of Magnetic Resonance Imaging in the Evaluation of Ring Enhancing Lesions in Brain in Comparison with Magnetic Resonance Spectroscopy

Role of Magnetic Resonance Imaging in the Evaluation of Ring Enhancing Lesions in Brain in Comparison with Magnetic Resonance Spectroscopy

Foreign Body Reaction After Endovascular Treatment with Pipeline Embolization Device (P8-5.031)

<h3>Objective:</h3> The following case elucidates a rare complication of a foreign body reaction to the hydrophilic coating fragments of the pipeline embolization device. <h3>Background:</h3> Intracranial aneurysms (IAs) are pathological dilatations of intracranial arteries. Unruptured IAs have a prevalence of 3% in the adult population worldwide. Endovascular treatment (EVT) is a common first line preventive repair for unruptured intracranial aneurysm. <h3>Design/Methods:</h3> NA <h3>Results:</h3> 50-year-old female presented to the ED with acute onset left-sided weakness of the upper and lower extremities and left-sided facial numbness 20 days following treatment of an unruptured anterior communicating artery aneurysm with Pipeline Flex Embolization Device (PED). Patient’s significant medical history includes multiple sclerosis (MS), rheumatoid arthritis, Crohn’s disease managed with Humira, and diabetes. The CT head without contrast showed confluent edema within the right MCA watershed region, suspicious for infarct. However, the CTA of head showed no vessel occlusion with a patent PED. Brain MRI identified numerous enhancing lesions throughout the right cerebral hemisphere with internal cavitations and significant perilesional vasogenic edema with regional mass effect without midline shift. Empiric antibiotics and antifungal were initiated to cover both typical and atypical causes due to Humira use for Crohn’s disease. Labs, blood cultures and CSF results were insignificant. Pulse-dose steroid for 5 days was started, after 72-hr negative blood cultures. Over time, the patient’s symptoms improved, and she regained her strength back. A repeat brain MRI after the course of steroids showed diminished enhancement, size, and number of brain lesions. The patient was discharged home on a long Prednisone taper and long-term intravenous vancomycin, ceftriaxone, and oral metronidazole. <h3>Conclusions:</h3> Foreign body reactions are rare complications of EVT. It is important to be aware of possible foreign body emboli in patients with the enhancing brain lesions located in the same vascular territory where the recent endovascular procedure was performed. <b>Disclosure:</b> Dr. Aung has nothing to disclose. Mr. Kaufman has nothing to disclose. Dr. Moroz has nothing to disclose. Dr. Axelband has nothing to disclose. Mr. Oselkin has nothing to disclose.

Improved Brain Tumor Conspicuity at 3 T Using Dark Blood, Fat-Suppressed, Dixon Unbalanced T1 Relaxation-Enhanced Steady-State MRI.

