bluuebunny/crossref_metadata_2025 huggingface dataset:
QOLP-01. THE DISCREPANCY IN GROWTH PROBLEMS BETWEEN PATIENTS WITH INTRACRANIAL GERM CELL TUMOURS ORIGINATING FROM DIFFERENT LOCATIONS
Authors: Li Bo , Li Youqi , Wang Jiayi , Qiu Xiaoguang
Published: November 2019

BACKGROUND

Growth problems are common in patients with intracranial germ cell tumours. However, the characteristics were not fully profiled, especially when stratified by orientation. Thus, we conducted this study.

METHODS

Patients newly diagnosed, ≤19 years, with confirmed pathology or tumour markers elevation were included. Patients with bifocal lesions or lost to follow-up were excluded. WHO AnthroPlus software, which was developed for the global application of the WHO Reference 2007 to monitor growth in children aged 5–19 years, was used. Based on age, sex, and height, the Z-scores of height(ZSOH) were calculated. A ZSOH< -1 indicates a slower physical development than that in peers, while a ZSOH >1 indicates faster growth than peers.

RESULTS

Among the 200 included patients, 75 had primary lesions originating from the sellar/suprasellar region(S/SS), 73 from the pineal gland(PG), and 52 from the basal ganglia/thalamus region(BG/T). At initial diagnosis, the median ZSOH in S/SS was -0.66(-3.76–3.05), which was significantly lower than that in PG(0.76,-2.23–5.19) and BG/T(0.64,-3.05–5.32)(p=0.001). However, the difference in ZSOH between PG and BG/T was comparable(p=0.61). In patients with S/SS who had paired data(n=36), the median ZSOH decreased from -0.22(-3.76–3.05) at diagnosis to -1.01(-3.42–1.89) at the last follow-up(p=0.001). The median ZSOHs in PG(n=38) and BG/T(n=28) remained in the normal range at last follow-up although the changes were statistically significant(p< 0.001). Linear regression analysis showed that, in S/SS, age at diagnosis(β=0.115,p=0.033), sex(β=1.337,p=0.002), radiotherapy dose(β=-0.061,p=0.007), and number of chemotherapy cycles(β=-0.177,p=0.038) were correlated with changes in median ZSOH. In BG/T, only the radiotherapy dose(β=-0.064,p=0.041) and number of chemotherapy cycles(β=-0.551,p=0.026) were correlated. However, none of the above were validated in PG.

CONCLUSIONS

Compared to intracranial germ cell tumours in the PG or BG/T, the growth problems in S/SS was more prominent and aggravated after treatments, especially in those with younger age, female sex, higher radiotherapy dose, and more chemotherapy cycles.
QOLP-10. PATIENT-REPORTED OUTCOMES DURING TREATMENT FOR GLIOBLASTOMA: SYMPTOM BURDEN AND ASSOCIATED IMPACT ON DAILY LIFE
Authors: Hultman Meghan , Tipps Megan , Liu Minda , Banerji Nilanjana , Bruns Patricia , Trusheim John
Published: November 2019

INTRODUCTION

Glioblastoma is the most common primary malignant brain tumor, with an annual incidence of 3–4 new cases per 100,000 people. Despite advances in chemotherapy, radiotherapy, and surgical interventions, prognosis remains poor. Aims of treatment for life-limiting diagnoses should extend beyond increasing survival time to include palliation of symptoms and promotion of quality of life. Here we describe patient-reported symptoms both early and late in the glioblastoma treatment trajectory, as well as their associated interference with daily life.

METHODS

Fifty patients with newly diagnosed glioblastoma were recruited between September 2015-March 2018. Demographic and clinical information was collected from medical records. Patients also completed the brain tumor-specific MD Anderson Symptom Inventory (MDASI-BT) approximately every 8 weeks from completion of chemoradiation through cessation of active disease treatment. Both individual and categories of related symptoms reported in the initial two (early treatment) and final two (late treatment) MDASI-BT assessments were examined for symptom frequency, severity, and relationships between symptom severity and interference with daily life. Patients still receiving treatment or who completed < 4 total MDASI-BT assessments were excluded from the analysis.

RESULTS

The most commonly reported symptoms were often, but not always, consistent with the symptoms rated as most severe. This was true for individual symptoms as well as categories of symptoms. The most common/severe symptoms also changed from early to late treatment. Overall symptom burden was positively correlated with symptom interference in daily life (r=0.67, p< 0.0001). Regression analysis identified different symptoms as predictors of interference in early as opposed to late treatment, and these predictors did not necessarily align with the most common/severe symptoms.

CONCLUSION

Symptom experience for patients with glioblastoma is complex and dynamic. Attention to symptom trajectories for patients with glioblastoma may direct approaches to assessment, early identification, and symptom management, thus promoting better quality of life.
QOLP-12. EVALUATION OF THE UCLA NEURO-ONCOLOGY PROGRAM PSYCHOSOCIAL PATIENT SCREENING FORM IN IDENTIFYING DEPRESSION, FATIGUE, AND PERCEIVED COGNITIVE FUNCTION IN PATIENTS WITH GLIOMAS
Authors: Choi Justin , Van Dyk Kathleen , Heimberg Brandon F , Cloughesy Timothy , Lai Albert , Fong Nanette , Michelson Lauren , Vargas Erika , Leia Nghiemphu P
Published: November 2019

