bluuebunny/crossref_metadata_2025 huggingface dataset:
QOLP-27. USE OF THE NEURO-QOL COGNITIVE FUNCTION SHORT-FORM AS A TOOL FOR ASSESSING PATIENT-PERCEIVED NEUROCOGNITION FOLLOWING RADIOTHERAPY
Authors: Choi Sung , Kowalski Emily , Khairnar Rahul , Mishra Mark
Published: December 2020

The Quality-of-Life in Neurological Disorders (Neuro-QOL) instruments are a practical set of validated tools utilized to measure a core set of health-related quality-of-life parameters that are relevant to patients with neurological disorders. The tools can be completed in approximately 1-minute. The primary objective of this study was to evaluate the feasibility of utilizing the eight-question Neuro-QoL Cognitive Function- Short Form (NCF-SF) tool (v2.0) to assess cognitive outcomes in patients with primary and secondary brain tumors undergoing radiotherapy. Patients completed the NCF-SF at baseline and during follow-up visits. Raw scores were converted to a standardized T-score that has been normalized to have mean score of 50 and standard deviation (SD) of 10. Descriptive statistical analyses were performed to assess the prevalence of baseline cognitive impairment (defined as > 1 SD below the normative mean), and to assess longitudinal changes in Neuro-QOL scores. A minimum clinically important difference (MCID) was defined as a change from baseline of >7.5, based on previously published literature. Ninety-one patients completed NCF-SF at baseline and at least one follow-up visit. The mean baseline score for the study cohort was 49.9 (SD 9.2). Nineteen percent of patients (n=17/91) had impaired function at baseline. Baseline scores did not differ based on tumor type (p=0.79): Glioma/ependymoma 49.6 (n=35); brain metastases 49.1 (n=24); Meningioma/benign 50.7 (n=32). Following radiation, 15% and 22% of patients experienced a MCID decline at 1- (n=60) and 3- months (n=65), respectively. However, 17% and 20% of patients demonstrated a MCID improvement at 1- and 3-months, respectively. In conclusion, this represents the first study to utilize the NCF-SF to measure cognitive function in patients undergoing brain radiotherapy. Use of NCG-SF was feasible, and identified patients with meaningful changes in cognitive function over time. Future clinical trials may consider use of Neuro-QOL to assess patient-perceived cognitive function.
QOLP-28. PREOPERATIVE SLEEP DISTURBANCE AND ITS ASSOCIATION WITH QUALITY OF LIFE IN ADULT BRAIN TUMOR PATIENTS
Authors: Chen Pin-Yuan , Chiu Hsiao-Yean , Lin Pei-Ching
Published: December 2020

BACKGROUND

Sleep disturbances are common complaints in adult brain tumor patients and impact their quality of life profoundly. The prevalence and pattern of preoperative sleep disturbances are still unknown.

MATERIAL AND METHOD

There were 36 adult patients with primary brain tumors who were recruited before craniotomy. All participants completed a battery of questionnaires, including the Athens Insomnia Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Brief Fatigue Inventory, Hospital Anxiety, and Depression Scale, Morningness-Eveningness Questionnaire, and EORTC-QLQ-BN20. Actigraphy was put on a non-dominant wrist for obtaining objective sleep parameters, such as the dichotomy index.

RESULT

The prevalence of preoperative insomnia, poor sleep quality, excessive daytimes sleepiness, and circadian disruption were all high but similar between benign and malignant brain tumor groups. Patients with glioma had poorer quality of life. Insomnia was the only sleep disturbance that significantly associated with quality of life in a multivariate linear regression modal.

CONCLUSION

Sleep disturbances are common in adult brain tumor patients. Insomnia worse the quality of life of these patients. A further longitudinal investigation of sleep disturbances and quality of life in brain tumor patients is worthful.
QOLP-29. INFORMATION ON HEADACHE FOR BRAIN TUMOR PATIENTS ON INTERNET – GUIDING OR MISLEADING?
Authors: Kallio Merja
Published: December 2020

Patients often consult the internet if they suspect a brain tumor. Migraine and tension type headache have an active prevalence of round 50%. 96% of the general population has had some kind of headache during their lifetime. There are many possible exacerbating factors for precipitating or worsening headache. Consequently headache makes many people suspect a brain tumor. Nowadays when MRI and CT are widely available making earlier diagnosis of brain tumors possible, it has been discovered that in adults headache is rarely the most important or even existing symptom. Nelson and Taylor (1) find headache in 2% of brain tumor patients and Posti et al (2) found it in 20% of glioma patients as presenting symptom but never as a sole symptom. What is the information the patients get on the internet sites? In order to find out the author analyzed 36 webpages concerning headache and brain tumors by brain tumor and cancer societies, Neuro-oncology clinics, University clinics and general health information pages in 4 different languages (Finnish, English, Swedish and German). On 13 of these 36 pages headache was considered the presenting or main symptom. Particularly different cancer and brain tumor societies (8 of 9) explain that headache is the main symptom. On some pages it was concluded that brain tumor patients often have headache but headache patients seldom brain tumors. This is obviously true but does not help patients much. Consequently many of these information sites give patients somewhat vague or even misleading information. This will cause unnecessary anxiety, fear and visits to healthcare. We should strive to make patient information both more clear and more accurate. In order to accomplish this we need more information of the current situation.
RADT-04. RESECTION CAVITY FAILURE OF MELANOMA BRAIN METASTASES WHEN TREATED WITH SYSTEMIC THERAPY, WITH OR WITHOUT FOCAL RADIOTHERAPY
Authors: Susko Matthew S , Vasudevan Harish N , Ma Lijun , Nakamura Jean , Raleigh David , Boreta Lauren , Fogh Shannon , Theodosopoulos Philip , McDermott Michael , Tsai Katy , Sneed Penny , Braunstein Steve
Published: December 2020

OBJECTIVES

Brain metastases are a common sequelae of advanced melanoma, and can lead to significant morbidity and mortality. Systemic therapy, inclusive of BRAF/MEK inhibitors and immunotherapy, are increasingly being utilized for metastatic melanoma brain metastases. This study sought to evaluate the clinical outcomes of resected melanoma brain metastases treated with systemic therapy, with or without focal radiotherapy.