Contrast-enhanced magnetic resonance imaging (MRI) is the cornerstone for brain tumor diagnosis and treatment planning. We have developed a novel dual-echo volumetric dark blood pulse sequence called Dixon unbalanced T1 relaxation-enhanced steady-state (uT 1 RESS) that improves the visibility of contrast-enhancing lesions while suppressing the tissue signals from blood vessels and fat. The purpose of this study was to test the hypothesis that Dixon uT 1 RESS would significantly improve the conspicuity of brain tumors compared with magnetization-prepared rapid gradient echo (MPRAGE), as well as to determine potential limitations of the technique. This retrospective study was approved by the hospital institutional review board. Forty-seven adult patients undergoing an MRI scan for a brain tumor indication were included. Contrast-enhanced MRI of the brain was performed at 3 T using both MPRAGE and Dixon uT 1 RESS. To control for any impact of contrast agent washout during the scan procedure, Dixon uT 1 RESS was acquired in approximately half the subjects immediately after MPRAGE, and in the other half immediately before MPRAGE. Image quality, artifacts, and lesion detection were scored by 3 readers, whereas lesion apparent signal-to-noise ratio and lesion-to-background Weber contrast were calculated from region-of-interest measurements. Image quality was not rated significantly different between MPRAGE and Dixon uT 1 RESS, whereas motion artifacts were slightly worse with Dixon uT 1 RESS. Comparing Dixon uT 1 RESS with MPRAGE, the respective values for mean lesion apparent signal-to-noise ratio were not significantly different (199.31 ± 99.05 vs 203.81 ± 110.23). Compared with MPRAGE, Dixon uT 1 RESS significantly increased the tumor-to-brain contrast (1.60 ± 1.18 vs 0.61 ± 0.47 when Dixon uT1RESS was acquired before MPRAGE and 1.94 ± 0.97 vs 0.82 ± 0.55 when Dixon uT 1 RESS was acquired after MPRAGE). In patients with metastatic disease, Dixon uT 1 RESS detected at least 1 enhancing brain lesion that was missed by MPRAGE on average in 24.7% of patients, whereas Dixon uT 1 RESS did not miss any lesions that were demonstrated by MPRAGE. Dixon uT 1 RESS better detected vascular and dural invasion in a small number of patients. In conclusion, brain tumors were significantly more conspicuous at 3 T using Dixon uT 1 RESS compared with MPRAGE, with an approximately 2.5-fold improvement in lesion-to-background contrast irrespective of sequence order. It outperformed MPRAGE for the detection of brain metastases, dural or vascular involvement. These results suggest that Dixon uT 1 RESS could prove to be a useful adjunct or alternative to existing neuroimaging techniques for the postcontrast evaluation of intracranial tumors.

CNS toxoplasmosis, a rare presentation in a patient with Myasthenia Gravis

We report the case of a 78-year-old man with a past medical history of non-Hodgkin's lymphoma s/p chemotherapy and Myasthenia Gravis on chronic mycophenolate mofetil (MMF), who presented with altered mental status and was found to have ring enhancing brain lesions. A brain biopsy revealed organisms consistent with Toxoplasma gondii. Cerebral toxoplasmosis has been rarely reported in patients with hematologic malignancies or in those receiving immunosuppressive agents. There needs to be a high degree of suspicion for T. gondii in HIV-negative individuals who are on immunosuppressants drugs including MMF.

Contrast-Enhanced 3D Spin Echo T1-Weighted Sequence Outperforms 3D Gradient Echo T1-Weighted Sequence for the Detection of Multiple Sclerosis Lesions on 3.0 T Brain MRI.

Using reliable contrast-enhanced T1 sequences is crucial to detect enhancing brain lesions for multiple sclerosis (MS) at the time of diagnosis and over follow-up. Contrast-enhanced 3D gradient-recalled echo (GRE) T1-weighted imaging (WI) and 3D turbo spin echo (TSE) T1-WI are both available for clinical practice and have never been compared within the context of this diagnosis. The aim of this study was to compare contrast-enhanced 3D GRE T1-WI and 3D TSE T1-WI for the detection of enhancing lesions in the brains of MS patients. This single-center prospective study enrolled patients with MS who underwent a 3.0 T brain MRI from August 2017 to April 2021 for follow-up. Contrast-enhanced 3D GRE T1-WI and 3D TSE T1-WI were acquired in randomized order. Two independent radiologists blinded to all data reported all contrast-enhanced lesions in each sequence. Their readings were compared with a reference standard established by a third expert neuroradiologist. Interobserver agreement, contrast ratio, and contrast-to-noise ratio were calculated for both sequences. A total of 158 MS patients were included (mean age, 40 ± 11 years; 95 women). Significantly more patients had at least 1 contrast-enhanced lesion on 3D TSE T1-WI than on 3D GRE T1-WI for both readers (61/158 [38.6%] vs 48/158 [30.4%] and 60/158 [38.6%] vs 47/158 [29.7%], P < 0.001). Significantly more contrast-enhanced lesions per patient were detected on 3D TSE T1-WI (mean 2.47 vs 1.56 and 2.56 vs 1.39, respectively, P < 0.001). Interobserver agreement was excellent for both sequences, κ = 0.96 (confidence interval [CI], 0.91-1.00) for 3D TSE T1-WI and 0.92 (CI, 0.86-0.99) for 3D GRE T1-WI. Contrast ratio and contrast-to-noise ratio were significantly higher on 3D TSE T1-WI (0.84 vs 0.53, P < 0.001, and 87.9 vs 57.8, P = 0.03, respectively). At 3.0 T, contrast-enhanced 3D TSE-T1-WI supports the detection of significantly more enhancing lesions than 3D GRE T1-WI and should therefore be used for MS patients requiring contrast-enhanced examination.

