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Background Bone marrow procedures cause anxiety and pain in adult patients with cancer. Music is a safe, inexpensive, noninvasive intervention that is easy to implement and is well received by patients and providers. Objectives The purpose of this quality improvement project was to develop, implement, evaluate, and sustain a music protocol during bone marrow biopsy and aspiration procedures for adult patients with hematologic malignancies. In addition, this project sought to decrease pain, anxiety, heart rate, and blood pressure in patients undergoing bone marrow procedures. Methods The project coordinator collected baseline data regarding toleration of bone marrow procedures and then implemented a music protocol during the procedures during a six-month intervention phase. Comparison variables included pain, anxiety, heart rate, blood pressure, and subjective impressions. Findings The music protocol resulted in improved patient anxiety, decreased procedure time, and decreased medication use during bone marrow procedures. All patients who used the music intervention indicated they would use it again.

Background Spirituality can impact patients’ attitudes and decisions about treatment and end-of-life care when coping with cancer. Previous studies documented health-related quality of life (HRQoL) and spiritual well-being (SWB) as positively correlated within a general cancer patient population, but little is known about their association in the primary brain tumor population. We sought to measure SWB in primary brain tumor patients and evaluate whether it was associated with HRQoL. Methods Six-hundred and six patients treated at The Preston Robert Tisch Brain Tumor Center at Duke between December 16, 2013 and February 28, 2014 with data in the PRoGREss registry are included in this retrospective analysis. Each patient completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-Sp-12) and -Fatigue (FACIT-F), and the Functional Assessment of Cancer Therapy-General and -Brain (FACT-G and FACT-Br). Results Mean age was 49.1 years (SD = 13.5 years), male (N = 328, 54.1%), married (N = 404, 66.7%), at least college-educated (N = 381, 62.9%), and diagnosed with a high-grade glioma (N = 412, 68.0%). Multiple regression analyses were performed on both the FACT-G and the FACT-Br using the FACIT-Sp-12 sub-scales of Meaning/Peace and Faith, FACIT-F, belief in God or a higher power, prayer, gender, tumor grade, and Karnofsky Performance Status (KPS) as predictors. We found that greater SWB (measured by FACIT-Sp-12) was associated with better HRQoL (measured by FACT-G and FACT-Br; p < .0001). Conclusion The association between reported SWB and reported improved HRQoL emphasizes the importance of spirituality in primary brain tumor patients, suggesting SWB must be considered in strategies to improve HRQoL.

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.

INTRODUCTION Neurocognitive dysfunction can result from radiation therapy which is the mainstay of treatment for high-grade glioma, particularly glioblastoma. Preclinical observations found that BMX-001, a novel metalloporphyrin, acts as a radioprotectant for normal CNS cells yet as a radiosensitizer to cancer cells in human GBM xenograft experiments. In a phase 1 study evaluating the safety of BMX-001 in combination with concurrent radiation therapy and temozolomide, we further studied neurocognitive function before and after concurrent radiation therapy and temozolomide in newly diagnosed high-grade glioma patients. METHODS We performed a phase 1 study of BMX-001 combined with radiation therapy (6-week total of 59.4-60 Gy) and temozolomide (75 mg/m2/day for 42 days). We administered BMX-001 as a subcutaneous injection at a loading dose before radiation therapy and temozolomide and then subsequent doses twice weekly for eight weeks. A key secondary endpoint was the evaluation of neurocognition. We performed neurocognitive testing with the computerized program CNS Vital Signsâ. This battery consists of seven tests: verbal memory, visual memory, finger tapping, symbol digit coding, the Stroop Test, a test of shifting attention, and a continuous performance test. We defined neurocognitive impairment at baseline as a z-score ≥ 1.5 SDs below the normative mean. We described improvements or declines in neurocognition at 2 and 6 months from baseline. RESULTS Fifteen patients (age 19-80 years) enrolled and underwent neurocognitive testing before and after RT. All patients had WHO grade 4 glioblastoma. Most subjects had neurocognitive impairment ranging from 46.7-to 80% on specific neurocognitive tests. At two months (N=15) and six months (N=9), most testing demonstrated improved neurocognitive performance. CONCLUSIONS Neurocognitive function is maintained and can improve after concurrent radiation therapy and temozolomide in this high-grade glioma cohort treated with BMX-001 during concurrent radiation therapy and temozolomide.

CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated. One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150–200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1–5 with aprepitant day 1: 125 mg, days 2–5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2–7), as well as safety and quality of life (QoL). Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity. Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV’s effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.

Background and purpose Little is known about complementary and integrative health intervention usage in the primary brain tumor population. We aimed to identify the percentage of patients using these practices and explore the impact on quality of life. Materials and methods Clinical records from patients seen in clinic between December 16, 2013 and February 28, 2014 were reviewed retrospectively. The questionnaires used were a modified version of the International Complementary and Alternative Medicine Questionnaire, the Functional Assessment of Cancer Therapy- Brain Cancer and the Functional Assessment of Chronic Illness Therapy- Fatigue. Results 76% of patients utilized a complementary and integrative health modality. The most frequently reported modalities used were vitamins, massage, and spiritual healing, prayer, diet and meditation. Conclusion These results confirm the usage of complementary and integrative health practices within the primary brain tumor population; however, there was no evidence of association between use and quality of life.

Nurses play an integral role in high-quality patient care. Thus, their skills in providing end-of-life care should be assessed and continually enhanced. Education intended to improve end-of-life skills must address the affective/emotional component of nursing care. Evidence demonstrates that emotional engagement and resilience among health care providers are correlated with improved quality outcomes and, conversely, that burnout and stress negatively affect patient safety. Addressing the emotional needs of health care providers is critical to improving quality throughout the health care system. An evidence-based workshop was implemented among direct care staff on a hospital-based palliative care unit, with the goal of fostering emotional engagement to improve staff perceptions and attitudes about caring for patients at or near the end of life. Although perceptions about quality of death were not affected by this intervention, there was a significant improvement in attitudes about end-of-life nursing care. Qualitative feedback also reflected appreciation for small group discussions and opportunities to debrief with peers away from the unit. This intervention reflected the value of emotional engagement in educational efforts to improve end-of-life nursing care.