Given the high prevalence of neurobehavioral symptoms such as depression, fatigue, and cognitive dysfunction in patients with gliomas, it is critical to regularly screen for these symptoms at each oncology visit. The current study evaluated the validity of the UCLA Neuro-Oncology Program Psychosocial Patient Screening Form (PPSF) to measure depression, fatigue, and cognitive complaints in a sample of 22 patients enrolled in a study observing neurocognitive and psychosocial change in long-term survivors. Patients were asked to complete the PPSF at regular clinical visits, and this data was retrospectively reviewed. The PPSF consisted of the Patient Health Questionnaire-2 (PHQ-2) and options to endorse experiencing more fatigue, as well as significant memory, speech, attention, or thinking difficulties. At the most recent visit, patients also completed a validated psychosocial assessment that included the Beck Depression Inventory-II (BDI-II), Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Endorsement of recent depressive symptoms, increased fatigue, and elevated cognitive difficulties on the PPSF at the most recent visit were found to be significantly correlated with abnormal mean scores on the BDI-II (M= 22.5, SD= 11.24, t= -3.47, p= 0.003), MFSI-SF (M= 26.08, SD= 15.51, t= -2.34, p= 0.029), and perceived cognitive abilities subscale of the FACT-Cog (M= 5, SD= 2, t= 4.642, p= 0.00), respectively. Abnormal scores on the MFSI-SF and FACT-Cog were also significantly correlated with endorsement of fatigue and cognitive complaints at any previous visit. Although other measures of screening for depression, fatigue, and cognitive complaints exist, the PPSF is effective in providing immediate, clinically significant information to the clinician for comprehensive patient care. The PPSF should be utilized to capture and address psychosocial changes and facilitate a deeper understanding of the effects of treatment on glioma patients.
QOLP-21. LONG-TERM FOLLOW-UP OF GERM CELL TUMOR SURVIVORS
Authors: Matsutani Tomoo , Horiguchi Kentarou , Ikegami Siro , Hirono Seiichiro , Murai Hisayuki , Saeki Naokatsu , Iwadate Yasuo
Published: November 2019

Germ cell tumor (GCT) is a juvenile tumor, completely cured by adequate treatments, including radiation therapy and chemotherapy. However, survivors require continuous medical treatment mostly due to hypopituitarism, and several issues could be observed during follow-up. In the present report, we analyzed medical records of long-term GCT survivors, retrospectively, and make the issues clear. Of ninety-three, 82 GCT patients with several medical and social information are included in the analysis. Median follow-up time is 11.95 years, and 47 patients followed more than ten years. Fifteen deaths are recorded, and 8 are tumor-progression, and 7 are treatment-related long-term events, including four subsequent gliomas, one cerebral vascular disease, one renal cancer, and one sudden death. Seven survivors developed subsequent malignancy, and all lived more than 19 years and received more than 50Gy of irradiation. The overall survival rate is gradually decreasing more than ten years follow-up, such as 10-, 15- and 25-years survival are 92.3, 87.7 and 73.3%, respectively. Long-term follow-up also clarified several social issues. Forty-two of 50 adult survivors had a job after the treatments, but only thirty-four (70.8%) are still working. Of note, only nine (18.8% of adults) survivors got married. All four women require any hormone replacement, while only one of 4 men requires the replacement. Long-term follow-up of GCT survivors revealed subsequent malignancy and social problems. Recent attempt to decrease radiation dose and to give adequate hormone replacement might overcome these problems. Clinicians still observed GCT patients closely.
QOLP-22. DRIVERS OF COST OF SURGERY IN NEWLY-DIAGNOSED GLIOBLASTOMA PATIENTS
Authors: Chandra Ankush , Young Jacob , Dalle-Ore Cecilia , Lau Darryl , Rick Jonathan , Wadhwa Harsh , McDermott Mike , Berger Mitchel , Aghi Manish
Published: November 2019

INTRODUCTION

Glioblastoma carries a high economic burden for patients and caregivers. We investigated drivers of hospital costs of surgery for newly-diagnosed glioblastoma.

METHODS

Retrospective review of GBM patients undergoing first resection at UCSF (2010–2015) and corresponding hospital charges. Our cohort was divided into low (LC) and high cost (HC) groups for total surgical cost. Multivariate regression was used to identify factors driving cost of surgery.

RESULTS

Of 242 patients, 36.7% (n=86) were females (median age=62 years). The mean total hospital cost for surgery among our patient cohort was $40,384. When comparing the LC and HC groups, mean total hospital cost for surgery for HC patients was almost twice as much as LC group ($51,744 vs $29,023, p< 0.001). Kaplan-Meier analysis revealed that having higher cost of surgery worsened patient prognosis, with a 21% longer overall survival in the LC cohort versus the HC cohort (14.7 vs 17.9 months, p=0.02; HR=1.41 [1.05–1.91], p= 0.023). Tumor diameter at diagnosis was largest for HC group (4.7 cm) versus LC patients (3.9 cm, p=0.002). Multivariate analysis revealed longer hospital stay (F-ratio=8.87; p=0.01), longer ICU stay (F-ratio= 12.34, p< 0.001), younger age at surgery (F-ratio=6.71, p=0.02) and multifocal disease (F-ratio=6.26, p=0.02) to be independent predictors of higher cost of surgery, while having PCP at diagnosis (F-ratio=6.92, p=0.02), health insurance coverage (F-ratio= 4.23, p=0.03) and being married (F-ratio=3.71, p=0.04) were independent predictors of lower cost of surgery.

CONCLUSIONS

Higher costs of surgery correlate with worse survival outcomes in glioblastoma patients. Beyond the anticipated finding that greater disease burden drives some of this inverse correlation between cost and survival, correctable socioeconomic factors such as PCP and insurance status also drive higher hospital charges for GBM surgery. Manipulation of these factors is necessary to minimize the economic burden of disease and adopt cost-effective surgical treatments for GBM patients.
QOLP-24. PATIENTS’/PARENTS’ EXPERIENCES OF RECEIVING OPTUNE DELIVERED TUMOR TREATMENT FIELDS: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY: PBTC-048
Authors: Lai Jin-Shei , Goldman Stewart , Hwang Eugene , Kocak Mehmet , Lulla Rishi , Dhall Girish , Robison Nathan , Onar-Thomas Arzu , Dunkel Ira
Published: November 2019

BACKGROUND

Optune-delivered TTFields is a promising anti-mitotic FDA-approved cancer therapy in adult patients with high-grade gliomas (HGG), although effectiveness is not yet proven in pediatric patients. A multicenter trial [NCT03033992] evaluating the feasibility and device-related toxicity for children with recurrent or progressive supratentorial high-grade glioma (HGG) and ependymoma is being conducted. This presentation reports the interim health-related quality of life (HRQOL) and device-use experiences reported by patients and parents.

