Central Nervous System Tumor Patients Research Articles

Information Needs Regarding Cognitive Late Effects of Caregivers of Central Nervous System Tumor Survivors.

Pediatric central nervous system (CNS) tumor survivors are at risk for experiencing cognitive late effects (CLEs). Caregivers of survivors may be unaware of these changes or receive untimely information regarding CLEs. Conversely, health care providers (HCPs) may face barriers to providing education. This study aims to (a) understand the knowledge and resource gap for caregivers regarding CLEs and (b) explore how HCPs currently provide education. Caregivers and HCPs were both interviewed. Qualitative analysis was performed using emergent coding. Fifteen caregivers and eight HCPs participated. Caregivers generally felt confident in assisting their survivor but experienced "information overload" during initial diagnosis and treatment. HCPs reported difficulties in determining appropriate timing for education and perceived that caregivers typically lack understanding of CLEs. Caregivers should be aware of and understand a survivor's risk for CLEs to help survivors manage changes. With increasing survival rates of pediatric CNS tumor patients, HCPs must be prepared to provide appropriate education and referrals regarding CLEs for long-term care.

Is the relationship between social support and depressive symptoms mediated by hope among Chinese central nervous system tumor patients?

It is common for central nervous system (CNS) tumor patients to suffer from depressive symptoms. If unrecognized or untreated, CNS tumors may lead to many serious problems in these patients. This study examines the association of social support with depressive symptoms in CNS tumor patients and explores the extent to which hope mediates this relationship. A total of 269 CNS tumor patients in China were included in this study. We assessed depressive symptoms using the Epidemiologic Studies Depression Scale (CES-D), social support using the Perceived Social Support Scale (PSSS), and hope using the Herth Hope Index (HHI). Questionnaires were distributed to collect these data. Hierarchical linear regression analyses explored the interrelationship between social support, hope, and depressive symptoms. After adjustment for demographic characteristics, patients with less social support exhibited more depressive symptoms (β = - 0.452, P < 0.01). Social support explained 19.1% of the variance in depressive symptoms. After adding hope to the regression model, the effect size for social support was reduced by over half but remained significant (from β = - 0.452 to β = - 0.218, P < 0.01). In addition, a lower level of hope (β = - 0.386, P < 0.01) was associated with more depressive symptoms, and this measure explained an additional 9.3% of the variance in depressive symptoms. Much of the relationship between social support and depressive symptoms is explained by hope. Thus, interventions boosting both social support and hope help to reduce depressive symptoms in patients with CNS tumors.

Expert consensus on re-irradiation for recurrent glioma

PurposeTo investigate radiation oncologists’ opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma.Materials and methodsA survey was conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario.ResultsSixty nine percent of responders have been practicing for greater than 10 years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2–5 re-RT cases per month and retreating 1–2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option.ConclusionThe experts’ practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey.

P18.14 Usefulness of providing assistive techniques for QOL of malignant CNS tumor clients in convalescent hospital rehabilitation: 2 case reports

Abstract Introduction: The desired goal of the neurological rehabilitation is the restoration of neurological deficit. Some compensatory means including assistive devices and orthoses improve client’s activities of daily living (ADLs) and instrumental ADLs (IADLs). In the rehabilitation for malignant central nervous system (CNS) tumor clients, providing their caregivers with assistive techniques sometimes seems effective in order to bring good quality of life (QOL). Authors report the experiences of the rehabilitation for malignant CNS tumor clients. CASE 1: Female; 62Y.O. She had undergone the surgery and radiotherapy 16 years before in a cancer center hospital owing to the right breast cancer. Hormone therapy was being continued. Magnetic resonance (MR) image showed a tumor in the right parietal area. This was assessed as the metastatic tumor. She underwent the cerebral tumor resection since she had fallen a lot of times. Her ADLs became worse owing to the left hemiparesis. Even after the hemiparesis improved by the rehabilitation in our hospital, she fell a few times due to stereoagnosis. An assistive device improved her ADLs and IADLs in home. Her participation in social activities was achieved with her husband’s assistive techniques. CASE 2: Male; 64Y.O. He had undergone several times of surgery, radiotherapy, and chemotherapy because of anaplastic astrocytoma in the left parietal area during 12 years at a university hospital. Right hemiparesis and memory disturbance deteriorated his ADLs after the last surgery. Histological examination showed glioblastoma. The rehabilitation in our hospital enabled him to walk with an ankle foot orthosis in 2 weeks. His wife’s assistive techniques were also helpful in the return to his domestic situation. Meningeal dissemination was found in MR image 6 weeks after the beginning of the rehabilitation. He underwent chemotherapy at the former hospital and died several weeks after the transition to home. DISCUSSION AND conclusions: The rehabilitation for malignant CNS tumor patients may have had little importance in the treatment owing to the rapid exacerbation of their diseases. While many patients survive by the developed treatment of malignant CNS tumors, the neurological deficits require the rehabilitation. The rehabilitation needs to aim not only to recover ADLs and IADLs, but also to aid the preparation for the client’s good QOL. Every rehabilitation staff needs to consider how the client will act in home and participate in the community. This view of consideration possibly benefits the client’s QOL. Assistive techniques can be useful for the client’s QOL even when the independent ADLs or IADLs are not expected during the inpatient rehabilitation.