METHODS

Patients at a single institution who underwent resection of a melanoma brain metastasis were retrospectively identified and reviewed. Patients were required to have received immunotherapy or BRAF/MEK inhibitors in the 3-month perioperative time period. This cohort was then analyzed by receipt of focal radiotherapy, including SRS and brachytherapy, for resection cavity failure, distant CNS progression, and adverse radiation effect, using the Kaplan Meier method.

RESULTS

From 2011-2020, 43 resections for melanoma brain metastases were performed, of which 29 patients and 37 resection cavities met criteria for analysis. Median MRI follow up was 15 months (IQR: 6-38). Twenty-two (59%) lesions were treated with focal radiotherapy and systemic therapy, and 15 (41%) were treated with systemic therapy alone. 12-month freedom from local recurrence was 64.8% (95% CI: 42.1-99.8%) for systemic therapy alone, and 93.3% (95% CI: 81.5-100%) for focal radiotherapy with systemic therapy (p=0.01). 12-month CNS progression free survival was 35.7% (95% CI: 17.7-72.1%) for systemic therapy alone, and 31.8% (95% CI: 17.3-58.7%) for focal radiotherapy (p=0.51). UVA demonstrated focal radiotherapy (HR: 0.10; 95% CI: 0.01-0.85; p=0.04) was the only significant factor associated with reduction of risk for surgical cavity recurrence.

CONCLUSIONS

Use of focal radiotherapy with systemic therapy for resected melanoma brain metastases significantly reduced surgical cavity recurrence compared to systemic therapy alone. Focal radiotherapy did not delay initiation of systemic therapy and should be the preferred treatment option for optimal local control of the surgical cavity in melanoma brain metastases.
RADT-06. VOLUME KINETICS FOLLOWING TWO-SESSION GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES (BM)
Authors: Damron Ethan , Esquenazi Yoshua , Tandon Nitin , Yu Tse-Kuan , Chafi Hatim , Martir Magda , Khwaja Shariq , Amsbaugh Mark , Blanco Angel
Published: December 2020

INTRODUCTION

Resection is a well-established treatment for BM ≥ 2 cm, albeit with potential for perioperative complications and delays in systemic treatment. Staged stereotactic radiosurgery (S-SRS) may improve outcomes versus traditional SRS, representing an alternative to surgery in responders. We reviewed institutional outcomes using 2-session S-SRS, focusing on lesion volume kinetics.

METHODS

25 patients with 27 lesions underwent S-SRS at our institution between 2014 and 2020. Tumor volumes (TV) were measured at both S-SRS sessions and on follow-up MRI studies.

RESULTS

Median age at S-SRS was 61 years (range (r:) 31–84). Nine patients (10 BM) were lost to follow-up. Two patients failed to receive their second S-SRS due to local progression. The median margin tumor doses at first and second S-SRS were 15 Gy (r: 12–18 Gy) and 15 Gy (r: 12–16 Gy). The median interval between stages was 32 days (r: 8–63), and median TV at the first and second stages were 9.3 cm3 (r: 1.5–34.7 cm3) and 3.3 cm3 (r: 0.76–26.1 cm3), respectively. The median absolute and relative decrement between S-SRS sessions was 3.7 cm3 (r: 2.8-16.5 cm3) and 49.5% (r: 17.1-87.1%), respectively. [1-2]-month, [3-5]-month, and [6-12]-month MRI scans were available for 17, 10, and 15 lesions. The median decrease in TV compared to baseline was 50.2%, 78.2%, 74.9%. Two of 17 lesions (12%) had initial control but subsequently experienced volumetric progression and required resection. There were no G3+ adverse events (AE). Crude tumor control was achieved in 14 of 17 individual lesions (82%).

CONCLUSION

Two-session S-SRS is an effective treatment modality for treating patients with large BM, which is feasible in over 80% of patients with sustained tumor control and early volumetric regression.
RADT-07. STEREOTACTIC RADIOSURGERY OF PATIENTS WITH BRAIN METASTASES AND POOR PROGNOSIS
Authors: Harat Maciej , Blok Maciej , Kowalewska Joanna , Miechowicz Iza
Published: December 2020

PURPOSE/OBJECTIVE(S)

Stereotactic radiosurgery (SRS) in patients with risk factors other than the number of intracranial metastases remains controversial. Here we define factors related to early death after SRS alone and compared SRS alone with WBRT in high-risk patients. The aim of our study was to verify if optimal brain treatment may extend survival in patients with poor prognosis and select optimal candidates.

MATERIALS AND METHODS

In this prospectively collected data, 180 patients with brain metastases and adverse prognostic factors not previously treated with WBRT were analyzed. SRS patients were divided into training (n=82) and validation (n=48) cohorts and compared to retrospective data of WBRT patients (n=50). Overall survival (OS) and probability of 3-month survival in relation to risk factors were defined by univariable and multivariable analyses.

