QUALITY OF LIFE/AFTERCARE

doi:10.1093/neuonc/nos106

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-01. GLUTATHIONE S-TRANSFERASE P1 SINGLE NUCLEOTIDE POLYMORPHISM PREDICTS PERMANENT OTOTOXICITY IN CHILDREN WITH MEDULLOBLASTOMA

Surya Rednam ¹, Michael Scheurer ¹, Adekunle Adesina ¹, Ching Lau ¹, Mehmet Okcu ¹

Abstract

BACKGROUND: Glutathione S-transferase (GST) enzymes are involved in detoxifying chemotherapy agents and clearing reactive oxygen species formed by radiation. In this study, we explored the relationship between the host GSTP1-105 polymorphism (rs1695), tumor GSTpi protein expression, and clinical outcomes in pediatric medulloblastoma. We hypothesized that the GSTP1-105 G-allele and increased tumor GSTpi expression would be associated with lower progression-free survival and fewer adverse events. METHODS: The study included 106 medulloblastoma/primitive neuroectodermal tumor (PNET) patients seen at Texas Children's Cancer Center. Genotyping was performed using an Illumina HumanOmni1-Quad BeadChip and tumor GSTpi expression was assessed using immunohistochemistry. We used the Kaplan-Meier method for survival analyses and multivariable logistic regression for toxicity comparisons. RESULTS: Patients with a GSTP1-105 AG/GG genotype or who had received a higher dose of craniospinal radiation (median 36 Gy) had a greater risk of requiring hearing aids than their respective counterparts (OR 4.0, 95%CI 1.2 - 13.6, and OR 3.1, 95%CI 1.1 - 8.8, respectively). Additionally, there was a statistically significant interaction between the two variables. Compared with the lowest risk group (GSTP1-105 AA-lower dose radiation) patients with a GSTP1-105 AG/GG genotype who received a higher dose radiation were 8.4 times more likely to require hearing aids (95%CI 1.4 - 49.9, p-trend = 0.005). When adjusted for age, gender, and amifostine use, the association remained. CONCLUSIONS: The GSTP1-105 G-allele is associated with permanent ototoxicity in pediatric medulloblastoma/PNET and strongly interacts with radiation dose. A possible mechanism for this finding is that the GSTP1-105 G-allele leads to reduced GSTpi free radical detoxification in the setting of multimodality therapy including cisplatin and radiation. Patients with this allele should be considered for clinical trials employing radiation dose modifications and more targeted cytoprotectant strategies than are currently being used with amifostine.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-02. COMPETENCE OF MOTHERS AS CAREGIVERS: ADOLESCENT AND YOUNG ADULT BRAIN TUMOR SURVIVORS LIVING AT HOME

Janet Deatrick ², Sue Ogle ¹, Michael Fisher ¹, Lamia Barakat ¹, Thomas Hardie ³, Yimei Li ¹, Jill Ginsberg ¹

Abstract

PURPOSE: Pediatric brain tumors patients have benefited significantly from treatment advances but may face significant physical, cognitive, and psychosocial late effects. Brain tumor survivors compared to survivors of other pediatric cancers are at the greatest risk for long-term cancer-related morbidities. Their mothers often lead dramatically altered lives, as they strive to support survivors to overcome significant neurocognitive late effects especially when must they remain at home into adulthood. The demands placed on mothers can challenge their sense of competence. The aim of this study was to explore survivor, caregiver (mother), and family functioning predictors of the caregivers' perceived competence. SUMMARIZED DESCRIPTION OF PROJECT: A model of Perceived Competence for Caregivers of Brain Tumor Survivors guided the study hypothesis: decreased caregiver competence would be predicted by increased caregiver demands, worse caregiver health, worse survivor health, and worse family functioning. Telephone interviews using structured self-report questionnaires were conducted in this cross-sectional study with a sample of 187 caregivers. Structural equation modeling was used to assess the hypothesized model. RESULTS: A path model explained that decreased caregiver competence is predicted by worse survivor health or worse family functioning, however, worse caregiver health only predicts decreased caregiver competence when there is increased caregiver demands and worse family functioning. Overall, the model showed adequate fit (CF I= 0.905, TFI = 0.880 and RMSEA = 0.081). All of the paths in the final model are significant at P <0.05, and the final model accounted for 47% of variance in the perceived caregiver competence. CONCLUSIONS: Based on the findings, we recommend targeting reducing caregiver demands and improving family functioning through family-based interventions to support improvement in caregiver competence. We also recommend that interventions targeted to survivor's health should consider the contribution of caregiver competence.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-03. S0CIAL REINTEGRATION AFTER CENTRAL NERVOUS SYSTEM TUMORS IN CHILDHOOD

