bluuebunny/crossref_metadata_2025 huggingface dataset:
EXTH-104. ROLE OF CLPP AND MITOCHONDRIAL METABOLISM IN THE ANTI-CANCER EFFECTS OF IMIPRIDONE ONC201 AND ONC206 IN GLIOBLASTOMA AND DIPG
Authors: Foster Scott , Lee Andrew , Maranto Cristina , Allen Joshua E , Lanier Randall , Sethna Phiroze , Prabhu Varun V
Published: November 2022

ONC201 is the first bitopic dopamine receptor D2 (DRD2) antagonist and allosteric mitochondrial protease ClpP agonist. ONC201 is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC206, a derivative of ONC201 currently in Phase I trials, is also a bitopic DRD2 antagonist and ClpP agonist with enhanced nanomolar potency relative to ONC201. We evaluated in vitro efficacy, mechanism(s) of action and acquired resistance for ONC201 and ONC206 in glioblastoma (GBM) (T98G, A172, U87MG), H3.3 K27M mutant DIPG (SF8628, SF7761) and astrocytoma (H4, U118MG) cell lines. ONC206 was more potent than ONC201 in cell viability assays for all line. A mutation in ClpP has previously been associated with resistance to imipridones. Accordingly, SF8628 cells with a CRISPR-mediated ClpP knockout were resistant to both ONC201 and ONC206. Polyclonal resistant cell lines were generated through prolonged passaging in increasing concentrations of ONC201 (SF8628 and T98G cells) or ONC206 (T98G cells). Cells with acquired resistance to ONC201 (ONC201Res) or ONC206 (ONC206Res) showed cross resistance to both imipridones. Time-stability of resistance was confirmed by removing drug for 2 to 4 weeks and retesting. Whole genome sequencing revealed ClpP mutations in both ONC201Res and ONC206Res T98G cells. RNAseq analysis revealed upregulation of the integrated stress response, apoptosis pathways, and amino acid metabolism with imipridone treatment in T98G parental cells but not resistant clones. Depleting glucose in the media enhanced cell viability inhibition by imipridones, indicating mitochondrial metabolism may contribute to their mechanism of action. Our results identify ClpP and mitochondrial metabolism as key aspects for the mechanism of action of ONC201 and ON206 in DIPG and GBM cell lines.
QLTI-05. HBA1C AND INSULIN COVERAGE FOR NEWLY DIAGNOSED HGG PATIENTS IN THE HOSPITAL
Authors: Regis Patrick , Cavaliere Robert
Published: November 2022

Corticosteroids are used in the management of patients with high-grade gliomas (HGG). Corticosteroids lead to elevated serum glucose levels, necessitating sliding-scale insulin. A hemoglobin A1c (HbA1c) reflects historical serum glucose levels but it’s unclear if it predicts corticosteroid-induced hyperglycemia. We retrospectively reviewed all newly diagnosed HGG patients who were admitted between Jan 2019 to July 2021 who had an HbA1c performed at the time of their diagnosis. HbA1c is classified into: normal (< 5.6%), elevated (5.7 – 6.4%) and diagnostic (> 6.5%). We identified 86 patients of whom 29 and 16 had elevated and diagnostic HbA1c, respectively. These patients were more likely to require sliding scale insulin at least twice during their hospitalization, 64% vs 13% of those with a normal HbA1c. Only 28% of patients had a history of diabetes. There was no correlation between elevated HbA1c and the likelihood of initiating post-operative therapy, surgical complications, or BMI results. When reviewing age, 39 patients were less than 65, of which 34% had at least an elevated HbA1c. Of those older than 65, 65% had at least an elevated HbA1c. Our analysis suggests there is a predictive value of HbA1c and the need for sliding-scale insulin while receiving corticosteroids in the HGG population, especially in the older population. We recommend screening all new HGG patients with an HbA1c at the time of diagnosis, regardless if they have a history of diabetes. We also recommend monitoring serum glucose less frequently with those who have a normal HbA1c. If the HbA1c is elevated or diagnostic, they should have monitored serum glucose levels with available sliding-scale insulin. If the patient is > 65 years of age, they should be considered a higher risk for having hyperglycemia and HbA1c should be reviewed. Further analysis is being conducted and will be reviewed at a later date.
QLTI-17. PROPHYLACTIC VANCOMYCIN REDUCES OMMAYA RESERVOIR-ASSOCIATED BACTERIAL MENINGITIS: A 12-MONTH PROSPECTIVE STUDY
Authors: Trifoi Mara , Sichinga Krishana , Levit Matthew , Aregawi Dawit , Zacharia Brad , Mansouri Alireza , Glantz Michael
Published: November 2022

INTRODUCTION

Intraventricular chemotherapy administered through an Ommaya reservoir (OR) constitutes the mainstay of therapy for adults with leptomeningeal metastases from solid and hematologic malignancies. Unfortunately, OR-associated bacterial meningitis remains a relatively frequent, costly, often morbid, and occasionally fatal complication, limiting the benefit of this approach. We investigated the potential efficacy, cost savings, and toxicity of intraventricular vancomycin co-administered with intraventricular chemotherapy.

METHODS

Detailed demographic, treatment, and outcome data were collected prospectively between 5/1/21 and 4/30/22 for 63 consecutive patients at our institution who underwent OR placement and subsequent intraventricular chemotherapy, co-administered with 10 mg of intraventricular vancomycin at each treatment. Reservoir-associated bacterial meningitis was defined as 2 consecutive positive cultures from the cerebrospinal fluid of the same organism or 1 positive culture in the presence of any other clinical or laboratory evidence of infection, or signs of infection at the surgical site.