METHODS

Participating patients (aged 5–21 years) and one of their parents completed the following measures at baseline and prior to each intervention cycle: PROMIS Fatigue, Anger, Anxiety, Depressive Symptoms, Mobility, Upper Extremity Function, and Peer Relationships and Neuro-QOL Stigma. Participants completed an exit survey when they were off the study regarding their experiences wearing the device.

RESULTS

This planned interim analysis included 11 patients (7 males/4 females) with supratentorial tumors: ten HGG and one ependymoma. Median age was 14.2 (6.4–21.3) years. Patients reported worse HRQOL than the norms on all domains. Of these 11 patients, 6 completed the exit survey. No significant changes (p< 0.05) between the baseline and the final assessment were found except for Stigma. Patients perceived less stigma at baseline than at the final assessment (t=2.82, p=0.0370). Of these 6 parents who completed the Exit Survey: most considered wearing the device to be easy (n=5).Patient reminders were unnecessary (n=5), patients rarely/didn’t complain (n=4) or refuse (n=5) to wear the device, there was rare/no (n=4) difficulty with daily activities because of the device, and patients were not (n=4) or sometimes (n=2) embarrassed to wear the device.

CONCLUSION

Preliminary results indicate Optune-delivered TTFields therapy is feasible and accepted by children and parent with no evidence of negatively impacting patients’ QOL. Accrual has been expanded beyond the interim analysis.
QOLP-27. CLINICAL FACTORS AND MOLECULAR MARKERS ASSOCIATED WITH POSTOPERATIVE SEIZURES IN GLIOBLASTOMA
Authors: Chandra Ankush , Kanungo Ishan , Rick Jonathan , Yue John , Dayani Fara , Nguyen Alan , Flanigan Patrick , Chang Edward , McDermott Mike , Berger Mitchel , Aghi Manish
Published: November 2019

INTRODUCTION

Glioblastoma has a poor prognosis, further complicated by postoperative seizures. We analyzed various factors associated with postoperative seizures in glioblastoma.

METHODS

Retrospective chart review of 932 patients who underwent craniotomy for glioblastoma (777=83.4% newly diagnosed; 155=16.6% recurrent) at our institution (2002–2014). Postoperative seizures were defined as those occurring within 14 days of surgery.

RESULTS

Our cohort consisted of 49.9% (n=465) males with mean age of 55.8 (range 9–91) years. In total, 69 (7.4%) had postoperative seizures with mean time from surgery to seizure of 3.1 days (IQR=1–4). Of 536 patients (57.5%) receiving seizure prophylaxis, those treated with Keppra were more likely to have postoperative seizures compared to those on Dilantin (10.9% vs 5.0%; p=0.022). Primary tumor patients were less likely to seize postoperatively compared to recurrent tumor patients (9.7% vs 19%; p=0.016). Patients presenting with seizure as chief complaint (12.1% vs 5.1%; p=0.025) and those with >20% of Chromosome 10 deletion were more likely to have seizures postoperatively (12.4% vs 6.1%; p=0.0029). Risk factors for postop seizures for newly-diagnosed patients included subtotal resection versus gross total resection (28.0% vs 7.1%; p=0.022). Risk factors for postop seizures for recurrent patients were >5% EGFR amplification (23.5% vs 5.8%; p=0.0021) and hyponatremia within mean 2.5 days (IQR 0–1) after surgery (20.8% vs 7.1%; p=0.035).

CONCLUSION

We identified several risk factors for postoperative seizures in glioblastoma patients, most of which were clinical (seizure as chief complaint, the antiepileptic chosen for prophylaxis, and extent of resection), while some were molecular and linked to genes whose products have demonstrated links to epileptogeneicity (Chromosome 10, EGFR). These findings may assist physicians in detecting glioblastoma patients that are at higher risk for postoperative seizures and in providing prophylaxis to reduce morbidity.
QOLP-37. QUALITATIVE RESEARCH IN LOWER GRADE GLIOMA: UNDERSTANDING SIGNS, SYMPTOMS, AND DISEASE IMPACTS DURING EXPECTANT MANAGEMENT
Authors: Boscoe Audra , Wells Ted , Graham Christina , Pohl Caitlin , Witherspoon Brooke , Kerkorian Christa , Steelman Lori , S Pandya Shuchi
Published: November 2019

BACKGROUND

Patients with lower grade glioma (LGG) (i.e., grade II or III) have limited treatment options. After surgical resection of their tumor, patients will undergo either a period of expectant management (watch and wait) or treatment with adjuvant chemotherapy and/or radiotherapy. Approximately 80% of patients with LGG have an isocitrate dehydrogenase mutation, which is a viable target for molecular therapy. This offers a therapeutic intervention that could potentially delay the need for chemotherapy and/or radiotherapy in select patients. Several prognostic and patient-specific factors contribute to the decision to recommend expectant management, including concerns about the side effects of chemotherapy and radiotherapy. The aim of this project was to understand patients’ signs and symptoms during the expectant management period and how LGG impacts their lives.

METHODS

Concept elicitation interviews were conducted in the US with patients with LGG as well as key opinion leaders (KOLs) with experience treating patients with LGG. Interview data were analyzed using Atlas.ti, and patient data were reviewed against KOL data.

RESULTS

Seven patients with ≥ 3 months of expectant management experience and three KOLs were interviewed. During their expectant management periods, patients reported 12 signs/symptoms, mostly related to deficits in cognition. Patients reported 16 impacts across four categories, with a substantial proportion of the impacts identified as negatively affecting emotional function. The signs/symptoms and impacts reported by patients were generally also reported by KOLs. During expectant management, patients typically resume their original quality of life post-surgery, but may also experience anxiety. Patients and KOLs indicated a preference for expectant management and delaying chemotherapy or radiotherapy.