Myriam Ben-Arush ¹, Elena Krivoy ¹, Rivka Rosenkranz ¹, Monique Peretz-Nahum ¹

Abstract

OBJECTIVES: This study was designed to assess the overall morbidity burden of survival from central nervous system (CNS) tumors and its impact on return to a normal lifestyle. METHODS: Economical status, health, physical and social well-being were evaluated in CNS survivors aged minimum 18 years. RESULTS: Forty patients (pts) were evaluated, 23 (57.5%) males and 17 (42.5%) females, mean age was 28.5 (18-38) years (y), mean age on diagnosis was 7y (1-19), mean y of FU was 19 y (8-29). Fourteen pts had medulloblastoma/primary neuroectodermal tumor, 20 had glioma, 3 had ependymoma, and 3 had germinoma. Thirty-six (90%) pts received cranial radiotherapy (CSP) and 14 (35%) had cranio-spinal irradiation. Eleven (28%) pts lived with a partner, 22 (55%) pts were studying at high school or university. Twenty-three (58%) pts had good social relations, 18 (45%) had satisfying economic levels, 19 (48%) felt in good health, 24 (60%) in good psychological status. Psychological status was significantly higher for pts with social or sporting activities (p = 0.06). Social or sporting activities and relationships with partners were significantly correlated (p= 0.008). Males compared to females had less psychomotor delay (31% versus 70 %) and better QOL (48% versus 30%). The 27 pts diagnosed at 6 y or older compared to the 13 younger pts had less mental retardation (30% versus 69%), better QOL, higher educational levels, and better occupational status (44% versus 23%). Nine of 14 pts treated by CSP had severe mental delay, and 13/14 pts had poor QOL. CONCLUSION: More than 50% of the CNS survivors have relatively good psychosocial status and educational levels. Risk of mental sequellae was correlated to female sex, young age at diagnosis, and cranio-spinal irradiation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-04. MAGNETIC RESONANCE SPECTROSCOPY FOR EVALUATION OF IRRADIATION-INDUCED BRAIN INJURY IN A JUVENILE MOUSE MODEL

Robert J Brown ¹, Joanne Love ¹, David Warburton ¹, William H McBride ², Stefan Bluml ¹

Abstract

BACKGROUND: Children undergoing therapeutic cranial irradiation are at increased risk of permanent long-term neurocognitive sequelae in addition to stroke and secondary malignancies. The mechanism of these side effects are poorly understood and adequate biomarkers for chronic injury are lacking. Magnetic resonance spectroscopy is a non-invasive, non-irradiation modality that can be performed on children with little or additional risk to standard disease surveillance MRI. PURPOSE: We investigated the utility of magnetic resonance spectroscopy in a mouse model of juvenile irradiation injury to characterize the metabolite profile derangements following cranial irradiation with the intention of correlating these profiles with histological evidence of irradiation-induced brain injury. METHODS: 4-week old juvenile wild-type mice were given single 16 Gray fraction of irradiation or sham and examined at baseline, 3-, 6-, 9, and 12-months post irradiation. The MR spectroscopy was compared to controls and correlated with histological characteristics. RESULTS: Lipid-based metabolites generally decreased with age while both macromolecules and neuronal metabolites increased with age up to one year. Irradiation at 1 month of age demonstrated detectable alterations in metabolites by 6 months of age and correlated with histological evidence of brain injury. CONCLUSION: Magnetic resonance spectroscopy is a useful non-invasive modality for identifying irradiation-induced brain injury in a mouse model.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-05. RISK OF FIRST AND RECURRENT STROKE IN PEDIATRIC CANCER SURVIVORS TREATED WITH CRANIAL RADIATION THERAPY

Sabine Mueller ¹, Katherine Sear ¹, Nancy Hills ¹, Nassim Chettout ¹, Shervin Afghani ², Leanne Lew ¹, Erica Tolentino ¹, Daphne Haas-Kogan ¹, Heather Fullerton ¹

