bluuebunny/crossref_metadata_2025 huggingface dataset:
QOLP-14. FROM SYMPTOMS TO RADIOTHERAPY: A QUALITATIVE ASSESSMENT OF PATIENT EXPERIENCE IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA
Authors: Chainey Jonathan , Kim Michael , Chan Vivien Ka-Ying , Au Karolyn
Published: December 2020

INTRODUCTION

Considering the poor prognosis of high-grade gliomas, past studies focusing on the felt experience and supportive care needs of patients concentrated on the end-of-life period. Little is known on these subjects during the initial acute portion of the patient’s journey, from symptom onset, through surgery, to chemoradiation. This period is one of substantial anxiety for patients and their caregivers, and one during which they struggle to comprehend a large amount of information and navigate a complex situation.

METHODS

Adult patients with a new histopathological diagnosis of high-grade glioma who underwent radiotherapy participated in a semi-structured, face-to-face interview. Different segments of the patient’s journey were explored, with a focus on patient’s emotions, interactions with healthcare providers, satisfaction during the process and access to supports. Descriptive thematic analysis in the tradition of grounded theory was performed.

RESULTS

Fifteen patients (7 males, age 34-71 years) were interviewed, and four themes emerged from the analysis. First, information conveyed by the medical team was frequently disconnected from patients’ understanding regarding diagnosis and treatment. Second, specific events created a lasting impression that the medical system, and at times medical care providers, lacked empathy. Third, patients’ perceptions of shortcomings within the medical system led to decreased trust, particularly regarding the follow-up process. Finally, although respondents identified multiple inadequacies during their journey, they nonetheless acknowledged the great support and quality of services they received.

CONCLUSION

This study provides insight into patients’ experiences and perceived shortcomings of the medical system, from the time of presentation until the end of radiotherapy treatment in patients with new diagnosis of high-grade glioma. These findings should influence clinicians’ attitudes and guide systematic changes including delivery of information and the referral process.
QOLP-16. EFFICACY OF SCRAMBLER THERAPY (CALMARE®) FOR THE TREATMENT OF CHRONIC CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
Authors: Prakash Neal , Tran Rachel , Strain Elizabeth
Published: December 2020

BACKGROUND

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious consequence of cancer treatment that, for up to 30% of patients, persists beyond six months of completing chemotherapy. Scrambler therapy (ST) is a therapeutic modality with emerging evidence supporting its ability to diminish CIPN symptoms.

METHODS

Data was from a convenience sample of 24 CIPN patients (with symptoms between 1-240 months after platinum-based, taxane, or combination chemotherapy) completing 10 sessions of ST using the Calmare® device in the City of Hope Outpatient Physical Therapy Department. Patients were treated for ~45 minutes per session over 10 sessions. Patients received a standardized assessment pre- and post ST that included: EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20), mono-filament testing, pain intensity numerical rating scale, numbness scale, extensor hallicus longus strength, Timed Up and Go, Romberg, and single leg balance.

RESULTS

Regardless of length of symptoms, significant changes were seen in post-treatment assessment of quality of life as measured by the QLQ-CIPN-20 and numbness scale. Post-treatment QLQ-CIPN-20 total scores decreased by an average of 7.1 points (n= 24, p< .01). Numbness in the left lower extremity decreased by an average of 1 point of the 0-4 point scale (n=24, p=.0007) and 1.09 points on the right lower extremity (n=24, p < .0004). There was a trend towards improvements in pain, monofilament testing, single leg balance, and Romberg test, though they did not reach a level of significance. Surprisingly, only 3 of 24 patients reported pain related to their CIPN at the start of treatment.

CONCLUSION

For patients with CIPN, scrambler therapy improves numbness and improves quality of life measures. This suggests an important role for this treatment modality in cancer patients suffering from this debilitating condition.
QOLP-17. GROUP MEDICAL PLAY EFFECTIVELY IMPROVES HOSPITALIZATIONADAPTABILITY OF PEDIATRIC PATIENTS WITH NEUROTUMOR
Authors: Zhang Xing , Zhang Fuqiang , Lai Mingyao , Li Juan , Zhang Yangqiong , Zhou Cheng , Shan Changguo , Cai Linbo
Published: December 2020

OBJECTIVE

To explore the effect of group medical games on the hospitalization adaptability of pediatric patients with neuro tumor.

METHODS

pediatric patients with neuro tumor (age:6 to 13 years) who were treated in hospital from June to December 2019 and were hospitalized for 1 month to 2 months. 29 pediatric patients(mean age:9y) were selected as the control group and treated as usual; 26 pediatric patients(meanage:8y) were selected as the experimental group for group therapeutic play intervention. Interventions last Monday, Wednesday and Friday of each week, with an average duration of one hour. Group medical play include: medical picture book education, medical preview game, emotional games, social table games. Two groups completed self-made questionnaires at the time of admission and two weeks after admission, including: diet, sleep, compliance, and social status, hospital adaptation and other related issues, two groups completed a satisfaction questionnaire after two weeks of admission, recorded analysis and compared the difference of questionnaire data and satisfaction of the two groups of pediatric patients.

RESULTS

There was no statistical difference in age and sex between the two groups, and there was no significant difference in baseline RESULTS: The re-test results showed that the experimental group was significantly better than the control group in terms of social status, hospital adaptation, compliance and family satisfaction(p＜0.05).