CONCLUSIONS

Patient and KOL interviews characterized the LGG experience and indicated a preference for expectant management, which may be supported by therapies that delay the initiation of chemotherapy and/or radiotherapy.
RDNA-09. RADIATION PRIMES SB28 GLIOBLASTOMA FOR RESPONSE TO TGFβ AND PD-L1 NEUTRALIZING ANTIBODIES
Authors: Borrero Garcia Luis , Reiners Oliver , Gonzalez-Junca Alba , Okada Hideho , Helen Barcellos-Hoff Mary
Published: November 2019

SB28 is a new luciferase expressing murine glioblastoma (GBM) cell line whose morphology, growth pattern, mutational burden immune infiltrate more closely resembles human GBM and is unresponsive to immunotherapy (OncoImmunology, 7:12, e1501137). Radiation therapy (RT) has the potential to improve response to combinations by multiple means: cell kill that may activate an immune response, effects on vascular system may improve drug access, induction of DNA damage that can be augmented by targeted or chemotherapy, and modulation of the tumor microenvironment. High transforming growth factor β (TGFβ) activity in most GBM, which increases with radiation, likely opposes effective therapy by endorsing an effective DNA damage response and being immunosuppressive. Here evaluated the response of SB28 to radiation in combination with PD-L1 checkpoint blockade or neutralizing TGFβ. Establishment of intracranial tumors was monitored by bioluminescence. We determined that SB28 endogenously activate TGFβ as evaluated by biomarkers. We used radiolabeled antibodies and PET-CT to demonstrate access to intracranial tumors, indicative of a compromised blood-brain barrier. TGFβ neutralizing antibody, 1D11, had little effect on tumor growth compared to mice receiving IgG control antibody (median survival control: 19 days vs 1D11: 20.5 days). A single dose of radiation of 10 Gy delivered to the tumor site increased median survival to 21 day, which was increased to 31 days in mice treated with 1D11. In a second experiment in which the radiation dose was 6 Gy, 1D11 provided no benefit. In contrast, median survival of mice treated with PD-L1 neutralizing antibodies 3 days after being irradiated with 6 Gy demonstrated increased median survival (Control: 18 day; anti-PD-L1 20.5; RT: 25 days; RT + anti- PD-L1: 28 days). Double treatment resulted in 1/7 long term survival and loss of bioluminescence indicative of tumor elimination. Thus, radiation can prime SB28 GBM for response to biological agents.
RTHP-22. EDEMA PROGRESSION DURING MRI-GUIDED GLIOBLASTOMA RADIOTHERAPY
Authors: Dooley Sarah , LLorente Ricardo , Jones Kolton , Ford John , Mellon Eric
Published: November 2019

PURPOSE

Despite the common finding of pseudoprogression or true progression one month after primary chemoradiotherapy for glioblastoma, there are few studies evaluating brain MRI changes that occur during concurrent chemotherapy and radiotherapy (RT). With the first generation combination MRI-RT device, daily predominantly T2-weighted MRIs are obtained of glioblastoma during RT. We quantified how many patients had significant MRI detectable volumetric changes through the six week course of primary chemoradiotherapy. This is of particular importance since glioblastoma RT is only planned at the beginning of therapy and not commonly re-planned for changes during therapy.

METHODS

We retrospectively reviewed the daily set-up imaging of 8 patients at our institution who received RT for glioblastoma using the Cobalt-60 MRI-RT system. Patients received standard chemoradiation at 60 Gy in 30 fractions with temozolomide per EORTC22981/26981. We contoured the abnormality on the initial ViewRay setup scan and the set-up scan for fraction 30. After rigid fusion of the contours of the initial setup MRI and fraction 30 MRI, the volumes were compared.

RESULTS

Of the 8 patients, 3 patients (37.5%) demonstrated edema expansion greater than 5 mm. The maximum distances of T2-weighted abnormality volume growth for these patients were 1.0 cm, 1.5 cm, and 4.1 cm. These findings were correlated with the post-treatment diagnostic MRIs at 3–4 weeks which demonstrated similar FLAIR abnormalities and expansion in T1 with gadolinium contrast volumes within these areas of the radiotherapy fields (pseudoprogression vs. true progression).

CONCLUSION

Review of MRIs obtained by daily MRI-RT for glioblastoma indicates that 3 of 8 patients had over 5 mm of change in T2-weighted dimensions from beginning to end of radiotherapy. Groups using limited CTV margins for treatment planning should be aware that MRI volumes could significantly increase during radiotherapy.
RTHP-29. HYPOFRACTIONNATED RADIOTHERAPY FOR REFRACTORY SKULL BASE CHORDOMA
Authors: Cai Linbo , Li Shaoqun , Lai Mingyao , Shan Changguo , Li Juan , Zhen Junjie , Hong Weiping
Published: November 2019

OBJECTIVE

Skull base chordoma is difficult to be totally excised by surgery because of the complex anatomical structures of skull base. Postoperative radiotherapy is one of the most important treatment options for skull base chordoma. However, the response of chordoma to conventional fractionation radiotherapy is poor. Therefore, it is of great value to explore the therapeutic effects of hypofractionnated radiotherapy for refractory skull base chordoma.

METHODS

A retrospective analysis was performed on the clinical data of patients with refractory skull base chordomas who were admitted to Guangdong Sanjiu Brain Hospital from 2007 to April 2019. The characteristics of the selected cases and prognosis-related factors were analyzed with Kaplan-Meier method.