QOS-54USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION

QOS-54. USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION Kathleen Dorris, Molly Hemenway, Jennifer Madden, Jean Mulcahy-Levy, Daniel Ambruso, Rajeev Vibhakar, and Nicholas Foreman; University of Colorado School of Medicine, Aurora, CO, USA BACKGROUND: Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of chemical components that are found in marijuana. Numerous studies in adults have examined the effects of cannabinoids in management of cancer-related symptoms, including nausea, anorexia, and pain. Interest in the lay community in the role of cannabinoids as anticancer therapy is increasing, as some pediatric central nervous system (CNS) tumors have been shown to express cannabinoid receptors. In addition, thepresenceof cannabinoid receptorson immunecells suggests apotential role for cannabinoids as immunomodulators. METHODS: A prospective observational study is underway in Colorado, USA to evaluate serially the impact of cannabinoids on quality of life of pediatric CNS tumor patients who selfmedicate with cannabinoid products using PedsQL 4.0 Generic Core Scales and Brain Tumor and Family Impact modules. Laboratory assessments of neutrophil and T-cell activity will be performed to determine whether cannabinoid use by children with CNS tumors affects immune function and alters risk for infection. Pharmacokinetic analyses of CBD, THC and associated metabolites are planned to gather data regarding metabolism of cannabinoid products in children. Diaries will collect exploratory information on cannabinoid use patterns. Neuropsychological testing is also planned. RESULTS: To date, threepatients (1 medulloblastoma, 1 glioblastoma,and 1 diffuse astrocytoma) have been enrolled. CONCLUSIONS: Accrual is on track to enroll the planned 50 pediatric CNS tumor patients over three years. This novel study should contribute to the increasing understanding of the potential role of cannabinoids in pediatric neuro-oncology. Neuro-Oncology 18:iii145–iii158, 2016. doi:10.1093/neuonc/now081.54 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Socioeconomic disparities in childhood cancer survival in Switzerland.

In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.

Liaison psychiatry in a central nervous system tumor service.

Tumors of the central nervous system (CNS) have physical and psychological effects that commonly interact and change over time. Although well suited to addressing problems at the interface between physical and psychological medicine, the role of the consultation-liaison psychiatrist has not been previously described in the management of these patients. The purpose of this paper is to summarize the experience of psychiatry liaison attachment within a CNS tumor service and to reflect on its utility within a complex multidisciplinary environment. A retrospective file review was performed on all cases seen by a psychiatrist in a CNS tumor service over the previous 5 years. A simple thematic inductive analysis was conducted of the common problems experienced by patients and their management by the psychiatrist and within the team. Five common themes were identified: (i) facilitating adaptation to diagnosis; (ii) supporting living with lower-grade tumors; (iii) managing mental disorders; (iv) neuropsychiatric symptoms of tumor progression; and (v) grief and uncertainty in the advanced stages of illness. The capacity of the psychiatrist to understand and integrate the clinical, pathological, radiological, and treatment information, in communication with colleagues, helped address these challenges. Psychological challenges in CNS tumor patients have both psychological and neurological underpinnings. In our experience, the addition of a liaison psychiatrist to a CNS tumor service was efficient and effective in improving patient management and led to enhanced communication and decision-making within the team.

Sports and childhood brain tumors: Can I play?