CONCLUSION

Group medical games can effectively improve the adaptability, compliance and family satisfaction of pediatric with neuro tumor.
QOLP-19. INSOMNIA IN BRAIN TUMOR PATIENTS: ASSESSING NEEDS IN NEURO-ONCOLOGY
Authors: Willis Kelcie , Ravyts Scott , Lanoye Autumn , Loughan Ashlee
Published: December 2020

BACKGROUND

Insomnia is a prevalent consequence of cancer diagnosis and treatment. In primary brain tumor (PBT) patients specifically, insomnia has been rated as one of the most severe symptoms and linked with other negative side effects, such as increased fatigue and emotional distress. Despite these findings, research has consistently omitted PBT patients in understanding the detailed effects and treatment for insomnia.

METHODS

Adult PBT patients (N=74) completed anonymous surveys at routine neuro-oncology appointments at an NCI-designated academic medical center. The surveys included validated measures of insomnia (ISI & PSQI), fatigue (BFI), and other original items (e.g., How would you describe your feelings towards medication treatment for insomnia?). The current investigation aimed to assess: 1) the prevalence of clinically elevated symptoms of insomnia, 2) the relationship between sleep disturbance and daytime fatigue and distress, and 3) patients’ preferences for pharmacological and non-pharmacological treatment for insomnia in PBT patients.

RESULTS

Of the sampled PBT patients, 38% reported significant sleep disturbance as measured by the PSQI. Moreover, 23% endorsed clinically elevated, moderate-severe symptoms of insomnia as measured by the ISI. Excessive worrying (r =.31) and bad dreams (r =.29, p< .05) were both associated, though not predictive of insomnia severity (p >.05). Insomnia symptoms predicted increased fatigue severity, F(1,72) =52.60, β=.65, p< .001, R2 =.42. Of the patients with clinical insomnia, 59% felt that their symptoms were not well-managed by their medical team; 53% expressed interest in pharmacological treatment and 47% in non-pharmacological treatment.

CONCLUSIONS

The prevalence and consequences of insomnia identified in PBT patients are similar to that of other cancers, yet the majority of PBT patients with insomnia reported their symptoms were poorly managed. Though there was slight preference for pharmacological treatment, the sizeable proportion of those interested in non-pharmacological treatments warrants investigations into such therapies (e.g., CBT-I) in medical settings
QOLP-22. POSTTRAUMATIC GROWTH IN NEURO-ONCOLOGY
Authors: Kovalchick Laurel , Willis Kelcie , Brechbiel Julia , Lanoye Autumn , Husain Mariya , Aslanzadeh Farah , Braun Sarah , Parker Kyra , Loughan Ashlee
Published: December 2020

BACKGROUND

Posttraumatic Growth (PTG) refers to the positive psychological change following a trauma and may include a heightened appreciation for life, greater value in meaningful relationships, and/ or spiritual development. A brain cancer diagnosis may be experienced as a traumatic event given the high risk of tumor progression, lack of curative treatments, and ultimately unexpected disheartening prognosis; however, there is limited research on PTG in neuro-oncology. The aim of this study was to determine the profile of PTG in patients diagnosed with primary brain tumors (PBTs).

METHODS

Patients with PBTs (N = 53, Mage = 48.17, 52.8% male) completed the Post Traumatic Growth Inventory (PTGI) during routine neuro-oncology clinic visits. Descriptive statistics and frequencies for the five factors of the PTGI and PTGI total were calculated.

RESULTS

PTG was evident across all domains with the most growth reported in appreciation for life and the least growth in new possibilities. Most patients endorsed low levels of growth across the five factors; 29-49% of patients endorse moderate-to-high severity in at least one PTG domain. Lastly, the average total score (M = 46.10) of this sample met the established cutoff for moderate-to-high PTG (> 46).

CONCLUSIONS

The results suggest that patients with PBTs may perceive positive psychological growth following the traumatic event of a brain tumor diagnosis. Specifically, patients may experience a greater appreciation for life but relatively less growth in new possibilities, perhaps due to the poor prognosis of many PBTs. In non-CNS cancer populations, patients with higher PTG reported better quality of life and lower distress. Further research to expand our knowledge of PTG and the associated factors, including the demographic, medical, and psychological correlates, will better equip providers to promote positive change in PBT patients.
RADT-18. LONG-TERM FOLLOW-UP OF PATIENTS TREATED WITH GAMMA KNIFE® STEREOTACTIC RADIOSURGERY (GK-SRS) FOR VESTIBULAR SCHWANNOMA (VS)
Authors: Retzlaff Amber , Straza Michael , Bovi Joseph , Siker Malika , Friedland David , Harris Michael , Zwagerman Nathan , Albano Katherine , Wu Ruizhe , Banerjee Anjishnu , Schultz Christopher
Published: December 2020

PURPOSE

GK-SRS is an accepted definitive treatment option for appropriately selected patients with VS. To assess long-term outcomes in VS patients treated with GK-SRS, we retrospectively evaluated all patients treated at our institution from 2007-2019.

METHODS

For VS patients treated with GK-SRS from 2007-2019, clinical data (symptoms, physical exams, audiograms, and imaging) was collected via retrospective chart review at pre-treatment and standard follow-up intervals (6 weeks, 6 months, 12 months, then annually). Descriptive analyses, including the proportions of patients in different grades of clinical parameters, are reported. For each clinical parameter, only patients with both pre- and post-treatment data were included in the evaluation set used for analysis.

