bluuebunny/crossref_metadata_2025 huggingface dataset:
QOLP-03. MEASURING CHANGE IN HEALTH-RELATED QUALITY OF LIFE: THE ADDED VALUE OF ANALYSIS ON THE INDIVIDUAL PATIENT LEVEL IN GLIOMA PATIENTS IN CLINICAL DECISION MAKING
Authors: Coomans Marijke , Taphoorn Martin , Aaronson Neil , Baumert Brigitta , van den Bent Martin , Bottomley Andrew , Brandes Alba , Chinot Olivier , Coens Corneel , Gorlia Thierry , Herrlinger Ulrich , Keime-Guibert Florence , Malmström Annika , Martinelli Francesca , Stupp Roger , Talacchi Andrea , Weller Michael , Wick Wolfgang , Reijneveld Jaap
Published: November 2019

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome in glioma research, reflecting the impact of disease and treatment on a patient’s functioning and wellbeing. Data on changes in HRQoL scores provide important information for clinical decision-making, but different analytical methods may lead to different interpretations of the impact of treatment on HRQoL. This study aimed to study whether different methods to evaluate change in HRQoL result in different interpretations. Methods: HRQoL and sociodemographical/clinical data from 15 randomized clinical trials were combined. Change in HRQoL scores was analyzed: (1)at the group level, comparing mean changes in scale/item scores between treatment arms over time, (2)at the patient level per scale/item by calculating the percentage of patients that deteriorated, improved or remained stable on a scale/item per scale/item, and (3)at the individual patient level combining all scales/items. Results: Data were available for 3727 patients. At the group scale/item level (method 1), only the item ‘hair loss’ showed a significant and clinically relevant change (i.e. ≥10 points) over time, whereas change scores on the other scales/items showed a statistically significant change only (all p< .001, range in change score:0.1–6.2). Analyses on the patient level per scale (method 2) indicated that, while a large proportion of patients had stable HRQoL over time (range:27–84%), many patients deteriorated (range:6–43%) or improved (range:8–32%) on a specific scale/item. At the individual patient level (method 3), the majority of patients (86%) showed both deterioration and improvement, while only 1% of the patients remained stable on all scales. Conclusion: Different analytical methods of changes in HRQoL result in distinct interpretations of treatment effects, all of which may be relevant for clinical decision-making. Additional information about the joint impact of treatment on all outcomes may help patients and physicians to make the best treatment decision.
QOLP-04. CALCULATING THE NET CLINICAL BENEFIT IN BRAIN TUMOR TRIALS BY COMBINING SURVIVAL AND HEALTH-RELATED QUALITY OF LIFE DATA USING TWO METHODS: QUALITY ADJUSTED SURVIVAL EFFECT SIZES AND JOINT MODELLING
Authors: Coomans Marijke , Dirven Linda , Bottomley Andrew , van den Bent Martin , Sloan Jeff , Stupp Roger , Weller Michael , Reijneveld Jaap , Taphoorn Martin , Aaronson Neil , Baumert Brigitta , Brandes Alba , Chinot Olivier , Coens Corneel , Gorlia Thierry , Herrlinger Ulrich , Keime-Guibert Florence , Malmström Annika , Martinelli Francesca , Talacchi Andrea , Wick Wolfgang
Published: November 2019

INTRODUCTION

The impact of treatment on both the quality and the quantity of life, i.e. the ‘net clinical benefit’, should be considered to facilitate shared decision making. Two methods that combine survival and health-related quality of life (HRQoL) data: Quality Adjusted Effect Sizes (QASES) and Joint Modelling (JM) were applied to gain insight in the net clinical benefit.

METHODS

The net clinical benefit in one RCT (EORTC 26951 comparing radiotherapy (RT) + PCV chemotherapy versus RT alone) was calculated as a proof of concept for other trials. With the QASES method, effect sizes for differences in survival and HRQoL between treatment arms were calculated. JM allows simultaneous modeling of a longitudinal outcome (HRQoL), and a time-to event outcome (survival). HRQoL scales/items that were selected for primary analysis in the main study were also selected for this analysis: fatigue, global health, social functioning, communication deficit, seizures, physical functioning, and nausea/vomiting.

RESULTS

288/386 patients completed baseline HRQoL forms and were included in the analysis. Overall survival (OS) was significantly longer with combined treatment (42.3 vs. 30.6 months). The percentage of patients who experienced a clinically relevant deterioration (≥10 points) in nausea/vomiting, fatigue, social functioning and global health up to one year after treatment compared to baseline was larger in the RT+PCV arm. QASES corresponded to a reduction in the median OS difference from 9.7 months up till 5.5 months, given equal weights to OS and HRQoL. JM analyses resulted in a theoretical loss of treatment effect in OS of 2–6% when adjusting for HRQoL.

CONCLUSION

Both methods showed that adjusting for the impact of treatment on a relevant HRQoL parameter reduced the survival benefit in the experimental treatment arm compared to standard treatment arm. Applying these methods may facilitate communicating the impact of treatment to patients in clinical practice.
QOLP-05. PREDICTING SURVIVAL WITH THE HEIDELBERG PROGNOSTIC MODEL AFTER SALVAGE STEREOTACTIC RADIOSURGERY OF PREVIOUSLY IRRADIATED PROGRESSIVE HIGH-GRADE GLIOMAS
Authors: Ampil Federico , Richards Troy , dela Cruz Nestor
Published: November 2019

BACKGROUND

The concept of repeat radiotherapy for previously irradiated, progressive high-grade gliomas (PHGG) is intuitively rational for a disease that has the potential to be a life-threatening illness and seriously affect the quality of remaining life. Recently, a simplified method of prognosis prediction (the Heidelberg prognostic model/HPM) was developed to evaluate survival after re-irradiation of PHGGs.