RESULTS

A total of 21 patients were enrolled in this study, including 11 male (52.4%) and 10 female (47.6%). Twenty patients received surgery, including gross total resection in 5 cases (25%), subtotal resection in 14 cases (70%) and biopsy in 1 case (5%). Among 18 patients who received radiotherapy, 17 (94.4%) received radiotherapy after the first diagnosis; 1 (5.6%) were treated with radiotherapy after tumor recurrence; and 3 (16.7%) received the secondary radiotherapy after tumor recurrence. The median overall survival of 11 patients receiving hypofractionnated radiotherapy (45-60Gy/8-20F) and 7 patients receiving conventional fractionation radiotherapy (40-60Gy/20-30F) reached 33 months (7–130) and 68 months (27–105), respectively. The results of Kaplan-Meier analysis revealed that the overall survival of patients who were treated with hypofractionnated radiotherapy was significantly longer than that of those receiving conventional fractionation radiotherapy. No one suffered from radiation-induced acute brain injury (≥grade 3), and only 1 patient who received hypofractionnated radiotherapy developed radiation-induced brain necrosis at 3 years after hypofractionnated radiotherapy.

CONCLUSION

Hypofractionnated radiotherapy for refractory skull base chordoma can not only achieve a therapeutic effect, but also reduce the risk of radiation-induced necrosis.
RTHP-31. EMERGENCY RADIOTHERAPY IN INTRACRANIAL GERM CELL TUMORS (GCTS) PATIENTS WITH KPS≤ 40: ARETROSPECTIVE ANALYSIS OF 27 CASES
Authors: Cai Linbo , Lai Mingyao , Li Juan , Zhou Cheng , Hu Qingjun , Zhou Zhaoming
Published: November 2019

OBJECTIVES

To evaluate the potential role of emergency radiotherapy in intracranial germ cell tumors GCTs) patients with KPS ≤ 40.

METHODS

A total of 27 primary intracranial germ cell tumors (GCTs) patients with KPS ≤ 40 between Jan 2007 and Dec 2018 were retrospectively evaluated. The median age at initial diagnosis was 15 years (range, 528 years). Among those, 11 patients were germinoma and 16 patients were nonseminomatous germ-cell tumors (NGGCTs). There were 9 solitary pineal, 5 suprasellar, 3 basal ganglia and 10 multifocal and disseminated tumors. All patients received emergency radiotherapy (2 Gy/fx/d). Prior to radiotherapy, 11 patients were manifested with hydrocephalus, 10 with hypopituitarism and 5 with intracranial tumo apoplexy.

RESULTS

The average follow up time was 44.4 months. The 5 year progression free survival rate and overall survival rate were 29.6% and 33.3%. The median overall survival time was 38 months. In particular, the median intracranial hypertension symptoms relief time was 2 days. The median KPS following radiotherapy was 80 comparing to 30 prior to radiotherapy (P < 0.05). A significant improvement on KPS of 46.7±27.3 was observed in this study.

CONCLUSION

Emergency radiotherapy is implicated as a promising intervention for GCTs patients with elevated intracranial pressure (ICP). These advantages can be interpreted as direct cell killing effect and fast tumor shrinkage by ionizing radiation. However, to substantiate our findings, further investigations were highly warranted.
RTHP-35. RE-IRRADIATION USING PULSED REDUCED DOSE RATE RADIATION THERAPY IN PATIENTS WITH GRADE 2 GLIOMAS
Authors: Harari Colin , Burr Adam , Ian Robins H , Howard Steven
Published: November 2019

BACKGROUND

The time course of progressive grade 2 glioma can span nearly a decade. However, much less is known about re-irradiation in this cohort than in high grade patients. Pulsed reduced dose rate (PRDR) radiation therapy is a method of radiation delivery, which may spare normal tissues by slowing the rate of radiation delivery to allow repair.

METHODS

We identified consecutive patients from an institutional database initially diagnosed with grade 2 glioma from 2001 to 2017 who underwent pulsed reduced dose rate radiation therapy. Radiation was delivered in 20 cGy pulses every three minutes, most commonly with a 3D conformal, three field technique, encompassing gross disease with a 1–2 cm margin. Kaplan Meier method was utilized to analyze patient outcomes.

RESULTS

35 patients with grade 2 glioma were identified. The median survival from the date of the first surgery was 103 months (95% CI 78–129 mo). 71% underwent at least a second resection and 86% of patients receiving chemotherapy. 80% of patients underwent transformation to grade 3 (51%) or grade 4 (29%) glioma. Overall survival from PRDR was 9.8 months (95% CI 4.5–14.5mo) and progression free survival was 6.2 months (95% CI 5.1–7.4) in all patients. Overall response rate was 37%. In patients who remained grade 2 histology, overall survival was 13.3 months and two patients remain disease free at 83 and 34 months with overall response of 71%. Four seizures were documented, otherwise treatment was well tolerated.

CONCLUSIONS

Progressive grade 2 glioma can progress and evolve over nearly the course of a decade. This study demonstrates the efficacy of re-irradiation in prolonging survival in these patients by delaying progression. In patients who remain with grade 2 disease, prolonged salvage of their disease appears possible.
RTHP-38. THE FEASIBILITY OF PSYCHOLOGICAL INTERVENTIONS FOR REDUCE THE NEED OF ANESTHESIA DURING RADIOTHERAPY IN < 5 YR PEDIATRIC PATIENTS WITH CNS MALIGNANCIES
Authors: Cai Linbo , Li Juan , Lai Mingyao , Hu Qingjun , Zhang Xing
Published: November 2019

OBJECTIVES

The aim of this study was to explore the psychological intervention to reduce the use of sedatives in children when undergoing radiotherapy.

METHODS

From January 2017 to December 2018, 53 pediatric patients, without limited consciousness, from 3 to 5 years old diagnosed with brain tumors and admitted to radiotherapy at the oncology centers of Guangdong Sanjiu Brain Hospital, received the systematic intervention (including desensitization, simulation play practice, distraction, etc.) to reduce medical fear for radiotherapy. A case-control study of semi-structured and play-based interventions was undertaken for psychological preparation of young children during radiotherapy.

