Living with a central nervous system (CNS) tumor: findings on long-term survivorship from the NIH Natural History Study.

BACKGROUND: Primary central nervous system (CNS) tumors are often associated with high symptom burden and a poor prognosis from the time of diagnosis. The purpose of this study is to describe patient-reported outcomes (PRO) data from long-term survivors (LTS; ≥5-year survival post-diagnosis). METHODS: Clinical/treatment/molecular characteristics and PROs (symptom burden/interference (MDASI-BT/SP), perceived cognition (Neuro-QoL), anxiety/depression (PROMIS), and general health status (EQ-5D-3L)) were collected on 248 adult LTS between 9/2016 and 8/2019. Descriptive statistics and regression analysis were used to report results. RESULTS: Participants had a median age of 47 years (19-82) and were primarily White (83%) males (51%) with high-grade tumors (59%) and few mutations. Forty-two percent of the 222 brain tumor LTS reported no moderate-to-severe symptoms, whereas 45% reported three or more; most common symptoms were fatigue (40%), difficulty remembering (29%), and drowsiness (28%). Among spine tumor LTS (n = 42), nearly half reported moderate-to-severe weakness, pain, fatigue, and numbness/tingling, with 72% experiencing activity-related interference. Severe anxiety, depression, and cognitive symptoms were reported in up to 23% of the sample. Brain tumor LTS at higher risk for severe symptoms were more likely to be young, unemployed, and have poor KPS (Karnofsky Performance Status), whereas high symptom-risk spinal cord tumor LTS had poor KPS and received any tumor treatment. CONCLUSIONS: Findings indicate LTS fall into distinct cohorts with no significant symptoms or very high symptom burden, regardless of tumor grade or mutational profile. These LTS data demonstrate the need for survivorship care programs and future studies to explore the symptom trajectory of all CNS tumor patients for prevention and early interventions.

Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas.

PURPOSE: To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma. PATIENTS AND METHODS: This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden. RESULTS: Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12-24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2_5347T>C (rs2470890) polymorphism was associated with higher AUCinf value. CONCLUSIONS: Zotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib.

Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Adult Medulloblastoma Workshop.

BACKGROUND: Medulloblastoma (MB) is a rare brain tumor occurring more frequently in children in whom research has been primarily focused. Treatment recommendations in adults are mainly based on retrospective data and pediatric experience; however, molecular features and treatment tolerance differ between the 2 age groups. In adults, prognostic tools are suboptimal, late recurrences are typical, and long-term sequelae remain understudied. Treatment has not adapted to molecular classification advances; thus, the survival rate of adult MB has not improved. METHODS: In 2017, the National Cancer Institute (NCI) received support from the Cancer Moonshot℠ to address the challenges and unmet needs of adults with rare central nervous system tumors through NCI-CONNECT, a program that creates partnerships among patients, health care professionals, researchers, and advocacy organizations. On November 25, 2019, NCI-CONNECT convened leading clinicians and scientists in a workshop to review advances in research, share scientific insights, and discuss clinical challenges in adult MB. RESULTS: Working groups identified unmet needs in clinical trial design, tissue acquisition and testing, tumor modeling, and measurement of clinical outcomes. CONCLUSIONS: Participants identified opportunities for collaboration; discussed plans to create a working group of clinicians, researchers, and patient advocates; and developed specific action items to expedite progress in adult MB.

The prevalence of altered body image in patients with primary brain tumors: an understudied population.

PURPOSE: Body image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT). METHODS: A cross-sectional survey of 100 PBT patients was conducted on an IRB approved prospective protocol using structured questionnaires. Participants completed the body image scale (BIS), Appearance Scheme Inventory Revised (ASI-R), MD Anderson Symptom Inventory Brain Tumor (MDASI-BT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Depression, Anxiety, and Psychosocial Impact Positive measures. RESULTS: The prevalence of clinically significant body image dissatisfaction (BIS ≥ 10) was 28% (95% CI 19-37%), median BIS score was 5 (range 0-27). The median ASI-R composite score was 2.9 (range 1.5-4.7). BIS was significantly correlated with the ASI-R (r = 0.53, 95% CI 0.37 to 0.65). The mean PROMIS Depression score was 48.4 (SD = 8.9), PROMIS Anxiety score was 49.4 (SD = 9.9), and PROMIS Psychosocial Illness Impact Positive score was 48.9 (SD = 9.7). BIS was significantly correlated with age, and trended with BMI and sex. The PROMIS Psychosocial Illness Impact Positive and PROMIS Anxiety scores were the most strongly related to BIS. CONCLUSIONS: This study, the first to explore altered body image in PBT patients, revealed clinically significant body image dissatisfaction in nearly 1/3 of patients, similar to other malignancies. These findings underscore the potential contribution of disease and treatment-related body image concerns on psychosocial wellbeing in patients with PBT.

Nursing Guide to Management of Major Symptoms in Patients with Malignant Glioma.