OBJECTIVE

This retrospective study aimed to assess whether salvage stereotactic radiosurgery (SSRS) is worthwhile in patients with PHGGs, and to determine which individuals are likely to benefit from retreatment using the HPM.

METHODS

Three hundred eighty-three people were diagnosed with intracranial glioma between 2000 and 2010 at our institution. From this population, 25 patients (7%) who had a history of prior irradiation and underwent SSRS for PHGGs formed the subjects of this clinical audit. In the HPM system, scores were assigned for clinicopathological features such as age, histology and interval duration between treatments. There were five and 20 patients with HPM determined low and high prognostic scores, respectively. The mean follow-up period was 9.9 months.

RESULTS

Overall median survival (MS) was 7 months, and the 6, 12- and 24-months crude survival rates (CSR) were 60%, 28% and 16%, respectively. The MS and CSRs for the low scoring patients were 20 months, 100%, 100% and 20%, respectively; for the 20 high-scoring individuals, the corresponding findings were 8 months, 75%, 35% and 10%, respectively. Among the evaluable 11 people, the quality of life was acceptable in approximately half of the cases. Local recurrence rate after SSRS was 12%. Adverse-related events were not observed.

CONCLUSION

A trend towards improved survival was observed in the HPM low-scoring patients. More documentation of favorable effects is required to support the useful role of SSRS as second line treatment of PHGGs.
QOLP-06. EXISTENTIAL DISTRESS: UNADDRESSED CONCERNS FOR ADULT NEURO-ONCOLOGY PATIENTS
Authors: Loughan Ashlee , Braun Sarah , Husain Mariya , Aslanzadeh Farah , Boutte Rachel , Lanoye Autumn
Published: November 2019

BACKGROUND

Primary brain tumor (PBT) patients may experience existential distress including fear of cancer recurrence and death anxiety; however, to date few have examined this issue. The objectives of this study were twofold: first, to systematically review PBT representation in the psycho-oncology literature on existential distress, and second, to preliminarily assess the prevalence and correlates of existential distress in a sample of PBT patients. PRIMARY OBJECTIVE METHODS/

RESULTS

Three databases (PsycINFO, PubMed, and CINAHL) were systematically searched to identify articles measuring fear of cancer recurrence, fear of dying, or death anxiety in oncology patients. Included studies were examined to determine the frequency of PBT patients and identify exclusion criteria relevant to neuro-oncology. For studies including PBT patients, a more thorough data extraction was undertaken. Systematic searching found 336 studies meeting inclusion criteria (N=133,027). Eight studies (0.16% of the participants) included PBT patients. Exclusion criteria such as cognitive impairment and specific treatment parameters may have prohibited PBT patient participation. Studies including PBT patients used mixed methods with limited demographic analyses; existential distress was correlated with heightened psychological distress and poor quality of life. SECONDARY OBJECTIVE METHODS/

RESULTS

A cross-sectional analysis of 81 PBT patients (20–86 years old) was conducted. Patients completed validated questionnaires of death anxiety, death distress, generalized anxiety, and depressive symptoms. Descriptive analyses, t-tests, chi-square, and Pearson correlations were conducted. Up to 79% of PBT patients endorsed death anxiety. These patients were significantly younger, more likely to be female, and have a low-grade brain tumor (p< 0.05). Significant correlations were found between death anxiety and distress and symptoms of anxiety and depression (p< 0.01).

CONCLUSIONS

PBT patients are underrepresented in existential psycho-oncology literature, despite preliminary findings suggesting prevalence of these concerns. Future investigations of existential distress in neuro-oncology is warranted to inform psychosocial screening and treatment for PBT patients.
QOLP-07. A PILOT STUDY TO ASSESS THE INTEGRATION OF A UNIQUE PROQOL TOOL AND EARLY PALLIATIVE CARE INTERVENTION IN THE CARE OF HIGH GRADE GLIOMA PATIENTS AND THEIR CAREGIVERS
Authors: Sharma Akanksha , Wolfe Eric , Barrera Celina , Williamson Samantha , Farfour Hannah , Mrugala Maciej , Edwin Mark , Sloan Jeff , Porter Alyx
Published: November 2019

BACKGROUND

Early involvement of palliative care (PC) in patients with metastatic cancer has been associated with improved quality of life (QOL). Patients with high grade glioma (pwHGG) and their caregivers have unique needs such that similar results are anticipated in this population but cannot be extrapolated. Recognizing that pwHGG often require a caregiver early in the course of disease, this patient population also experiences significant personal and caregiver distress that has been given limited attention and resources. AIM: To assess the feasibility of implementation of a novel patient reported outcomes (PRO) quality of life (QOL) tool administered by smart device in routine office visit (OV) and early integration of palliative care (PC) for pwHGG and their caregivers to improve QOL for both. DESIGN: Prospective, single-center cluster-randomized pilot conducted for 6 months during completion of adjuvant therapy for newly diagnosed high grade glioma. After informed consent was obtained, 15 pwHGG and their caregivers were randomized to: routine OV with basic QOL survey; OV with PROQOL; or PC consultation, in addition to OV with PROQOL.

RESULTS

Two elderly patients with declining performance status transitioned to hospice after initial visit, and one moved out of state prior to adjuvant visits. Thus far 5/15 patients/caregivers have successfully completed the pilot with the 6 remaining participants due to complete in November 2019.

