bluuebunny/crossref_metadata_2025_split huggingface dataset:
RBTT-09. A PHASE 1 STUDY OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY (R/R) SOLID AND CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Kline Cassie , Schoenfeld Jonathan D , Catalano Paul J , Li Jingjin , Paccaly Anne J , Sims Tasha N , Bredlau Amy-Lee , Prados Michael , Haas-Kogan Daphne , Mueller Sabine 
Published: November 2019

Abstract
DIPG and HGG lead to the majority of pediatric cancer-related deaths. Despite multimodal treatment, the 2-year survival rates for DIPG and HGG are less than 10% and 20%, respectively. Anti-PD-1 therapy combined with radiotherapy has demonstrated synergistic anti-tumor effects. Cemiplimab, a human PD-1 monoclonal antibody, has demonstrated safety and efficacy in patients with advanced malignancies. Combination of cemiplimab with radiation has the potential to be an effective treatment for pediatric patients with DIPG or HGG. This is a multicenter, Phase 1 and early efficacy study (NCT03690869). Phase 1 will enroll pediatric patients with R/R solid or CNS tumors (N≥30) into two age cohorts (0 to < 12 and 12 to < 18 years). Cemiplimab will be administered intravenously every 2 weeks as monotherapy. Primary objectives of Phase 1 are to confirm safety and assess the pharmacokinetics (PK) of cemiplimab to recommend a Phase 2 dose (RP2D) for clinical efficacy assessment. The Efficacy phase will enroll patients with newly diagnosed DIPG or HGG (dose escalation: N≥12 patients each; dose expansion: N≤40 patients each), or recurrent HGG (dose escalation: N≥6 patients; dose expansion: ≤20 patients) into two age cohorts (≥3 to < 12 years and 12 to ≤25 years). There will be two treatment arms for patients with newly diagnosed DIPG or HGG: cemiplimab in combination with conventionally fractionated (Arm 1) or hypofractionated (Arm 2) radiotherapy. Patients with recurrent HGG will receive cemiplimab concomitantly with reirradiation. All patients will continue cemiplimab as monotherapy at completion of combination therapy. Primary objectives of Efficacy Phase are to confirm safety and anticipated RP2D, assess PK, and determine survival and antitumor activity at 12 months (overall survival for newly diagnosed DIPG and recurrent HGG; progression-free survival for newly diagnosed HGG) of cemiplimab when given concomitantly with radiation. This study is currently recruiting patients across multiple sites.
RARE-01. NATIONWIDE TRENDS IN MANAGEMENT OF ADULT MYXOPAPILLARY EPENDYMOMA
Authors: Baracena Daphne , Kelly Patrick , Khudanyan Arpine , Turina Claire , Jaboin Jerry , McClelland III Shearwood 
Published: November 2019

Abstract

INTRODUCTION
Myxopapillary ependymomas (MPE) are WHO Grade I ependymomas that occur in the spine and have an annual incidence of 0.05–0.08 per 100,000 people. Maximal, safe surgical resection is the recommended first line therapy. Due to the rarity of the disease there is a relatively poor understanding of the use of radiotherapy (RT) in the management of disease.

METHODS
Using the National Cancer Database (NCDB), we analyzed the patterns and impact of RT on spinal MPE in adults diagnosed between 2002 and 2016.

RESULTS
Of 753 qualifying cases, the majority of patients underwent resection (n = 617, 81.9%). A relatively small portion received RT (n = 103, 13.3%) with most receiving RT after surgical resection (n = 98, 95.1%). The likelihood of patients to undergo resection and RT was significantly associated with patient age at diagnosis (p = 0.002), tumor size (p < 0.001), and race (p = 0.017). Chemotherapy was not widely utilized (only 0.27% of patients).

DISCUSSION
Although practice patterns can be highlighted from this 15-year analysis, given the high survival in this disease entity, progression-free survival (PFS) is an important outcome not available from this database. As expected, surgery is the primary means to manage adult MPE. For spinal MPE, it is understood that gross total resection (GTR) should be attempted whenever possible as GTR has been associated with improved PFS in several studies. RT and chemotherapy are used infrequently. In univariate analyses, RT was employed more often for larger tumor sizes, Latino/Hispanic ethnicity, and younger age at diagnosis. The impact of RT on overall survival is indeterminate given the 1.6% death rate in the cohort. Analyses of the impact of RT on PFS in a larger database would be beneficial for determining an algorithm for post-operative and definitive radiotherapy in this disease entity.
RARE-04. TARGETED TREATMENT OF PAPILLARY CRANIOPHARYNGIOMAS HARBORING BRAFV600E MUTATIONS
Authors: Juratli Tareq , Jones Pamela , Wang Nancy , Subramanian Megha , Aylwin Simon , Odia Yazmin , Rostami Elham , Gudjonsson Olafur , Shaw Brian , Cahill Daniel , Uhm Joon , Galanis Evanthia , Barker Fred , Santagata Sandro , Brastianos Priscilla 
Published: November 2019