RESULTS

In multivariable analysis, GPA (OR 0.44, 95%CI 0.21-0.95; p=0.001), extensive extracranial disease (OR 0.13, 95%CI 0.02-0.66; p=0.013), and serious neurological deficits (OR 0.13, 95%CI 0.04-0.45; p=0.001) were associated with early death. If one factor was favorable, 73% (training) and 92% (validation) of patients survived 3 months. Patients with coexisting GPA< 2, serious neurological deficits, and extracranial extensive disease had the highest risk of death within 3 months (AUC 0.822 training; 0.932 validation). Median survival of the WBRT and SRS cohorts was 86 days (interquartile range (IQR): 38-172 days) and 201 days (IQR: 86-not reached), respectively (p< 0.0001). OS in very high-risk patients (GPA< 2) was significantly longer in the SRS vs. WBRT group (123 vs. 58 days; p=0.008).

CONCLUSIONS

Extracranial oligometastatic disease, intact neurological status, or GPA ≥2 should be present to justify SRS in patients with 1-10 brain metastases. SRS alone is a viable treatment option in comparison to WBRT and most importantly survival benefits may be expected even for high-risk patients (GPA< 2).
RADT-12. DISEASE CHARACTERISTICS IN ACUTE SEIZURE FOLLOWING RADIOTHERAPY FOR BRAIN METASTASES
Authors: Levin-Epstein Rebecca , Tenn Stephen , Ruan Dan , Lahlaf Safiya , Chu Brian , Lee Seung , Steinberg Michael , Yang Isaac , Pouratian Nader , Kim Won , Hegde John , Kaprealian Tania
Published: December 2020

INTRODUCTION

Acute seizure following radiotherapy (RT) for brain metastases is an infrequent but significant adverse event that has not been well-described. Prophylactic antiepileptic drug (AED) or steroid therapy is not recommended for asymptomatic lesions. However, there is minimal data incorporating individualized factors into acute seizure risk-assessment with respect to RT.

METHODS

We retrospectively examined patients treated for brain metastases with any RT modality from 2013-2020 who experienced acute post-treatment seizure, which we defined as within 4 weeks post-RT.

RESULTS

Twenty patients experienced acute seizure at median 2 days post-treatment (range 0-27); 15 (75%) within 7 days and 7 (35%) on day 0 (radiosurgery date or during fractionated RT). Seizures occurred after radiosurgery (n=9, 45%), fractionated stereotactic RT (n=3, 15%), whole-brain RT (n=5, 25%), and post-operative RT (n=3, 15%). All RT encompassed at least one supratentorial lesion; 11 (55%) had >1 lesion treated. Median lesion size was 23mm (range 7-51mm). Moderate-to-severe perilesional edema was present in 12 (60%) and hemorrhage in 8 (40%) cases. Seizures occurred despite AED therapy in 8 (40%) overall; 5/8 (63%) were hemorrhagic and 7/8 (88%) had moderate-to-severe edema. Nine (45%) patients receiving steroids developed seizures. Primary pathologies were: melanoma (5), non-small cell lung (5), renal cell carcinoma (4), breast (3), colon (1), Merkel cell (1), and thyroid (1). Patients with melanoma who developed acute seizure had mainly non-hemorrhagic (80%), small lesions (median 9mm), not receiving AED (0%) or steroid (20%) therapy.

CONCLUSIONS

In acute post-RT seizure, lesions were predominantly supratentorial, >23mm, and had moderate-to-severe edema. Breakthrough seizures were common in edematous and/or hemorrhagic lesions. However, acute seizure also occurred with smaller, non-hemorrhagic melanoma lesions not receiving AED therapy. A larger series is needed to further evaluate these identified characteristics in acute seizure, and whether prophylactic therapy may be appropriate.
RADT-14. COMPARISON OF MACHINE LEARNING ALGORITHMS IN DISTINGUISHING RADIATION NECROSIS FROM PROGRESSION OF BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY (SRS)
Authors: Chen Xuguang , Parekh Vishwa , peng Luke , Chan Michael , Soike Michael , McTyre Emory , Jacobs Michael , Kleinberg Lawrence
Published: December 2020

PURPOSE

To test the effectiveness of machine learning algorithms in distinguishing radiation necrosis (RN) from tumor progression (TP) using MRI radiomic features.

METHODS

Brain metastases were treated with SRS to a median dose of 18Gy. Lesions that showed evidence of progression on follow-up MRI were sampled surgically, and diagnoses confirmed by histopathology. Cases from 2 institutions were combined and randomly assigned for training (70%) and testing (30%). T1 post-contrast (T1c) and T2 fluid attenuated inversion recovery (T2 FLAIR) MRI were used for radiomic feature extraction (50 features each). Three subsets of radiomic features were obtained and tested: Signature #1 included 10 previously published features that correlated with diagnosis on T test; signature #2 and #3 included 5 and 12 features obtained through recursive elimination using random forest (RF) and support vector machine (SVM), respectively. Supervised machine learning models were trained using RF, SVM (radial kernel) and regularized discriminant analysis (RDA) algorithms based on all three radiomics signatures. Receiver operator characteristics (ROC) were compared between signatures and algorithms.

RESULTS

A total of 135 individual lesions (37 RN and 98 TP) were included. Signature #3 demonstrated the highest area under the curve in the training set (average AUC=0.98, vs 0.95 and 0.92 for signature #1 and #2), as well as the testing set (average AUC=0.83, vs 0.74 and 0.79 for signature #1 and #2). RF and SVM demonstrated similar performance in both training (average AUC 0.99-1) and testing datasets (average AUC 0.79-0.80) among all three signatures. Both RF and SVM were superior to RDA in performance (average training AUC 0.83, testing AUC 0.77). The greatest sensitivity (83%) and specificity (100%) in the testing set were achieved using signature #3 and SVM.