DISCUSSION

The PROQOL appears to be easily integrated into OV without significant patient, caregiver, or provider burden. Providers confirmed utility in prioritizing symptoms and concerns. Thus far, it appears that patients (and caregivers) appeared to benefit from the PROQOL and PC support as evidenced by longitudinal improvement in QOL scores over the control group.

CONCLUSIONS

A unique PROQOL tool and early PC can be easily integrated into practice, and may improve the QOL of pwHGG and their caregivers.
QOLP-17. FACTORS ASSOCIATED WITH PSYCHOLOGICAL DISTRESS IN CAREGIVERS OF PATIENTS WITH MALIGNANT GLIOMAS
Authors: Landay Sophia , Anand Maya , Horick Nora , Jacobs Jamie , Quain Kit , Temel Jennifer , Forst Deborah
Published: November 2019

BACKGROUND

Caregivers of patients with newly diagnosed malignant gliomas experience high rates of psychological distress. However, the factors associated with distress in this population have not been well described. We sought to evaluate patient-related, caregiver-related and tumor-related factors associated with depression and anxiety in this caregiver population.

METHODS

We conducted a prospective study in patients with newly diagnosed malignant gliomas and their caregivers, collecting self-report data within 6 weeks of diagnosis. Patients’ and caregivers’ depression and anxiety were assessed using the Hospital Anxiety and Depression Scale, with subscale scores >7 considered clinically significant. Information about the tumor location and molecular features was extracted from the medical record. We used univariate and multivariate linear models to evaluate the association between caregiver anxiety and depression at baseline and specific caregiver-, patient- and tumor-related factors.

RESULTS

We enrolled 61 patient-caregiver dyads in this study. 26.2% (16/61) of caregivers had significant depression symptoms, and 47.5% (29/61) had significant anxiety. In the multivariable analysis, factors associated with higher caregiver depression score included younger caregiver age (< 65 years old; B=4.24, p=0.0002), left-sided tumor location (B=1.98, p=0.030), IDH wild-type tumor status (B=3.44, p=0.0008) and patient anxiety (B=2.28, p=0.017). Factors associated with higher caregiver anxiety were younger caregiver age (B=2.47, p=0.089) and left-sided tumor location (B=4.23, p=0.001).

CONCLUSIONS

Younger caregiver age and caring for a patient with a tumor on the left side of the brain were associated with worse caregiver depression and anxiety. Higher caregiver depression was correlated with caregivers whose loved one had significant anxiety or had an IDH wild-type tumor. Understanding the factors associated with caregiver anxiety and depression may guide neuro-oncology clinicians in identifying caregivers who may be at an increased risk for psychological distress at the time of their loved one’s diagnosis, allowing for earlier initiation of support services for these caregivers.
QOLP-20. IMPACT OF GLIOBLASTOMA ON PATIENT-REPORTED SYMPTOM BURDEN AND PHYSICAL ACTIVITY ASSESSED BY CONVENTIONAL INSTRUMENTS AND A NOVEL DEVICE–BASED TECHNOLOGY
Authors: Armstrong Terri , Puduvalli Vinay , Walbert Tobias , Peters Katherine , Loughan Ashlee , Ahluwalia Manmeet , Province Warren Paula , Cachia David , Taylor Jennie , O Blakeley Jaishri , Ganguli Arijit , Khandelwal Nikhil , Kamalakar Rajesh , Noe Les , Kumthekar Priya
Published: November 2019

Glioblastoma (GBM) is a rapidly progressing disease associated with significant deterioration in quality of life. This study evaluated clinical patient-reported outcomes (PROs) and the physical activity of patients with GBM. Adults with GBM (n=180) were stratified across 4 groups representing specific stages in the disease course: Group 1=newly diagnosed; 2=postradiation; 3=stable disease; 4=recurrence. Self-reported physical function (EORTC-QLQC30), motor dysfunction (BN20), symptom burden and interference (MDASI-BT), and objective physical activity level (via Fitbit®) were compared across groups by ANOVA. Associations between outcomes were assessed with a Pearson correlation (r) test. Patients were highly symptomatic, with overall mean (MDASI-BT) symptom severity (1.7–2.4; P=0.23) and interference (2.3–3.2; P=0.68) scores similar across groups. Patients with recurrent disease experienced the numerically greatest symptom severity and interference. Self-reported activity-related interference scores (2.7–3.6, P=0.48) were highest in patients with newly diagnosed or recurrent disease. Motor dysfunction (BN20) mean scores were highest in postradiation (22) and recurrent (22) disease groups (P=0.95). Mean physical function (EORTC-QLQC30) scores were worse in patients with recurrent disease (67) than in those with stable disease (79; P=0.38). Newly diagnosed patients and those with stable disease were the most active (≈4000 and ≈4500 mean steps/day, respectively), whereas those with recurrent disease were least active (≈2300 mean steps/day; P=0.032). Greater physical activity (via Fitbit®) correlated with better self-reported physical function (EORTC-QLQC30) for all groups (Group 1, r=0.0292; Group 2, r=0.0211; Group 3, r=0.0008; Group 4, r=0.0002). Greater motor dysfunction was correlated with lower physical activity in patients with stable (r=0.0003) and recurrent (r=0.0441) disease. Patients in this study were highly symptomatic throughout the disease stages with disease recurrence associated with worse motor and physical function. Future studies exploring these findings in a longitudinal cohort are needed to assess this relationship.
QOLP-33. ACCEPTABILITY RANDOMIZED CONTROLLED TRIAL A COUPLES-BASED MIND-BODY INTERVENTION FOR PATIENTS WITH HIGH GRADE GLIOMA AND THEIR PARTNERS
Authors: Milbury Kathrin , Pei Weathers Shiao- , Durrani Sania , Li Yisheng , Carmack Cindy , Bruera Eduardo
Published: November 2019

BACKGROUND

Given the incurable nature, short survival and high symptom burden of high grade glioma (HGG), patients and their partners are at risk of experiencing psychological and existential/spiritual distress. To address these concerns, we developed a dyadic intervention integrating meditation training with emotional disclosure exercises. The primary aim was to examine feasibility and acceptability of the intervention study procedures.