Abstract
Craniopharyngiomas are surgically challenging brain tumors. Postoperatively, quality of life is often significantly impaired due to neurological and endocrinological complications. Currently, FDA approved systemic treatments are not available for patients in whom craniopharyngiomas recur after surgery and radiation. Papillary craniopharyngiomas are characterized by the presence of BRAFV600E mutations. To date, five case reports have been published on the treatment of BRAFV600E mutant papillary craniopharyngiomas with BRAF and/or MEK inhibitors. In this presentation, authors from all five previously published reports share their collective experience and provide updated follow-up on their patients, thus generating an overview of all currently available information on targeted therapy in patients with BRAFV600E mutant papillary craniopharyngiomas. We have also included information on an additional patient with a papillary craniopharyngioma recently treated with BRAF and MEK inhibitors after tumor biopsy alone, in the absence of recurrence, highlighting the potential for a neo-adjuvant therapeutic approach. All six cases in our series showed dramatic responses to targeted treatment with BRAF (and MEK) inhibitors. Collectively, our cases are highly promising and informative for patient treatment, although uncertainty remains with regards to the optimal timing, the specific agents (single agent or dual therapy) to be used and the duration of treatment. The ongoing multicenter phase II Alliance A071601 trial (NCT03224767) of vemurafenib and cobimetinib for patients with biopsy-proven residual or recurrent papillary craniopharyngiomas should provide additional information to help guide patient management.
RARE-05. ARE TRANSGENDER INDIVIDUALS STRONGLY PREDISPOSED TO DEVELOPMENT OF PROLACTINOMAS?
Authors: Kleinschmidt-DeMasters Bette 
Published: November 2019

Abstract
Transgender individuals usually receive long-term hormone treatment in the course of their sexual transition. Although the effects of this on possible development of neoplasia are largely unknown, very limited literature has suggested they may be predisposed to development of prolactinomas. We queried our databases to determine if we had encountered such cases at our tertiary care center for sellar region masses. Pathology databases from 2000–2019 were searched by the text word “transgender” to identify pituitary adenomas; cases were compared with all tissue specimens obtained from transgender persons. 2 pituitary adenomas were identified, out of approximately 1800+ sellar region masses at our institution during this same time period; neither were prolactinomas. The first occurred in a 71-year-old transgender male-to female who had undergone high-dose hormone therapy followed by orchiectomy 30 years prior; since that time various doses of estrogen had been received, most recently Premarin, .625 daily. Chronic hypertension associated with dizziness and vertigo prompted an endocrine workup which revealed an IGF-1 of 575 (normal < 150 ng/ml). MRI disclosed a 10 X 7 X 13 mm. pituitary mass which proved to be a mixed somatotroph/ lactotroph adenoma. The second occurred in a 53-year-old transgender female-to-male who was being evaluated by an endocrinologist for hormone therapy for his transition when a slightly elevated prolactin level was discovered. MRI disclosed a 10 x 7 x 13 mm. pituitary mass. Transsphenoidal hypophysectomy showed a gonadotroph adenoma with patchy immunostaining for follicle stimulating hormone (FSH). In comparison, during this same time period, 60 other surgical specimens had been received, including 33 bilateral mastectomies, 15 hysterectomies, and 4 orchiectomies, almost all for gender transition purposes. Clinicians and pathologists may wish to be aware of the occurrence of pituitary adenomas in transgender individuals, although the incidence is quite low (2/1800 sellar region masses in our system).
RARE-06. A CASE OF RECURRENT SUPRATENTORIAL EXTRAVENTRICULAR ANAPLASTIC EPENDYMOMA IN ADULT
Authors: Kang Dong-Gee , Kang Ho-Jun 
Published: November 2019