RESULTS

Of 177 patients identified, 46 were excluded from the evaluable set (age < 18 years, prior resection, NF-2, or no follow-up). Among the remaining 131, median follow-up was 42 months (6 weeks to 11 years), and 36.6% completed 5+ years of follow-up. At time of treatment, median age was 61 years, and median Karnofsky Performance Score was 90. 58.0% of lesions were left-sided, and 42.0% were right-sided. The majority were Koos grade II (37.4%) or III (38.2%); the remainder were grade I (13.0%) or IV (11.5%). Pre-treatment central necrosis and ventriculomegaly were present in 39.7% and 4.6%, respectively. Following treatment, audiogram analysis with Gardner-Robertson Hearing Score demonstrated no change in 48.9%, some level of decline in 47.8%, and improvement in 3.3% at last follow-up. 97.7% had House-Brackmann scores of I at diagnosis; the remainder were House-Brackmann II. House-Brackmann scores remained unchanged at last follow-up for 96.9%, improved for 1.6%, and worsened for 1.6%. Salvage therapy in the form of surgery (n=5) or repeat GK-SRS (n=2) was necessary in 5.3% (n=6 for progression; n=1 for trigeminal symptoms).

CONCLUSION

Long-term follow-up demonstrates that GK-SRS remains a well-tolerated, primary definitive treatment for VS.
RADT-20. HISTOPATHOLOGIC FINDINGS IN MALIGNANT PERIPHERAL NERVE SHEATH TUMOR ARE BOTH PROGNOSTIC FOR OVERALL SURVIVAL AND PREDICTIVE FOR RESPONSE TO RADIATION THERAPY
Authors: Vasudevan Harish N , Lucas Calixto-Hope G , Chen William , Magill Stephen , Braunstein Steve , jacques Line , Dahiya Sonika , Rodriguez Fausto , Horvai Andrew , Perry Arie , Pekmezci Melike , Raleigh David
Published: December 2020

BACKGROUND

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive neoplasm associated with neurofibromatosis type 1 (NF1). Despite multimodal therapy, clinical outcomes remain poor. To elucidate markers of MPNST treatment response, we retrospectively reviewed the medical records of MPNST patients at a single institution and performed histopathological and immunohistochemical (IHC) analysis for predictive and prognostic features.

METHODS

We identified 54 consecutive patients treated at University of California San Francisco between 1990 and 2018 that met diagnostic criteria for MPNST on pathologic review with sufficient tissue available for histology and immunohistochemistry (IHC) assays. IHC was performed for Ki-67, EGFR, p53, H3K27me3, neurofibromin, S100, p75NTR, SOX10, p16, and SOX2. Overall survival (OS), metastasis free survival (MFS), and locoregional failure free rate (LFFR), were estimated using the Kaplan-Meier method. Log-rank test, Cox Proportional Hazards regression, and hierarchical clustering were performed in R.

RESULTS

With a median follow up of 19.2 months, the 5-year OS, MFS, and LFFR were 58%, 68%, and 66%, respectively, with no significant differences between NF1 associated (n=32) and sporadic tumors (n=22). Radiation therapy significantly improved 5-year LFFR (80% versus 49%, p=0.05), but not OS or MFS. Tumor grade was associated with worse OS by Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grading (p=0.02). Furthermore, elevated Ki-67 index was associated with worse 5-year OS (39% versus 73% for Ki-67 index ³ 60 and Ki-67 index < 60, p=0.01). Finally, hierarchical clustering of IHC data identified a predictive signature defined by elevated Ki-67 and EGFR expression associated with improved responses to radiation therapy (5-year OS 86% versus 10%, p=0.004).

CONCLUSIONS

Our data provide insights into the diagnosis and treatment of MPNST. Additional investigation is needed to understand the biologic mechanisms and generalizability of the signatures uncovered in our analysis.
RADT-26. LASER INTERSTITIAL THERMAL THERAPY FOR RECURRENT GLIOBLASTOMA: POOLED ANALYSES OF AVAILABLE LITERATURE
Authors: Munoz Casabella Amanda , Rahman Masum , Alvi Mohammed , Brown Desmond
Published: December 2020

INTRODUCTION

Laser Interstitial Thermal Therapy (LITT) is a novel treatment modality that has been used for an array of intracranial pathology. In the current manuscript, we sought to conduct a systematic review and meta-analysis to summarize all available literature to date, on outcomes of patients with recurrent GBM (r-GBM) undergoing LITT, pooling together quantitatively the overall survival and progression-free survival data.

METHODS

A comprehensive literature search was performed to retrieve all studies investigating overall survival, post-procedure survival, and progression-free survival outcomes of patients with r-GBM undergoing LITT. All statistics were pooled together by the meta-analysis of the mean using a weighted random-effects (RE) or fixed-effect (FE) model.

RESULTS

Eleven studies were included in the final cohort, representing a total of 134 patients with rGBM. The pooled mean age of the cohort at the time of recurrence diagnosis was found to be 56.7 ± 4.56 while 41% of the cohort were females. For the delivery of LITT, two studies utilized neodymium-yttrium aluminum-garnet laser (Neodp-YAG Laser), three studies utilized the Visualase system, five studies utilized the Neuroblate system, and one study used both the Neuroblate and the Visualase system. A total of eight studies with 107 patients had available data for overall median survival. The pooled overall survival was found to be 18.6 months (95%CI 16.2-21.1). A total of six studies with 93 patients had available data for post-LITT survival. The pooled post-LITT survival was found to be 10.1 months (95%CI 8.8-11.6). A total of eight studies with 119 patients had available data for progression-free survival. The pooled progression-free survival was found to be 6 months (95%CI 5.3-6.7).