RESULTS

The infection rate was 0% [95% CI 0-6.75%] among the 63 patients and 0% [0-0.76%] in the 501 consecutive treatments administered over the 12-month study period compared to 10.25% [7.39- 14.0%] in 322 patients and 1.71% [1.22-2.39%] in 1932 treatments over the preceding 5 years. The absolute risk reduction was 10.3% [3.83 - 14.04], p = 0.0049. The number needed to treat was 10 [7-26]. Cost per vancomycin dose was $10.00 ($5,010 over 12 months). The cost of non-surgical treatment of one OR-associated infection is $88,337.70, which translates into a $618,363.90 savings for the estimated 7 patients over 12 months spared an OR-associated infection. Savings were even further increased if OR removal and subsequent replacement was required. The only other covariate associated with (increased) infection risk on multivariable analysis was treatment number. No treatment-associated toxicity was observed.

CONCLUSION

Prophylactic intraventricular vancomycin eliminated OR-associated infection in patients receiving intraventricular chemotherapy. Dramatic cost savings were achieved without added toxicity.
QLTI-24. ANALYSIS OF DISPARITIES IN PEDIATRIC BRAIN TUMOR BANK ENROLLMENT AS FOUNDATION FOR QUALITY IMPROVEMENT INITIATIVES AT DANA-FARBER CANCER INSTITUTE/BOSTON CHILDREN’S CANCER AND BLOOD DISORDERS CENTER
Authors: Tabatneck Mary , Umaretiya Puja , Sousa Cecilia , Vogelzang Jayne , Ligon Keith , Baird Lissa , Cooney Tabitha
Published: November 2022

BACKGROUND

Tissue biobanks play a vital role in oncology research; however, disparities have been reported in enrollment. The representativeness of biobanks is an important consideration in the extrapolation of research to the broader population. We sought to identify associations between sociodemographic characteristics and pediatric brain tumor bank enrollment at Dana-Farber Cancer Institute and Boston Children’s Cancer and Blood Disorders Center (DFCI/BCCBDC) to identify opportunities for improving equitable and representative enrollment.

METHODS

We conducted a retrospective cohort study of all patients qualified for enrollment in DFCI/BCCBDC Integrated Tissue and Clinical Data Bank for Patients with Neurological Disorders from 2014-2017 and extracted sociodemographic information from the medical record. The primary outcome was biobank enrollment, and the secondary outcome was approach for enrollment among non-enrolled patients. Exposures of interest included sex, language, interpreter need, race, and ethnicity.

RESULTS

We identified 652 eligible patients of which 580 (89%) enrolled and 72 (11%) were non-enrolled. Non-enrolled patients were more likely to be non-English speaking compared to enrolled patients (20% vs 11%; p = 0.0019) and were more likely to require an interpreter (15% vs. 8%; p = 0.025). Non-enrolled patients were more likely to identify as non-white/other/multiple races compared to enrolled patients (29% and 17%; p = 0.0023). Sex and ethnicity were not associated with enrollment. Of the 72 non-enrolled patients, 19 (26%) were approached to discuss enrollment but declined consent. There were no sociodemographic differences between approached and not approached patients.

CONCLUSION

While overall enrollment rates in this single center pediatric brain tumor bank were high, non-English primary language, interpreter need, and non-white race were significantly associated with non-enrollment. There were no differences in terms of approach for enrollment, suggesting that opportunities to improve representation may include understanding the reasons for declining enrollment and improving the consent process for patients from historically marginalized groups.
QLTI-25. CREATING A CHEMOTHERAPY COMPETENCY METRIC FOR NEURO-ONCOLOGY FELLOWSHIP TRAINEES
Authors: Peters Katherine B , Patel Mallika , Mrugala Maciej
Published: November 2022

Neuro-oncology fellowship trainees have varied academic backgrounds before subspecialty certification with most completing neurology residency ( > 90%) and a minority coming from medical oncology and neurosurgery programs. Given the variability in background and training of fellows, concerns about competency, particularly in prescribing chemotherapy and understanding associated toxicities, need to be addressed. Providing a metric to track and assess competency can enhance trainees’ skills and bolster confidence during a neuro-oncology fellowship. In an IRB-exempt quality improvement project, we developed a competency test that was primarily case-based and guided knowledge of treatment indications, dosing, and management of associated toxicities. All questions were created based on NCCN guidelines and linked to a quality metric from ASCO-QOPI. Question content included 1. Prescribing, 2. Prescription review 3. Planning management, 4. Communicating information, 5. Drug dose calculation skills, 6. Adverse drug reactions, 7. Drug monitoring, and 8. Data interpretation. At the start of the fellowship, trainees took a pre-assessment test with a validated Likert scale for self-efficacy/confidence. These tests were scored, and directed elements were delivered via didactics to fellows by practicing neuro-oncologist and clinical pharmacist. The same assessments were performed at 6 and 12 months. All tests were scored and compared to the level of self-efficacy/confidence. Four fellows were included in this project across two institutions. Higher level of proficiency correlated with a higher level of self-reported confidence at the pre-assessment time point. Assessment at six months revealed an improvement in test scores and associated confidence and this trend continued at fellowship completion. This metric is the first known tool to evaluate chemotherapy competency and confidence in neuro-oncology fellows. Performance and self-efficacy/confidence are positively linked. This chemotherapy competency metric can be introduced to all neuro-oncology fellowship programs and used for national certification.
QOL-04. THE EFFECT OF ART THERAPY ON PATIENT AND CAREGIVER QUALITY OF LIFE IN NEWLY DIAGNOSED HIGH GRADE GLIOMA: A PROSPECTIVE PILOT STUDY
Authors: Mohamud Jamal , Nevel Kathryn , Hildenbrandt Ashley , Girard Maggie , VanderVossen Barbra
Published: November 2022

BACKGROUND

High grade gliomas (HGGs) are incurable primary brain tumors, with limited survival times. Patients experience a variety of physical, cognitive, psycho-social changes that may negatively impact patient’s quality of life (QOL). Moreover, patient caregivers’ QOL are also often negatively impacted. As such, interventions to improve patient and caregiver QOL are needed. This study aims to evaluate whether art therapy positively impacts QOL among patients with HGG and their caregivers.