Glioblastoma (GBM) patients can use tumor-treating fields (TTFs) with adjuvant temozolomide (TMZ) to treat their disease. TTFs involve wearing transfixed transducers to the shaved scalp, and the transducers are wired to a battery pack that is either fixed or carried (weighing 2.7 pounds). EF-14 clinical trial did evaluate health-related quality of life with standardized patient-report outcome measures but did not measure exercise behavior. We sought to evaluate the exercise behavior of GBM patients using TTFs. We consented GBM patients who intended to use TTFs with adjuvant TMZ after completion of chemoradiation. After informed consent and before starting TTFs, patients completed a self-administered questionnaire, Godin Leisure-Time Exercise Questionnaire, to assess exercise behavior/physical function. To calculate our primary outcome of total exercise behavior, the frequency of exercise sessions per week within each intensity category was multiplied by the average reported duration, weighted by an estimate of the MET, summed across all intensities, and expressed as average MET-hr/wk. Prior work has defined that physical function can be compared as < 9 MET-h/wk vs. ≥ 9 MET-h/wk. We evaluated at baseline and up to 24-week exercise behavior in patients with TTFs vs. historical controls not using TTFs. We enrolled 19 total GBM patients, with 14 proceeding to use TTFs. Of the 14 patients on TTFs, seven patients (50%) completed ≥ 9 MET-h/wk of exercise, and this level was maintained 8, 16, and 24 weeks after starting TTFs. Six months after the completion of chemoradiation, mean MET-h/wk was decreased in the TTFs group (n=6) (10.71 sd=7.06) vs. historical controls (n=38) (27.35 sd=46.94). TTFs did not interfere with exercise behavior in our GBM cohort, but when compared to GBM patients not utilizing TTFs, there could be a long-term impact on exercise behavior. More research is needed to evaluate exercise behavior in GBM patients using TTFs.

Purpose: At diagnosis and throughout the disease course, patients with high-grade glioma (HGG) experience a diminished quality of life (QOL) and increased fatigue. Naltrexone, an orally semisynthetic opiate antagonist, is FDA-approved for the treatment of heroin/alcohol addiction, and low dose naltrexone (LDN) has been observed to improve QOL and lower fatigue in other neurological illnesses, such as multiple sclerosis. LDN is believed to function as a partial agonist and can lead to shifts in neurochemicals that reduce fatigue. Based on this, we sought to study whether LDN has an impact on QOL and fatigue in patients with HGG. Methods: In a placebo-controlled, double-blind study, we randomized 110 HGG patients to receive placebo (N=56) or LDN 4.5 mg orally at night (N=54). Subjects received LDN or placebo at day 1 of concurrent radiation and temozolomide therapy and continued for 16 weeks. Change from baseline in patient-reported outcomes of QOL (Functional Assessment of Cancer Therapy-Brain) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) was assessed. Results: Demographics were WHO grade IV (85%), male (56%), KPS 90-100 (51%), grossly resected (55%), and mean age of 56 years. QOL and fatigue changes between baseline and post concurrent chemotherapy and radiation therapy were not significantly different between patients receiving LDN or placebo. The adverse event profile for LDN and placebo were similar and attributed to concomitant use of temozolomide. Conclusions: While safe to administer, LDN has no effect on QOL and fatigue in HGG patients during concurrent chemotherapy and radiation therapy. United States National Library of Medicine Clinical Trials.gov NCT01303835, Date 2/25/2011

BACKGROUND Low grade gliomas (LGGs) develop in young adults and represent 10-15% of all glial tumors. While LGG patients can have longer survival than higher grade tumors, progression, transformation, and ultimately mortality occurs. Mutations in Isocitrate dehydrogenase 1/2 (IDH1/IDH2) are prevalent in LGG and are responsible for gliomagenesis. The classic IDH1 mutation is located at 132 codon and represented as p.Arg132His, but there are non-canonical IDH1 and IDH2 mutations. We sought to compare clinical characteristics of LGG patients with classic IDH1 p.Arg132His mutation to LGG patients with non-canonical IDH1 and IDH2 mutations. METHODS We queried an IRB-approved registry retrospectively from 12/2004- 9/2019. We included IDH1/IDH2 mutant LGG (WHO grade II) and known IDH1 and IDH2 targeted mutation analysis using standard PCR followed by DNA sequencing to detect point mutations in IDH1/IDH2 genes. We obtained available clinical and histopathological data. We estimated progression-free survival (PFS), time to transformation (TT), and overall survival (OS) using Kaplan-Meier methods. RESULTS We identified 267 LGG patients with median follow-up of 9.1 yrs (95%CI 8.4-9.9 yrs). Classic IDH1 p.Arg132His mutation occurred in 223 (83.9%) patients. IDH2 mutations occurred in 14 (5.2%) patients. Non-canonical IDH1 mutations were in 30 (11.2%) patients and included the following mutations: p.Arg132Cys (13), p.Arg132Gly (10), p.Arg132Ser (4), p.Arg132Leu (1), p.Arg119Gln (1), and p.Arg172Met (1). Initial presentation, OS, and TT did not differ between IDH1/IDH2 groups. PFS differed significantly between groups with improved median PFS in IDH2 mutant LGG (5.4 yrs; 95%CI 3.5-25.2) versus classic IDH1 mutant LGG (4.1 yrs; 95%CI 3.7-4.9 yrs) and non-canonical IDH1 mutant LGG (2.6 yrs; 95%CI 2.1-4.8) (log-rank p=0.019). Notably, non-canonical mutations were more common in astrocytoma (22/30; 73.3%) than other LGG histologies (p=0.018). CONCLUSIONS In this cohort, LGG patients with non-canonical mutations have a shorter time to progression than patients with classic p.Arg132His mutation and IDH2 mutations.

INTRODUCTION We previously reported to SNO, high levels of psychosocial distress in adult patients with primary brain tumors (PBTs), particularly during the first 6 months following diagnosis. The purpose of this follow-up study was to identify patterns of distress among older (≥ 65 years) patients with glioblastoma (GBM) compared to their younger (ages 18-64) counterparts. METHODS In our initial cross-sectional study, we collected the National Comprehensive Cancer Network’s Distress Thermometer (NCCN-DT) and problem list from adult patients with PBTs (WHO grades I-IV) seen at our institution between December 2013 and February 2016. We performed subsequent analyses on a subset of patients with GBM. RESULTS We identified 343 patients with GBM from the original dataset, of which 23.0% (n= 78) were ≥ 65 years old. The proportion of patients ≥ 65 years old with elevated distress (i.e. DT ≥ 4) was greater than the proportion of younger patients reporting elevated distress (47.4% vs 30.6%; p= 0.0068). Elevated distress was significantly greater during the first 6 months post diagnosis for all ages (p= 0.008). In subgroup analyses, a decrease in distress beyond 6 months was seen in younger patients (45.7% vs 27.4%; p= 0.021), but not in older patients. In older patients, a greater number of problems were selected on the NCCN DT and problem list tool: emotional and physical concerns were reported more frequently compared to their younger counterparts. Older patients were more likely to report difficulty with “bathing” and “getting around” (p= 0.009, p< 0.001, respectively). There were no differences in older versus younger GBM patients with regard to housing, transportation, treatment decisions, depression, fatigue, or memory. CONCLUSIONS In contrast to their younger counterparts, older patients with GBM experienced elevated levels of distress and a greater absolute number of specific psychosocial problems, mostly related to emotional and physical concerns.