It is unknown whether children with brain tumors have a higher risk of complications while participating in sports. We sought to estimate the prevalence of such events by conducting a systematic review of the literature, and we surveyed providers involved with pediatric central nervous system (CNS) tumor patients. A systematic review of the literature in the PubMed, Scopus, and Cochrane databases was conducted for original articles addressing sport-related complications in the brain-tumor population. An online questionnaire was created to survey providers involved with pediatric CNS tumor patients about their current recommendations and experience regarding sports and brain tumors. We retrieved 32 subjects, including 19 pediatric cases from the literature. Most lesions associated with sport complications were arachnoid cysts (n = 21), followed by glioma (n = 5). The sports in which symptom onset most commonly occurred were soccer (n = 7), football (n = 5), and running (n = 5). We surveyed 111 pediatric neuro-oncology providers. Sport restriction varied greatly from none to 14 sports. Time to return to play in sports with contact also varied considerably between providers. Rationales for limiting sports activities were partly related to subspecialty. Responders reported 9 sport-related adverse events in patients with brain tumor. Sport-related complications are uncommon in children with brain tumors. Patients might not be at a significantly higher risk and should not need to be excluded from most sports activities.

Histopathological and immunohistochemical profile in anaplastic gangliogliomas

The anaplastic ganglioglioma (AG) is the high-grade counterpart of ganglioglioma, a rare mixed tumor composed of neuronal/ganglion and glial cells. We describe the histopathology and immunohistochemistry in 7 cases of AG and correlate them with the clinical and radiological features. Our AG patients correspond to 2.5% of the central nervous system tumor patients evaluated in our institution. The mean age at presentation was 25.7 years, with a male predominance. The most common clinical presentation was generalized tonic-clonic seizures (3/7 cases), in correlation with frequent cortical/subcortical location (6/7 cases). Histopathologically, all our cases showed high-grade features in glial (glial fibrillary acid protein-positive) and neuron-ganglion cells (synaptophysin, PGP-9.5, neurofilament, NSE and CD56-positive), as well as moderate cellularity, frequent mitotic figures and a Ki-67 labeling index >5%. All our patients had poor survival. We found that a typical histopathological and immunohistochemical profile is constant and can be useful in early diagnosis of these aggressive neoplasms.

The Evangelismos hospital central nervous system tumor registry: Analysis of 1414 cases (1998-2009)

Background:The Evangelismos Hospital central nervous system (CNS) Tumor Registry represents the current effort of the Departments of Neurosurgery and Pathology to collect data for primary and metastatic CNS tumor patients. In the present study, 12-year hospital data (1998-2009) were reviewed and analyzed.Methods:Patients that underwent surgery for CNS tumors for the first time were identified. Histologically confirmed tumor rates by age and gender were compared. Time trends in annual rates for specific tumor types were investigated. In-hospital mortality rates and length of hospital stay were analyzed by age and gender and their putative variations across the study period investigated.Results:A total of 1414 patients (age 15-89 years) were identified. The most frequently encountered histologies were gliomas and meningiomas, accounting for, respectively, 32.8% and 29.1% of the total sample. A greater proportion of meningiomas was found in women; the proportion of glioblastomas and metastatic tumors, as well as of mixed gliomas, were greater in men. Increased rates of glioblastoma and meningioma with advancing age at diagnosis were also apparent. There were no significant variations in time trends for specific tumor types. In-hospital mortality was significantly higher for older patients (≥70 years). An increase in the length of hospital stay was apparent between the first and middle third of the study period.Conclusions:Analysis of tumor rates in relation to age at diagnosis and gender showed significant bias in accordance with salient literature. Available data indicated no significant variations in time trends for specific tumor types across the study period, while an adverse effect of advanced age on in-hospital mortality was shown. The present findings can guide the formulation of future treatment programs and preventive strategies and provide the basis for further intra- and/or interdepartmental research.

Tumor Locus Moderates Anxiety Symptoms in a Pediatric Neuro-Oncologic Sample

Despite the prevalence of pediatric Central Nervous System (CNS) solid tumors, little is understood about patients' disease-related anxiety experience. Data from 25 remitted pediatric CNS tumor patients posttreatment were collected. Significant symptoms of anxiety were reported by 32% of patients. MRI studies showed all anxious patients had right cortical tumors or left cerebellar tumors. Confound analyses suggest these results are not better accounted for by demographic, disease, or treatment variables. These results evidence the risk some pediatric neuro-oncologic patients face for developing significant anxiety symptoms.