METHODS

This is a planned study with a target of 20 newly diagnosed or early treatment HGG patients and their caregiver matches. Each patient (with the option of one caregiver per patient) will participate in six (6) monthly art therapy sessions with licensed art therapists and structured curriculum. Patient and caregiver QOL will be assessed before, during, and after the six-month study period using validated scales including the HADS, EORTC-QL-C30, and COQL-C. The data will be aggregated following study completion for statistical modeling.

DISCUSSION

The positive impact of art therapy on QOL has previously been well established in patients with oncologic and neurologic conditions. However, there is a gap in our understanding of the impact of such therapies among patients with primary neuro-oncologic disorders. These patients face uniquely difficult physical, cognitive, and psychosocial challenges as a result of their unique disease process. It would stand to reason that newly diagnosed HGG patients may benefit from early enrolment and participation in these therapies to improve their overall QOL, particularly shortly after diagnosis and during active anti-cancer therapies.

CONCLUSION

To our knowledge, this is the first study to assess the impact of such intervention in newly diagnosed HGG patients. This pilot study will assess if early intervention with such therapies can lead to significant changes in patients and/or caregiver measurable QOL metrics.
QOL-08. PHASE II RANDOMIZED STUDY TO EVALUATE EFFICACY AND SATISFACTION OF ROLAPITANT PLUS ONDANSETRON VS. ONDANSETRON MONOTHERAPY IN PREVENTING NAUSEA/VOMITING FOR GLIOMAS RECEIVING RADIATION/TEMOZOLOMIDE
Authors: Affronti Mary Lou , Patel Mallika , Severance Erin , Loughlin Charles , Bradbury Claire , Herndon James E , Boyd Kendra , Lipp Eric S , Friedman Henry S , Desjardins Annick , Johnson Margaret , Peters Katherine B
Published: November 2022

BACKGROUND

Nausea and vomiting remain the most feared cancer treatment-related side effects. Trials establishing antiemetic guidelines exclude malignant glioma (MG) patients. In MG patients receiving radiation with concurrent temozolomide, chemoradiation-induced nausea and vomiting (cRINV) rates are 35 and 26%, respectively, which reduce quality of life, treatment adherence, and potentially cancer control.OBJECTIVES: In a randomized phase II open label trial, we compared patient satisfaction and efficacy of ondansetron monotherapy (short-acting 5HT3-RA; 3h half-life) vs. rolapitant (long-acting NK1-RA; 180h half-life) plus ondansetron in preventing cRINV during 6-weeks of daily temozolomide (75 mg/m2/dX42d) with radiation.

METHODS

Fifty-three eligible patients receiving chemoradiation were randomized to Arm-A (ondansetron 8mg Days 1-42, rolapitant 180mg on Day 21) or Arm-B (rolapitant on Day 1 plus daily ondansetron). Primary endpoint included the percentage achieving cRINV-complete response (CR; no vomiting or antiemetic rescue) during the first 2-weeks of radiation. Secondary endpoints included cRIN/cRIV rates, preference for rolapitant plus ondansetron, and toxicity.

RESULTS

Forty-eight initiated protocol treatment. Mean age=53, 58% male, median KPS 90%, 71% low alcohol N/V risk factor, 73% glioblastoma. During the first 2-weeks of radiation, cRINV-CR was 60% for 25 evaluable patients receiving ondansetron monotherapy and 65% for 23 receiving rolapitant/ondansetron (p< 0.71). Patient-reported cRINV-CR was 61% and 74%, respectively (p< 0.41); cRIN rates (44% Arm-A; 53% Arm-B) were more than cRIV rates (28% Arm-A; 11% Arm-B). More patients receiving ondansetron alone vomited the first 2-weeks (22%) than with rolapitant/ondansetron (0%); p< 0.05. Among 32 patients who completed the study, patients preferred ondansetron (63%) over rolapitant/ondansetron (19%); p< 0.0039; 19% had no preference. Adverse events attributable to antiemetic treatment (fatigue/constipation) were all grade 1-2.

CONCLUSIONS

While patients prefer ondansetron monotherapy, there was no difference in cRINV-CR between the first 2-week treatments and some had less vomiting with rolapitant plus ondansetron. We will present overall N/V results.
QOL-11. COMMUNICATION IN THE CONTEXT OF GLIOBLASTOMA TREATMENT: WHAT MATTERS MOST
Authors: Boele Florien , Butler Sean , Nicklin Emma , Pointon Lucy , Short Susan , Murray Louise
Published: November 2022

BACKGROUND

Given the poor prognosis of glioblastoma, it is critical that the benefits and burdens of treatments are clearly discussed with patients and family caregivers. We investigated experiences and preferences around glioblastoma treatment communication in patients, caregivers, and healthcare professionals (HCPs).