Patients with glioblastoma have poor overall survival and experience significant burden from neurologic decline and adverse treatment effects. Despite the well-known benefits of early palliative care integration with oncology care, utilization of palliative care is low. The purpose of this quality improvement (QI) project is to investigate the feasibility, value, and effectiveness of using an adapted palliative care screening tool to improve outpatient palliative care screening and referral of glioblastoma patients. This QI project was conducted over a 10-week period. A glioma palliative care screening tool was developed and integrated into outpatient visits. Providers were required to use the screening tool during each patient visit. Patients 18 years or older who were diagnosed with a World Health Organization grade IV glioma and returning to the neuro-oncology clinic for a brain MRI evaluation were targeted. Screening, palliative care discussion, and referral rates were evaluated. Among 530 eligible patients who returned to the clinic over a 10-week period, the tool was available for 433 patients. Fifty-six percent (n = 294/530) of the patients were screened. Nine percent (n = 27) of screened patients were identified as candidates for a palliative care referral (score ≥ 5 on the screening tool). Of these 27 patients, the proportion of patients who had a palliative care discussion was 63% (n = 17). Overall, 71% (n = 12) of patients who had a palliative care discussion were referred to a palliative care provider. Integrating a glioma palliative care screening tool with outpatient visits can draw attention to palliative care needs and lead to a referral to palliative care.

OBJECTIVE There is no validated model for delivering palliative care (PC) in the glioblastoma (GBM) population. The primary objectives were to assess the feasibility and determine the acceptability of a time-based model of integrated specialty PC to patients and providers. Secondary objectives were to estimate the impact on healthcare utilization and quality of life (QoL) compared to historical controls. METHODS We consented and referred patients to PC at their initial Neuro-Oncology consultation between 4/2018 and 5/2019. We conducted QoL assessments (NCCN Distress Tool; Functional Assessment of Cancer Therapy-Brain (FACT-BR); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); Epworth Sleepiness Scale (ESS)) at (1) baseline (2) immediately after chemoradiation, and (3) 6 months following chemoradiation. Ongoing PC follow-up was at the discretion of the PC provider. We administered the Edmonton Symptom Assessment System (ESAS) before and after PC visits. We measured patient and referring provider satisfaction using FAMCARE-16 and a PC departmental survey, respectively. RESULTS We did not meet our goal enrollment of 50 patients. 32 were offered participation, 12 consented and 8 attended at least one PC visit. The mean number of PC visits was 1.6. Mean age was 62 (42–79). 75% had a KPS ≥80. Of those that did not complete the study, 2 died and 5 either withdrew consent or declined further visits. At baseline, 91.7 % had a NCCN distress score ≥4. Patients were overall satisfied with the intervention. CONCLUSION Introduction of specialty PC at the time of GBM diagnosis is challenging. Participants reported their experience as overall positive. Results from referring providers are pending. Due to low-enrollment we did not pursue further statistical comparisons regarding healthcare utilization compared to historical controls.

With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress of the patient are important in the clinical care of the patient. Mindfulness meditation is a mind-body therapy that has been recently investigated in the oncology field as a non-pharmacological strategy to ameliorate cancer symptoms and to improve QoL. This practice has not been studied in the primary brain tumor population. We initiated a pilot study among newly diagnosed brain tumor patients with the hypothesis that mindfulness meditation practice may benefit the patient by decreasing stress and anxiety and provide a means to cope with their new diagnosis. The specific aim of this pilot study is to determine the feasibility of a mindfulness meditation program to this population during standard of care chemoradiation and to determine whether it merits additional research in a subsequent trial. The intervention consists of six weekly one hour telephone-based mindfulness sessions followed by one in- person mindfulness session consisting of: mindfulness and healing, understanding stress, abiding in kindness, working with difficult emotions, finding peace, going forward and living fully. Subjects are provided with downloadable guided meditations. We plan to enroll fifteen newly diagnosed WHO grade III or IV malignant glioma subjects prior to their 6 week chemoradiation course. We will determine the percentage of subjects approached vs enrolled, number of sessions that each subject attends, completion of study questionnaires and satisfaction of the subjects. QoL surveys include: Functional Assessment of Cancer Therapy- Brain, Functional Assessment of Cancer Therapy- Cognitive Function, Pittsburgh Sleep Quality Index, Functional Assessment of Chronic Illness Therapy-Fatigue and the Five Facet Mindfulness Questionnaire – short form. 13 subjects have been approached and 8 signed consent over a two-month period. We will provide final study results at time of presentation.

Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in grade II-III gliomas, and the mutant enzyme leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG is responsible for the gliomagenesis associated with these tumors and the promotion of seizures via glutamate receptors. Ivosidenib, a small molecule oral mIDH1 inhibitor, has shown promise in clinical trials to treat IDH1 mutant gliomas, and providers can utilize this agent in IDH1 mutant glioma patients. We evaluated our IDH1 mutant glioma patients treated off-label with ivosidenib and described the radiographic response and seizure control in this cohort when ivosidenib was initiated between October 2020 to February 2021. Radiographic response was determined using RANO criteria, and seizure control was determined by comparing seizures per month before and after initiation of ivosidenib. All patients represented received single-agent ivosidenib dosed at 500 mg orally once a day. One patient required a dose reduction to 250 mg orally once a day because of drug-induced diarrhea. In our cohort of six patients, patient age range was 31 to 74 years with four female patients and two male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=3) oligodendroglioma (WHO), IDH1 mutant, 1p19q co-deleted (n=2), and anaplastic astrocytoma IDH1 mutant (n=1). Three patients experienced a reduction of seizure frequency, two patients did not have seizures before or after therapy, and one patient remained with the same level of seizures (1 seizure/month). Radiographic responses recorded included three patients with stable disease, two patients with minor responses, and one patient with a partial response. Treatment with ivosidenib is ongoing for this cohort of mIDH1 glioma patients. Updated information on prolonged disease control and seizure control in this cohort of IDH1 mutant glioma patients will be presented. Therapeutics, such as ivosidenib, can lead to improved seizure control and radiographic outcomes in IDH1 mutant glioma patients.