RESULTS

After receiving interventions, 49 children were willing to cooperate with treatment, with the success rate of 92.45%. There were 19 children behaving cooperative in the 3-year-old group, while there were both 17 patients showing compliance in the 4-year-old group and 5-year-old group. Compared with the success rate of the 3-year-old group (84.21%), psychological interventions were more appropriate for the 4-year-old group (94.12%) and 5-year-old group (100%). For those failed cases, 2 children aged 3 used anesthesia during the whole radiotherapy sessions; 2 children aged 3 and 4 took sedatives in the early session of radiotherapy.

CONCLUSION

This study suggested that psychological intervention was able to improve the adherence of pediatric patients to the whole treatment course and reduce the occurrence of drug resistance due to non-compliance.
RTHP-42. OUTCOMES AFTER FRACTIONATED STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Anderson Rebecca , Bonestroo Liberty , Spencer Christopher
Published: November 2019

PURPOSE

To examine outcomes in patients undergoing linear accelerator (LINAC) based fractionated stereotactic radiosurgery (fSRS) to 30 Gy in 5 fractions.

METHODS

We completed a retrospective review of patients with brain metastases treated with 5-fraction LINAC fSRS at Phelps Health. All patients with CNS metastatic disease treated with fSRS were included in the study. Incidence of symptomatic radionecrosis (sRN), local brain failure (LBF), time to death, target volume and dose, prior whole brain radiotherapy (WBRT), prior surgical resection, and concurrent immunotherapy were assessed. sRN was defined as grade 2 or higher per CTCAE v4.0.

RESULTS

From 2016–2019, 28 patients and 60 lesions were treated. The most common metastasis histology was non-small cell lung cancer (n = 22), renal cell carcinoma (n = 12), and melanoma (n = 11). Median follow-up time was 6.49 months (range 0.33 – 23.96). Of 60 lesions, three lesions developed sRN and one asymptomatic patient developed radiographic evidence of radiation necrosis. Mean GTV was 1.03cm3 in patients with sRN. Of 57 lesions without sRN, median GTV was 1.45cm3 (range 0.11 - 20.1). Mean time to sRN was 3.17 months. Two symptomatic patients received prior WBRT. One symptomatic patient received concurrent immunotherapy. No symptomatic patients had surgical resection prior to fSRS. Among 24 lesions without prior radiation, 1 (4.2%) developed sRN. 10 lesions underwent surgical resection prior to fSRS with none developing sRN. 34 lesions were treated with concurrent immunotherapy and one developed sRN (2.9%). Local failure occurred in 9 lesions (15%). Median time to death for all patients was 4.50 months (range 1.02 - 19.40).

CONCLUSIONS

fSRS to 30 Gy in 5 fractions has promising efficacy with low incidence of sRN in treatment of CNS metastatic disease. Further investigation is required to determine predictors in patient outcome.
RBTT-01. A PHASE 2 TRIAL WITH ABI-009 (NAB-SIROLIMUS) AS SINGLE-AGENT AND COMBINATIONS IN RECURRENT HIGH-GRADE GLIOMA (rHGG) AND IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)
Authors: Kesari Santosh , Juarez Tiffany , Carrillo Jose , Truong Judy , Nguyen Minhdan , Heng Annie , Gill Jaya , Nguyen Hanh , Nomura Natsuko , Grigorian Berta , Hou Shihe , Schmid Anita , Desai Neil
Published: November 2019

BACKGROUND

The mTOR pathway is frequently activated in patients with GBM and is associated with reduced survival, making this pathway a promising target. However, mTOR inhibitors, including everolimus and temsirolimus, have poor brain penetration, limiting their potential use for GBM. ABI-009 is a novel albumin-bound mTOR inhibitor that has a distinct PK profile and biodistribution, including CNS penetration. The goal of this prospective, multi-cohort open-label phase 2 study is to evaluate the efficacy and safety of ABI-009 monotherapy and combination therapy in rHGG and ndGBM.

METHODS

Eligible patients are ≥18 years old, KPS score ≥70, and have histologically confirmed rHGG or ndGBM. Arm A has 5 cohorts in patients with rHGG, naïve to mTOR inhibitors: 1) ABI-009 single agent IV 100 mg/m2; 2–5) ABI-009 60mg/m2 plus TMZ 50mg/m2 or BEV 5mg/kg or marizomib 0.8mg/m2 or CCNU 90mg/m2. In Arm B for patients with ndGBM, ABI-009 100mg/m2 is given weekly for 4 weeks (Induction) after surgery, followed by ABI-009 at 60mg/m2 plus RT/TMZ. Up to 19 patients per cohort will be enrolled: initial 9 patients with a stopping rule that only if there are ≥2 responses will the study proceed to further enrollment of the next 10 patients (Simon’s 2-stage design). Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint for all cohorts is overall response rate per RANO criteria; secondary endpoints are median PFS and OS, 6-month and 12-month PFS, 12-month OS, and safety. This study is open and actively enrolling patients. The anticipated enrollment period is 24 months. NCT03463265
RBTT-04. DGM1 MAY SERVE AS A NOVEL GENETIC BIOMARKER OF RESPONSE TO ENZASTAURIN IN GLIOBLASTOMA
Authors: Butowski Nicholas , Zhang Lei , Sun Hong , Han Isabel , jivani Manoj , Li Ling , Luo Wen
Published: November 2019

BACKGROUND

No significant progress has been made over the last decade in therapies available for glioblastoma (GBM) with survival remaining poor. Meaningful advances in treating this deadly malignancy may rely on precision medicine. A novel pharmacogenomic biomarker, Denovo Genomic Marker 1 (DGM1), for enzastaurin (enz) in treating lymphoma was discovered. It was evaluated to predict enz response in GBM.

METHODS

Biomarker discovery was performed by a genome-wide screen using DNA extracted from blood samples of a ph 3 enz lymphoma trial and confirmed in an independent ph 2 lymphoma trial. The biomarker was evaluated for its predictability in GBM using the archived DNA samples from a ph 1/2 enz GBM trial.