METHODS

Semi-structured qualitative interviews were conducted with adult glioblastoma patients, their caregivers, and HCPs. Purposive sampling was used to capture views across the entire disease trajectory and different specialties. Interviews were recorded, transcribed verbatim, and analysed thematically.

RESULTS

In total, 15 patients, 13 caregivers (in N=12 individual and N=8 dyadic interviews), and five HCPs participated (N=5 individual interviews). Four main themes were identified. 1) Communication practice and preferences. Risks and side-effects of anti-tumour treatments were explained clearly, with information layered and revisited frequently to aid understanding. Treatment was often understood to be ‘the only option’, particularly at recurrence. Understanding the impact of side-effects on daily life could be enhanced, including those from supportive medication (e.g., corticosteroids); alongside more proactive communication about support services. 2) What matters most. Patients/caregivers valued being well-supported by a trusted treatment team, feeling involved, having a sense of control, and quality of life. HCPs similarly highlighted trust, maintaining independence and quality of life, and emotional support as key. 3) Decision-making. With limited treatment options, trust and control are crucial in decision-making among patients, caregivers, and HCPs. While patients ultimately prefer to follow HCP advice they want to be involved, consider all alternatives, and voice what matters to them. 4) Impact of Covid-19. During the pandemic, greater efforts to maintain good communication were necessary. While negative impacts of Covid-19 were limited, caregivers appeared most disadvantaged by pandemic-related restrictions (e.g., limited visiting).

DISCUSSION

In glioblastoma treatment communication, building trusting relationships, maintaining a sense of control, and good support are identified by patients, caregivers, and HCPs as critical.
QOL-14. IDENTIFICATION OF CHALLENGES FACED BY CAREGIVERS OF PATIENTS WITH NEWLY DIAGNOSED GLIOMAS
Authors: Gomez Julia , Hemminger Lauryn , Seshadri Sandhya , Serventi Jennifer , Mohile Nimish , Kluger Benzi
Published: November 2022

OBJECTIVE

Describe the most common and challenging issues facing caregivers of patients with newly diagnosed gliomas.

BACKGROUND

Despite growing evidence that caregivers of brain cancer patients have high burden, there are no studies on what specific aspects of caregiving are most challenging. Understanding these specifics can inform better approaches to support them.

METHODS

Prospective study of caregivers of patients with newly diagnosed gliomas (glioblastomas, anaplastic astrocytomas, and low-grade gliomas). Caregivers (n=57 at baseline) used free-text fields to report the most challenging aspects of caregiving at baseline, 3 months, 6 months, and 12 months after diagnosis. Responses were grouped into categories for analyses and examined utilizing the Model to Guide Patient and Family Care.

RESULTS

Caregiver participants included spouses (n=34), children (n=12), and others (n=11) and the majority of tumors were high-grade gliomas. The most common challenges at each time point were coping with diagnosis and associated mortality and uncertainty (32% at baseline), providing hands-on care (27% at 3 months), dealing with the patient’s emotions (33% at 6 months), and providing hands-on care, witnessing cognitive/behavioral changes, and seeing physical deficits (each 30% at 12 months). Psychological challenges such as dealing with emotions, coping with the diagnosis, or witnessing cognitive/behavioral changes were common across all time points. Social challenges such as communication difficulties and shifting relationships and family dynamics were less common. At baseline, coping with the new diagnosis was most challenging for caregivers, whereas at 12-months, the patients’ cognitive, behavioral, emotional, and physical difficulties became more pronounced resulting in the need for more hands-on care. The data was limited by dropouts, particularly at 12-months(n=20).

CONCLUSION

Caregivers of glioma patients experience challenges that evolve in the 12 months following diagnosis. These results provide a starting point to better screen caregivers for distress and develop targeted interventions to improve caregivers’ quality of life.
QOL-16. SYMON-SAYS (SYMPTOM MONITORING & SYSTEMATIC ASSESSMENT AND REPORTING SYSTEM IN YOUNG SURVIVORS) PROGRAM HAS THE POTENTIAL TO DECREASE SYMPTOM BURDEN ON CHILDREN WITH CANCER
Authors: Lai Jin-Shei , Peipert Devin , Jensen Sally , Urban Megan , Goldman Stewart , Lenzen Alicia
Published: November 2022

AIMS

The unrelieved symptoms and side effects of often-aggressive cancer treatments can lead to poor outcomes. SyMon-SAYS was developed to minimize symptom management barriers and symptom burdens by routinely collecting and interpreting patient-reported outcomes in pediatric oncology ambulatory settings. This paper reports the preliminary results of the 16-week SyMon-SAYS trial.

METHODS

Children (ages 8-17) with cancer (on-therapy or within 6-M post-treatment) were randomly assigned to either intervention (IG; weeks 1-16 intervention) or waitlist (WG; weeks 1-8 waitlist, weeks 9-16 intervention) group. Children in the intervention phase reported on 9 symptoms (fatigue, sadness, itch, pain, worry, appetite, nausea, sleep, headache) weekly via an electronic medical record patient portal. Scores exceeding a pre-defined threshold triggered an alert to the treatment team. Parents completed a symptom management barriers questionnaire (SMBQ) at baseline, weeks 8 (primary time-point and analyzed in this paper) and 16. Mixed-effects models were used to evaluate symptom burden over time.

RESULTS

Data from 75 children (37 IG, 38 WG) were analyzed (mean age=13.3 years, 58.8% male, 74.7% white). Of them, 43.9% had leukemia, and 17.5% brain tumor. On average, the IG completed 11 (possible min=0 max=16) and the WG completed 5 (possible min=0 max=8) symptom checklists; of them, 60% triggered symptom alerts. Results of the mixed-effects models showed significantly (p< 0.05) improvement in fatigue, sadness, worry, appetite and headache. No significant changes were found on others. For SMBQ, IG parents reported significantly in favor of “enough time with my child's doctors/nurses to talk about symptoms” than WG parents from baseline to week 8. No significant differences between IG and WG over time on other SMBQ items.