OBJECTIVES: To provide an overview of the symptoms commonly experienced by patients with malignant glioma, and discuss the pathophysiology and interventions associated with those. DATA SOURCES: A review of published scientific literature and clinical literature, and online information from National Comprehensive Cancer Network, Oncology Nursing Society, Epilepsy Foundation of America, and the American Brain Tumor Association. CONCLUSION: The unique symptom burden associated with a malignant glioma diagnosis often disrupts the lives of patients and their caregivers. Clinical support and interventions addressing malignant glioma-related focal deficits, seizures, headaches, venous thromboembolism, mood disturbances, fatigue, and sleep-wake disturbance can positively impact patient and caregiver experiences while living with malignant glioma. IMPLICATIONS FOR NURSING PRACTICE: Understanding the pathophysiology of these symptoms and reviewing nursing-led and supported interventions will empower the nurse in providing comprehensive care to patients with malignant glioma and their caregivers.

Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) are being investigated in clinical trials for patients with glioblastoma. While these therapies hold great promise, management of the patients receiving such treatment can be complicated due to the challenges in recognizing immune-related adverse events caused by checkpoint inhibitor treatment. Brain imaging changes that are the consequence of an inflammatory response may be misinterpreted as disease progression leading to inappropriate premature cessation of treatment. The aim of this study was to, by way of a series of cases, underscore the challenges in determining the nature of contrast-enhancing masses that develop during the treatment of patients with glioblastoma treated with ICPIs. CASE PRESENTATION: We reviewed the clinical course and management of 4 patients on ICPIs who developed signs of tumor progression on imaging. These findings were examined in the context of Immunotherapy Response Assessment in Neuro-Oncology (iRANO) guidelines. Although all 4 patients had very similar imaging findings, 2 of the 4 patients were later found to have intense inflammatory changes (pseudoprogression) by pathologic examination. CONCLUSIONS: A high index of suspicion for pseudoprogression needs to be maintained when a patient with brain tumor on immunotherapy presents with worsening in an area of a pre-existing tumor or a new lesion in brain. Our findings strongly suggest that pathological diagnosis remains the gold standard for distinguishing tumor progression from pseudoprogression in patients receiving immunotherapy. There is a large unmet need to develop reliable non-invasive imaging diagnostic techniques. TRIAL REGISTRATION: ClinicalTrials.gov NCT02311920. Registered 8 December 2014.

A strategy for multimodal deformable image registration to integrate PET/MR into radiotherapy treatment planning.

BACKGROUND: Combined positron emission tomography (PET)/magnetic resonance imaging (MRI) is highly promising for biologically individualized radiotherapy (RT). Hence, the purpose of this work was to develop an accurate and robust registration strategy to integrate combined PET/MR data into RT treatment planning. Material and methods. Eight patient datasets consisting of an FDG PET/computed tomography (CT) and a subsequently acquired PET/MR of the head and neck (HN) region were available. Registration strategies were developed based on CT and MR data only, whereas the PET components were fused with the resulting deformation field. Following a rigid registration, deformable registration was performed with a transform parametrized by B-splines. Three different optimization metrics were investigated: global mutual information (GMI), GMI combined with a bending energy penalty (BEP) for regularization (GMI+ BEP) and localized mutual information with BEP (LMI+ BEP). Different quantitative registration quality measures were developed, including volumetric overlap and mean distance measures for structures segmented on CT and MR as well as anatomical landmark distances. Moreover, the local registration quality in the tumor region was assessed by the normalized cross correlation (NCC) of the two PET datasets. RESULTS: LMI+ BEP yielded the most robust and accurate registration results. For GMI, GMI+ BEP and LMI+ BEP, mean landmark distances (standard deviations) were 23.9 mm (15.5 mm), 4.8 mm (4.0 mm) and 3.0 mm (1.0 mm), and mean NCC values (standard deviations) were 0.29 (0.29), 0.84 (0.14) and 0.88 (0.06), respectively. CONCLUSION: Accurate and robust multimodal deformable image registration of CT and MR in the HN region can be performed using a B-spline parametrized transform and LMI+ BEP as optimization metric. With this strategy, biologically individualized RT based on combined PET/MRI in terms of dose painting is possible.

Preschoolers, parents, and teachers (PPT): a preventive intervention with an at risk population.

The importance of early intervention with children who are at risk for mental health problems is widely recognized. Relationships with significant adults (parents, other caregivers, and teachers) are critically important in young children's lives and can make a tremendous difference in the trajectory of a child's future. This study utilized a waiting-control group design to examine the effects on student behavior and parent stress of play-based interventions designed to improve the relationships between parents and their children (i.e., Filial Therapy), and teachers and their students (i.e., Kinder Training). To incorporate the benefits of group work, the eight-week intervention was delivered to parents in a small-group format. Teachers participated in a one-day group training with weekly coaching and dyadic consultation for on-going support. Results at post-intervention indicated that teachers perceived children in the intervention group to exhibit significantly less problem behavior than students in the waiting-control group. Although results suggest that the intervention had no demonstrable effect on parent stress, qualitative results indicate otherwise. Implications for practice and research are discussed.