Parental Fears Following Their Child's Brain Tumor Diagnosis and Treatment

The objective of this study is to portray the illness-related threats experienced by parents of children after the diagnosis of central nervous system (CNS) tumor. Parents were asked to rate the extent to which they experienced a set of specific fears related to their child's brain tumor and its treatment. Outcomes for parents of CNS tumor patients (n = 82) were compared with those of reference parents of patients treated for acute lymphoblastic leukemia (n = 208). The fears about an illness recurrence and the late effects of treatment were most prominent among parents of CNS tumor patients. For 7 out of 11 kinds of fear, parents of CNS tumor patients expressed a stronger fear than the reference group. More than a quarter of the parents of children treated for CNS tumors feared a complete decline of the child. Parents of CNS tumor patients experience relatively heightened cancer related fears in several domains. The fear of devastating consequences felt by one fourth of parents signals the need of individualized psychological support and information at diagnosis and follow-up to facilitate parental coping with the posttreatment situation.

CNS atypical teratoid/rhabdoid tumor registry: An update

12507 Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor of the central nervous system (CNS) in childhood, comprising up to 20% of malignant CNS tumors in patients &lt; 3 years old. Although aggressive approaches including surgery, chemotherapy, intrathecal chemotherapy, high dose chemotherapy with hematopoietic stem cell transplant (HD-HSCT) and/or radiation have resulted in prolonged survival, overall survival remains poor. Methods: We reviewed pediatric patients with AT/RT on an IRB- approved registry formed in 1995 with new insight based on updated outcomes and additional patient enrollment. Upon patient entry, the managing physician submitted pertinent medical records for data abstraction. Physicians were contacted in accordance with privacy regulations for updated records. The Kaplan-Meier method was used to estimate survival time (from diagnosis to death or most recent status update) and groups were compared using the log-rank test at a significance level of p&lt;0.05 with SAS® software version 9.1. Results: Analysis was conducted on 73 patients with a 4:3 male to female ratio. Age at diagnosis ranged from 5 days to 234 months, median = 19 months. Twenty-five patients have no evidence of disease, median 59 months from diagnosis (range 10–140). Forty-three patients (59%) developed recurrent or progressive disease; 6 of these patients are alive at a median of 28 months from recurrence (range 4–38). Forty-four patients (60%) are dead of disease; median time to death was 7 months from diagnosis (range 0–62). Factors correlating with survival are: primary tumor site not in spinal cord (p=0.029), lack of metastatic disease (p=0.024), gross total resection (p&lt;0.001), and upfront radiation particularly in children &lt; 3 years old (p&lt;0.001). HD-HSCT appears to result in improved survival in children &lt; 3 years of age who do not receive radiation, though the small sample size does not yield a statistically significant survival advantage. Conclusions: In treatment of AT/RT, extent of surgical resection and upfront radiation are beneficial for overall survival, particularly in young children. Early information regarding upfront HD-HSCT in lieu of radiation for children &lt; 3 years of age with AT/RT suggests it may be effective. Prospective studies are warranted to further investigate this treatment. No significant financial relationships to disclose.

P-5-669 - Hypercoaulability state in central nervous system tumor patients

P-5-669 - Hypercoaulability state in central nervous system tumor patients

Insulin-like growth factor-binding protein-2 concentrations in cerebrospinal fluid and serum of children with malignant solid tumors or acute leukemia.