Abstract
Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of very low prevalence, SEAE has been reported only a few cases. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus of optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after gross total resection(GTR) followed by conventional radiotherapy. A 42- year- old male had a persistent mild headache, left facial palsy, and dysarthria. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma, After seven years of initial therapy, a regular follow-up MRI showed a 3-cm –sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE
RARE-07. HOW TO TREAT THE INCIDENTAL THALAMIC PRESUMED LOW-GRADE GLIOMAS
Authors: Kumabe Toshihiro , Shibahara Ichiyo , Kanamori Masayuki , Saito Ryuta , Hide Takuichiro , Sato Sumito , Sonoda Yukihiko , Tominaga Teiji 
Published: November 2019

Abstract
Medical intervention for patients with incidentally found presumed low grade gliomas (iLGGs) is controversial. We experienced 5 consecutive thalamic iLGGs, and discuss the follow-up methods and the timing of the intervention. Age at the initial MRI was 19, 57, 58, 70, 70, respectively. Only the bilateral thalamic iLGG of 19-year-old male was radically resected soon after the initial MRI, because of the large tumor size. The histological diagnosis was a diffuse astrocytoma, IDH-wildtype, without H3K27M mutation. This patient was treated by chemoradiation, still alive for 24 months with KPS of 90%. The other four cases were strictly followed by MRI. One case of 70-year-old female is followed for 38 months without increasing the tumor volume. The other 3 cases had been followed by MRI for 15, 91, 154 months, respectively. Stereotactic biopsy or ventriculo-peritoneal shunting (VPS) was performed after that because of the tumor progression. The histological diagnosis of 57-year-old male followed for 15 months was a diffuse astrocytoma, IDH-wildtype. This patient selected further follow-up, although volume of the tumor increased exponentially. Radical resection was performed 11 months after the stereotactic biopsy, disclosed malignant transformation. This patient was treated by chemoradiation, finally died of tumor dissemination 15 months after the radical resection. Long-term followed patients, such as 91 and 154 months, showed slow linear tumor volume increasing. The latter patient with bilateral iLGG was treated by VPS followed by radiation therapy. This patient could keep KPS of 100% for 13 years after the initial MRI and live for 20 years. Our case series suggests that conservative management and close follow-up of thalamic iLGGs is a safe and effective strategy. However, volumetric analysis must be performed for every follow-up MRI. Once the steep volume increasing is detected, surgical intervention and/or chemoradiation should be considered without delay.
RARE-09. CYSTIC GLIOBLASTOMA PRESENTATION AS A BENEFICIAL PROGNOSTIC INDICATOR FOR OVERALL SURVIVAL
Authors: Curtin Lee , Whitmire Paula , Rickertsen Cassandra , Canoll Peter D , Mrugala Maciej , Swanson Kristin , Hu Leland 
Published: November 2019

Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor with a median overall survival of 15 months with standard-of-care treatment. GBM patients sometimes present with a cystic component, which can be identified through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–22% of GBM patients and have reported mixed results regarding whether cystic GBM have a survival benefit compared to noncystic GBM. Using our large retrospective cohort of 493 first-diagnosis GBM patients, we aim to elucidate this link between cystic GBM and survival. Within this cohort, 88 patients had a significant cystic component at presentation as identified on MRI. Compared to noncystic GBM (n=405), cystic GBM patients had significantly better overall survival (15 vs 22 months median, log-rank, p=0.001) and were significantly younger at the time of presentation (t-test, p=0.002). However, within patients that received current standard-of-care treatment (n=184), cystic GBM (n=40) was not as beneficial for outcome (22 vs 25 months, log-rank, p=0.3). We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to cystic GBM patients diagnosed before the standard was established (n=19, 25 vs 23 months, log-rank, p=0.3), but the analogous result for noncystic GBM patients gives a sizeable benefit, as expected (n=144, n=111, respectively, 22 vs 12 months, log-rank p < 0.0001). Together, these results on current standard-of-care may explain later studies that note no significant survival benefit for cystic GBM patients receiving current standard-of-care. We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and in prognostic impact of cysts based on sex. We discuss current hypotheses for these observed differences, including the possibility that the presence of a cyst could be indicative of a less aggressive tumor.
RARE-11. SELLAR GERMINOMA MASQUERADING FOR SIX YEARS AS AUTOIMMUNE HYPOPHYSITIS IN A 16-YEAR-OLD GIRL WITHOUT DIABETES INSIPIDUS
Authors: Hrachova Maya , Perez Rosenthal Mari , Xiao-Tang Kong 
Published: November 2019