CONCLUSION

LITT is a novel minimally invasive procedure which, when used with optimal adjuvant therapy, may confer survival benefit for patients with r-GBM.
RADT-28. RADIATION DOSE-DEPENDENT LONG-TERM NEUROCOGNITIVE DECLINE IN LOW GRADE GLIOMA PATIENTS: RESULTS OF A CROSS-SECTIONAL STUDY
Authors: Sinnige Peter , van der Weide Hiske , Kramer Miranda , Enting Roelien , Bosma Ingeborg , Rakers Sandra , Huitema Rients , Buunk Anne , Spikman Jacoba , Langendijk Johannes
Published: December 2020

BACKGROUND

Radiotherapy is a well-known risk factor for neurocognitive decline in glioma patients. Advanced radiotherapy techniques enable more selective brain irradiation. However, limited data exists on which brain regions are most relevant to avoid. The aim of this study was to explore the dose-effect relationship between brain subvolumes and neurocognitive performance.

METHODS

In this cross-sectional study, patients with grade II or III glioma treated with radiotherapy who were free of progression for at least one year were eligible. Patients underwent a neurocognitive test battery, including Rey Auditory Verbal Learning Test; (RAVLT), Trail Making Test (TMT), Copy of Rey’s Complex Figure Test (RCFT), Single Digit Modalities Test (SDMT) and Verbal Fluency tests (letters and categories). Test scores were correlated to radiation dose distributions in brain subvolumes using non-parametric tests.

RESULTS

The study was composed of 17 right-handed patients with grade II (n= 14) and grade III (n= 3) gliomas. The mean follow up after radiotherapy was 42 months, and the mean age 47 years. Performance on all tests was significantly worse for patients compared to healthy matched controls. Correlations were found between: 1) dose to the left hippocampus and performance on the RAVLT (Delayed Recall) (r= -0.60; p= 0.011); 2) dose to the supratentorial brain and performance on the TMT-A (r= 0.54; p= 0.025) and 3) dose to the left hemisphere and SDMT (r= -0.64; p= 0.006) and verbal fluency tests (for letters score: r= -0.73; p= 0.001).

CONCLUSIONS

We found significant correlations between radiation dose to the left hippocampus and hemisphere and neurocognitive performance. In this small sample we could not account for the effect of tumor location as a confounder. Reducing radiation dose to the left hippocampus and hemisphere by using advanced radiotherapy techniques may give superior neurocognitive outcomes.
RADT-30. COPLANAR AND NON-COPLANAR VMAT ARC SETTING FOR GLIOBLASTOMA MULTIFORME – DOSIMETRIC AND RADIOBIOLOGICAL COMPARISONS
Authors: Moldoveanu Vanessa , Dumitrache Mihai , Bacinschi Xenia , Serbanescu Luiza , Anghel Rodica
Published: December 2020

OBJECTIVES

To evaluate three different arc arrangements in glioblastoma multiforme (GBM) treatment planning.

METHODS

Eighteen GBM patients were replanned by using one full arc (1FA), two full coplanar arcs (2FA), and three full non- coplanar arcs (3FA). Dose-volume histograms (DVHs) were used to calculate conformity (CI), homogeneity (HI) and gradient indices (GI), the dose received by 5% (D5%) and 95% (D95%) of the planning target volume (PTV) and maximum (Dmax) and minimum (Dmin) absorbed dose for organs at risk (OARs), including normal brain (brain excluding PTV). General equivalent uniform dose (gEUD) for both PTV and OARs and EUD based tumor control probability (TCP) and normal tissue control probability (NTCP) were calculated as radiobiological parameters. Monitor units (MUs) were also computed and compared.

RESULTS

All three plans resulted in similar conformity, while 2FA resulted in a better homogeneity than 1FA (0.06vs. 0.07, p=0.007). 2FA vs. 1FA dose analysis for PTV revealed a lower D5% (61.28 vs. 61.37 Gy, p=0.014), a higher D95% (58.7 vs. 58.47 Gy, p=0.008) and a higher TCP (37.73 vs.37.38%, p=0.008). The utilization of 3FA did not significantly change the outcome of PTV but managed to decrease GI in comparison to both 1FA and 2FA (4.11 vs. 5.19 and 5.49, p< 0.05). Regarding NB, 1FA scored a higher Dmax than 2FA (62.32 vs. 61.98 Gy, p=0.005), while 3FA scored a higher Dmin than 1FA and 2FA (2.52 vs. 1.08 and 1.10 Gy, p< 0.05). No difference in NB NTCP was noted between techniques. Furthermore, 3FA yielded more MUs when compared to coplanar patters (566.74 vs. 486.78, p= 0.015 for 1FA and 495.98, p=0.019 for 2FA).

CONCLUSION

Although all three approaches resulted in clinical admissible outcome, the utilization of complex non-coplanar arrangement resulted in a stepper dose fall off but did not improve PTV results and increased machine MUs.
RADT-32. NATIONAL TRENDS IN RADIATION DOSE FOR LOW GRADE GLIOMAS
Authors: Wegner Rodney , Horne Zachary , Abel Stephen , Xu Linda , Yu Alexander , Ranjan Tulika , Karlovits Stephen
Published: December 2020

BACKGROUND

Adjuvant radiation is used in patients with low grade gliomas (LGG) with high risk characteristics. Randomized trials have examined dosing schemes ranging from as low as 45 Gy to higher than 60 Gy, with no difference in outcome. We used the National Cancer Database (NCDB) to see which doses were used in this patient population, and if any difference were seen in outcome.