RESULTS

DGM1, a germline polymorphism on chromosome 8, was found to be highly correlated with response to enz in the two lymphoma trials. Using DNA extracted from pts blood of the single-arm ph 1/2 study with newly diagnosed GBM receiving enz added to radiation and temozolomide (tmz), we found median OS for DGM1+ pts treated with enz was 18 mon vs 12.8 mon for DGM1- pts, HR (95% CI) 0.68 (0.25, 1.81), p = 0.12. Pts receiving a mean daily dose of enz ≥ 245 mg had an OS of 19.8 mon vs 14.9 mon for pts receiving a mean daily dose of < 245 mg [HR (95% CI) 0.55 (0.34, 0.90)].

CONCLUSION

These data are supportive of DGM1 as a potentially predictive biomarker for enz response in both lymphoma and GBM. There is an ongoing biomarker-driven pivotal study in lymphoma. DGM1 in GBM will be further evaluated in a planned randomized ph 2b study in newly diagnosed GBM with 500 mg/day of enz in combination with tmz.
RBTT-06. TESSA JOWELL BRAIN MATRIX STUDY: A BRITISH FEASIBILITY STUDY OF MOLECULAR STRATIFICATION AND TARGETED THERAPY TO OPTIMIZE THE CLINICAL MANAGEMENT OF PATIENTS WITH GLIOMA
Authors: Watts Colin , Apps John , Ansorg Olaf , Savage Josh , Fox Richard , Chalmers Anthony , Short Susan C , Thompson Gerard , Waldman Adam , Capper David , Hargrave Darren , Brennan Paul , Smith Stuart , Ashkan Keyoumars , Wykes Victoria , Kurian Kathreena , Jamal-Hanjani Mariam , Swanton Charles , Buckle Peter , Bulbeck Helen , Stead Lucy F , Vivanco Igor , Bowden Sarah
Published: November 2019

In 2016 there were 5250 brain cancer deaths in the UK. Standard treatment is surgical resection followed by chemo-radiotherapy. In most cases of diffuse glioma, complete tumour resection is not feasible. Many chemotherapy drugs have untested penetration through the blood brain barrier, potentially leading to sub-therapeutic concentrations in the tumour. There is need to refine current treatment strategies in relation to the understanding of tumour biology, and rapidly introduce and evaluate novel therapeutic approaches and agents through delivering rigorous clinical trials. The TESSA JOWELL BRAIN MATRIX Study will evaluate the feasibility of delivering precision medicine for brain cancer patients within the NHS. A multicentre, platform feasibility study of 1200 patients with diffuse glioma will build on the 100,000 genome project to develop and evaluate an infrastructure to collect and integrate: 1) real time comprehensive integrated molecular analysis, including whole genome sequencing and epigenetic classification; 2) serial sampling and annotation of tumours; 3) collection of matched clinical data; 4) assessment of patient quality of life; 5) centralised radiological review and response assessment as per RANO criteria. Once developed this will allow rapid introduction of therapeutic trials to specific patient groups. Secondary objectives include: understanding the association between extent of resection and molecular stratification to refine the role of surgery; optimisation and harmonisation of protocols to best collect, manage and store tissue, clinical data, and radiological images in order to provide a resource for researchers, both within and outside of the study. Improve patient recruitment by identifying and removing recruitment barriers and improve the information and consent processes for patients. Promote the development of a national network with expertise in brain cancer. Enrolment of the first patient is expected in late 2019. For further information, please contact the Brain Matrix Trial Office BrainMatrix@trials.bham.ac.uk.
RARE-14. STRUCTURAL BRAIN PLASTICITY OF THE GRAY MATTER IN PATIENTS WITH BASAL GANGLIA GERM CELL TUMORS: A VBM STUDY
Authors: Li Yanong
Published: November 2019

OBJECTIVE

To assess the whole brain structural plasticity in case of unilateral basal ganglia germ cell tumors (BGGCTs).

METHODS

To detect changes in gray matter volume of the whole brain from structural Magnetic Resonance Imaging (MRI), we used voxel-based morphometry (VBM) in a sample of 41 patients with BGGCTs invading the left basal ganglia (BasalG_L group; n = 22) or the right basal ganglia (BasalG_R group; n = 19) and a sample of 16 patients with GCTs arising in pineal or suprasellar regions, comparing these groups with 16 age-matched normal controls (NCs) by two-sample t test after that.

RESULTS

To left BGGCTs patients, the regions of whole brain VBM analysis emphasized a large cluster of voxels with gray matter volume increase in left para hippocampal (k = 529 voxels, T=4.18, p< 0.01) and decrease in left thalamus (k = 527 voxels, T=-4.88, p< 0.01). At the same time, the cluster of voxels with gray matter volume increase in right middle cingulate cortex (rMCC) (k = 172 voxels, T=3.96, p< 0.01), and decrease in right inferior frontal gyrus (rIFG), pars opercular (k = 495 voxels, T= -4.29, p< 0.01) in right BGGCTs patients. Furthermore, gray matter volume showed no significant difference between groups of patients with GCTs arising in pineal or suprasellar regions and NCs by two-sample t test. And the results were corrected by family-wise-error correction.