Abstract

INTRODUCTION
Germinomas are rare malignant intracranial neoplasms which most commonly occur in young males in the pineal and suprasellar region. Less commonly, germinomas arise in the sellar region, where there is slight female predominance. Diagnostic challenges may arise, as autoimmune hypophysitis has similar clinical, imaging and histopathological features to germinoma. CASE REPORT: A 16-year-old girl (46, XX) presented with primary amenorrhea, failure of sexual development and growth delay. Stimulation tests confirmed panhypopituitarism except diabetes insipidus. Infectious and rheumatological workup was negative. She had normal levels of beta HCG, CEA and alpha-fetoprotein. MRI brain identified an enhancing hypothalamic pituitary stalk and pituitary mass. A biopsy was performed which showed a lymphocyte rich infiltration of the pituitary gland, suggesting autoimmune hypophysitis. She completed 4 cycles of low dose methotrexate weekly and remained on hormone replacement therapy for panhypopituitarism for three years until she developed daily headaches, blurry vision, and secondary amenorrhea. MR imaging showed increased nodularity at the pituitary infundibulum with involvement of the optic chiasm. This lesion progressed on mycophenolic acid, increased doses of hydrocortisone, high doses of prednisone and IV methylprednisolone. She was unable to tolerate azathioprine and rituximab after one year. Subsequently, she underwent partial resection of the suprasellar lesion with the pathology showing germinoma admixed with abundant lymphohistiocytic inflammation. A nongerminomatous component was not present histologically and CSF only showed an elevated beta HCG. Given that the tumor is localized to the central nervous system she is receiving treatment via SIOP CNS GCT 96 protocol.

DISCUSSION
Autoimmune hypophysitis and germinoma can share similar clinical, radiological and histopathological features. Our case demonstrates the need for careful histologic examination, close clinical and radiological follow up in patients with lymphocyte-rich suprasellar lesions if no response to immunosuppressant therapy is noted.
RARE-12. EARLY FOCAL RADIOTHERAPY AND TEMOZOLOMIDE FOLLOWING COMPLETE RESECTION APPEAR SUPERIOR TO INTENSIVE CHEMOTHERAPY IN CHILDREN WITH EMBRYONAL TUMORS WITH MULTILAYERED ROSETTES (ETMR)
Authors: Slavc Irene , Mayr Lisa , Gojo Johannes , Peyrl Andreas , Azizi Amedeo , Dieckmann Karin , Haberler Christine , Czech Thomas 
Published: November 2019

Abstract

BACKGROUND
Embryonal tumor with multilayered rosettes (ETMR) is an extremely rare entity characterized by LIN28A expression and alterations in the C19MC locus. ETMRs predominantly occur in young children and have a dismal prognosis. We report on our single institution experience in seven consecutive patients.

METHODS
Between 2006 and 2016, seven patients were diagnosed with ETMR. Diagnosis was established prospectively by characteristic histopathologic features, LIN28A immunostaining and amplification of the C19MC region in five patients and retrospectively confirmed in two additional patients originally diagnosed as central nervous system primitive neuroectodermal tumor. Tumor location was supratentorial in all patients. Median age at diagnosis was 25 months (range 5–38). Male to female ratio was 1:6.

RESULTS
All patients received gross total tumor resection and four patients were treated with intensive chemotherapy regimens including high-dose chemotherapy in three patients. Four patients recurred after a median of 6 months (range 2–11 months) and all except one patient who died after high-dose chemotherapy, succumbed to their disease after a median of 13 months (range 7–28 months). Consequently, the two most recent patients were treated with gross total tumor resection, primary focal radiotherapy and concomitant temozolomide followed by temozolomide for one year. Due to the high risk of leptomeningeal dissemination intraventricular chemotherapy was administered to all except one patient. Both patients who were treated with primary focal radiotherapy are in continuous complete remission 41 and 36 months after diagnosis.