NIMG-93. CORRELATING RELATIVE LEVEL OF IMMUNOCOMPETENCE FOR CNS LYMPHOMA BY RADIOLOGIC CHARACTERISTICS: A CASE SERIES

Abstract Radiologically, central nervous system lymphoma (CNSL) presents differently in immunocompetent versus immunosuppressed states. Most patients with immunocompetent CNS lymphoma present with a solitary, deep, homogeneously enhancing lesion while patients with immunocompromised CNS lymphoma frequently have multifocal, centrally necrotic enhancing brain lesions. To date, there have been no radiologic features described along a spectrum of relative levels of immunocompetence. A single institution review on twelve patients with primary and secondary CNSL included clinical factors at diagnosis that are associated with varying levels of relative immunocompromised state. We collected qualitative data on age, prior cancer, radiation, chemotherapy, HIV, diabetes mellitus, steroid/immunosuppressant use, and quantifiable data including white blood cell, neutrophil, and lymphocyte counts. These factors were stratified for severity and correlated with findings on imaging. Our study identified patients with a minor level of immunocompromised state were more likely to develop multifocal disease, while patients with more severe immunocompromised states were likely to develop necrosis. Although our study is limited as a retrospective analysis, these findings suggest that the radiographic findings can present as a spectrum which can reflect a relative level of immunocompetence. This study warrants further evaluation in a larger and prospective cohort for validation.

0826 A Case of Propriospinal Myoclonus in a patient with Multiple Sclerosis

Abstract Introduction Described first in 1991, by Brown et al, Propriospinal Myoclonus is a rare movement disorder of rhythmic, typically flexor, jerking motions most pronounced when lying supine. Although most cases are thought to be idiopathic, identified causes have been infection, spinal lesions, and psychogenic. Report of Cases: A 38-year-old female with medical history of multiple sclerosis, anxiety and PCOS was referred for jerking body movements with sleep onset. Symptoms of nightly, full body jerking, beginning in her back, were described as “legs being pulled up towards the chest” and present only while lying supine in bed with symptom onset of 1 month. Difficulty initiating sleep and daytime sleepiness ensued as a result of these jerks. Work-up with in-lab polysomnogram failed to demonstrate obstructive sleep apnea (AHI 2.8/hr), however, did demonstrate periodic limb movements of sleep. MRI of the brain, cervical spine, and thoracic spine were negative for new or enhancing brain or spinal cord lesions. CBC, CMP, TSH and ceruloplasmin were ordered for a complete myoclonus evaluation and found to be within normal limits. She was started on Klonopin 0.5 mg at night. Three month follow-up revealed improvement of symptoms, with the frequency of her myoclonus decreased to 1-2 episodes per week with reported less intensity of each event. Conclusion While proper work-ups are always important, this case reminds us of the diligence required when certain conditions exist. Although our patient had a negative myoclonus work-up, and is thought to have idiopathic myoclonus, the presence of multiple sclerosis made the investigation increasingly relevant. Work-up should include an MRI to rule-out spinal cord lesions. Support (If Any) None

CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma

AbstractCD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity. Here, we report the outcome of a subset of patients with primary CNS lymphoma (PCNSL; n = 5) who were treated with CD19CAR T cells in our ongoing phase 1 clinical trial. All patients developed grade ≥ 1 cytokine release syndrome and neurotoxicity post-CAR T-cell infusion; toxicities were reversible and tolerable, and there were no treatment-related deaths. At initial disease response, 3 of 5 patients (60%; 90% confidence interval, 19-92%) seemed to achieve complete remission, as indicated by resolution of enhancing brain lesions; the remaining 2 patients had stable disease. Although the study cohort was small, we demonstrate that using CD19CAR T cells to treat PCNSL can be safe and feasible. This trial was registered at www.clinicaltrials.gov as #NCT02153580.