CONCLUSIONS

The revealed results demonstrate that slow-growing but destructive lesion of the BGGCTs markedly and asymmetrically atrophies the gray matter volume in specific brain regions and shows compensatory plasticity in each side of cerebral hemisphere. Our findings direct focus on the whole cerebral adaptation that perhaps be a physiologic basis for the high level of functional compensation and partially explain the relationships between gray matter remodeling and cognitive disturbances observed in patients with BGGCTs.
RARE-17. PRIMARY DIFFUSE LEPTOMENINGEAL GLIOMATOSIS OF HIGH GRADE TUMORS
Authors: Kwon Ji-Eyon , Ko Gyung-Oh , Hwan Hwang Gi , Ah Kim In , Woo Wee Chan , Jung Kim Yu , Choe Gheeyoung , Choi Byung-Se , Ho Han Jung , Kim Chae-Yong
Published: November 2019

Primary diffuse leptomeningeal gliomatosis(PDLG) of high grade glioma(HGG) is a rarely documented phenomenon observed in less than 5% of glioblastoma(GBM). Purposes of this study are to investigate the clinical outcomes of PDLG of HGG and to analyze the results according to the procedures of operations. We retrospectively reviewed the medical records of 469 patients of HGG at our institute between 2004 and 2019 and 9 of who with PDLG were enrolled in our study. These 9 patients satisfying the condition of Karnofsky performance status ≥70 and Eastern Cooperative Oncology Group performance status ≤2 were conducted the primary surgical biopsy with or without intracranial pressure control. All patients finished the surgery within about 11 days after the detection of leptomeningeal seeding(LMS) on preoperative MRI images and completed the concurrent chemoradiotherapy(CCRT) with temozolomide(TMZ). Among 9 patients, 7 patients started adjuvant temozolomide and 3 patients completed the six cycles of it. 7 patients had done ICP control operation such as ommaya reservoir insertion, extraventricular drainage, and ventriculoperitoneal shunt within 23.3 days after defined as PLDG and survived nearly 10 months. Their pathologic findings were turned out to be seven glioblastomas and two anaplastic astrocytomas. Their median overall survival was 14 months and the 1- and 2-year overall survival rates were 50.8±17.7% and 16.9±15%, respectively. Compared to the 10-year study of GBM in the same institute between 2004 and 2011, in which 67 patients finished with CCRT with TMZ, the median overall survival was 19 months and the 1- and 2-year overall survival rates were 78.3% and 41.7%. The results indicate that PLDG has a worse outcome and overall survival rate is lower than GBM without LMS, so the earlier start of standard CCRT right after aggressive control of increased ICP like conducting CSF diversion might be helpful for the elongation of life expectancy.
RARE-20. ANALYSIS OF CLINICAL FEATURES ON DEATH FROM INTRACRANIAL GERM CELL TUMORS (GCTS): ARETROSPECTIVE COHORT STUDY
Authors: Cai Linbo , Li Juan , Lai Mingyao , Zhou Cheng , Hu Qingjun , Zhou Zhaoming , Wang Lichao
Published: November 2019

OBJECTIVES

The present study aimed to investigate the clinical features associating with intracranial germ cell tumors(GCTs) of poor prognosis.

METHODS

We retrospectively analyzed the death data cohort based on 47 patients (30 males and 17 females) who had been diagnosed with GCTs between 2005 and 2018 in our hospital. The median age at initial diagnosis was 16 years (range, 3¬60 years). Among those, 18 patients were germinoma and 29 patients were non¬seminomatous germ-cell tumors (NGGCTs).

RESULTS

According to Kaplan-Meier survival analysis, children aged ≤ 10 years were observed with a very short survival compared to patients aged > 10 years, indicating a 5-year survival rate of 0 and 50%, respectively (P < 0.001). To be more specific, disseminated tumors were found to be the most prominent factor for prognosis in children aged ≤ 10 years: the 1-year survival for MR positive versus MR negative of disseminated tumors were 0 and 62.5%, respectively (P < 0.05). On the other hand, the pre¬treatment serum alpha-fetoprotein (AFP) level was found to be an important surrogate for prognosis. In the subgroup of patients > 10 years, the 5-year survival for AFP > 1.5ng/ml was 25%, in comparison to 66% for AFP ≤ 1.5ng/ml (P < 0.05). Further, solid survival advantages were found in patients received stereotactic radiosurgery (SRS) compared to none. The 5¬year survival for SRS versus non-SRS patients were 62% and 29%, respectively (P < 0.05).

CONCLUSION

Our data highlights a number of critical factors that may facilitate the prognosis stratifications of GCTs. What’s more, neither the locations of the primary tumors nor the numbers of lesions are associated with the prognosis of GCTs. These results warrant further investigation via randomized prospective studies.
RARE-25. CLINICAL FEATURES OF PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION (PPTID): A SINGLE INSTITUTION REVIEW
Authors: Kunigelis Katherine , Kleinschmidt-DeMasters Bette , Ryan Ormond D
Published: November 2019

Pineal parenchymal tumors of intermediate differentiation (PPTID) are rare. Even in the most recent WHO 2016, definitive histological criteria to distinguish grade II from III lesions remain to be defined. While no single institution has large numbers of cases, our experience has been that the clinical course is more varied and complicated than reported. The University of Colorado Health pathology database was queried for cases diagnosed as PPTID, 2006 – 2019, inclusive. Twelve adult patients were identified. Mean age at diagnosis was 40 years (range 26–78). There were 9 female and 3 male patients. Seven patients had well-documented clinical courses at our primary institution. At initial diagnosis, all were treated with surgery and 3/6 documented a gross total resection (GTR). Adjuvant radiation therapy to the resection bed in was administered in 5 of 7 (71%) of patients (4 IMRT, 1 SRS). Mean follow-up time was 71 months (range 13–195); 5/7 (71%) of patients developed a recurrence. Median progression free survival was 37 months (range 13- 73 months), with tendency to be longer for male gender (57.5 versus 17 months in females, p=0.17), and GTR (40 months versus 16 months in subtotal resection, p=0.49). Eighty percent of first recurrent disease had leptomeningeal dissemination. First recurrences were treated with radiation alone in 3 (60%) patients (1 SRS, 1 IMRT), craniospinal radiation with multi-agent chemotherapy in 1 (20%) patient, and surgery with radiation therapy in 1 (20%). At last follow-up, 2 patients (28.5%) had died, with median OS of 168.5 months. Although PPTIDs have a known potential for local recurrence and craniospinal dissemination (quoted as 22% and 10%, respectively in WHO 2016), our data show a more dismal experience with 71% recurrence and 80% dissemination at first recurrence. Lack of standardized therapies results in challenges in individual patient management.