CONCLUSIONS

Our preliminary findings showed SyMon-SAYS alleviated emotional related symptoms over time. Physical symptoms might be related more to disease severity and treatment intensity, which we plan to investigate when more data is available.
QOL-17. UNDERSTANDING MULTIDISCIPLINARY PROVIDER PERSPECTIVES AND PREFERENCES FOR INCORPORATING EXERCISE INTO PRIMARY BRAIN TUMOR MANAGEMENT
Authors: Fogh Shannon , Hernandez Yanel , Ambati Vardhaan , Collis Sophia , Tawil Michael , Zhang Lucy , Greenstein Alexa , Frederic Regan , Destri Mary , Hoffer Naomi , Mishra Kavita , Marshall Natalie , Chang Susan M , Taylor Jennie
Published: November 2022

BACKGROUND

Exercise has proven benefit in patients with cancer with most studies focused on patients with high functional and neurocognitive status. Patients with brain tumors, however, frequently have deficits in cognition, motor, balance, or other symptoms that are further exacerbated by surgery and adjuvant treatment. We sought to determine providers’ knowledge, attitudes, motivating factors and preferences for integrating exercise into the treatment of patients with brain tumors.

METHODS

We surveyed multidisciplinary providers in Neurosurgery, Radiation Oncology and Neuro-Oncology from a single, quaternary medical center. Questions assessed demographics, current practices, attitudes, knowledge, motivating factors and barriers for integrating exercise into treatment. Questions were extrapolated from existing published questionnaires and sent electronically.

RESULTS

Most providers (92%) reported that exercise was important for patients' lifestyle and 80% felt it should be integrated into the treatment of patients with primary brain tumors. Nighty-six percent felt that exercise improved quality of life, decreased fatigue (100%) and reduced treatment related side effects (92%) yet only 57% of providers initiated a conversation about exercise with patients. Top motivating factors for promoting exercise were perceived benefit to patients’ quality of life and disease outcomes. Barriers to provider/patient discussions about exercise included, lack of time or appropriate expertise to discuss exercise with patients, and concern that patients have competing priorities. Some providers (23%) were concerned about potential limitations/complications with patients exercising including inability to participate from side effects of treatment (38%), physical deficits (61%) and fatigue (42%).

CONCLUSION

Understanding barriers for providers to incorporate exercise into their patients’ treatment regimens is critical to strategizing best practices. Findings from this study help to expand our understanding of barriers and facilitators to incorporating exercise interventions into brain cancer treatment and will assist with the implementation of a structured exercise program to enhance physical health for our patients.
QOL-19. RETURNING TO WORK AFTER A BRAIN TUMOUR – “I THOUGHT I WOULD BE BACK AT WORK THE NEXT WEEK, HOW WRONG I WAS!”
Authors: Nicklin Emma , Phang Isaac , Short Susan , Hoogendoorn Petra , Boele Florien
Published: November 2022

BACKGROUND

Returning to work is important for patients' and their families’ well-being, financial circumstances and quality of life. Side-effects of brain tumour (BT) treatment or clinical deterioration from BT progression often causes temporary or permanent inability to work. Aim: To explore the occupational expectations, experiences and satisfaction of BT patients (and their caregivers) following diagnosis/treatment.

METHODS

Qualitative semi-structured interviews were conducted with adults diagnosed with a primary BT, in employment/self-employed before diagnosis, currently in follow-up care; and their caregivers. Purposive sampling ensured a mixed BT sample. Participants were recruited from two UK tertiary referral hospitals. Data collection and thematic analysis are ongoing and will be completed by August 2022.

RESULTS

To date, 17 interviews (13 patient/4 caregiver) have taken place (59% female, aged 26-73,M= 43). Early findings: 1) Managing expectations: Patients underestimated the impact of surgery and how long it would take to return to work (if they had). Many would have liked more information prior to treatment about potential side-effects (e.g., extreme fatigue). 2) Prior financial support: Most patients suffered financially, often resulting in returning to work before they felt ready. Patients wanted more information prior to treatment about financial support. 3) Ongoing communication: Employers who were emotionally and practically supportive throughout the BT trajectory were highly valued. Some interviewees believed their employers needed to receive better education about BTs. 4) Flexible working: Patients returning to work with enhanced employer support (e.g., reduced hours, working from home and lighter duties) were more satisfied. 5) Better caregiver support: Many caregivers were unsupported by their employers to take carer leave, some worked more to support the family financially.