METHODS

Dyads completed baseline self-report measures and were randomized to a couple-based mind-body (CBMB) or a waitlist control (WLC) group. Couples in the CBMB groups attended 4 weekly (60 min each) therapist-led sessions that were delivered via FaceTime. The CBMB program focused on cultivating mindfulness, compassion, gratitude and purpose. All groups were reassessed, 1 month and 3 months after baseline.

RESULTS

We approached 60 eligible patient-partner dyads of which 37 (62%) consented and 18 were randomized to the CBMB and 16 to the WLC group. Of those randomized, 23 dyads (67%) completed all assessments (n= 12 in CBMB; n=11 in WLC). Attrition was due to patients’ death (n=3), symptom burden (n=5) or passive withdrawal (n=3). Patients (57% male; mean age=57 years) and partners’ (59% female; mean age=54 years) attended a mean of 3.17 sessions (SD=1.2) with 83% attending at least 2 sessions. All dyads in the CBMB group reported the intervention as beneficial and useful and would recommend this program to other couples. Of note, 60% of couples would have preferred in-person delivery and 95% of patients but only 33% of partners stated that a dyadic intervention is their preference.

CONCLUSION

It seems to be feasible, acceptable and possibly efficacious to deliver a dyadic intervention via FaceTime to couples coping with HGG. Although both members of the dyad reported to have benefited, dyadic delivery appears to be less desirable for partners.
RTHP-01. PENTOXIFYLLINE AND VITAMIN E FOR THE TREATMENT OF RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY
Authors: Sudmeier Lisa , Switchenko Jeffrey , Eaton Bree , Shu Hui-Kuo
Published: November 2019

BACKGROUND

The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. A 2008 study showed an average decrease in edema with the use of Ptx + VitE in 11 patients with suspected radiation necrosis after stereotactic radiosurgery (SRS). Here we review outcomes in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis.

METHODS

48 patients were included in this analysis. All patients were treated with SRS, had evidence of radiation necrosis, and had MR imaging before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Official radiology reports were also reviewed.

RESULTS

43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening radiation necrosis on imaging after starting Ptx + VitE. One patient had a mixed response; 5 patients (10.4%) had disease progression. The median time to response assessment after starting Ptx + Vit E was 3.17 months. 9 patients progressed significantly on Ptx + VitE and required Bevacizumab, hyperbaric oxygen therapy or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement on imaging after Ptx + VitE (p=0.037). 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) Ptx + VitE. Use of dexamethasone was not associated with improved response to Ptx + VitE (p=0.471). 3 patients stopped Ptx + VitE due to reported side effects.

CONCLUSION

Ptx + VitE appears safe for the treatment of radiation necrosis, but randomized data are needed to assess efficacy.
RTHP-02. INTRACRANIAL BASAL GANGLIA/THALAMUS GERM CELL TUMOURS: CLINICAL CHARACTERISTICS, TREATMENT OUTCOMES, AND QUALITY OF LIFE OF 211 PATIENTS FROM A SINGLE CENTRE
Authors: Li Bo , Wang Jiayi , Li Youqi , Qiu Xiaoguang
Published: November 2019

PURPOSE

Intracranial germ cell tumours (iGCTs) originating from the basal ganglia/thalamus (BG/T) region are rare. We report the findings from a large single-centre series to explore the clinical features of this disease.

PATIENTS AND METHODS

Patients diagnosed as having BG/T iGCTs from January 2000 to December 2017 at our hospital were screened. Newly diagnosed patients who had histology-proven/tumour marker-elevated disease and received at least radiotherapy were eligible for analysis.

RESULTS

Of the 401 patients screened, 211 were eligible. The median age was 12 years (range, 5–41 years). The median duration of follow-up for surviving patients was 68 months (range, 12–189 months). In germinoma patients (n = 112), the 5-year disease-free survival (DFS) and overall survival (OS) were 94.9% and 98.2%, respectively. Multivariate analysis showed that the dose of radiotherapy could predict the DFS (hazard ratio [HR] 0.991, 95% confidence interval [CI] 0.983–0.998, p = 0.015). In non-germinomatous GCT (NGGCT) patients (n = 99), the 5-year DFS and OS were 83.8% and 88.6%, respectively. Multivariate analysis showed that irradiation field (whole-brain radiotherapy vs. local radiotherapy, HR = 0.163, 95% CI 0.031–0.897, p = 0.037; cranial spinal radiotherapy vs. local radiotherapy, HR = 0.095, 95% CI 0.009–1.031, p = 0.053) and chemotherapy cycle (>3 vs. ≤3) (HR 0.234, 95% CI 0.055–0.996, p = 0.049) were independent factors for DFS. The median Z-score for height and body mass index (BMI) in patients ≤19 years of age (n = 69) at the last follow-up were -0.45 (range, -2.67 to 3.41) and 0.59 (range, -4.73 to 3.1), respectively.