Monocyte Gene Expression Distinguishes Enhancing Brain Parenchymal Cysticercal Granulomas From Tuberculomas.

BackgroundIn patients with enhancing brain parenchymal lesions, parenchymal neurocysticercosis (pNCC) is often difficult to distinguish from tuberculoma, necessitating biopsy or empirical therapy.MethodsIn a prospective study, peripheral blood monocytes were isolated from patients with definitive pNCC (n = 39) and brain tuberculomas (n = 20). Patients with tuberculomas were diagnosed by the presence of concurrent systemic tuberculosis (n = 7), pathological or bacteriological confirmation (n = 5), and resolution of typical brain lesions following a therapeutic trial of antituberculous therapy (n = 8). Expressions of 14 NCC-associated monocyte genes were determined by quantitative polymerase chain reaction and analyzed for diagnostic usefulness between the 2 groups.ResultsExpression of 7 genes (TAX1BP1, RAP1A, PLCG2, TOR3A, GBP1P1, LRRFIP2, and FEZ2) was significantly higher in pNCC patients than in tuberculoma patients, with TAX1BP1 and RAP1A expressions more than 22- and 5-fold higher in pNCC patients. TAX1BP1 had the highest sensitivity of 66.7% at a specificity of 100% in discriminating pNCC from tuberculoma. A combination of TAX1BP1 and RAP1A increased the sensitivity to 84.6%, and including GBP1P1 with TAX1BP1 and RAP1A further increased sensitivity to 87.2% while maintaining specificity of 100%.ConclusionsExpression of a panel of genes in blood monocytes distinguishes pNCC from brain tuberculomas in patients with enhancing brain lesions.

Surgicel Mimicking Brain Abscess: A Case Report

Hemostasis is one of the most essential measures in Neurological procedures. Surgicel (Oxidized cellulose) is one of the most frequently used hemostatic agent used worldwide during surgical procedures. We aim to present a case of radiological diagnostic dilemma of a ring enhancing brain lesion where brain abscess, intracranial hematoma and surgicelloma was identified as challenging differential diagnosis. In this paper, we present a case, where a complication occurred with the use of surgicel following craniectomy and evacuation of hematoma.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Disseminated Toxoplasmosis in a Child Following Allogeneic Hematopoietic Cell Transplantation

A 23-month old female with hypoplastic myelodysplastic syndrome underwent allogenic hematopoietic cell transplantation (HCT), complicated by development of acute exotropia. Bilateral chorioretinal scars and a ring enhancing brain lesion were identified in further workup. Disseminated toxoplasmosis post-allogeneic HCT was subsequently confirmed by serologic and polymerase chain reaction testing results.

Role of Magnetic Resonance Spectroscopy in Differentiating Neoplastic From Non- Neoplastic Ring Enhancing Brain Lesions Taking Surgical Findings as Gold Standard

Objective: To evaluate the diagnostic accuracy of Magnetic Resonance spectroscopy (MRS) in distinguishing neoplastic from non-neoplastic ring enhancing brain lesions taking histopathological findings as gold standard. Study Design and Setting: The cross sectional study was conducted at Radiology department of Jinnah Postgraduate Medical Centre. Methodology: Total 102 patients with ring enhancing lesions detected on MRI brain contrast studies were selected for this study. Cases were referred from Outpatient Department of Neurology Clinics who were suspected of having space occupying lesions in brain. Full history, clinical examination and laboratory investigations (Complete Blood Count and ESR) were carried out. The patients having claustrophobia, metallic implants, cardiac pacemaker and having metallic foreign body in situ were excluded from the study. Informed consent was taken from the research and MRS was performed. On MRS, lesion was categorized and final diagnosis was taken based on histopathology results. All the information was recorded into predesigned proforma. Patients Data was scrutinized by using Statistical Package for Social Sciences (SPSS 21.0). Mean + SD was calculated for age, gender, duration of symptoms and size of the lesion. Results: The average age of the patients was 35.45±10.36 years. Sensitivity, specificity, PPV, NPV and accuracy of MRS was 87.5%, 93.3%, 95.5%, 89.7% and 92.1% respectively. Conclusion: Magnetic resonance spectroscopy can be effective in discerning neoplastic from non-neoplastic ring enhancing cerebral lesions, thus avoiding an invasive procedure like brain biopsy