CONCLUSION

RF and SVM are effective in distinguishing RN from TP in a multi-institution dataset using radiomic signatures.
RADT-21. NATIONAL PRACTICE PATTERNS AND OUTCOMES OF STEREOTACTIC BODY RADIOTHERAPY VS. CONVENTIONAL EXTERNAL BEAM RADIOTHERAPY FOR SPINAL METASTASES
Authors: Lak Asad , Lamba Nayan , Smith Timothy , Iorgulescu Bryan
Published: December 2020

INTRODUCTION

Up to 10% of cancer patients experience spinal cord compression from metastatic disease. Palliation and local control were traditionally pursued with conventional external beam radiotherapy (cEBRT), but advancements in image-guidance and intensity-modulation for stereotactic body radiotherapy (SBRT) have dramatically changed the management of these lesions. Herein we evaluate the national practice patterns and outcomes associated with cEBRT vs. SBRT.

METHODS

U.S. patients newly diagnosed with metastatic cancer necessitating RT to the spine were identified from the National Cancer Database (2004-2016), stratified by RT modality and cancer type, and evaluated using multivariable logistic regression and Cox proportional hazards.

RESULTS

34,759 U.S. patients required spinal RT within 3 months of initial stage 4 cancer presentation, primarily for lung adenocarcinoma (25%), lung small cell carcinoma (14%), and prostatic (12%) metastases. Patients overwhelming received cEBRT (30Gy/10; 50%), followed by hypo-fractionated SBRT (15-30Gy/2-6; 11%) and single-fraction SBRT (i.e. stereotactic radiosurgery, SRS; 15-24Gy/1; 0.9%); whereas 38% received another regimen (e.g. 30-37.5Gy/12-15 or 40Gy/20). From 2004→2016, the rates of single-fraction SRS (0.4→1.9%) and hypo-fractionated SBRT (13.1→23.6%) increased, whereas cEBRT (86.5→74.4%) decreased. SBRT was significantly more likely to be utilized at academic hospitals as compared to cEBRT (OR 0.57; 95% CI: 0.49-0.66; p< 0.01). SBRT was more likely utilized for elderly or high comorbidity patients and varied across cancer types. Survival analysis indicated that across all cancer types, single-fraction SRS, was independently associated with improved overall survival compared to cEBRT (HR 1.51; 95%CI: 1.31-1.74; p< 0.01) after adjusting for patient characteristics, care setting, tumor type and systemic treatment.

CONCLUSIONS

Through analysis of cancer registry data, we found that practice patterns of RT for spinal metastases have been evolving nationally, with an increase in the use of SBRT. Single-fraction SBRT was associated with improved adjusted OS. Notably, we found that utilization of SBRT lags in the community setting.
RADT-22. RE-IRRADIATION FOR RECURRENT GLIOBLASTOMAS (GBM)
Authors: Moro Mario
Published: December 2020

AIMS

In this report, we describe our experience in dealing with recurrent GBMs in terms of efficacy and toxicity of second RT course (re-RT) with 3DCTR or VMAT protocols. We carefully reviewed our patient’s outcomes and additionally performed a comprehensive and updated meta-analysis of recent recurrent re-RT GBMs literature to compare our results with the ongoing findings of the t studies.

METHODS

We retrospectively collected data between 2017 and 2020 at our Institution. Also, we used the random-effects model to pool outcomes across studies about re-RT GBMs from the recent literature (prospective studies from 2010 to 2020, ≥ 30 patients, re-RT with 3DCTR or IMRT-VMAT) to have a more homogenous cohort in terms of treatment modalities, thus reducing the selection bias.

RESULTS

Re-irradiation was performed at a median interval time of 13.5 (range 4 - 192 months) months from the first RT. The median re-RT dose was 18 Gy (range 12–36 Gy), and the median fraction size was 3,45 Gy (range 1,8–6 Gy). The total median equivalent dose (EQD2) was 84 Gy (range 65.7 – 110 Gy). Our cohort median PFS is 12.5 months (range 4 – 192 months), while the median OS was 26 months (range 6 – 213 months). Our results show that OS-6 and OS-12, from time of re-irradiation, to be 69.2% and 30.7% respectively and the PFS-6 and PFS-12 to be 76.9% and 23.0%, respectively. None of our patients experienced acute toxicity. In our literature research, we found 22 eligible studies, including 1065 patients. The results of the pooled outcomes were: OS-12 rate 35% (95% CI: 30–40%), PFS-12 rate 16% (95% CI 13–19%), and Grade 3 + AE rate < 5% (95% CI 0–10%).

CONCLUSIONS

Our data confirm re-RT is safe and feasible treatment with a limited toxicity for salvage treatment in recurrent GBMs.
RADT-29. EFFECT OF RADIATION THERAPY ON OVERALL SURVIVAL FOLLOWING SUBTOTAL RESECTION OF ADULT PILOCYTIC ASTROCYTOMA
Authors: Khalafallah Adham , Jimenez Adrian , Brem Henry , Mukherjee Debraj
Published: December 2020

BACKGROUND

Pilocytic astrocytoma (PCA) is a low-grade glioma common in children but also rarely diagnosed in adults. The role of adjuvant radiation therapy (RT) in treating these tumors remains unclear.