CONCLUSIONS

Preliminary findings offer novel data in an under-researched area. More knowledge around the experiences, barriers and facilitators influencing patients’ return to work will allow the planning of tailored occupational support and resources.
QOL-22. IDENTIFYING HEALTH STATUS PROFILES AMONG LONG-TERM CNS TUMOR SURVIVORS: A LATENT PROFILE ANALYSIS
Authors: Stockdill Macy , Armstrong Terri , Mendoza Tito , Miaskowski Christine , Cooper Bruce , Vera Elizabeth
Published: November 2022

CNS tumors are associated with a high mortality rate, quick onset, limited therapeutic options, and a devastating symptom burden that has a negative impact on general health status and results in functional limitations. While research is focused on development of new therapies, little is known about the health status of long-term survivors. We aimed to identify subgroups of CNS tumor survivors ( > 5 years from diagnosis) with distinct health profiles using latent profile analysis ordinal logit estimation in Mplus V8.8. General health status was measured using the EQ-5D-3L (dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Associations with demographic/clinical characteristics were identified with Pearson’s correlations and chi-square tests. Sample median age was 48 years (range: 21-85), 54% were male, 82% Caucasian, 56% employed, and 53% had a KPS ≥ 90. Most had a high-grade glioma (60%), at least one recurrence (70%), and 17% were on active treatment. Two subgroups were identified: good health status (GHS) (n=183) and poor health status (PHS) (n=115). Most patients in the GHS ( > 86%) reported no issues with mobility or usual activities and 100% had no self-care issues. However, 38% did report some problems with anxiety and depression and 21% had pain. PHS class was characterized by > 94% having at least moderate issues with mobility and usual activities and over 50% having pain, self-care issues, and anxiety and depression. Older age (r=0.21), spine tumors (OR=3.3), active treatment at assessment (OR=2.9), tumor recurrence (OR=4.2), unemployment (OR=3.5), and poor KPS scores (OR=18.1) were associated with belonging in the PHS. While maintaining physical health and function may contribute to better health status in long-term survivors, patients dealing with tumor recurrence, ongoing treatments, and spine tumors may face significant challenges. These functional profiles can be used to develop survivorship care plans and supportive care interventions.
QOL-23. TOWARDS PATIENT-REPORTED OUTCOME ASSESSMENT IN THE MOLECULAR TUMOR BOARD – CANCER PATIENTS UNDER TARGETED THERAPY: APP-BASED ASSESSMENT OF PATIENT-REPORTED OUTCOMES (TRACE)
Authors: Renovanz Mirjam , Bombach Paula , Grosse Lucia , Rieger Johannes , Skardelly Marco , Rieger David , Hille Hanni , Volkmer Sebastian , Dörner Lorenz , Kurz Sylvia , Hippler Melina , Paulsen Frank , Öner Öznur , Ruhm Kristina , Beha Janina , Sundberg-Malek Holly , Möller Yvonne , Tatagiba Marcos , Wallwiener Markus , Eckert Nils , Escher Pascal , Pfeiffer Nico , Forschner Andrea , Bauer Armin , Zips Daniel , Bitzer Michael , Malek Nisar , Gani Cihan , Tabatabai Ghazaleh
Published: November 2022

Comprehensive genomic profiling and biomarker-based therapeutic strategies are currently used in clinical trials and in innovative health care systems including the center for personalized medicine network. Systematic assessments of patient-reported outcomes are warranted to gain insight into the perspective of patients and their relatives during biomarker-based therapies. In the present study, we focused on health-related quality of life (HRQoL), psychosocial situation, and physical symptoms in patients treated at the Center for Personalized Medicine Tübingen. First, we retrospectively evaluated symptom burden of n=265 (neuro-)oncological patients in the Molecular Tumor Board (MTB). Sixty percent of patients reported at least 1 neurological symptom, and psychosocial burden/unmet needs were high (overall 156/265; 59%, patients with malignant tumors n=86/106; 81%, Fisher’s exact, p < 0.0001). We therefore developed an app by 14 expert rounds and pretesting including validated assessments of HRoL, symptom und psychological burden and tested it in a pilot study. We conducted a structured interview with users 3 months afterwards to assess the app’s usability and feasibility. The interview was transcribed and analyzed according to a qualitative content analysis. So far, a total of 10 patients and caregivers have been enrolled in this pilot study. They reported that (i) the app is compatible with their daily routine (median 9.3, range 0-10), that (ii) they are more aware of their health status, which was rated as positive, and that (iii) completing app-based questionnaires was easier compared to paper questionnaires. Two patients reported technical problems, which were resolved timely. The pilot study proved feasibility and acceptance of the app. The app might optimize symptom burden assessment, adapted to the patients’ profiles. The next step is to prospectively compare HRQoL before and after start of targeted therapy in a multicenter study.
RBIO-03. A MULTI-INSTITUTIONAL EXPERIENCE OF GAMMATILE BRACHYTHERAPY AS TREATMENT FOR RECURRENT GLIOBLASTOMAS
Authors: Chen Clark , Ferreira Clara , Dusenbery Kathryn , Hoang Kimberly , Lee Stuart , Smith Kris
Published: November 2022

BACKGROUND

Recurrent glioblastoma remains a disease without established standard of care. Here, we report the safety profile and survival outcome of recurrent glioblastoma patients treated with maximal safe resection followed by intraoperative placement of GammaTile (GT), a collagen tile-embedded Cs-131 brachytherapy platform.

METHODS

The study included isocitrate Dehydrogenase (IDH) wild-type glioblastoma patients who suffered tissue confirmed recurrence after concurrent temozolomide-radiation therapy. The series included consecutively patients treated at the University of Minnesota, Barrow Neurological Institute, Vidant Health, and Emory University Hospital. Survival results were stratified by methyl-guanine methyl transferase (MGMT) promoter methylation status

RESULTS

In total 48 patients were treated between 2019 and 2022 in this multi-institutional experience. The median days of hospitalization following the procedure was two (range: 1-15), with 72.5% of the GT implanted patients discharged home before postoperative day three. In terms of post-operative course, two patients suffered new-onset seizure post-surgery (4.0%). There was one (2%) 30-day mortality from intracranial hemorrhage secondary to heparinization for an ischemic limb. There were 13% readmission within 30 days, including hydrocephalus (n=2), urinary tract infection (n=1), deep venous thrombosis (n=1), failure to thrive (n=1), and infected wound (n=1). Of note, the patient with the infected wound had suffered a previous wound infection prior to the GT implantation and the pathogenic organism for both infections were the same (S. aureus). With a median follow-up of 250 days, twelve-month local control was 82%. Median overall survival (OS) from the time of diagnosis was 19 and 33 months for the MGMT unmethylated and methylated tumors, respectively. Select patients (n = 6) treated with adjuvant ketogenic diet in addition to GT and subsequent chemotherapy exhibited survival beyond expectation (> 14 mo, median survival not reached).