METHODS

We queried the NCDB for patients with WHO Grade 2 brain tumors treated with surgery and adjuvant radiotherapy. We divided the cohort into dose groups: 45-50 Gy, 50.4-54 Gy, and >54 Gy. Multivariable logistic regression was used to identify predictors of low and high dose radiation. Propensity matching was used to account for indication bias.

RESULTS

We identified 1,437 patients meeting the above criteria. Median age was 45 years. Forty-eight percent had astrocytoma subtype and 70% had subtotal resection. The majority of patients (69%) were treated to between 50.4-54 Gy. Half of all patients were treated with radiation alone. 1p19q status was recorded in 32% of patients, and 13% overall were co-deleted. Predictors of high dose radiation were increased income, astrocytoma subtype, chemotherapy receipt, and treatment in 2014. Patients treated to a dose of >54 Gy had a median survival of 73.5 months and was not reached in those treated to a lower dose (p=0.0041). Subset analysis of patients with astrocytoma subtype showed median survivals of 79.0 and 51.2 months for low and high dose, respectively (p=0.13). When limited to oligodendrogliomas corresponding 5 year survival rates were 86% and 65%, in favor of lower doses (p=0.0004).

CONCLUSIONS

This analysis shows that 50.4-54 Gy is the most widely used radiation regimen for ow grade gliomas. There appeared to be no benefit to higher doses, although factors not recorded are likely confounding the RESULTS:
RADT-35. POSTOPERATIVE RADIOTHERAPY FOR WHO GRADE II–III INTRACRANIAL EPENDYMOMA IN ADULTS: AN INTERGROUP COLLABORATIVE STUDY (KROG 18-06/KNOG 18-01)
Authors: Woo Wee Chan , Kim Il Han , Park Chul-Kee , Lim Do Hoon , Nam Do-Hyun , Yoon Hong In , Suh Chang-Ok , Chang Jong Hee , Chung Woong-Ki , Jung Tae-Young , Park Shin-Hyung , Kim Chae-Yong , Kim Young Zoon , Gwak Ho Shin , Cho Kwan Ho , Kim Jin Hee , Im Jung Ho , Kim Woo Chul , Kim Sung-Hwan , Kim In Ah
Published: December 2020

BACKGROUND

To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II–III intracranial ependymoma (IEPN).

METHODS

A total of 172 pathologically confirmed adult grade II–III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis.

RESULTS

The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P=0.002), PFS (P=0.002), and OS (P=0.043). Older age (P< 0.001), WHO grade III (P< 0.001), larger tumor size (P=0.004), and lesser surgical extent (P< 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P=0.010), PFS (P=0.007), and OS (P=0.069) on multivariate analysis for grade II IEPNs.

CONCLUSION

This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II–III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.
RBIO-06. IMPLEMENTATION OF HUMAN INDUCED PLURIPOTENT STEM CELL DERIVED CEREBRAL ORGANOIDS TO MODEL NORMAL TISSUE RADIORESPONSE
Authors: Bronk Lawrence , Singh Sanjay , Thomas Riya , Parkitny Luke , Maletic-Savatic Mirjana , Mohan Radhe , Lang Frederick , Grosshans David
Published: December 2020

Treatment-related sequelae following cranial irradiation have life changing impacts for patients and their caregivers. Characterization of the basic response of human brain tissue to irradiation has been difficult due to a lack of preclinical models. The direct study of human brain tissue in vitro is becoming possible due to advances in stem cell biology, neuroscience, and tissue engineering with the development of organoids as novel model systems which enable experimentation with human tissue models. We sought to establish a cerebral organoid (CO) model to study the radioresponse of normal human brain tissue. COs were grown using human induced pluripotent stem cells and a modified Lancaster protocol. Compositional analysis during development of the COs showed expected populations of neurons and glia. We confirmed a population of microglia-like cells within the model positive for the makers Iba1 and CD68. After 2-months of maturation, COs were irradiated to 0, 10, and 20 Gy using a Shepard Mark-II Cs-137 irradiator and returned to culture. Subsets of COs were prepared for immunostaining at 30- and 70-days post-irradiation. To examine the effect of irradiation on the neural stem cell (NSC) population, sections were stained for SOX2 and Ki-67 expression denoting NSCs and proliferation respectively. Slides were imaged and scored using the CellProfiler software package. The percentage of proliferating NSCs 30-days post-irradiation was found to be significantly reduced for irradiated COs (5.7% (P=0.007) and 3.4% (P=0.001) for 10 and 20 Gy respectively) compared to control (12.7%). The reduction in the proliferating NSC population subsequently translated to a reduced population of NeuN-labeled mature neurons 70 days post-irradiation. The loss of proliferating NSCs and subsequent reduction in mature neurons demonstrates the long-term effects of radiation. Our initial results indicate COs will be a valuable model to study the effects of radiation therapy on normal and diseased human tissue.
RTID-09. A RANDOMIZED, DOUBLE-BLINDED, PHASE 3 STUDY OF ENZASTAURIN ADDED TO TEMOZOLOMIDE DURING AND FOLLOWING RADIATION THERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS WHO POSSESS THE NOVEL BIOMARKER, DGM1
Authors: Butowski Nicholas , Mao Ying , Wu Wilson , Luo Wen , Ge Lan , Pertschuk Daniel , Dewitt Theresa , Han Isabel , Heineman Thomas
Published: December 2020

BACKGROUND

Limited progress has been made in improving therapeutic outcomes for glioblastoma (GBM) patients. Enzastaurin (enza) is an oral PKC-β inhibitor that suppresses signaling through the PKC and PI3K/AKT pathways. Although enza did not significantly improve survival in a prior Phase 1/2 study, we have identified a novel genomic biomarker, DGM1, that may predict a response to enza in GBM.