INTRODUCTION There is increasing recognition that palliative care (PC) can benefit patients with advanced cancers. However, early referral to PC is not yet a reality for patients diagnosed with a primary brain tumor. We hypothesize that lack of knowledge and/or misperceptions regarding PC by patients, caregivers, or their providers remain barriers. METHODS This is an IRB-exempt, one-time QR-accessible REDcap questionnaire administered to patients, caregivers, and providers at the Preston Robert Tisch Brain Tumor Center between September 2020 and May 2021. We administered 9 questions regarding knowledge and beliefs about PC from the Health Information National Trends Survey 5, Cycle 2: results of this nationally representative U.S. sample are publicly available and used for comparison. RESULTS We had 141 survey respondents: 25 providers, 59 patients, and 57 caregivers. The median patient and caregiver ages were 49 (21-74) and 50 years (24-73), respectively. Caregivers were more likely female (55.2 %) and identified as a spouse or domestic partner (58.2%). Providers, were equally distributed by years of experience. Compared to patients and caregivers, providers reported more baseline knowledge of PC (p< 0.0001, p< 0.0001) and better understood the role of PC in pain/symptom management (p=0.0038, p=0.0087) and social/emotional support (p=0.0044, p=0.0279). Interestingly, most providers (76.0%) disagreed with the statement “the goal of palliative care is to give patients more time at the end of life.” Compared to a general U.S. sample (n=1,162) our patients (n=39) were better informed in only 2 of 9 questions. Whereas, caregivers (n=48) were better informed in 6 of 9 questions. CONCLUSION Neuro-oncology providers were knowledgeable, but a minor gap in understanding the goal of PC was identified. Caregivers were overall more knowledgeable than patients. However, Neuro-oncology patients, had similar knowledge and beliefs compared to a nationally representative sample. PC interventions should prioritize filling knowledge gaps for Neuro-oncology patients.

BACKGROUND Neuro-oncology advanced practitioners (APs - nurse practitioners, physician assistants) require specialization beyond the scope of population-based generalist training and education. There are no specialty standards or certifications for neuro-oncology APs, no formal training programs, and no literature that addresses the competency requirements of neuro-oncology APs. The burden of AP turnover at an academic medical center ambulatory neuro-oncology practice was as high as 50%. This quality improvement project’s purpose was to develop a professional practice model (PPM) to support the professional development and retention of APs. METHODS Using the Focus, Analyze, Develop, Execute and Evaluate (FADE) quality improvement methodology the authors (1) reviewed literature and relevant professional organizations to identify possible professional competencies for neuro-oncology APs, (2) analyzed data to develop evidenced-based practice domains, (3) used purposive sampling to recruit a team of neuro-oncology experts, (4) conducted a Delphi study with the experts to gain consensus on practice domains and professional competencies, and finally (5) utilized the Delphi study results to create a PPM for neuro-oncology APs. RESULTS The authors recruited twenty-three participants (39% were physicians, 57% were APs, and 4% were administrators) for the Delphi study, which was executed via electronic transmission using Qualtrics. Participants reached consensus on six domains of practice (Medical Knowledge, Interprofessional Collaboration/Communication, System-based Practice, Professionalism, Practice-based learning, Patient/family-centered care) and fifty corresponding competency statements after two rounds of the Delphi. With the implementation of the PPM and the development of standardized onboarding, the AP turnover rate decreased from 50% to 12% in just two years. CONCLUSION This QI project successfully created a PPM for a neuro-oncology AP team. The PPM supports neuro-oncology APs by validating their unique skill set that combines several specialties. The PPM provided the framework to standardize orientation/training, evaluate performance, and promote job satisfaction and retention.

Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert TischBrain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2–5), overall CINV CR (days 1–5), and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL–DEX dose administrations 1–3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade≥3 PAL–DEX treatment-related toxicities.Conclusion: Data suggest that PAL–DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma. Keywords: chemotherapy, nausea, chemotherapy-induced nausea and vomiting, antiemetic guidelines, evidence-based practice, glioma

OBJECTIVES: To describe the adaptability to the patterns in symptoms and quality of life (QoL) during 6 months post low-grade glioma diagnosis by valid and reliable tools; to identify through qualitative interviews patient/provider adaptive techniques and strategies; and to assess associations among patient characteristics, symptoms and QoL, and adaptive techniques or strategies. DATA SOURCES: Demographic, clinical and pathologic data from medical records. Validated instruments that assess QoL, fatigue, depression, and distress were completed at 2, 4, and 6 months post diagnosis. Qualitative interviews identifying the symptoms, challenges, adaptive techniques and strategies were conducted at 4 and 6 months. CONCLUSION: The most frequently used adaptive strategies included: obtaining community support (87%), managing expectations (73%) and support systems (67%), and seeking out knowledge about physical (67%) and behav-ioral symptoms (53%). Seizures were reported with IDH1(mut) (11%) but not IDH1(wildtype). Patients with either IDH1(mut) or TERT(mut) consistently reported lower QoL and higher distress, depression, and fatigue scores. IDH1/TERT(mut) may be related to lower QoL because of IDH1(mut)-related seizures. IMPLICATIONS FOR NURSING PRACTICE: Findings provide a list of adaptive strategies and characteristics to address the problems and symptoms that may improve overall QoL in patients with low-grade glioma.

INTRODUCTION: Meningiomas, the most common CNS neoplasm, are often deemed less threatening than their glial counterparts. Unfortunately, these tumors recur and necessitate surgery, radiation, and/or systemic treatment. We explored the psychosocial distress of patients with recurrent meningioma using The National Comprehensive Cancer Network Distress Thermometer (NCCN-DT) and Problem List. METHODS: This was a retrospective analysis of patients with recurrent meningioma seen at the Preston Robert Tisch Brain Tumor Center between 12/31/2004–10/10/2018 who completed a NCCN-DT and Problem List. The first or only NCCN-DT assessment after initial recurrence was used for analysis with a score of 4 indicating moderate to severe distress. RESULTS: 45 patients were identified, 56% female, median age was 61 years and 58% had unifocal disease. 60% were Grade 1, 33% Grade II, 4% Grade III, and 2% indeterminate recurrent meningioma. The median NCCN-DT score was 3, and 49% had a NCCN-DT score 4 indicating moderate to severe distress. 64% of females vs 30% of males reported distress scores 4 (p=0.04). 65% of patients with unifocal disease reported 4 scores compared to 26% with multifocal disease (p=0.02). Fatigue (N=24), Worry (N=23), Nervousness (N=22), Depression (N=19) and Memory/Concentration (N=19) were the most commonly reported problems. A higher incidence of worry among females (64%) than males (35%) was the only problem showing a trend towards significance (p=0.08). Between initial recurrence and NCCN assessment, the type and number of treatments patients received included: surgery (median=1, range 0–5), radiation (median=2, range 0–5), systemic treatment (median=2, range 0–12). There was no association between distress and the number of surgeries (p=0.99), radiation treatments (p=0.49) or systemic therapies (p=0.87). CONCLUSIONS: In our study population, nearly half of recurrent meningioma patients reported moderate to severe distress. Therefore, even in this benign tumor population, the NCCN-DT and problem list should be administered at every clinic visit.