CONCLUSION

This multi-institutional experience supports further investigation of GT brachytherapy as a treatment for recurrent glioblastomas.
RBIO-07. HIGHER CSF IL-10 CORRELATE WITH BRAIN ATROPHY AFTER WHOLE BRAIN RADIATION THERAPY IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Nagashima Hiroaki , Hori Tatsuo , Iwahashi Hirofumi , Tanaka Kazuhiro , Sasayama Takashi
Published: November 2022

Whole brain radiation therapy (WBRT) to primary central nervous system lymphoma (PCNSL) correlate with brain atrophy and leukoencephalopathy on serial computed tomography or MRI scans, negatively impacting cognitive function and quality of life. We retrospectively evaluated 53 patients with histologically proven PCNSL who underwent cerebrospinal fluid (CSF) examination including β2-MG, sIL2R, CXCL13, and IL-10 preoperatively. All patients were newly diagnosed and followed up every 3 months from the day they were discharged from the hospital. Follow up period is at least 1 year from last day of chemotherapy. Clinical data included patient demographics, radiological and characteristics; whole brain volume (mm2) calculated from BainLabTM automatically, Global Cortical Atrophy (GCA) for global brain atrophy, Medial Temporal Atrophy (MTA) for temporal atrophy, and Fazekas scale for white matter lesions. The unpaired t test and multivariable liner regression were used to examine the clinical, CSF and radiological characteristics of patients. The mean age at symptom onset was 65.2 years (47-85 years). Thirty three of 53 (62%) patients underwent WBRT with chemotherapy (WBRT group). In all patients, multivariable analysis revealed WBRT correlate with brain volume reduction (p=0.0005) and progression of temporal lobe atrophy (p=0.0056). In addition, Age correlated with increasing white matter lesions at 1 year after chemotherapy (p=0.0422). In WBRT group, multivariable analysis indicated that high CSF IL-10 level accelerated brain volume reduction (p=0.0122) and temporal lobe atrophy (p=0.0343) at 6 months after chemotherapy. However, there were no significant factor for influencing brain atrophy at 1 year. Higher IL-10 ( > 100mg/ml) level demonstrated higher brain atrophy rate (p=0.0366) and severe temporal atrophy at 1 year (p=0.0214). In elderly patients with high preoperative CSF IL-10 levels, cerebral atrophy and toxic leukoencephalopathy may progress in short period of time after WBRT. We should consider treatment strategy that avoid WBRT, such as R-MPV chemotherapy, for PCNSL patients.
RTID-06. A RANDOMIZED CONTROLLED TRIAL USING ACCELERATOR-BASED BNCT SYSTEM FOR REFRACTORY RECURRENT HIGH-GRADE MENINGIOMA
Authors: Miyatake Shin-Ichi , Wanibuchi Masahiko , Kawabata Shinji , Furuse Motomasa , Ono Koji , Nihei Keiji , Akita Kazuhiko , Ko Naonori
Published: November 2022

BACKGROUNDS

Recently, nuclear reactors have been replaced with accelerator-based neutron sources (ABNS) for boron neutron capture therapy (BNCT). High-grade meningiomas (HGM) are refractory, especially recurred after some radiotherapy. We are now applying randomized controlled trial (RCT) of “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent high-grade meningioma”.

STUDY DESIGN

PMDA in Japan which is a counter part of FDA in USA suggested the importance of RCT even for this exploratory clinical trial for HGM. Along to this suggestion, we prepared 2 study groups, BNCT test treatment group and control best supportive care (BSC) group. Progression free survival (PFS) was set-up as primary endpoint. Rescue BNCT is allowed for control group patients, if they showed progress disease (PD) during observation. Two-dimensional modified Macdonald criteria is adopted for assessment.

METHODS

The trial started in August 2019. Eighteen subjects were enrolled and divided in 12 and 6 subjects for BNCT and control BSC group, respectively. Cyclotron-based ABNS system was used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. The last patient-in was August 2021.

INTERIM RESULTS

(as of April 30, 2022): All 6 cases of control group were judges as PD. Seven out of 11 cases of BNCT group were judged as PD. One case of BNCT group dropped out from the study with withdrawal of consent. Median PFS were 8 and 64 weeks for control group and BNCT group, respectively. Log-rank test showed marked statistical difference with p-value of 0.000401 between these 2 groups.

CONCLUSIONS

This RCT showed a marked difference of PFS between accelerator-based BNCT group and control group, so far. We will keep on observation at least next 2 years for other endpoints.
SURG-02. INTRAOPERATIVE RADIOTHERAPY FOR BRAIN METASTASES: EVALUATION OF ELECTROCORTICOGRAPHY AND PERI-OPERATIVE SEIZURE RISK
Authors: Cifarelli Christopher
Published: November 2022

BACKGROUND

Intraoperative radiotherapy (IORT) has emerged as a viable tool for consolidation of surgery and radiation for brain metastases into a single episode of care, but its relative novelty compared to SRS or fractionated radiotherapy warrants evaluation of its safety. While post-operative seizure risk is typically minimal with the use of anti-epileptic drugs during the peri-operative phase, the risk of intra-operative epileptiform discharge remains unknown.