OBJECTIVE

We investigated the effect of RT on overall survival, specifically among adult patients who had undergone subtotal PCA resection.

METHODS

Information on adult patients (age 18 years old) who had undergone subtotal PCA resection between 2004 and 2016 was collected from the National Cancer Database (NCDB). A multivariate Cox proportional hazards model was utilized to determine factors independently associated with overall survival.

RESULTS

A total of 451 patients were identified. The mean age of our patient cohort was 36.8 years old, and the majority of patients (83.4%) did not receive radiation treatment following subtotal PCA resection. Overall median survival was 93.8 months. Survival was longer (p < 0.001) in the patients who did not receive post-surgical RT (median: 98.3 months) compared to patients who did (median: 54.8 months). Patients who had older age at diagnosis (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.03-1.07, p < 0.01), were Black or African American (HR=2.76, CI=1.12-6.46, p=0.019), received radiation during their initial treatment (HR=4.53, CI=2.08-9.89, p < 0.01), or had a Charlson/Deyo score of > 1 (HR=3.68, CI=1.55, p=0.003) had a significantly higher risk of death following subtotal PCA resection.

CONCLUSION

Postoperative RT is independently associated with a significantly higher risk of death among adults who underwent subtotal PCA resection. Our findings provide a rationale for further investigation into the efficacy and safety of RT within this patient population.
RADT-34. PREDICTIVE FACTORS FOR OVERALL SURVIVAL IN SURGICAL CASES OF GLIOMATOSIS CEREBRI FROM THE NATIONAL CANCER DATABASE
Authors: Khalafallah Adham , Kopparapu Srujan , Mukherjee Debraj
Published: December 2020

Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI]=11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p=0.01) while radiation therapy (p=0.07) and extent of resection (p=0.48) did not. On multivariate analysis, older patients (hazard ratio [HR]=1.07, CI=1.03-1.11, p< 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR=3.47, CI=1.40-8.60, p< 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.
RADT-37. THE IMPACT OF POSTOPERATIVE RADIATION THERAPY (PORT) AND EXTENT OF SURGERY ON CLINICAL OUTCOMES OF ATYPICAL MENINGIOMA (AM): A META-ANALYSIS
Authors: Haddad Philip , Akhtar Furqan , Gallagher Kevin
Published: December 2020

BACKGROUND

Although meningiomas are among the most prevalent types of brain tumors, AMs account for around 4% of all meningiomas. AMs tend to be more aggressive with relatively higher rates of recurrence and mortality. Gross total resection (GTR) has been the standard of care when possible. However, GTR itself is not always enough to prevent the recurrence of AMs. The role of PORT remains controversial in AM as the comparative studies to support its use have provided conflicting RESULTS: The purpose of this meta-analysis is to evaluate the impact of PORT on clinical outcomes according to the extent of resection in AMs.

METHODS

A review of the medical literature was conducted using online databases. Inclusion criteria consisted of AM diagnosis, English language, Simpson graded resections, and comparative studies reporting recurrence rates (RcR), Progression-Free Survival (PFS), and Overall Survival (OS) with hazard ratios (HR) or Kaplan-Meier curves. A meta-analysis was conducted using an inverse variance method with a random-effects model.

RESULTS

Twenty-two comparative studies with a total of 5,129 patients were included and analyzed. When GTR was attained, PORT was associated with improved RcR (HR =0.72, 95%CI:0.59-0.86) and PFS (HR=0.77, 95%CI:0.65-0.90), but not OS (HR=0.93, 95%CI:0.83-1.04). When subtotal resection (STR) was attained, PORT was associated with improved PFS (HR=0.35, 95%CI:0.26-0.48) as well as OS (HR=0.70, 95%CI:0.54-0.89). The extent of surgery also impacted AM outcomes as GTR demonstrated superior PFS (HR=0.45, 95%CI:0.31-0.65) and OS (HR=0.30, 95%CI:0.13-0.72).

CONCLUSIONS

This is the first meta-analysis to show that PORT is associated with PFS benefit in AMs with GTR and STR. Moreover, PORT significantly improved OS of AMs that underwent STR but had no impact on OS when GTR was achieved. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of PORT in this patient population.
RADT-39. 68Ga- DOTATATE CT/PET FOR GAMMA KNIFE RADIOSURGERY PLANNING AND TARGET DELINEATION IN PATIENTS WITH MENINGIOMA
Authors: Ma Daniel , Rana Zaker , Viswanatha Sirisha , Potters Louis , Chang Jenghwa , Schulder Michael , Goenka Anuj
Published: December 2020

BACKGROUND

Stereotactic radiosurgery (SRS) planning for patients with meningiomas can be confounded by difficulty in identifying the tumor boundary, especially in those who have had prior surgery. Recent data have suggested the benefit of 68Ga-DOTATATE CT/PET scans in delineation of meningioma compared to MRI alone. We propose that incorporating 68Ga-DOTATATE PET scans in addition to MRI in SRS planning will provide better target identification and tumor coverage compared to MRI alone.

METHODS

We reviewed patients with meningioma who had MRI and 68Ga-DOTATATE PET imaging over 12 months. Images were imported into Velocity treatment planning software and separated into two different sessions, one in which only the MRI was accessible, and a second which had the PET scan fused to the MRI. Three different users were asked to contour the residual meningioma as gross tumor volume (GTV) first with MRI alone, and then with the PET/MRI fusion. The volume of each GTV pre-and post-PET fusion was compared and a Dice index was generated.