INTRODUCTION Malignant glioma (MG) patients often experience chemotherapy-induced nausea and vomiting (CINV). Olanzapine has recently been added to national anti-emesis guidelines for patients on moderately/highly emetogenic chemotherapy. In this retrospective study, we investigated the use of olanzapine for refractory-CINV (R-CINV) in MG patients. METHODS In this chart review, we queried adult MG patients with KPS ≥ 70 who received olanzapine from January 2019-March 2020. Patients were included if they were prescribed olanzapine for CINV. Data on nausea/vomiting improvement, olanzapine dosing/schedule, number of refractory anti-emetic trials, concomitant corticosteroid use, and demographics were collected. RESULTS We identified 21 MG patients who were prescribed olanzapine, with 9 of those patients receiving olanzapine specifically for CINV. Seven patients had WHO grade IV glioma, and 2 patients had anaplastic astrocytoma (WHO grade III). Five of 9 patients (55.6%) were male, all were Caucasian and median age was 54 years. Patients tried an average of 3 anti-emetics prior to initiating olanzapine for R-CINV. Only one patient was taking concomitant corticosteroids; which is not in concordance with national anti-emesis guidelines. Four of 9 patients (44.4%) achieved control of R-CINV with olanzapine. The olanzapine dose and key biomarkers (IDH-status, MGMT promoter methylation) were similar between those experiencing R-CINV and those without symptoms. CONCLUSIONS In this study, we find that approximately half of patients with R-CINV achieved improved nausea and vomiting control with the addition of olanzapine. The lack of corticosteroid use for anti-emesis in MG continues to make this population challenging to manage. The relatively high success rate in patients that had failed, on average, 3 anti-emetics, suggests that olanzapine may be a potent addition to the anti-emetic toolkit for MG patients. These results inspire further large-scale research to validate this observation and define the optimal role for olanzapine in treating R-CINV in MG patients.

BACKGROUND Primary brain tumor patients experience high levels of distress due to their diagnosis and treatment leading to changes in their health-related quality of life (HRQoL). Even with the standard treatment of 6 weeks of radiation with concurrent temozolomide for malignant gliomas, the prognosis remains poor. We sought to provide a new intervention and coping skill for our patients during chemoradiation to alleviate some of their stress and anxiety. Mindfulness meditation is a mind-body therapy used in many other cancer groups which can alleviate stress and improve fatigue, cognition, and sleep. METHODS 15 newly diagnosed malignant glioma subjects started 1-hour weekly phone mindfulness sessions during the 6 weeks of chemoradiation. They completed an in-person mindfulness session and interview upon return to the clinic with a final follow up survey 2 months later. Patient reported outcomes questionnaires were collected at each time point. RESULTS 0/15 subjects completed their post-chemo/in-person visit, and 9 completed their final follow-up surveys 2 months later. Scores for perceived cognition, fatigue, sleep, anxiety, spiritual-well being and mindfulness improved over these time points. Completed HRQoL patient-reported outcome questionnaires with positive trends noted from the mean (SD) post-chemo/in-person visit change from baseline and the follow-up change from baseline were: FACT-Cog perceived Cognitive Impairments subscale 4.11(13.55), 9.14(16.77); FACT-G total -5.48(16.02), 7.02(13.44); FACT-Br total -3.15(24.76), 13.17(23.37); FACIT-F -5(7.68), 0(7.92); and the FACIT-Sp12 -1.38(7.6), 2.17(4.88). Trail making Part A completion times from baseline to follow up decreased over time in 8/9 subjects and 7/9 subjects in Part B. Per the final follow up survey, 7/9 subjects continued their meditation practices after the training sessions and subjectively noted benefits with their stress and anxiety. Conclusion: Despite this small sample size, this mindfulness meditation intervention did positively impact patient-report outcomes of HRQoL in this patient population, thereby larger randomized studies are warranted.

BACKGROUND From the time of diagnosis to end of life, patients with primary brain tumors experience challenges to maintain quality of life. While traditional research focuses on clinical trials that involve directly treating cancer, we have designed a specific research committee at our institution that promotes supportive care research to improve patients’ and caregivers’ quality of life. Past research has shown that issues key to patients and caregivers often differ from what researchers and providers might appreciate as important. Incorporating input from brain tumor patients and caregivers is vital to direct the most relevant and necessary supportive care research. METHODS As part of an IRB-approved quality improvement project, we sought the opinions of our supportive care research committee about what are the essential quality of life issues for brain tumor patients and caregivers. We polled our committee before and after a session with patients and caregivers discussing factors relevant to their quality of life. After this patient/caregiver intervention, we used a group discussion and note comparison technique to distill down key elements to advance supportive care research for this population. RESULTS Engagement of the committee included members that were neuro-oncology providers, biostatisticians, and data/regulatory/clinical trial staff. Before the intervention, common themes about key issues for patients and caregivers were comfort, pain management, counteracting side effects, cognitive issues, and financial toxicity. While similar themes emerged after the patient/caregiver intervention, the committee gleaned that aspects of communicating outcomes and support of caregivers were consistently mentioned from the discussion session with patients and caregivers. CONCLUSIONS Opinions of brain tumor patients and caregivers are crucial in driving future direction and relevance of supportive care research in neuro-oncology. Our supportive care research committee will continue to engage patients and caregivers and are planning interventions to improve communication and support for caregivers.

In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control. We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54–60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m2/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules. We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67–79 %. Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ.

In medicine, neuro-oncology practice falls outside the scope of established practice requirements for the specialties of neurology, medical oncology, and neurosurgery, justifying the prerequisite of specialized training to practice neuro-oncology. Neuro-oncology advanced practitioners (AP) also require specialization beyond the scope of population-based generalist training and education. This quality improvement project's primary purpose was to develop a professional practice model (PPM) for APs employed at an academic medical center (AMC) ambulatory neuro-oncology practice. Using the focus, analyze, develop, execute, and evaluate (FADE) quality improvement methodology, the authors (1) reviewed literature and relevant professional organizations to identify possible professional competencies for neuro-oncology APs; (2) analyzed data to develop evidence-based practice domains; (3) used purposive sampling to recruit an interprofessional team of neuro-oncology experts; and (4) conducted a Delphi study with an interprofessional team of experts to gain consensus on practice domains and professional competencies. Twenty-three participants (n = 23) were recruited for the Delphi study, which was executed via electronic transmission using the Web-based software Qualtrics. After two rounds of the Delphi survey, the expert team reached consensus on six domains of practice, with 50 corresponding competency statements. Through interprofessional collaboration and consensus, this quality improvement project successfully created a PPM for an AMC neuro-oncology AP team. The PPM supports neuro-oncology APs by validating the unique set of skills that combines several specialties. The PPM provided the framework to standardize orientation and training, evaluate performance, and support the professional development of an AMC neuro-oncology AP team.