PRIMARY OBJECTIVE

To assess whether enza added to temozolomide and radiation therapy (RT) improves overall survival (OS) in newly diagnosed GBM patients who possess the DGM1 biomarker.

POPULATION

Adults with newly diagnosed GBM regardless of DGM1 status who have undergone surgical resection and are candidates for chemoradiation. Approximately 318 patients will be enrolled. DGM1 status will be determined prior to analysis.

DESIGN

This is a randomized, double-blinded, placebo-controlled study. Patients will be stratified by MGMT and IDH1 status and by geographic region. Treatment will be divided into 3 phases. In the Concurrent Phase (6 weeks), patients will receive RT plus temozolomide and either enzastaurin or placebo. Patients will then enter the Single-Agent Phase and receive either enza or placebo (21-35 days). Then, patients will enter the Adjuvant Phase and receive temozolomide with either enza or placebo (6-12 cycles) followed by enza or placebo alone (to 24 cycles total).

ANALYSIS

The primary efficacy endpoint of OS will be analyzed using stratified log-rank test for all DGM1-positive randomized patients. The study has approximately 90% power to detect a HR of 0.63 assuming 196 OS events based on a 2.5% one-sided false positive error rate. Statistical significance would be achieved with an estimated observed HR < 0.76. Safety evaluation will include all patients receiving at least one dose of enza or placebo. If OS in DGM1-positive patients is statistically significant, OS in the overall population will be assessed.
STEM-01. TARGETING BRAIN METASTASIS-INITIATING CELLS: A PREVENTATIVE APPROACH
Authors: Kieliszek Agata , Venugopal Chitra , Bassey-Archibong Blessing , Lam Fred , Singh Sheila , Aghaei Nikoo
Published: December 2020

BACKGROUND

The incidence of brain metastases (BM) is tenfold higher than primary brain tumors. BM commonly originate from primary lung, breast, and melanoma tumors with a 90% mortality rate within one year of diagnosis. Current standard of care for BM includes surgical resection with concurrent chemoradiation, but does not extend median survival past 16 months, posing a large unmet need to identify novel therapies against BM.

METHODS

From a large in-house biobank of patient-derived BM cell lines, the Singh Lab has generated murine orthotopic patient-derived xenograft (PDX) models of lung, breast, and melanoma BM that recapitulate the stages of BM progression as seen in humans. Using these three PDX models, we identified a population of “pre-metastatic” brain metastasis-initiating cells (BMICs) that are newly arrived in the brain but have yet to form detectable tumors. Pre-metastatic BMICs are not detectable in human patients but are important therapeutic targets with the potential to prevent BM in at-risk patients.

RESULTS

RNA sequencing of pre-metastatic BMICs from all three PDX primary tumor models with subsequent Connectivity Map analysis identified novel compounds that have the potential of killing all three types of BMICs. In particular, we identified two compounds that have selective killing of BMICs in vitro from all three primary tumor cohorts while sparing non-cancerous cells. We further characterized their ability to inhibit the self-renewal and proliferative properties of BMICs. Ongoing in vivo work will investigate the compounds’ preclinical utilities in preventing BM.

CONCLUSION

Identification of novel small molecules that target BMICs could prevent the formation of BM completely and dramatically improve the prognosis of at-risk cancer patients.
STEM-11. INTERROGATING INTRATUMORAL TRANSCRIPTOMIC HETEROGENEITY AND PLASTICITY AS RESISTANCE MECHANISMS IN GLIOBLASTOMA
Authors: A Yabo Yahaya , Arns Thais , Oudin Anais , Grzyb Kamil , Poovathingal Suresh , Michelucci Alessandro , Skupin Alexander , Niclou Simone P , Golebiewska Anna
Published: December 2020

Intratumoral heterogeneity is one of the major barriers in the treatment of many tumor types. In glioblastoma (GBM) – the most aggressive brain tumor - survival of patients following standard therapy has stagnated to an average of 14 months, largely due to the inherent heterogeneity and phenotypic plasticity. Patient-derived orthotopic xenografts (PDOX) are important tools for preclinical cancer studies. We have shown that they recapitulate histological and molecular features of patient tumors, thus producing more clinically relevant study outcomes when compared to other preclinical models. To understand the impact of treatment on intratumoral heterogeneity and interactions of tumor cells with the microenvironment, we applied single-cell RNA-seq in GBM PDOX models generated from naive and treatment exposed patient tumors. Here we show that PDOX models recapitulate all the major cell types and transcriptional programs reported in GBM patient samples. We demonstrate that GBM tumor cells occur in distinct phenotypic states dictated by microenvironmental cues and treatment-induced pressure. Non-neoplastic cells present within xenografts undergo transcriptomic adaptation similar to the GBM microenvironment in patients. Analysis of treated PDOXs and longitudinal PDOX models derived from patients prior and after treatment allows us to investigate short-term and stable long-term transcriptomic adaptations. We aim to reveal key molecular regulators enhancing tumor cell plasticity and resistance, that could be targeted in combinatory treatments. Our GBM PDOX models provide a platform for high-quality pre-clinical research and an improved clinical relevance in the development and testing of novel therapeutics.
STEM-16. IGF1/N-CADHERIN/b-CATENIN/CLUSTERIN SIGNALING AXIS MEDIATES ADAPTIVE RADIORESISTANCE IN GLIOBLASTOMA
Authors: Osuka Satoru , Zhu Dan , Zhang Zhaobin , Sampetrean Oltea , Olson Jeffrey , Saya Hideyuki , Van Meir Erwin
Published: December 2020