Many tumor cell lines express insulin-like growth factors (IGFs) as autocrine growth factors and IGF-binding protein-2 (IGFBP-2) as a major IGFBP, which, in turn, regulates the bioavailability and bioactivity of IGFs. The aim of our study was to investigate 1) whether children with malignancies have elevated IGFBP-2 levels in cerebrospinal fluid (CSF) and serum, and 2) whether IGFBP-2 levels in these biological fluids could be useful markers for the diagnosis and follow-up of certain tumor types. We, therefore, measured IGFBP-2 levels in the CSF and serum of children with malignancies by Western ligand blot analysis; RIA with alpha IGFBP-2, a polyclonal antibody for human IGFBP-2; and immunoprecipitation with alpha IGFBP-2 and alpha Hec-1a, a polyclonal antibody that recognizes IGFBP-2 and -3. Furthermore, the expression of IGFBP-2 messenger ribonucleic acid in tumor tissue from three central nervous system (CNS) tumor patients was analyzed by Northern blot analysis. We examined CSF from 21 children with malignant CNS tumors, 25 patients with acute leukemia, and 4 patients with peripheral solid tumors and compared the IGFBP-2 levels with those in CSF from 21 patients who received a lumbar puncture to exclude meningitis. Serum was obtained from 7 patients with solid tumor, 12 patients with malignant CNS tumor, and 16 patients with acute leukemia. The serum IGFBP-2 levels were compared to serum levels in 5 patients with sarcoma who had reached complete remission and 13 normal control children. CSF and serum were collected at the same time, before initiation of therapy. Patients with malignant CNS tumors showed elevated IGFBP-2 levels in CSF (P < 0.001), whereas patients with solid peripheral tumor or acute leukemia had normal IGFBP-2 levels in CSF. CNS tumor patients with microscopically detectable malignant cells in the CSF had the highest CSF IGFBP-2 levels. Serum IGFBP-2 levels were increased in patients with solid peripheral tumors (P < 0.05), whereas patients in complete remission had normal serum IGFBP-2 levels. In summary, IGFBP-2 was elevated specifically in CSF from patients with CNS tumor, whereas IGFBP-2 serum levels were elevated in children with various peripheral tumors. We conclude that IGFBP-2 in CSF could be a specific marker for malignant CNS tumors. We detected high IGFBP-2 messenger ribonucleic acid expression in 1 of 3 CNS tumor tissues analyzed.

Concentrations of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3), IGF, and IGFBP-3 protease activity in cerebrospinal fluid of children with leukemia, central nervous system tumor, or meningitis.

Insulin-like growth factor-II (IGF-II) is the major IGF in human cerebrospinal fluid (CSF), whereas IGF-I is only detectable in trace amounts. The major IGFBPs in CSF are IGFBP-2 and IGFBP-4. Normally, IGFBP-3 is a minor component in CSF of healthy subjects, but may be increased in pathological states. We investigated IGF-I, IGF-II, and IGFBP-3 levels by specific RIAs in CSF from patients with central nervous system (CNS) tumor or leukemia and compared them with values in patients with meningitis. Further, as proteolysis of IGFBP-3 is part of the modulation of IGF activity, IGFBP-3 fragmentation was quantified by densitometric analysis of [125I]IGFBP-3 protease assays. We examined CSFs of 23 children with malignant CNS tumors, 18 children with leukemia, and 13 children with meningitis. The CSF from 38 children who received lumbar punctures to exclude meningitis was used to define the normal range for IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease activity in CSF. CNS tumor and leukemia patients had normal levels of IGF-I and IGF-II in CSF, whereas the IGF-II concentration in CSF of meningitis patients was elevated (P < 0.0001). Only 2 of 13 (15%) meningitis patients had elevation of CSF IGFBP-3 concentrations, despite high numbers of inflammatory cells. By comparison, elevated IGFBP-3 concentrations were found in the CSF of 16 of 23 (70%) CNS tumor patients and 6 of 7 (86%) CNS tumor patients with microscopically detectable malignant cells in CSF. Twelve of 13 (92%) patients with medulloblastoma or ependymoma and all 7 medulloblastoma/ependymoma patients with malignant cells in CSF had elevated IGFBP-3 concentrations. The IGFBP-3 protease activity in CSF was elevated in 15 of 16 (94%) patients with CNS tumors of high grade histological malignancy. Five of 6 patients (83%) with acute leukemia and microscopically detectable malignant cells in CSF at the time of diagnosis showed elevated IGFBP-3 concentrations, with normalization after chemotherapy. Leukemia patients without malignant cells in CSF had normal IGFBP-3 concentrations. We conclude that in CSF of children with highly malignant CNS tumor or CNS leukemia, IGFBP-3 is elevated. This phenomenon could be caused by disruption of the blood-CSF barrier and entry of IGFBP-3 from serum, although this appears unlikely, especially for CNS leukemia. More likely possibilities are 1) local production of IGFBP-3 by CNS tumor tissue and secretion into the CSF, or 2) local production of IGFBP-3 by malignant cells within the CSF.