Fatigue is one of the most common symptoms experienced by patients with GBM. Whether it is associated with disease or treatment, we have shown in previous studies that fatigue is an independent prognostic factor for survival, and more fatigue is associated with a poorer overall survival. The association between tumor progression and fatigue in newly diagnosed GBM patients was explored within a clinical study investigating the use of bevacizumab (BV) with concurrent chemoradiation, followed by BV and temozolomide with the continuation of BV following progression. In this prospective single-center study, fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at time of study enrollment (before chemoradiation), after chemoradiation, and then every 6 mos until study discontinuation or subject demise. Higher scores on the FACIT-F indicate less reported fatigue. 68 newly diagnosed GBM patients were enrolled with a mean age of 55.4 yrs (sd=10.7 yrs). KPS ranged 70-100 with the following distribution: 70 (n=4), 80 (n=28), 90 (n=34), and 100 (n=2). Subjects who continued study participation 6 mos after the completion of chemoradiation were divided into two groups: subjects with (n=15) and without (n=35) tumor progression 6 mos after chemoradiation completion. Both groups had similar FACIT-F scores at baseline (group with progression mean=38.33 (sd=10.91) and group without progression mean=38.48 (sd=9.30)). Fatigue increased in subjects that had tumor progression to mean=33.60 (sd=11.94) and remained relatively stable in subjects that did not progress with mean=39.05 (sd=9.77). These findings suggest that newly diagnosed GBM patients with similar levels of baseline fatigue will experience increased fatigue when tumor progression occurs. With the association of fatigue levels and survival, more research is needed to combat fatigue and deleterious effects of this symptom on morbidity and mortality in GBM patients.

Lessons Learned Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival. Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis. Background Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3–11 months with bevacizumab (BEV)-containing regimens. BEV in rMG has 6-month progression free survival (PFS-6) of ∼40% and an objective response rate of 21.2%. BEV-containing regimens improve PFS-6 to 42.6%–50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor [VEGF]) by c-Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth. Methods Thirty-six BEV-naïve rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro-Oncology [RANO] criteria), PFS-6, overall survival (OS), and toxicity. Results Median patient follow-up was 65.0 months. Objective response rate was 27.8% (95% confidence interval [CI]: 15.7%–44.1%). Median OS was 11.2 months (95% CI: 7–17.5). PFS-6 was 41.7% (95% CI: 25.6%–57.0%). Most frequent treatment-related grade ≤2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ≥3 events included venous thromboembolism (four patients), including one death from pulmonary embolism. Conclusion Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.

Primary brain tumor patients experience high levels of distress. The purpose of this cross-sectional, retrospective study is to evaluate the level and different sources of psychosocial distress and how these pertain to health-related quality of life (HRQoL). The Primary and Recurrent Glioma registry at Duke’s The Preston Robert Tisch Brain Tumor Center was queried retrospectively for demographic and clinical information on patients seen between December 2013 and February 2014. Data also included the National Comprehensive Cancer Network’s Distress Thermometer (NCCN-DT), Functional Assessment of Cancer Therapy-Brain Cancer (FACT-Br), and Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F). 829 subjects completed questionnaires. 54% were male; 96% completed the NCCN-DT; 33.3% had a DT score ≥4 (moderate/severe distress). Women reported DT ≥ 4 more often than men (38.6 vs 29.0%; p = 0.005). Patients within 1 year of diagnosis reported DT ≥ 4 more often than those 1+ years after diagnosis (38.8 vs 30.9%; p = 0.034). 73.0% reported physical problems; the most frequent being fatigue (43.2%) and memory/concentration (40.9%). 42.0% complained of emotional problems with worry (29.4%) and nervousness (22.4%) being the most common. Patients who reported at least one practical, family, emotional or physical problem had significantly lower HRQoL scores (p

Purpose Chemotherapy-induced nausea and vomiting (CINV) can be prevented in most patients with use of guideline-recommended antiemetic regimens. However, studies have suggested that adherence to antiemetic guidelines is suboptimal. Oncology nurses, as part of a multidisciplinary team, can help promote appropriate antiemetic prophylaxis. Therefore, nurses were surveyed to assess antiemetic guideline awareness and practice patterns of antiemetic use, determine adherence to guideline recommendations, and query barriers to adherence. Methods In September 2015, 531 US-based oncology nurses participated in an online survey administered and analyzed by ONS:Edge. Results Nurses were most familiar with National Comprehensive Cancer Network (73%) and American Society of Clinical Oncology (48%) antiemetic guidelines. While most (77%) felt that antiemetics prescribed were consistent with guideline recommendations, practice patterns of antiemetic use revealed low adherence to those guidelines, particularly during the delayed (25–120 h) phase following highly emetogenic chemotherapy, where only 25% of nurses reported administration of guideline-recommended agents. Overutilization of phenothiazines and benzodiazepines was common. Only 17% of respondents reported that most (> 75%) of their patients have CINV optimally controlled; 39% reported between 6 and 20% of patients have an alteration in their chemotherapy due to CINV, and reports of emergency department/hospital visits due to poorly controlled CINV were high. The predominant barrier interfering guideline-recommended antiemetic prophylaxis was reported as physician preference (71%). Conclusions This survey revealed an opportunity to increase awareness of antiemetic guidelines and a critical need to address barriers interfering with utilization of guideline-recommended antiemetic agents in order to optimize CINV control for patients undergoing emetogenic chemotherapy. Electronic supplementary material The online version of this article (10.1007/s00520-017-3866-6) contains supplementary material, which is available to authorized users.

Prevention of chemotherapy-induced nausea and vomiting (CINV) is a key component of treatment for patients with cancer. Guidelines are available to assist prescribers in the management of CINV associated with single-day chemotherapy regimens. However, currently there are no clear guidelines for management of CINV in patients receiving multiple-day chemotherapy regimens. Serotonin (5-HT3) receptor antagonists are a mainstay in preventing CINV, and palonosetron, given its longer half-life and duration of action relative to other 5-HT3 receptor antagonists, may be a useful option for managing CINV in multiple-day chemotherapy. Here we provide an overview of CINV and CINV treatment options, with a focus on palonosetron. We describe existing challenges in managing CINV, and discuss two patients receiving multiple-day chemotherapy, in whom CINV was managed successfully with palonosetron.

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients’ quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)’s usual practice demonstrates a high incidence (45 %) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network (NCCN)’s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58 %) to antiemetic guidelines may have explained our high CINV incidence. One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL. Adherence to ordering MEC guideline antiemetics increased significantly, from 58 % to a sustained 90 %, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84 % of patients, respectively, did not experience CINV. There was no significant change in QOL. Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.