Frequency and Evolution of New Postoperative Enhancement on 3 Tesla Intraoperative and Early Postoperative Magnetic Resonance Imaging.

Intraoperative magnetic resonance imaging (IO-MRI) provides real-time assessment of extent of resection of brain tumor. Development of new enhancement during IO-MRI can confound interpretation of residual enhancing tumor, although the incidence of this finding is unknown. To determine the frequency of new enhancement during brain tumor resection on intraoperative 3 Tesla (3T) MRI. To optimize the postoperative imaging window after brain tumor resection using 1.5 and 3T MRI. We retrospectively evaluated 64 IO-MRI performed for patients with enhancing brain lesions referred for biopsy or resection as well as a subset with an early postoperative MRI (EP-MRI) within 72 h of surgery (N=42), and a subset with a late postoperative MRI (LP-MRI) performed between 120 h and 8 wk postsurgery (N=34). Three radiologists assessed for new enhancement on IO-MRI, and change in enhancement on available EP-MRI and LP-MRI. Consensus was determined by majority response. Inter-rater agreement was assessed using percentage agreement. A total of 10 out of 64 (16%) of the IO-MRI demonstrated new enhancement. Seven of 10 patients with available EP-MRI demonstrated decreased/resolved enhancement. One out of 42 (2%) of the EP-MRI demonstrated new enhancement, which decreased on LP-MRI. Agreement was 74% for the assessment of new enhancement on IO-MRI and 81% for the assessment of new enhancement on the EP-MRI. New enhancement occurs in intraoperative 3T MRI in 16% of patients after brain tumor resection, which decreases or resolves on subsequent MRI within 72 h of surgery. Our findings indicate the opportunity for further study to optimize the postoperative imaging window.

Late Contrast Enhancing Brain Lesions in Proton-Treated Patients With Low-Grade Glioma: Clinical Evidence for Increased Periventricular Sensitivity and Variable RBE

Late radiation-induced contrast-enhancing brain lesions (CEBLs) on magnetic resonance imaging (MRI) after proton therapy of brain tumors have been observed to occur frequently in regions of high linear energy transfer (LET) and in proximity to the ventricular system. We analyzed 110 patients with low-grade glioma treated with proton therapy to determine whether the risk for CEBLs is increased in proximity to the ventricular system and if there is a relationship between relative biological effectiveness (RBE) and LET. We contoured CEBLs identified on follow-up T1-MRI scans and computed dose and dose-averaged LET (LETd) distributions for all patients using the Monte Carlo method. We then performed cross-validated voxel-level logistic regression to predict local risks for image change and to extract model parameters, such as the RBE. From the voxel-level model, we derived a model for patient-level risk prediction based on the treatment plan. Of 110 patients, 23 exhibited 1 or several CEBLs on follow-up MRI scans. The voxel-level logistic model has an accuracy as follows: area under the curve of 0.94 and Brier score of 2.6 × 10-5. Model predictions are a 3-fold increased risk in the 4 mm region around the ventricular system and an LETd-dependent RBE of, for example, 1.20 for LETd = 2 keV/μm and 1.50 for LETd = 5 keV/μm. The patient-level risk model has an accuracy as follows: area under the curve of 0.78 and Brier score of 0.13. Our findings present clinical evidence for an increased risk in ventricular proximity and for a proton RBE that increases significantly with increasing LET. We present a voxel-level model that accurately predicts the localization of late MRI contrast change and extrapolate a patient-level model that allows treatment plan-based risk prediction.