METHODS

Five consecutive cases of surgically resected brain metastases treated with IORT underwent electrocorticography via direct cortical electrode recordings adjacent to the resection cavity with paddle electrodes used for mapping of phase reversal. Continuous recordings were made before, during, and after radiation delivery and analyzed for evidence of radiation-associated changes.

RESULTS

No evidence of significant electrophysiological change was noted in any of the cases, nor was there any clinical evidence of seizure in the immediate peri-operative period. These data represent the first direct cortical recordings in human subjects during the delivery of radiation.

CONCLUSIONS

In this small cohort of IORT treated resected brain metastases, the delivery of intra-operative radiation does not appear to impact cortical activity or precipitate post-operative seizures. Further studies are needed to determine the long-term incidence of treatment associated changes if they exist.
SURG-06. PREOPERATIVE NEOADJUVANT GAMMA KNIFE RADIOSURGERY IN THE TREATMENT OF LARGE BRAIN METASTASIS: AN INITIAL CASE SERIES OF SINGLE INSTITUTE
Authors: Kim Seon-Hwan , Kim Kyung Hwan , Lee Han-Joo , Kwon Hyon-Jo , Choi Seung-Won , Koh Hyeon-Song , Youm Jin-Young
Published: November 2022

BACKGROUND

Postoperative stereotactic radiosurgery (SRS) following the surgical resection of large brain metastasis is a promising therapeutic option to reduce local recurrence. However, there is an increased risk of radiation necrosis and leptomeningeal spreading and an issue of problematic target delineation. Neoadjuvant SRS, also called preoperative SRS, is an emerging treatment paradigm which delivers radiation in the preoperative setting. An initial series of single-institute cases treated with the neoadjuvant SRS followed by surgical resection of a large BM was reviewed. Method: Between 2019 and 2022, 5 patients underwent neoadjuvant SRS using Gamma Knife radiosurgery (GKS) unit, followed by surgical resection. Local tumor recurrence, distant tumor recurrence, leptomeningeal seeding, and overall survival were investigated. Pathologic findings and surgical gross findings were reviewed.

RESULTS

The mean age was 59 and 3 patients were female. All patients had multiple lesions, ranged 2 to 7, including a large lesion (mean tumor volume: 29.8 cc). The interval between GKS and surgery was varied between 1 to 14 days. The prescribed dose of plan-to-resect lesion was 12 Gy in four patients and 14 Gy in one patient. All patients underwent gross total resection without surgical complications and had no radiation-induced toxicity. 3 patients were died of extracranial progression during follow-up period, including 1 patient who died before the first follow-up image. Local tumor progression was noted in 1 patient 9 months after treatment. The mean overall survival was 4.5 months although two patients continued to require follow-up.

CONCLUSIONS

Neoadjuvant SRS may be safe and advantageous for the treatment of BM that require surgical intervention. Long-term investigation with larger patient cohorts and further randomized trials are essential to verify the efficacy of the approach.
SURG-10. PERMANENT CARRIER-EMBEDDED CESIUM-131 BRACHYTHERAPY FOR THE SALVAGE TREATMENT OF PREVIOUSLY IRRADIATED, RECURRENT BRAIN METASTASES
Authors: Imber Brandon , Beal Kathryn , Reiner Anne , Giantini-Larsen Alexandra , Yang Jonathan , Aramburu-Nunez David , Cohen Gil’ad , Brennan Cameron , Tabar Viviane , Young Robert , Moss Nelson
Published: November 2022

BACKGROUND

Salvage of recurrent, previously-irradiated brain metastases (rBrM) is a significant clinical challenge. High local failure is seen following salvage resection without adjuvant re-irradiation, while re-irradiation is associated with high radionecrosis rates. Salvage surgery plus intraoperative Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced integral brain dose versus re-irradiation.

METHODS

A prospective registry of consecutively treated patients with post-stereotactic radiosurgery (SRS) rBrM was analyzed. Following resection, cavities were implanted with commercially-available, collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60Gy at 5mm from the cavity.

RESULTS

Twenty patients underwent 24 operations with Cs131 implantation in 25 cavities. Previous SRS occurred a median of 358d preoperatively (range=56-1334). Median maximum preoperative diameter was 3.0cm (range=1.1-6.3) and enhancing volume was 9.5cm3 (range=0.6-69.7). Gross- or near-total resection was achieved in 60%. A median of 16 Cs131 seeds (range=6-30), with a median activity of 3.5U/seed were implanted. Maximal preoperative diameter and enhancing volume were weakly associated with the number of implanted seeds (correlation coefficients=0.50, 0.41, respectively). There was one postoperative wound dehiscence in a multiply resected and irradiated patient with hydrocephalus. With median follow-up of 1.6 years for survivors, 2 tumors recurred (one in-field, one marginal) resulting in 9.8% 1-year progression incidence (95%CI=0.0-23.2). Radiographic seed migration was identified in 7/25 cavities (28%) on scans ranging from 1.9-11.7 months post-implantation, without clinical sequelae.

CONCLUSIONS

With >1 year of follow-up, intraoperative brachytherapy with Cs131 implants was associated with a high rate of local control and a favorable toxicity profile. Modest correlation between preoperative tumor geometry and implanted tiles with high associated cost suggests a need to optimize planning criteria. A randomized trial of salvage resection with or without Cs131 is ongoing (NCT04690348) to assess the incremental benefit of brachytherapy.