BACKGROUND: Glioblastoma (GBM) occurs commonly in 6th to 7th decades of life. GBM in young adults (age 18–39 yrs) is rare and the implications of this diagnosis during young adulthood has different considerations than in their older counterparts. We planned to identify young adults with GBM and to evaluate the clinical and histopathological factors in this rare group. METHODS: We queried retrospectively an IRB-approved database registry from 12/2004- 10/2016. We included GBM patients by these factors: 1. Age at diagnosis as 18–39 yrs, 2. Confirmed GBM pathology at initial diagnosis, and 3. Usable information on time to first progression. We excluded patients with an initial diagnosis of WHO grades II-III glioma. We obtained available clinical and histopathological information. We estimated progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier methods. RESULTS: We found 184 young adult patients that met our criteria for inclusion in this evaluation. Median age was 33 yrs with a majority being males (n=109, 59.2%). The majority (89.1%) had surgical resection at time of diagnosis (GTR, n=106 and STR, n=58). Median OS was 41.6 mos (95% CI: 31.2, 51.6), with a 5-year OS of 38.9% (95% CI: 31.2%, 46.5%). Median PFS was 17.2 mos (95% CI: 14.1, 21). Recurrence occurred in 148 patients (80%) and 25% (n=37) were enrolled in clinical trials after 1st recurrence. While most had pathology described as GBM, there were 50 variants (27.2%) including giant cell (n=20), small cell (n=15), oligodendroglial (n=10), PNET (n=4), and rhabdoid (n=1). Known IDH1 status was 29 mutant (15.8%) and 51 wild type (27.7%) CONCLUSIONS: Diagnosis of GBM in young adults associated with a longer OS. Surgical resection at diagnosis and participation in clinical trials are common. Histopathology for this group can be heterogeneous. Providers should tailor treatment and survivorship planning uniquely to the young adult GBM population.

BACKGROUND: Nausea (N) and vomiting (V) continues to be one of the most feared side effects of individuals undergoing cancer treatment with 10–40% (or 60–90% not) experiencing NV with modern-day antiemetics. Trials establishing antiemetic guidelines excluded glioma patients. OBJECTIVES: To assess overall NV efficacy and safety across multiple glioma trials using palonosetron (PAL), aprepitant plus ondansetron, or ondansetron alone in glioma patients receiving either concomitant radiation therapy and temozolomide, adjuvant temozolomide post-chemoradiation, or irinotecan and bevacizumab in the recurrent setting. METHODS: Review of 270 patients enrolled in four Phase II glioma antiemetic trials was conducted to evaluate complete response (CR) rate defined as no vomiting or use of rescue anti-emetic on day 1 (Acute-CR), days 2–5/7 (Delayed-CR), and overall (Complete Control: CC) during 1 week of treatment. Chemotherapy-induced nausea (CIN) and vomiting (CIV) rates were defined as no nausea or no vomiting during the study period, respectively. RESULTS: Mean age=54.8, 61% male, median KPS 80%, 83% GBM. CC for patients receiving PAL with radiation and temozolomide was 74%; Acute-CR was 87%; Delayed-CR was 82%. CIN rates (6779%) were less than CIV rates (8797%). For 63 recurrent patients receiving irinotecan and bevacizumab, the CC rate was 47%, Acute-CR was 62%, and Delayed-CR was 62%. PAL with 5-day adjuvant temozolomide demonstrated a CC of 88%, Acute-CR of 94%, and Delayed-CR of 88 % in 33 patients. CR rates for the 70 patients in the aprepitant/ondansetron arm receiving adjuvant temozolomide were CC: 58.6%; Acute-CR: 97.1%; Delayed-CR: 58.6% and for the 66 in the ondansetron alone arm were CC: 54.5%; Acute-CR 87.9%; Delayed-CR 57.6%. Main attributable adverse events included constipation, headache, and diarrhea and were all grade 1–2. CONCLUSIONS: Review of NV rates in glioma patients are comparable to other cancers. Meta-analysis and safety results will be presented.

BACKGROUND: BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to oxidative stress caused by radiation therapy (RT)and chemotherapy, both critical components in the treatment of high-grade gliomas (HGG). In preclinical studies, BMX-001 functions as a radioprotectant of normal tissue, for example protection of central nervous system white matter and radiosensitizer of human glioblastoma (GBM) xenografts. Therefore, we underwent a phase 1 study to evaluate safety of BMX-001 in newly diagnosed patients with HGG receiving concurrent RT and temozolomide (TMZ). METHODS: We performed a phase 1, single-center, dose-escalation study of BMX-001 in combination with concurrent RT (daily fractions of 1.8–2 Gy given 5 days/week for 6 weeks for a total of 59.4–60 Gy) and TMZ (75 mg/m2 daily X 42 days). We administered BMX-001 as a subcutaneous injection at a loading dose before start of RT and TMZ and then subsequently 2 times/week for 8 weeks. Primary endpoint was determination of the maximum tolerated dose (MTD). We assessed safety using National Cancer Institute Common Terminology Criteria for Adverse Events 4.03. RESULTS: We enrolled 15 subjects with GBM (WHO grade IV) with age range of 19 to 80 years. BMX-001 at 42 mg loading dose and 20 mg subsequent dose was the maximum administered dose and 28 mg loading dose and 14 mg subsequent dose was the MTD. Sinus tachycardia (grade 3) was the dose-limiting toxicity at 42 mg loading dose (n=1). Only other related grade ≥ 3 event seen was hypotension (grade 3) (n=1). Most common related toxicity was grade 1 injection site reaction (n=7). CONCLUSIONS: BMX-001 with RT plus TMZ and post-RT TMZ for patients with newly diagnosed HGG was safe and well-tolerated. Phase II study with BMX-001 in combination with concurrent RT and TMZ in subjects with newly diagnosed HGG is planned.

BACKGROUND: Prognosis of recurrent MG remains poor with a median survival of 3-11 months for patients on BEV-containing regimens. Few active evidence-based treatments are available & response rates have been

Complementary and Alternative Medicine (CAM) uses diverse practices and products that are not a part of standard of care while Integrative Medicine combines both CAM and conventional medicine. Given the poor prognosis of glioblastoma (GBM), many patients will explore other options to improve survival or quality of life. We sought to examine the association between CAM modalities and survivorship. In this cross-sectional retrospective analysis, data about CAM treatment and self-help practices were obtained from the modified International Complementary and Alternative Medicine Questionnaire (I-CAM-Q). CAM treatment included modalities such as vitamins/supplements, massage, energy work, or acupuncture, while CAM self-help practices consisted of praying, exercise, visualization, meditation, relaxation, or diet. Survival was defined by date of questionnaire completion to date of death. There were 365 GBM patients (31% censored) with a median overall survival (mOS) of 14.1months, 95% CI: 12.2, 17.0. Those patients who used CAM self-help practices (n=188, mOS =16.2 months, 95% CI: 12.2, 18.1) and CAM treatments (n=237, mOS = 15.5 months, 95% CI: 9.9, 18.1) did not have any association with survival compared to those who did not use self-help (n=65; mOS = 20.9 months, 95% CI: 12.7, 39.1) or CAM treatments (n=74, mOS = 15.5 months, 95% CI: 9.9, 18.1). The most popular modalities used, prayer (n=171, 15.1 vs 22.7 months) and supplements (n=220; 14.7 vs 16.5 months) were also not associated with survival. The use of CAM was not a predictor of survival whereas those who were multifocal, grade IV, older than 55, or had recurrent disease had significantly poorer survival. It is difficult to accurately predict survival benefit because of this study’s cross-sectional design. Due to the increased interest in CAM in the primary brain tumor population, a prospective analysis utilizing some of these self- help practices or treatments may be warranted.