CONCLUSION
Gross total resection followed by early focal radiotherapy, temozolomide, and intrathecal chemotherapy seem to be superior to intensive chemotherapy including high-dose chemotherapy.
RARE-22. CHALLENGES IN MANAGEMENT OF CNS INVOLVEMENT OF CUTANEOUS T-CELL LYMPHOMA
Authors: Chukwueke Ugonma , Kim Albert , Ng Samuel , Fisher David , Stuver Robert , Larocca Cecilia , Louissaint Abner , Weinstock David , Nayak Lakshmi , Meredith David 
Published: November 2019

Abstract

BACKGROUND
Cutaneous T-cell lymphoma (CTCL) is a group of T-cell lymphomas occurring primarily in the skin, without evidence of disease elsewhere. Central nervous system (CNS) involvement of CTCL is extremely rare, with a reported incidence of 5–9%. Due to its infrequency and radiographic appearance which mimics other CNS processes, CNS CTCL may be misdiagnosed. Here, we describe 8 cases of CNS CTCL at a single institution.

METHODS
The electronic medical records at our institution were queried for cases of CNS involvement by CTCL, between 2004–19. Clinical data, imaging and surgical pathology were reviewed.

RESULTS
Eight patients were diagnosed with CNS CTCL with median age of 68 and median time to development of CNS disease of 17 months. 1 patient had synchronous presentation of cutaneous and CNS disease identified at autopsy. Seven out of eight patients presented neurologically with behavioral and mental status changes and 1 patient had concurrent intraocular disease. Imaging showed bilateral non-enhancing T2/FLAIR signal changes in three patients; multifocal enhancement was noted in the others. Malignancy, inflammatory processes and infections including progressive multifocal leukoencephalopathy (PML) were often included in the radiographic differential diagnosis. Prior systemic therapies were variable, including palliative radiation, phototherapy, myeloablative chemotherapy followed by allogeneic stem cell transplant and oral methotrexate. 5 of 8 patients had active cutaneous disease at the time of CNS relapse. Six patients received initial treatment for CNS disease with high-dose methotrexate (HD-MTX). Comprehensive genomic analysis revealed recurrent alterations in genes associated with regulatory T-cell differentiation (SOCS1, NOTCH1), tumor suppressors (CDKN2A, PTEN, TP53); one case was hypermutated.

CONCLUSIONS
CNS involvement of CTCL is rare, occurring more than a year after initial cutaneous disease. Clinical and radiographic findings may be variable, necessitating high clinical suspicion. Most patients respond to HD-MTX. Further molecular analysis is ongoing.
RARE-28. HYPOTHALAMIC GERMINOMA AND NEUROSARCOIDOSIS: A TALE OF TWO PATHOLOGIES
Authors: Puri Sushant , Valy-Nagy Tibor , Sweiss Nadera , Maraka Stefania , Nicholas Martin 
Published: November 2019

Abstract
CASE 1: 30-year-old Caucasian male with a history of hereditary cavernomas, testicular germ cell tumor s/p orchiectomy 2017 presented next year with a chief complain of increasing lethargy. MRI Brain showed a new expansile, homogenously enhancing hypothalamic lesion causing obstructive dilatation of the lateral ventricles. MRI of neuraxis was not concerning for leptomeningeal spread. Initial differentials included suprasellar germinoma vs chiasmatic hypothalamic glioma vs metastatic lesion. Biopsies X2 showed gliosis and granulomatous inflammation. Despite radiation treatment for the hypothalamic mass clinical course continued to deteriorate. CSF results showed RBC - 1,200; WBC - 51 with 77% lymphocytes, 3% neutrophils, 20% monocytes. FDG-PET did not reveal evidence of metastatic disease. He was treated presumptively for neurosarcoidosis with high-dose corticosteroids and azathioprine and later transitioned to methotrexate and infliximab. Follow up MRI scans showed a reduction in the hypothalamic mass. CASE 2: A 23-year-old African American male treated for ADEM in 2010 presented to clinic with behavioral problems in 2017. Initial presentation included lethargy with imaging showing an incidental hypothalamic mass. Initial differentials included germinoma vs infundibular hypophysitis vs granulomatous process. He was treated with immunotherapy (corticosteroids and IVIG) with partial resolution of the growth. He was later diagnosed with suprasellar germinoma on biopsy subsequently treated with 2 cycles chemotherapy and proton beam radiotherapy in 2012. In 2017. to exclude tumor recurrence an LP showed elevated ACE however remainder of the clinical picture was not suggestive of neurosarcoidosis. DISCUSSION: Multiple case series have been described wherein hypothalamic germinoma mimics isolated neurosarcoidosis and vice-versa. Because of similar clinical picture and radiographic findings, the diagnosis is challenging. ACE is a nonspecific test for neurosarcoidosis, and it can be positive in the setting of germinoma as well. Hence specific molecular markers may be helpful in the diagnosis.