Sharma, Akanksha

Abstract Background Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. Methods In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population. Results The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field. Conclusions The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by “dancing” eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Objective: To evaluate the incidence of and characterize the presentation of neuropsychiatric symptoms and/or Parkinsonism as a presentation of central nervous system lymphoma (CNSL) in either its primary CNSL form or when it spreads to the brain in systemic diffuse large B-cell lymphoma (secondary CNSL). Patients and Methods: With Institutional Review Board approval we identified patients who had been treated at Mayo Clinic from 1998 to 2018 and were recorded to have a combination of ICD 9/10 codes for CNSL and various psychiatric diagnoses. Results: A total of 20 of the 232 patients (9%) were noted to have neuropsychiatric symptoms preceding diagnosis. The average age at diagnosis was 62, with even split for sex. The majority (85%) of patients had primary CNSL. The average duration of symptoms before the diagnosis was 4.8 months. Confusion (80%), depression (40%), apathy (30%), anxiety (30%), and agitation (30%) were the most common symptoms identified. The majority (65%) of patients had subcortical lesions followed by the frontal lobe (50%). Parkinsonism was identified in 5 of the 20 patients with 4 demonstrating resolution of symptoms with treatment of the lymphoma. Conclusions: Neuropsychiatric symptoms are a rare but notable symptom before the presentation of CNSL. There is an increasing awareness of neurological illness presenting as pure psychiatric disturbance, prompting the need to exclude organic and treatable diseases, particularly in elderly patients. Acknowledgment and diagnosis are important for an appropriate management as there is a significant impact on patient and caregiver quality of life.

Objective:Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN.Methods:We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes.Results:Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%,P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality.Conclusions:This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Abstract BACKGROUND Treatment options and prognosis are limited for patients with high grade glioma (pwHGG), underscoring the importance of patient and caregiver understanding to prioritize goals of care and quality of life (QOL). Although addressed by multiple providers, patients and caregivers may experience discordance in understanding the prognosis. This may be related to patient/caregiver perception, cognitive decline as a result of the tumor and/or treatment, or failure by the clinician to clearly articulate this information under emotional circumstances. AIMS: To evaluate the longitudinal perception of prognosis of patients compared to their caregivers and their providers during the adjuvant treatment of newly diagnosed HGG. METHODS After IRB approval, 16 pwHGG, their caregivers and their providers reported an overall survival estimate at each monthly visit during adjuvant treatment, as part of a larger survey. Options included “weeks,” “weeks to several months,” “several months to years,” “indefinite number of years”, or “I do not wish to answer.” RESULTS Seven of the sixteen patient/caregiver clusters have completed the appropriate duration of the study with the remaining completing in November. The perception of the patient differs from the caregiver at almost each visit. Regardless of the counseling provided by provider, the perception of both tends to change at each visit and can vary from dismal to overtly optimistic. There does not appear to be discrepancy between the neuro-oncology and palliative care provider’s perception of prognosis. CONCLUSION Newly diagnosed pwHGG and caregivers vary in their perception of prognosis, deviating not only from each other but also differing at each visit throughout the course of their illness. The providers’ perception appeared to remain consistent but often varied from that of the patient and caregiver. Providers need to be aware that prognostic understanding appears to fluctuate throughout the course of illness and cannot be clarified via a single discussion.

Abstract BACKGROUND Early involvement of palliative care (PC) in patients with metastatic cancer has been associated with improved quality of life (QOL). Patients with high grade glioma (pwHGG) and their caregivers have unique needs such that similar results are anticipated in this population but cannot be extrapolated. Recognizing that pwHGG often require a caregiver early in the course of disease, this patient population also experiences significant personal and caregiver distress that has been given limited attention and resources. AIM: To assess the feasibility of implementation of a novel patient reported outcomes (PRO) quality of life (QOL) tool administered by smart device in routine office visit (OV) and early integration of palliative care (PC) for pwHGG and their caregivers to improve QOL for both. DESIGN: Prospective, single-center cluster-randomized pilot conducted for 6 months during completion of adjuvant therapy for newly diagnosed high grade glioma. After informed consent was obtained, 15 pwHGG and their caregivers were randomized to: routine OV with basic QOL survey; OV with PROQOL; or PC consultation, in addition to OV with PROQOL. RESULTS Two elderly patients with declining performance status transitioned to hospice after initial visit, and one moved out of state prior to adjuvant visits. Thus far 5/15 patients/caregivers have successfully completed the pilot with the 6 remaining participants due to complete in November 2019. DISCUSSION The PROQOL appears to be easily integrated into OV without significant patient, caregiver, or provider burden. Providers confirmed utility in prioritizing symptoms and concerns. Thus far, it appears that patients (and caregivers) appeared to benefit from the PROQOL and PC support as evidenced by longitudinal improvement in QOL scores over the control group. CONCLUSIONS A unique PROQOL tool and early PC can be easily integrated into practice, and may improve the QOL of pwHGG and their caregivers.