Glioblastoma (GBM) is composed of heterogeneous tumor cell populations including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by increased cell-cell adhesion, slower proliferation, an elevation of stemness properties and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of b-catenin at the cell surface, which suppressed Wnt/ b-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. Restoration of wild type N-cadherin, but not mutant N-cad lacking b-catenin binding region, led to induce radioresistance in N-cadherin knockout GSCs, indicating the importance of the binding between N-cadherin and b-catenin. We also demonstrated that N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin (PPP), a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation. Moreover, the elevation of N-cad and Clusterin are related to prognosis of GBM in the TCGA dataset. In conclusion, our data indicate that IGF1R inhibitor can block the N-cadherin-mediated resistance pathway. Our study deepens our understanding of adaptive radioresistance during repeated irradiation in GBM, and validates the IGF1/N-cadherin/b-catenin/Clusterin signaling axis as a novel target for radio-sensitization, which has direct therapeutic applicability.
STEM-26. SMALL MOLECULE DRUG CBL0137 INHIBITS THE FACT COMPLEX AND SENSITIZES GLIOBLASTOMA CANCER STEM CELLS TO RADIOTHERAPY
Authors: Tallman Miranda , Zalenski Abigail , Deighen Amanda , Schrock Morgan , Mortach Sherry , Grubb Treg , Kastury Preetham , Huntoon Kristin , Summers Matthew , Venere Monica
Published: December 2020

Glioblastoma (GBM) is a malignant brain tumor with nearly universal recurrence. GBM cancer stem cells (CSCs), a subpopulation of radio- and chemo-resistant cancer cells capable of self-renewal, contribute to the high rate of recurrence. The anti-cancer agent, CBL0137, inhibits the FACT (facilitates chromatin transcription) complex leading to cancer cell specific cytotoxicity. Here, we show that CBL0137 sensitized GBM CSCs to radiotherapy using both in vitro and in vivo models. Treatment of CBL0137 combined with radiotherapy led to increased DNA damage in GBM patient specimens and failure to resolve the damage led to decreased cell viability. Using clonogenic assays, we confirmed that CBL0137 radiosensitized the CSCs. To validate that combination therapy impacted CSCs, we used an in vivo subcutaneous model and showed a decrease in the frequency of cancer stem cells present in tumors as well as decreased tumor volume. Using an orthotopic model of GBM, we confirmed that treatment with CBL0137 followed by radiotherapy led to significantly increased survival compared to either treatment alone. Radiotherapy remains a critical component of patient care for GBM, even though there exists a resistant subpopulation. Radio-sensitizing agents, including CBL0137, pose an exciting treatment paradigm to increase the efficacy of irradiation, especially by inclusively targeting CSCs.
SURG-06. MANAGEMENT OF HYDROCEPHALUS IN ADULT PATIENTS WITH BRAIN METASTASES
Authors: Vaynerman A , Coombs L , Nickols H , LaRocca R , Sinicrope K , Ishihara D , Spalding A , Sun D
Published: December 2020

BACKGROUND

Traditionally patients presenting with hydrocephalus in the setting of brain metastases were associated with poor outcomes. However, in the area of improved systemic therapies, the prognosis of brain metastases has improved, warranting investigation into the management of concomitant hydrocephalus.

METHODS

We conducted a retrospective review of 12 consecutive patients with brain metastases presenting with hydrocephalus treated with either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) from June 2013 to December 2018. We then compared our outcomes to 77 historical controls from the literature to test the hypothesis that management of hydrocephalus in patients who respond to systemic therapy is associated with improved outcomes.

RESULTS

The medial overall survival in our cohort was 182 days compared with 91 days in the reported previous studies, with an odds ratio of 0.5 (95% CI 0.24-1.04). In the 5 patients who underwent ETV, the median survival was 182 days versus 77 days reported in the literature, an odds ratio of 0.42 (95% CI 1.28-1.40). Patients with one brain metastasis did not reach median survival with 4 of 5 patients alive at last follow up, while only 3 of 7 patients with at least two metastases were alive at follow up with a median survival of 182 days. Patients who had immunotherapy were associated with improved survival, while leptomeningeal carcinomatosis still was associated with a negative outcome.