ATIM-17. A PHASE I TRIAL OF HYPOFRACTIONATED STEREOTACTIC IRRADIATION (HFSRT) COMBINED WITH NIVOLUMAB (NIVO), IPILIMUMAB (IPI) AND BEVACIZUMAB (BEV) IN PATIENTS (PTS) WITH RECURRENT HIGH GRADE GLIOMAS

Abstract BACKGROUND There is strong pre-clinical evidence that combining CTLA4 and PD-1/PDL-1 blockade with antiangiogenic agents and HFSRT independently enhance anti-tumor immune responses and tumor regression. METHODS This phase I study includes a safety cohort of 6 pts followed by dose expansion cohort of 26 pts. Pts with Bev naïve recurrent WHO grade III or IV gliomas (maximum diameter of enhancing brain lesion ≤ 4 cm) are eligible. An interval of at least 6 months after the end of prior RT is required unless there is a new recurrence outside of the previous RT treatment field. Eligible pts are treated with HFSRT to the recurrent tumor (30 Gy in 5 fractions) and 4 cycles of Nivo (3 mg/kg), Ipi (1 mg/kg) and Bev (15 mg/kg) every 3 weeks followed by Nivo 240 mg and Bev 10 mg/kg every 2 weeks for 4 months. After 4 months, Nivo is administered every 4 weeks at 480 mg flat dose and Bev is continued at every 2 week schedule. The primary study objectives are to determine safety and tolerability of above treatment. Secondary endpoints include response rate, 6 and 9-months survival rates, and exploring tissue and imaging biomarkers. RESULTS As of June 2019, safety cohort has been completed and accrual to dose expansion cohort is ongoing. Combination of HFSRT, Nivo, Ipi and Bev as above is well tolerated. The most common toxicities were grade 1 anorexia, grade 1 diarrhea, grade 1 elevation of alanine aminotransferase, grade 1 elevation of lipase and grade 1 infusion related reaction. One patient had grade 3 confusion which was reversible with use of corticosteroids. No dose limiting toxicity has been observed. CONCLUSIONS Combination of HFSRT with Nivo, Ipi and Bev was considered safe to be studied in expansion cohort. Updated safety and efficacy data will be presented.

P14.111 Successful treatment of extensive metastatic disease with successive use of two different EGF receptor antagonists: case report and review of the literature

Abstract INTRODUCTION EGFR-targeted agents can be useful in the treatment of systemic metastatic cancer including that which has spread to the brain. We present the case of a patient with two different EGFR mutations that responded to receptor blockade. CASE REPORT A 38 year old right-handed female presented with a one week history of progressive left-sided weakness and focal seizures. Neuroimaging revealed multiple enhancing brain lesions and a lesion in the left maxillary antrum. Body imaging revealed a right lung mass, hilar and mediastinal nodes and multiple bony lesions. Biopsy of the maxillary antrum lesion showed metastatic poorly differentiated adenocarcinoma, TTF-1 positive, suggesting a lung primary. ALK was not mutated but there was an EGFR mutation (exon 19 deletion). The patient underwent treatment with dexamethasone, levetiracetam, whole brain radiation and afatinib, an oral EGFR-targeted agent. Most of the brain lesions responded completely with only two small residual lesions. Seizures were controlled. There was major partial response from the systemic lesions. Two years later the patient was clinically well but the lung lesion, mediastinal nodes and bony lesions were all enlarging. A new pituitary lesion was identified on brain MRI. A liquid biopsy (blood) revealed a T790M mutation and the patient underwent stereotactic body radiation and EGFR-targeted therapy with osimertinib. All lesions responded to treatment and four years after initial diagnosis the patient is clinically well with stable disease. DISCUSSION Successful treatment of widespread metastatic disease is possible with the use of multiple EGFR-targeted agents in certain patients.