RESULTS

Four patients with 6 GTV targets were identified. PET fusion identified new lesions close to the initial GTV targets in 2 patients. The first was a discontinuous dural lesion in the post-op bed. The second was a nodular dural lesion along the left high parietal convexity adjacent to a prior craniectomy and mesh duraplasty site. In the third patient, PET scan identified a greater extent of disease in the skull base. Across all observers, GTV volumes were significantly increased when PET fusion was used. The average volume (cc) increase was 111.6%±66.2%. The average Dice index was 0.58±0.17.

CONCLUSION

68Ga-DOTATATE PET scan fused with MRI improved the visualization of meningiomas in patients undergoing SRS. A larger experience is needed to confirm this trend. We have begun to use DOTATATE-PET imaging regularly when imaging patients with meningiomas for SRS.
RADT-44. STEREOTATIC RADIOSURGERY FOR RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS AFTER CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY
Authors: Lai Mingyao , Li Juan , Hu Qingjun , Zhou Jiangfen , Zhen Junjie , Wen Lei , Cai Linbo
Published: December 2020

OBJECTIVE

To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy.

METHODS

The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter > 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined.

RESULTS

The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP＞500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy.

CONCLUSION

SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the combination of conventional radiotherapy and SRS warrants further investigations in a large-scale randomized controlled clinical trials.
RBIO-01. PROSPECTIVE OBSERVATIONAL STUDY TO DETERMINE THE IMMUNE SYSTEM RESPONSE TO GAMMA KNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS
Authors: Silverman Joshua S , Gurewitz Jason , Gunter Courtney , Cooper Benjamin , Palermo Amy , Boulio Lynda , Schafrick Jessica , Lim Whei Ying , Karhan Ece , Renzullo Stephanie , Kozhaya Lina , Golfinos John , Sulman Erik , Unutmaz Derya , Kondziolka Douglas
Published: December 2020

INTRODUCTION

The effects of radiosurgery for primary intracranial tumors on systemic immune response are unknown. Vestibular schwannomas (VS) treated with Gamma Knife (GK) have high control rates and low risk of adverse effects. This study examines if radiosurgery for VS is associated with an immune response detectable by peripheral blood sampling, and if that response can be correlated with tumoral expansion and/or toxicity.

METHODS

50 patients treated with GK for VS were enrolled on an IRB-approved, prospective study at initial consultation. Blood samples were drawn preceding GK and 6 months and 1 year follow-up. Neurological and hearing outcomes were assessed. Tumor volume was measured at treatment, 6 months, and 1 year follow-up. Tumoral expansion (TE) was defined by volumetric increase >20%. Immunophenotyping via multicolor flow cytometry panels evaluated lymphoid and myeloid differentiation, phenotypic characterization, activation, tissue homing, and immune exhaustion.

RESULTS

Median volume at radiosurgery was 0.55cc (range 0.04-11.94) and median margin dose was 12.5Gy (11.5-13) prescribed to the 50% isodose line (50-60). 22 tumors exhibited TE, 20 at six months and 2 at one year. No VS with TE grew at median follow-up of 30.8 months (9.8-52.8). 1 tumor, non-expanding (NE) post-GK, showed progression at 24 months. Presence of cranial neuropathy and hearing decline was similar in both groups. Immunophenotyping showed numerous significant (p< .05) changes in the TE group, not seen in NE, at 6 months and 1 year follow-up compared to baseline. Major changes were observed in cytokine secretion (e.g. IFNg, TNF or IL-17) of CD4+ and CD8+ memory T cells, frequencies of regulatory T cells, increased death of CD8+ effector cells in culture, suggesting chronic activated state.

CONCLUSION

Vestibular schwannomas that expand after GK are associated with a peripherally measurable change in systemic immune response that is absent from non-expanding tumors. The biologic underpinnings of these findings require further study.
RBIO-03. HETEROGENEITY OF HUMAN PATIENT-DERIVED XENOGRAFTS GROWTH RATES RESPONSES TO THE RADIATED MICROENVIRONMENT
Authors: zhang Jibo , Olson Ian E , Carlstrom Lucas P , Rahman Masum , Rajani Karishma , Gupta Kshama , Liu Libo , Tang Zhi , Sananikone Eliot F , Dong Anqin Dong , Warrington Arthur E , Rodriguez Moses , Chen Jincao , Schroeder Mark A , Ikram Samar , Sarkaria Jann , Burma Sandeep , Burns Terry C
Published: December 2020

BACKGROUND

Radiotherapy, combined with surgical resection and chemotherapy, remains a first-line treatment for infiltrative gliomas. However, these tumors are not surgically curable, and often recur, even within the prior radiation field, and may demonstrate a more aggressive phenotype. Importantly, high grade gliomas display diverse molecular phenotypes, and whether this genetic variability leads to divergent behaviour in the radiated tumor microenvironment is unknown. Herein, we characterize the effects of the irradiated brain microenvinroment on nine additional unique GBM cell lines to better understand the nuances of how tumor molecular phenotypes influence cellular dynamics.

METHODS

Female athymic nude mice were randomly divided into cranial radiation (15 Gy) and non-radiated groups. Mice then underwent intracranial implantation with one of the selected patient-derived xenograft (PDX) GBM cell lines (GBM 6, 10, 12, 39, 46, 76, 123, 164, 196; total n=8-15, per group, per line). Kaplan-Meyer (K-M) and log-rank tests were performed to compare the survival between irradiated and non-irradiated groups.