CONCLUSION

BG/T GCTs had unique characteristics. Radiation dose was an independent factor influencing the DFS in cases of germinoma. In NGGCTs, extended field radiation and more chemotherapy cycles yielded better disease control. Physical development after treatment was within the normal range for most patients.
RTHP-10. PREDICTORS OF LINEAR ACCELERATOR VERSUS GAMMA KNIFE STEREOTACTIC RADIOSURGERY USE FOR BRAIN METASTASES IN THE UNITED STATES
Authors: McClelland III Shearwood , Degnin Catherine , Chen Yiyi , Watson Gordon , Jaboin Jerry
Published: November 2019

INTRODUCTION

Stereotactic radiosurgery (SRS) for brain metastases is predominantly delivered via single-fraction Gamma Knife SRS (GKRS) or linear accelerator (LINAC) in 1–5 fractions. Predictors of SRS modality have been sparsely examined on a nationwide level.

METHODS

The 2010–2016 National Cancer Database identified brain metastases patients from non-small cell lung cancer throughout the United States (US) having undergone SRS. A multivariable logistic regression model characterized SRS receipt, adjusting for patient age, dose, geographic location of treatment, facility type, and distance from treatment facility.

RESULTS

A total of 1,760 patients received GKRS, while 1,064 patients received LINAC SRS. Treatment at non-academic facilities was associated with increased LINAC SRS receipt, most prominently in the Midwestern (OR= 6.23; p< 0.001), Northeastern (OR= 4.42; p< 0.001), and Southern US (OR= 1.96;p< 0.001). Administered doses of 18–19 Gy (OR= 1.42;p= 0.025), 20–21 Gy (OR= 1.82;p< 0.001), and 22–24 Gy (OR= 3.11;p< 0.001) were associated with increased LINAC SRS receipt, as was patient location within 20 miles of a radiation treatment facility (OR= 1.27;p= 0.007).

CONCLUSIONS

Despite Gamma Knife being more prominently used over LINAC for SRS, patients treated at non-academic facilities outside of the Western US were substantially more likely to receive LINAC over Gamma Knife. Patients located in the Midwest were 523% more likely, Northeast 342% more likely, and South 96% more likely to receive LINAC when treated at a non-academic facility. Increasing dose independently predicted LINAC over GKRS, indicating that smaller tumors – particularly those less than two centimeters (consistent with RTOG 90-05 recommendations) – are being treated with LINAC. Finally, patients residing in close proximity to a treatment center were 27% more likely to receive LINAC, likely indicative of the increased geographic accessibility of LINAC compared with GKRS. These findings should result in hypothesis-generating questions to further explore predictors of LINAC versus GKRS.
RTHP-32. FIRST EXPERIENCE WITH GAMMATILE PERMANENT IMPLANTS FOR RECURRENT BRAIN TUMORS
Authors: Ferreira Clara , Alaei Parham , Chen Clark , Reynolds Margaret , Sterling David , Dusenbery Kathryn
Published: November 2019

GammatileTM permanent brachytherapy implants have been FDA cleared for patients with recurrent brain tumors. We report our experience with the first 6 patients with recurrent high grade primary brain tumors treated with re-resection and implantation. Each tile contains 4 encapsulated radioactive Cs-131 seeds embedded in collagen. To determine the number of tiles needed, the potential tumor cavity surface area was estimated using the preoperative MRI images. The anticipated cavity surface area was calculated, the surface area of anticipated surgical approach was subtracted. This area was divided by 40mm2 (tile area) and this number of tiles were ordered. At the time of surgery, after maximal safe tumor resection, tiles were placed into the resection cavity and the surgical cavity closed as usual. On post-implant day 1, CT and MRI scans were performed. The cavity was contoured, then expanded by 5mm to create HRCTV. T1 MRI enhanced lesions were contoured as residual GTV (GTVr). A dose of 60Gy over the course of treatment was prescribed to HRCTV. In each of these 6 cases, over 95% of the HRCTV was covered by the 60Gy isodose surface, and GTVr D90 ranged from 22.9Gy to 113.8Gy. The additional time required for the tile placement in all cases was less than 10 minutes. Post-operatively exposure rates at 1m were less than 6 mR/hr (ranging from 1.3 to 3.2mR/h). Permanent GammaTile for recurrent brain tumors is a viable option for selected previously irradiated patients who are operative candidates. Benefits include irradiation of the tumor bed starting immediately after resection with no need to wait for wound healing, and no need to subsequently surgically remove the tile. We were able to accurately predict the number of tiles needed, although in one case collagen spacers were utilized. Due to low exposure rates, radiation protection issues are very manageable.
RBTT-02. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS FOR BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS TRIAL
Authors: Mehta Minesh , Gondi Vinai , Ahluwalia Manmeet , Brown Paul
Published: November 2019