CONCLUSIONS

Patients with brain metastases and hydrocephalus who underwent neurosurgical CSF diversion had improved survival compared with historical controls, particularly in patients with one metastasis or who received immunotherapy. This study supports initial interdisciplinary evaluation of patients with brain metastases by medical and radiation oncology together with neurosurgery to facilitate immediate systemic therapy after relief of hydrocephalus.
SURG-16. PREDICTORS OF LOCAL CONTROL FOLLOWING LASER INTERSTITIAL THERMAL THERAPY FOR GLIAL TUMORS
Authors: Haider Sameah , Pawloski Jacob , Fadel Hassan , Zakaria Hesham , Chaudhry Farhan , Bartlett Seamus , Bazydlo Michael , Kalkanis Steven , Lee Ian
Published: December 2020

INTRODUCTION

Laser Interstitial thermal therapy (LITT) is a minimal-access procedure for intracranial tumors that are either refractory to standard treatment paradigms or difficult to access via conventional open surgery.

OBJECTIVE

To evaluate predictors of local disease control following LITT in patients with primary and secondary brain tumors.

METHODS

Single-center retrospective cohort study of all consecutive LITT ablations between 2014 and 2019. Demographic and procedural characteristics analyzed with respect to local disease control at 6 months. Chi-square tests for categorical variables, T-tests/Wilcoxon Rank-Sum tests for continuous variables for parametric and non-parametric data, respectively. Poisson regression models were used to approximate relative risk (RR) with 95% confidence intervals.

RESULTS

A total of 76 patients underwent LITT with a median follow up of 12.3 months; pathology at time of ablation was glioblastoma multiforme (GBM, 36%), WHO grade III primary CNS (24%), low grade CNS (20%), and metastatic lesions (19%) with respective local control rates of 26%, 20%, 29%, and 26%. Pathology of GBM (RR 0.46, 0.21-1.02, p=0.055) and a 5-year increase in age at the time of ablation (RR 0.91, 0.83-0.99, p=0.028) were associated with a lower likelihood of local control at 6 months. Preoperative Karnofsky performance status (KPS) of 100 (RR 2.04, 1.13-3.69, p=0.019) was associated with a higher likelihood of local control. Extent of ablation (EOA) demonstrated a direct relationship with local control; when EOA=100% local control was 59%, with this rate dropping down to 21% when EOA=90%. Tumor location, lesion volume, gender, BMI, ethnicity, or whether there existed multiple foci of disease at the time of ablation had no strong association with local control.

CONCLUSION

Our series demonstrates that preoperative performance status and age were strong predictors of local disease control following LITT. Incomplete ablation and histology of high-grade glioma portended a higher risk of local recurrence.
SURG-20. USE OF NICO MYRIAD NOVUS DEVICE WITH LIGHT SOURCE AND REAL-TIME STEREOTACTIC NAVIGATION TO OPTIMIZE SURGICAL RESECTION OF DEEP-SEATED TUMORS
Authors: Hwang Lee , Mohammadi Alireza
Published: December 2020

Maximal and safe surgical resection remains a critical component of the standard of care for patients with brain tumors. Stereotactic navigation tools are often incorporated into the surgical planning and implementation. The NICO Myriad NOVUS device couples a light source with the resecting tip to allow enhanced visualization of the surgical cavity and surrounding anatomical structures. At the Cleveland Clinic, we were the first group in the U.S. to start utilizing this augmented technology to maximize the resection of particularly deep-seated brain tumors, using the xenon light and real-time stereotactic navigation of the tool tip with the BrainLAB cranial setting. The navigated tip allows us to reach the deep corners of tumors with or without a tubular retracting device by sparing large corticotomies. Furthermore, the light source within the handheld device is easier to handle and manipulate than a large microscope to illuminate the surgical cavity. In addition, this new tool allows for automated tumor and peri-tumoral tissue harvesting, annotating each sample by location intraoperatively, as well as biological preservation of the harvested tissue for post-surgical molecular analysis. We describe the techniques and advantages of using this novel technology in patients while following and preliminarily reporting their surgical outcomes. With the emergence of novel technological advances, we must adapt as neurosurgeons and develop innovative methods to optimize the surgical resection of brain tumors.
SURG-24. REPEAT CONVECTION-ENHANCED DELIVERY FOR DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Bander Evan , Ramos Alexander , Wembacher-Schroeder Eva , Ivasyk Iryna , Thomson Rowena , Morgenstern Peter , Souweidane Mark
Published: December 2020

INTRODUCTION

While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single dose drug infusions, agents for oncologic therapy require repeated or chronic infusions to maintain therapeutic concentrations. Repeat/chronic CED infusions have rarely been described for oncologic purposes. We report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma (DIPG).

METHODS

Patients were enrolled in a phase I single center clinical trial using 124I-8H9 monoclonal antibody (124I-Omburtamab, Y-mAbs Therapeutics) administered by CED (NCT01502917). Retrospective chart review was used to assess demographic data, CED infusion data, and post-operative neurologic and surgical outcomes. MRI scans were analyzed using iPlan® Flow software (Brainlab AG, Munich, Germany) for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the Clearpoint imaging software (Clearpoint®, MRI Interventions Inc. Irvine, USA).

RESULTS

Seven patients underwent two or more sequential CED infusions. No patients experienced deficits Clinical Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater. One patient had persistent grade 2 cranial nerve deficit after a second infusion. No patients experienced hemorrhage or stroke post-operatively. There was a statistically significant decrease in radial error (p= 0.005) and absolute tip error (p=0.008) for infusion two compared to the initial infusion. Sequential infusions did not result in significantly different distribution capacity between the first and second infusion (Vd:Vi ratio: 2.66 ± 0.35 versus 2.42 ± 0.75; p=0.45).

CONCLUSIONS

This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural work flow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncologic purposes.