RESULT

Of nine previously untested human GBM lines, we found that five demonstrated shorter survival in the pre-radiated brain (GBM 6, 46, 76, 164, 196). However, two lines yielded prolonged survival in the pre-radiated brain (GBM 10, 12); GBM 39, 123 whose rate of growth was not impacted by the radiated brain.

CONCLUSION

These results highlight the likely critical impact of the irradiated microenvironment on tumor behaviour, yet illustrate that different tumors may exhibit opposing responses. Although further evaluation will be needed to understand mechanisms of divergent behavior, our data suggest the increased rate of growth in the radiated microenvironment may not apply to the fastest-growing tumor lines, which could instead demonstrate a paradoxical response.
RBIO-05. MITOTIC ENRICHMENT AS AN EFFICIENT STRATEGY TO RADIOSENSITIZE GLIOBLASTOMA
Authors: de Gooijer Mark C , Slangen Paul L G , Çitirikkaya Ceren H , Çolakoğlu Hilal , El Ouazani Amal , Shah Ronak , Borst Gerben R , van Tellingen Olaf
Published: December 2020

Their location and highly aggressive nature renders glioblastoma (GBM) among the most deadly and devastating of human malignancies. Despite extensive treatment involving surgery and adjuvant chemo-radiotherapy, the prognosis is still dismal and novel treatment strategies are urgently needed. Of all existing adjuvant therapies, radiotherapy contributes the most to extending the median overall survival. Increasing the efficacy of existing radiotherapeutic regimens is therefore a logical avenue to improve the survival of GBM patients. We have developed a novel radiosensitization strategy called ‘induction of mitotic enrichment’. It has long been known that the radiosensitivity of a cell depends on the phase of the cell cycle and that especially mitotic cells are especially vulnerable. Enriching the tumor for mitotic cells by arresting them during division prior to each radiotherapy fraction should therefore render the tumor population more sensitive to irradiation. Ideally, induction of mitotic enrichment should be reversible and non-cytotoxic to prevent healthy tissue toxicity and be compatible with clinically applied hyperfractionated radiotherapy regimens. We have now identified an orally available targeted tubulin polymerization inhibitor that can achieve repeated and reversible mitotic enrichment for up to 10 hours prior to radiotherapy, without causing cytotoxicity in vitro or healthy tissue toxicity in vivo. Most importantly, this tubulin inhibitor efficiently radiosensitizes a range of preclinical GBM models in vitro and in vivo, including GSC models, and significantly improves survival, but only in a mitotic enrichment setup when given 6-8 hours prior to radiotherapy to allow accumulation in mitosis. We are currently expanding our preclinical development of mitotic enrichment as a radiosensitization strategy to other mitotic targets and different intra- and extracranial cancer models representing several diseases for which radiotherapy is a mainstay treatment. In parallel, we are preparing a phase 0 trial to demonstrate induction of mitotic enrichment in human GBM.
RTID-03. A PHASE I CLINICAL TRIAL TO EVALUATE MTD OF PERAMPANEL AND MEMANTINE IN COMBINATION WITH STANDARD CHEMORADIOTHERAPY FOR THE TREATMENT OF PATIENTS WITH NEWLY DIAGNOSED GBM –A STUDY DESIGN
Authors: Kong Xiao-Tang , Albala Bruce , Du Senxi , Hrachova Maya , Bota Daniela
Published: December 2020

BACKGROUND

Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults with poor prognosis. Effective treatment is urgently needed. Recent studies demonstrated cross-talk between neuron and glioma through neuro-transmitter glutamate receptors (AMPA and NMDA receptors) promotes glioma invasion and progression in vitro and in vivo. Therefore, dual blocking AMPA and NMDA receptor therapy is a potential strategy to prevent and treat GBM progression, particularly given the fact that the two blockers act through different anti-glioma mechanism. OBJECTIVE/

HYPOTHESIS

We hypothesize that adding Perampanel (an AMPA receptor blocker) and Memantine (a NMDA receptor antagonist) to standard temozolomide plus radiation therapy for the treatment of newly diagnosed GBM patients may be well tolerated and have a safe profile to prevent tumor progression, seizure recurrence or cognition impairment from radiation.

STUDY DESIGN

3 + 3 DESIGN: Maximum Tolerated Dose (MTD) is dose level at which 0/3 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT. MTD will not be more than FDA approved maximized doses for Perampanel (12 mg daily) and Memantine (20 mg bid) for the treatment of neurological diseases. Once the MTD is found, the patient will continue at MTD for the completion of concurrent chemoradiation therapy plus completion of 6 cycles of adjuvant temozolomide therapy.

A Phase I trial to study the safety and toxicity of combined Perampanel and Memantine with standard chemo-radiation therapy to treat patients with newly diagnosed glioblastoma (GBM). To find Maximum Tolerated Dose (MTD) Levels of Perampanel and Memantine at concurrent chemoradiation therapy phase and adjuvant chemotherapy phase to prepare for future phase II or III trial.
RTID-11. GBM AGILE: A GLOBAL, PHASE 2/3 ADAPTIVE PLATFORM TRIAL TO EVALUATE MULTIPLE REGIMENS IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA
Authors: Buxton Meredith , Alexander Brian , Berry Donald , Cavenee Webster , Colman Howard , de Groot John , Ellingson Benjamin , Gordon Gary , Khasraw Mustafa , Lassman Andrew , Lee Wenbin , Lim Michael , Mellinghoff Ingo , Perry James , Sulman Erik , Tanner Kirk , Weller Michael , Wen Patrick , Yung W K Alfred , Cloughesy Timothy , Investigators G B M Agile
Published: December 2020