BACKGROUND: Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The METIS study [NCT02831959] investigates the efficacy and safety of TTFields in NSCLC patients with brain metastases. Study Design: NSCLC patients (N=270) with 1–10 brain metastases are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, > 18 hours/day) within 7 days of SRS or supportive care. The portable device delivers TTFields to the brain using 4 transducer arrays, while patients receive the best standard-of-care for systemic disease. Patients are followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; and optimal therapy for extracranial disease. Prior WBRT or surgical resection of metastases, a single resectable lesion or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at two sided alpha of 0.05 to detect a hazard ratio of 0.57. In August 2018, an independent Data Monitoring Committee (DMC) performed a review of the METIS trial data collected to that point. The DMC concluded that no unexpected safety issues had emerged and recommended continuation of the METIS study as planned.
RARE-02. SYMPTOMATIC SALIVARY GLAND-LIKE TUMORS OF THE SELLAR REGION: ADDITIONAL FEATURES AND REVIEW OF THE LITERATURE
Authors: Kleinschmidt-DeMasters Bette , Rosenblum Marc , Kerr Janice , Lillehei Kevin
Published: November 2019

INTRODUCTION

Sellar symptomatic salivary gland-like tumors (SSGTs) are exceedingly rare, with less than a dozen case reports in the literature. They usually consist of amorphous colloid identical to Rathke cleft cyst (RCC) contents, but additionally the cyst wall contains a large, cohesive collection of benign salivary glands. We report two new examples, one of which represents the first instance of recurrence of symptoms 2 years after first surgery, the second time with cyst confined to infundibular stalk and causing severe gliosis, indicative of mass effect. The second example underscores that SSGT remains poorly recognized, even today amongst experts.

METHODS

One case each was retrieved from the files of University of Colorado Denver (UCD) and Memorial Sloan Kettering (MSK); the UCD case represents the sole example in 2000+ sellar region masses seen at our institution since 1997. The MSK case had been recently received in consultation.

RESULTS

Case 1 is a 20-year-old female who presented with 3 weeks of symptoms referable to obstructive hydrocephalus; neuroimaging disclosed a sellar/suprasellar 2.4 x 2.2 x 2.4 cm mass. Following surgical resection, SSGT was diagnosed. She received no adjuvant therapy, but recurrence of headaches and blurred vision 2 years later prompted her return to medical attention. MRI revealed a recurrent cyst confined to the center of a thickened, bulbous infundibular stalk. Second resection yielded amorphous mucin within the cystic and severely-gliotic infundibular stalk, but no salivary-type glands. She has been followed for the last 6 years without tumor recurrence. Case 2 is a 29-year-old female with headache. The lesion was seen initially by a neuropathologist at another institution before it was sent to MSK for consultation and SSGT was diagnosed.

CONCLUSION

Few pathologists or neuropathologists have encountered SSGT in their practices; case 1 produced recurrence and significant local stalk damage, features not previously reported.
RARE-03. CNS GERMINOMA WITH SYNCHRONOUS LESIONS IN THE SELLAR AND PINEAL REGIONS
Authors: Simonyan Armen , Mikhaylova Anna , Lepsveridze Levan , Semenov Maksim
Published: November 2019

Germinomas comprise approximately 2–5% of all CNS malignancies, and have a favourable prognosis. Bad outcomes are relatively rare. Synchronous lesions occurs in 5–10% of cases. We report a case of 28 years old male, presented with motor aphasia, visual impairment and dysphagia. In period of last 15 months patient underwent 3 surgical interventions due to occlusive hydrocephalus. MRI revealed volume formations of the pineal and sellar regions. Taking into account the severity of the patient’s condition, consilium decided to refrain from surgical intervention and adjuvant therapy. Patient was transferred to the palliative unit. He died after 3 months. According to the results of the autopsy, the histological changes in tumors of the pineal and infundibular regions, corresponds to the germinoma. Due to the lack of information about patient’s treatment, carried out until hospitalization in our center, we don’t undertake to judge whether there was diagnostic omission, or incorrect treatment in this clinical case. But in our opinion, in case of suspected CNS germinoma, it is necessary to conduct more “aggressive treatment” (Tumor biopsy, followed by radiotherapy and chemotherapy). Symptomatic treatment should be used in cases, where the treatment of main disease is impossible. We hope that this sad clinical case will help Neurosurgeons in making decisions in a difficult situation.
RARE-08. ROSAI-DORFMAN-DESTOMBES DISEASE OF THE NERVOUS SYSTEM; A SYSTEMATIC LITERATURE REVIEW
Authors: Alshiekh Nasany Ruham , Reiner Anne , Panageas Katherine , Diamond Eli
Published: November 2019

INTRODUCTION

Rosai-Dorfman-Destombes disease (RDD) is a rare non–Langerhans cell histiocytosis with neurologic involvement in fewer than 5% of cases. Data about neurologic RDD is limited. Our objective was to synthesize the clinical literature about presentation, treatments, and outcomes of neurologic RDD.

METHODS

A multi-database English systematic review search using keywords related to (1) histiocytosis and (2) neurologic involvement. Candidate articles were screened for clinical content. Secondary literature and cases without treatment information were excluded. Sites of involvement, presenting symptoms, treatments, and therapeutic responses were reviewed.

RESULTS

Of 4768 screened, 153 articles presenting 223 patients were included. Mean age was 37.7 years (range 2–79; IQR 23.5–52.5). 149 patients (66.8%) were male and 74 (33.2%) were female. RDD lesions were located in the dura in 111 (49.8%) of cases, spine in 16.6%, brain parenchyma in 9.0%, orbit in 7.2%, calvarium in 2.7%, and in multiple sites in 13.5%. The most frequent presenting symptoms were headache in 101 (45.3%.), focal neurological deficits (32.7%), visual symptoms (31.8%), seizures (24.7%), cranial (11.7%), and cerebellar dysfunction (11.2%). Cognitive decline, masses were less common presentations. First-line treatments included resection, radiation, corticosteroids, chemotherapy, and combinations of these. First-line treatment led to complete (CR) or partial response (PR) in 153 (68.6%) of cases, stable disease in 30 (13.5%), and progressive disease in 40 (17.9%). CR or PR was observed in the calvarium in 5/6 (83.3%), dura in 82/111 (73.9%), spine in 29/37 (78.4%), orbit 8/16 (50.0%), parenchyma in 15/20 (75.0%), and multiple sites in 14/30 (46.7%). 47 (21.1%) of patients required second-line therapy.