Newly diagnosed GBM patients experience challenges to maintain their health related QoL throughout the disease course. Disease- and treatment-related factors impact health related QoL. We sought to evaluate the trajectory of health related QoL in newly diagnosed glioblastoma patients treated with bevacizumab at diagnosis, through the disease course, and beyond progression. In this prospective single-center study, newly diagnosed subjects with GBM were treated with concurrent radiation and temozolomide plus bevacizumab followed by adjuvant temozolomide and bevacizumab. At progression, bevacizumab use was continued but chemotherapy could be changed per the treating neuro-oncologist recommendation. Health related QoL was evaluated using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) at time of study enrollment (before chemoradiation), after chemoradiation, and then every 6 mos until study discontinuation or subject demise. Higher scores on the FACT-Br correspond to better QoL. 68 newly diagnosed GBM patients were enrolled with a mean age of 55.4 yrs (sd=10.7 yrs). KPS ranged 70-100 with the following distribution: 70 (n=4), 80 (n=28), 90 (n=34), and 100 (n=2). FACT-Br scores were relatively maintained from baseline evaluation (mean=96.71, sd=17.64) to 20 months from baseline (mean=100.68, sd=22.12). Subjects who continued study participation 6 mos after the completion of chemoradiation were divided into two groups: subjects with (n=16) and without (n=35) tumor progression 6 mos after chemoradiation completion. Regardless of disease progression, both groups maintained QoL (with progression baseline (mean=98.06, sd=17.18) and 14 months from baseline (mean=91.80, sd 7.16) and without progression baseline (mean=96.34 sd=17.09) and 14 months from baseline (mean=96.75, sd=24.95)). Our observations of health related QoL throughout the disease course and beyond progression suggest that health related QoL can be maintained in GBM patients treated with bevacizumab. Continued evaluation of health related QoL throughout the disease course is warranted in the evaluation of novel treatment regimens in GBM.

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P

We conducted this study to determine event-free and overall survival among women with hormone-insensitive or hormone-resistant metastatic breast cancer receiving consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus no further chemotherapy after intensive induction chemotherapy. Eligible patients received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4 cycles. Women in complete remission were randomized to immediate HDC with cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic support or to no further therapy. Patients on the observation arm of therapy were offered salvage HDC at the time of relapse. Partial responders to AFM were offered immediate HDC. A total of 425 patients were enrolled onto the study. The median event-free survival for women randomized to induction therapy alone was 3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of the patients randomized to observation, 5 (10%) of 51 remain event free, compared with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women converted to a complete response by salvage HDC after a partial response to AFM, overall survival was similar to that in women randomized to immediate HDC. Follow-up is now in excess of 5 years. The 5-year event-free survival is 15% (95% confidence interval, 12%-18%), and the 5-year overall survival is 20% (95% confidence interval, 17%-25%). Immediate HDC after a complete response to AFM produced some durable long-term responses in hormone-insensitive/-resistant metastatic breast cancer. Salvage HDC converted 30% of partial responders to complete responders with similar survivals. The addition of novel targeted therapies to intensive-dose chemotherapy regimens may further improve survival in metastatic breast cancer.

After diagnosis, glioblastoma (GBM) patients quickly experience the neurological, physical, and emotional impact of their disease. Even before chemoradiation treatment, health-related quality of life (HRQoL) can be impaired and fatigue can be present due to neurological dysfunction, co-morbidities (e.g. seizures, depression), and medications (e.g. corticosteroids, anti-epileptics). We evaluated the impact of HRQoL and fatigue on survival in newly diagnosed GBM. Data collected within the Preston Robert Tisch Brain Tumor Center at Duke as part of the PRoGREss registry between 11/21/2011 and 10/10/2013 were queried retrospectively. In addition to demographic and clinical information, data were obtained from patient-reported outcome questionnaires including Functional Assessment of Cancer Therapy-Brain Cancer (FACT-Br) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Cox proportional hazard models were utilized to evaluate the effect of HRQoL and fatigue on overall survival. For this study, 322 subjects were identified. Mean age was 59 (SD = 13) years. KPS ranged from 40-100 with KPS ≥90 for 36.7%, KPS = 80 for 34.5%, KPS ≤ 70 for 21.4% and unknown for 7.5%. In univariate Cox analyses, the FACT-Br Total (HR = 0.986 (CI 95%: 0.98, 0.992) and FACIT-F (HR = 0.969 (CI 95%: 0.955, 0.982)) were both significant predictors of overall survival. Both the FACT-Br Total and FACIT-F added prognostic information beyond that provided by KPS alone (Likelihood ratio (LR) p = 0.003 and p = 0.004, respectively), but did not provide additional prognostic information when KPS, age, gender, and extent of resection were added to the multivariate model (LR p = 0.17 and p = 0.19, respectively). In fact, the strongest predictor of overall survival in this population was extent of resection (gross total resection vs biopsy, (HR = 3.11 (CI 95%: 2.12, 4.57))). Based on these findings, HRQoL and fatigue in newly diagnosed GBM are independent predictors of survival that provide incremental prognostic value to KPS but not to other prognostic factors such as extent of resection.

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical evidence of synergism between Gliadel wafers and TEMO, a phase I study was designed to evaluate the toxicity of combining these 2 agents in the treatment of patients with recurrent supratentorial malignant glioma. All patients had surgical resection of the tumor at relapse, and up to 8 Gliadel (3.85%) wafers were placed in the surgical cavity following resection. Two weeks after surgery, TEMO was given orally daily for 5 days. Cohorts of 3 patients received TEMO at daily doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2, respectively. Patients were assessed for toxicity 4 weeks after start of the first course of TEMO. Contrast-enhanced MRI of the brain was used to assesstumor response after the first cycle of TEMO. Patients with stable disease or response after the first cycle of TEMO were allowed to continue treatment at the same dose every 4 weeks for 12 cycles or until disease progression or unacceptable toxicity. Ten patients with a median age of 47 years (range, 22-66 years) were enrolled in this study. There were 7 patients with glioblastoma multiforme and 3 patients with anaplastic astrocytoma. Three patients were treated with TEMO at the first dose level of 100 mg/m2, 4 at the second dose level of 150 mg/m2, and 3 at the third dose level of 200 mg/m2. The 10 patients received a median of 3 cycles (range, 1-12 cycles) of TEMO following placement of Gliadel wafers. The treatment was well tolerated, with only 1 patient suffering grade III thrombocytopenia at the highest dose level. Two patients at each dose level had no evidence of disease progression after treatment. Four patients suffered progressive disease on therapy. Our study demonstrates that TEMO can be given safely after placement of Gliadel (3.85%) wafers. The recommended dosage for TEMO for a phase II study of this combination is 200 mg/m2 per day for 5 days.