Abstract INTRODUCTION Opsoclonus–myoclonus syndrome (OMS) is a rare neurological disorder characterized by spontaneous multidirectional saccadic eye movements, myoclonus, and ataxia. It is suspected to be an autoimmune mediated process precipitated by a paraneoplastic or infectious trigger. Among the pediatric population, OMS is often associated with neuroblastoma and anti-Hu antibody. Paraneoplastic syndromes in adults manifesting as OMS are most commonly described in breast, gynecological and small cell lung cancer with associated anti-neuronal antibodies (ANNA-2; anti-Ri). We describe the first case of OMS associated with lung adenocarcinoma and Contactin-associated protein-like 2 (Caspr2) antibody. CASE REPORT: A 46-year-old-woman with history of limited small cell lung cancer (SCLC) status-post chemotherapy with cisplatin and etoposide and prophylactic whole brain radiation, presented with new onset gait instability, nausea, vomiting, vertigo, and opsoclonus. Two months prior to her presentation, a chest computed topography (CT) revealed no evidence of recurrent disease. Brain MRI revealed T2 hyperintensities in the white matter and central pons presumably related to chronic small vessel ischemic changes, unchanged from prior imaging. CSF studies revealed normal cell count, glucose, and protein. Gram stain, culture and meningoencephalitis panel were negative. Her paraneoplastic panel revealed a positive Caspr2 antibody. A repeat CT chest for cancer surveillance revealed a new lung mass. Immunotherapy treatment included plasmapheresis, corticosteroids, and intravenous immunoglobulin therapy. She underwent a biopsy of the new pulmonary lesion and the pathology was consistent with non-small cell lung carcinoma. Her symptoms slowly improved after treatment. Unfortunately, her disease progressed on repeat PET scan despite surgical resection of the lung mass. She ultimately elected for hospice. CONCLUSION We report a novel antibody, Caspr2, occurring in association with paraneoplastic OMS. While SCLC is the most common neoplasm associated with OMS among adults, non-small cell lung carcinoma should be considered. Prompt immunotherapy and neoplasm treatment may result in improvement.

Abstract PURPOSE Brain tumor related epilepsy (BTE) is a major co-morbidity in patients with glioma. It is difficult to determine whether the use of anti-epileptic drugs is necessary. We attempted to build a machine-learning model to predict the probability of seizure presentation (SP) with glioma. METHODS We trained a random forest classifier using the following variables: volumetric data of pre-treatment MR images (T1Gd and T2-FLAIR sequences), patient demographics (age; sex), and measurements of tumor proliferation (log(ρ)), invasiveness (log(D)) and their relative ratio (log(ρ/D)). Our cohort consisted of 221 patients total. Using an 80-20 ratio, we used 176 patients (76 SP, 100 nSP) for training and the remaining 45 patients (19 SP, 26 nSP) were used for testing. We also trained on male-only and female-only cohorts to evaluate any sex differences in prediction. For training, 108 males (53 SP, 55 nSP) were used and 28 for testing (14 SP, 14 nSP). We used 72 females (21 SP, 49 nSP) for training and 15 (7 SP, 8 nSP) for testing. We corrected for class imbalance in the female cohort before training. Using 10-fold cross-validation and a separate testing set, we measured performance by ROC curve (AUC), accuracy, sensitivity, and specificity of predictions (average of folds in cross validation). RESULTS The female model achieved the highest AUC (0.853) followed by the mixed model (0.726) and the male model (0.651). In the validation set, the accuracy/sensitivity/specificity of the three cohorts were as follows: mixed (0.726/0.696/0.750), female (0.853/0.830/0.875), and male (0.651/0.577/0.722). The performance of the testing set, in terms of accuracy/sensitivity/specificity were: mixed (0.733/0.74/0.73), female (0.8/0.57/1), and male (0.714/0.64/0.79). CONCLUSION We found a negative correlation between seizure probability and size and invasiveness of tumors. Our model shows promising performance on testing set data. Further cohort studies and training is warranted.

Abstract BACKGROUND Radiation is an integral component of the multidisciplinary treatment of patients with intracranial metastasis (ICM) from melanoma. The risk of radiation necrosis (RN) post-treatment can range from 5–25%. We retrospectively evaluated pre- and post-radiation clinical and radiographical characteristics in patients with ICM from melanoma to identify potential risk factors for RN. METHODS After IRB approval, patients with ICM from melanoma who received radiation at our institution between 2013 and 2018 were retrospectively reviewed. We recorded demographics, intracranial metastasis (burden and location), systemic therapy, resection, stereotactic radiosurgery versus whole brain radiation, and outcomes. Brain MRI was evaluated using the Response Assessment in Neuro-Oncology criteria (RANO). RESULTS A total of 27 patients were included in the study. RN was diagnosed in 14 patients (52%) at one month to three years following radiation. Cerebellar location (n=7) was significantly associated with RN (p=0.0058). Metastasis-associated hemorrhage was present in 7 patients, 6 of which developed RN (43% vs 8%, p=0.08). Surgical resection prior to radiation was performed in 9 patients, 7 of which developed RN (50% vs 15%, p=0.1). RN appeared to be less often diagnosed when ICM were treated with higher doses of radiation (24 Gy vs 20 Gy, p=0.07). Systemic treatment was administered prior to radiation in 25 patients and we found no relationship with systemic therapy type and RN. Presumed RN was treated in 12 of 14 patients (86%). Steroids or surgical resection were the primary treatment modalities, with laser ablation used in 1 case. Following treatment, improvement was noted in 3 patients radiographically and in 1 of these clinically. CONCLUSIONS This series of patients with radiotherapy-treated brain metastases from melanoma reveals cerebellar involvement, hemorrhage, and prior surgical resection as potential risk factors for radiation necrosis. Neoadjuvant systemic treatment did not appear to be a risk factor in our review.