DISCUSSION

Neurologic RDD is a rare form of histiocytosis with varying sites of involvement, clinical presentations, and responses to treatment. Further investigation of effective therapies for neurologic RDD may improve outcomes for this disease.
RARE-27. UNUSUAL CASE OF TEENAGER WITH PRIMARY SPINAL GERMINOMA WITH INTRACRANIAL RELAPSE POST-THERAPY
Authors: Kooken Maria , Wait Scott , Fasola Carolina , Jacobsen Chad , Gass David
Published: November 2019

We present a case of a 14-year-old male who presented with back pain and difficulty walking and was found to have an intradural intramedullary germinoma in the thoracolumbar spine. After debulking, he was treated with four cycles of carboplatin and etoposide and then received local spinal radiotherapy (RT) to the initial area of disease with margin to 30 Gy in 17 fractions. Six months following completion of therapy, he was found to have an intracranial relapse. CLINICAL IMPORTANCE: Our patient is the second ever Hispanic and twelfth pediatric patient reported with primary spinal germinoma. We reviewed 54 total cases published in literature over last 35 years. Twenty-one patients (39%) were treated with surgery followed by local spinal RT (n=12) or CSI (n=9). Twenty-eight patients (52%) were treated with chemotherapy in addition to surgery and radiation. The remaining 5 patients (9%) either had surgery alone or details of their treatment plan were not reported. Six of the 54 patients experienced disease recurrence. None of the patients treated with CSI experienced disease recurrence after CSI. Ninety-six percent of patients were alive at last follow up. CLINICAL OUTCOME: Our patient had his relapsed disease resected and CSI to 23.4 GY in 13 fractions and focal boost to 21.6 Gy in 12 fractions was delivered to all sites of relapsed disease. He is undergoing surveillance of his tumor and there is no disease recurrence 3 months post-CSI. CONCLUSION: Primary spinal germinomas appear chemo responsive and radiosensitive; however, the optimal management to maximize disease control and minimize side effects is not clear. When using local spinal RT, close surveillance with brain and spine imaging seems indicated as relapses anywhere in the central nervous system are possible. Further study is needed to determine the optimum treatment approach to this tumor.
RARE-43. PRIMARY CENTRAL NERVOUS SYSTEM EWING SARCOMA: A SINGLE INSTITUTION EXPERIENCE
Authors: Yorio Florencia , Alessandro Lucas , Arakaki Naomi , Palomar Nicolas , Muggeri Alejandro , Diez Blanca
Published: November 2019

INTRODUCTION

Ewing Sarcoma (ES) is defined by molecular markers, being t(11,22) the most frequent. Intracranial ES/pPNET usually represent metastases from extracranial sites. Primary Central Nervous System (CNS) lesions are extremely rare.

MATERIAL AND METHODS

Retrospective review of clinical records from patients with primary CNS ES/pPNET assessed at a neurological center in Argentina between 2007–2019. All confirmed with molecular marker. Clinical characteristics, imaging, histopathology, and treatment response were evaluated. Extensive workup included whole-body CT scan, skeletal-scintigraphy, and positron-emission tomography, excluding extracranial primary lesions in all cases.

RESULTS

Total 24p. Median age 22yo (2–65); M:F 2:1. Clinical presentation: intracranial hypertension, focal neurological deficit or seizures. In brain MRI 11 supratentorial lesions, 7 infratentorial and 6 diffuse leptomeningeal. Histopathology: diffuse pattern with small round blue cells 13/24p, other patterns were also described. CD99 marked positive in all cases and T(11.22) confirmed as well: 22 PCR and 2 FISH for EWSR1-rearrangement. Misdiagnosis lead to median delay for accuracy of 7,5mo (0–124); including other CNS primary tumors (n= 13), infectious diseases (n= 5) and other diagnoses (n= 4). Most patients (n= 10) were treated with Euro99-protocol (6 cycles plus local radiotherapy (RT)), 4 with Temozolomide, Irinotecan plus RT, 7 with other regimens and 2 received no treatment. Mean overall survival (OS): 58mo (0–132) and progression-free survival 22mo (0–85). Five year OS:41%.

CONCLUSION

Clinical behavior in primary CNS ES deferred from extraosseous ES, being necessary to apply a specific regimen for this pathology as there is no standard regime for intracranial ES/pPNET. Results showed two different groups of patients with long and very short survival. Presentation, histology, and outcomes are so uneven that we propose if a more specific molecular classification should be necessary. This is, to our knowledge, the largest case series reported describing a heterogeneous group despite the presence of accurate molecular diagnosis.
RARE-52. AN EXTRA-VENTRICULAR NEUROCYTOMA PRESENTING WITH DIFFUSE LEPTOMENINGEAL DISEASE WITH OPTIC NEURITIS, A CASE REPORT
Authors: Eduardo Silva Correia Carlos , Alshiekh Nasany Ruham
Published: November 2019