Developing new therapies for patients with glioblastoma (GBM) requires focused interaction between industry, academia, nonprofits, patient advocacy, and health authorities, and novel approaches to clinical trials. GBM Adaptive Global Innovative Learning Environment (GBM AGILE) Trial was designed by over 130 global key opinion leaders in consultation with health authorities to provide an optimal mechanism for phase 2/3 development in GBM. The Sponsor of GBM AGILE is the Global Coalition for Adaptive Research, whose mission is to accelerate the development of treatments rare and deadly diseases by serving as sponsor of innovative trials. GBM AGILE is an international platform trial designed to evaluate multiple therapies in newly diagnosed and recurrent GBM. Its goals are to identify effective therapies for GBM and match effective therapies with patient subtypes, with data generated to support regulatory filing for new drug applications. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. The primary endpoint is overall survival. The trial is being conducted under a master Investigational New Drug Application/Clinical Trial Agreement and Master Protocol, allowing multiple drugs from different companies to be evaluated simultaneously and/or over time. The plan is to add experimental therapies as new information is identified and remove therapies as they complete their individual evaluation against a common control. GBM AGILE received IND approval from the FDA in April 2019, screening its first patient in June 2019. As of June 2020 over 200 patients have been screened. Expansion to Canada, Europe, China, and Australia is also underway. There is currently one investigational arm under evaluation in the trial, with two additional arms to be added in Q4 2020/ Q1 2021. Clinical trial information: NCT03970447.
STEM-02. IN VIVO PHAGE DISPLAY IDENTIFIES PEPTIDE TARGETING N-CADHERIN ON GLIOMA STEM CELLS
Authors: Potez Marine , Kim Jongmyung , She Chunhua , Chaudhary Neelkamal , Liu James
Published: December 2020

Glioblastoma (GBM) is the most aggressive primary brain tumor with high mortality rates and resistance to conventional therapy. Glioma stem cells (GSCs) comprise a sub-population of glioma tumor cells with the ability of self-renewal and tumor recapitulation, and may be responsible for GBM’s treatment resistant properties. Identification of surface receptors that are novel and specific to GSCs may be the key to the development of effective therapeutic strategies. We have selected a GSC specific targeting peptide isolated through in vitro and in vivo phage display biopanning. This screening technique allowed us to determine a peptide (GBM-IC2) which binds specifically to GSCs in vitro, and to GBM tissue in vivo. Although this screening process allows for isolation of cell specific targeting peptides, it does so without identification of the cellular binding partner. Given the specificity of the peptide, identification of the cellular receptor may allow for discovery of novel markers to identify GSCs. To identify the peptide binding partner of GBM-IC2, the biotinylated peptide was incubated with GSC protein lysate. The peptide, along with its binding partner, was isolated using streptavidin agarose resin. The binding partner protein was then identified using mass spectroscopy. This revealed N-cadherin (CDH2) as a potential binding partner for the GBM-IC2 peptide. GBM-IC2 demonstrated specificity for targeting CDH2 compared to control peptide using ELISA. Lentiviral induced overexpression of CDH2 in HEK293 cells allowed for GBM-IC2 peptide binding. Competition assay was performed by applying anti-CDH2 antibody to GBM-IC2 peptide and GSCs in culture. Application of anti-CDH2 antibody decreased peptide binding to GSCs, confirming CDH2 as the binding partner for GBM-IC2. These results demonstrate that cell specific targeting peptides isolated through phage display may lead to the isolation of novel cell specific proteins through immunoprecipitation isolation and mass spectroscopy analysis.
STEM-04. PLATELETS DRIVE GLIOBLASTOMA ONCOGENESIS BY ENHANCING THE GLIOMA STEM CELL PHENOTYPE
Authors: Sloan Anthony , Lee-Poturalski Christine , Elder Theresa , Harris Peggy , Cioffi Gino , Raghavan Alankrita , Willis John , Rich Jeremy , Kerstetter-Fogle Amber , Barnholtz-Sloan Jill S , Jankowsky Eckhard , Sloan Andrew E
Published: December 2020

Glioblastoma (GBM) is recognized as one of the deadliest forms of cancer, despite aggressive therapy consisting of maximal surgical resection followed by concurrent radiation and chemotherapy, the median survival remains ~12 months. Glioma stem cells (GSCs) possess potent tumor-initiating properties and comprise a cellular hierarchy that is responsible for treatment resistance and progression. Specifically targeting GSCs has been considered a promising therapeutic approach, however no clear method has been identified. Histologically, it is known that GSCs are found in perivascular and pseudsopalisading regions of GBM. Similarly, platelet aggregates are often found in pseudsopalisading necrotic regions, suggesting a potential interaction between platelets and GSCs due to their spatial locations. High platelet counts have been associated with poor clinical outcome in many cancers including ovarian and endometrial cancer. While platelets are known to affect progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Our work aimed to understand the crosstalk between GSCs and platelets within GBM solid tumors that work to enhance disease progression and treatment resistance. Our clinical studies suggest elevated platelet counts positively correlate with tumor growth and negatively correlate to overall patient survival. We found platelets and GSC co-localization in GBM solid tissue; platelet exposure to GSCs results in increased proliferation of GSCs specifically, by increasing the self-renewing capacity of GSCs in a dose dependent manner, and resulted in an increased “Stem-like” transcriptional pattern. Inhibiting the GSC-platelet interaction results in a decrease in GSC renewal and stemness. These results introduce a novel interaction between GSCs and platelets and elucidate a novel therapeutic approach specifically targeting GSCs by disrupting the GSC-platelet interaction.