INTRODUCTION

Neurocytoma is classically a rare intraventricular tumor that affects young adults. Due to its location, it usually presents with obstructive hydrocephalus and typically has a favorable prognosis after adequate surgical intervention. CASE: In this report, we describe the case of a 19-year-old man who developed progressive decreased visual acuity and headaches that led to a diagnosed of hydrocephalus and a ventriculoperitoneal shunt (VPS) placement. Work up at presentation revealed a thoracic spinal cord tumor which was completed resected and pathology was consistent with extra-ventricular neurocytoma. With no further intervention, he experienced signs of worsening intracranial pressure (ICP) and visual acuity, becoming steroid-dependent. Repeat imaging 3 months later showed early signs of leptomeningeal disease (LMD), optic nerve enhancement, and diffuse dural thickening. A dural biopsy was done and read as nonspecific inflammation. He then came to our center for a second opinion. We reviewed pathology from original tumor and confirmed extra-ventricular neurocytoma. We, however, read the dural biopsy as an organizing subdural hematoma. We analyzed his cerebrospinal fluid (CSF) and cytology showed neurocytoma cells, linking his LMD to initial diagnosis. He went on to receive photon craniospinal radiation (CSI) with clinical improvement and decreased steroid requirements. Most recent imaging showed improving LMD.

DISCUSSION

Extra-ventricular neurocytoma is an extremely rare disease with very few cases reported in the literature and our case is unique due to the severe leptomeningeal involvement affecting the optic nerves and the presence of neurocytoma cells on the CSF. There is no consensus on how to best treat these cases, however, our patient improved after CSI.
STEM-07. THE ATYPICAL METALLOPROTEINASE ADAMDEC1 MAINTAINS A NOVEL FGF MEDIATED SIGNALLING NETWORK IN GLIOBLASTOMA CANCER STEM CELLS
Authors: Jimenez-Pascual Ana , Hale James , Bayik Defne , Silver Daniel , Roversi Gustavo , Alban Tyler , McIntyre Thomas , Colombo Giorgio , Taraboletti Giulia , Holmberg Karl , Forsberg-Nilsson Karin , Lathia Justin , Siebzehnrubl Florian
Published: November 2019

Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (CSCs), but how CSCs maintain their stemness is incompletely understood and the subject of intense investigation. CSCs rely both on cell intrinsic programs and microenvironmental interactions to regulate their maintenance. Recent work has demonstrated that CSCs can modulate their surrounding microenvironment by metalloproteinase expression, allowing direct modification of the extracellular matrix that provides structural tissue integrity, and instructive signalling via engagement of key cell surface receptors and sequestration of essential growth factors. Here, we identify a novel growth factor signalling loop that induces and maintains CSCs via an atypical metalloproteinase, a disintegrin and metalloproteinase domain-like protein decysin 1 (ADAMDEC1), secreted by CSCs. ADAMDEC1 solubilizes fibroblast growth factor-2 (FGF2) in the tumor microenvironment. We find that CSCs exclusively express FGF receptor 1 (FGFR1), which upon binding of FGF2 induces upregulation of Zinc finger E-box-binding homeobox 1 (ZEB1). ZEB1 is a regulator of stemness and tumor initiation, and therefore ADAMDEC1-FGF2-FGFR1 signalling promotes malignancy in GBM. We further show that ERK phosphorylation drives ZEB1, which regulates ADAMDEC1 expression, creating a positive feedback loop via repression of microRNA-203. Genetic or pharmacological targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signalling axis for CSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM. In addition, these findings provide a new paradigm for GBM growth through which key growth factors embedded within the extracellular matrix can be selectively accessed by CSC for their maintenance.
STEM-18. DISTINCT BUT PREDICTABLE MECHANISMS DRIVE GENETIC VS. EPIGENETIC RESISTANCE TO TARGETED THERAPY
Authors: George Joshy , Chen Yaohui , Abdelfattah Nourhan , Yamamoto Keiko , Adamson Scott , Rybinski Bradley , Baskin David , Chuang Jeffrey , Yun Kyuson
Published: November 2019

Emergence of therapy resistance greatly reduces long-term utility of effective targeted therapies, including SMO/SHH pathway inhibitors. SHH signaling is activated in ~25% of human medulloblastomas (MB) and FDA approved SMOi (to treat basal cell carcinoma (BCC)) are currently in clinical trials for MBs and acute myeloid leukemia (AML). Accumulating clinical experience suggests that a significant number of BCC patients treated with SMOi develop acquired resistance over time and some show de novo resistance. A similar pattern is observed in MB patients, indicating the need to elucidate resistance mechanisms, particularly those driving de novo vs. acquired resistance, and develop new strategies to overcome both de novo and acquired resistance to SMOi. We report that we have discovered a novel, epigenetic mechanism of therapy resistance to SMOi that underlie de novo resistance. Using two different mouse models of SHH MB, we tested our original hypothesis that the selective pressure on cancer stem cells (CSCs), but not bulk tumor cells, will determine the resistance mechanism at the molecular level. We show that acquired mutations in the SHH pathway genes (previously reported mechanism of resistance) occur only in tumors that contain CSCs that depend on the SHH pathway. In tumors where only the bulk tumor cells, but not CSCs, depend on SHH signaling, no acquired mutations in the SHH pathway genes are detected. Instead, in these tumors, epigenetic reprogramming through selective degradation of specific histone modifiers results in global changes in the epigenetic cell state and gene expression patterns. Importantly, we can predict the mechanism of resistance in individual tumors prior to treatment based on CSC phenotypes. Finally, we also report biomarkers that can be used to identify tumors with CSCs that are independent of SHH pathway, which can be exploited to design anticipatory combination therapies in the future.