Abstract

OBJECTIVE: To assess rates and predictors of first and recurrent stroke in childhood cancer survivors treated with cranial radiation therapy (CRT). METHODS: In a retrospective cohort study of children who received CRT at one institution,1980-2009, we performed chart abstraction (n = 384) and phone interviews (n = 104) to measure first and recurrent stroke. Incidence of first-stroke was calculated as the number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine the cumulative incidence of first stroke after radiation, and recurrent stroke after first stroke; we used Cox proportional hazards models to examine potential predictors of first stroke. RESULTS: Median age of children at the time of CRT treatment was 8 years (IQR 4-13). A total of 19 first-strokes (12 ischemic, 3 hemorrhagic, 4 unknown sub-type) were identified at a median age of 24 years (IQR 17-33 years): 6 from chart review, 10 from interview, 3 from both. Imaging was available in 14 cases and consistent with stroke in all. The overall rate of first-stroke was 625 (95% CI 577-676) per 100,000 person-years. The cumulative incidence of first stroke was 2% (95% CI 0.01-5.3%) at 5 years post radiation therapy and 4% (95% CI: 2.0-8.4%) at 10 years. Males had a 3-fold hazard of first stroke compared to females (95% C.I. 1.1-10.9; p = 0.04). There were 6 recurrent strokes (2 ischemic, 3 hemorrhagic, 1 unknown) at a median of 15 months after first stroke (range 5.6 months to 8.9 years); brain imaging was available in 1 case and was consistent with stroke. The cumulative incidence of recurrent stroke was 26% (95% CI 9-51%) at 5 years post first-stroke and 32% (95% CI 13-57%) at 10 years. CONCLUSION: Survivors of childhood cancer who received CRT are at high risk for first and recurrent stroke.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-06. PROCESSING SPEED AND WHITE MATTER ASSOCIATION IN CHILDREN THREE YEARS POST TREATMENT FOR MEDULLOBLASTOMA

Wilburn Reddick ¹, Shawna Palmer ¹, John Glass ¹, Yimei Li ¹, Robert Ogg ¹, Amar Gajjar ¹

Abstract

INTRODUCTION: Children treated for medulloblastoma experience damage to white matter tracts and reduced cognitive processing speed (PS). This study explores relationships between white matter microstructure, fractional anisotropy (FA), and PS using tract-based spatial statistics. METHODS: Forty patients (12.9 + 4.4 years) at 36 months post diagnosis with medulloblastoma and 40 age and gender matched controls were evaluated. Standardized measures of visual perceptual, semantic and overall PS were derived from the Woodcock-Johnson Test of Cognitive Abilities. Diffusion tensor imaging was acquired and then processed following the TBSS pipeline. Multiple regression analyses treating age as a covariate were run controlling for family-wise error rates and regions were labeled anatomically. Three tests were performed: 1) FA different between groups, 2) FA associated with PS, and 3) association between FA and PS different between groups. Individual FA values were extracted from regions identified in the third analysis and partial correlation analyses were performed between mean FA values and neuropsychological scores controlling for age. RESULTS: Controls had higher overall PS than patients (controls: 107.5 + 11.4; patients: 85.6 + 15.0; p < 0.001). FA throughout most fiber tracts was greater in controls than patients. Overall PS was associated with fiber tracts throughout the brain, and there was significant group-by-processing speed interaction. Post-hoc analyses demonstrated associations in the commissural fibers of the corpus callosum for both semantic and visual perceptual speed of processing. Semantic processing was associated with the projection fibers of the posterior thalamic radiation while perceptual processing was associated with the projection fibers of the external capsule. CONCLUSIONS: Children treated for medulloblastoma have lower PS associated with decreased FA compared to their peers in the commissural fibers within the corpus callosum and projection fibers of the posterior thalamic radiation and external capsule. Specific attention to change in these vulnerable fiber bundles during treatment may help identify a need for cognitive remediation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-07. COMPLICATED MIGRAINE WITH COMPLEX REGIONAL PAIN SYNDROME AFTER CRANIOSPINAL IRRADIATION FOR MEDULLOBLASTOMA: A POSSIBLE SMART VARIANT

Ayman Omar ¹

Abstract

Stroke like migraine attacks after radiation therapy (SMART syndrome) is a rare delayed complication of cranial radiation. It is characterized by migraine headaches associated with reversible neurologic deficits that typically occur years after cranial or craniospinal radiation. Here, we report a previously undescribed variant of SMART syndrome, namely complicated migraine attacks associated with complex regional pain syndrome in a patient with medulloblastoma. A 22-year-old female was diagnosed with an M3A medulloblastoma of the fourth ventricle at age 12. She was initially treated with surgery, craniospinal radiation followed by carboplatin, vincristine and cytoxan (COG protocol 99701). Six years after completion of treatment she began experiencing episodes of right sided headaches with visual changes associated with transient bluish discoloration of the left upper extremitytogether with excruciating left shoulder and left upper extremity pain and left sided numbness involving the face and arm. Three years later the attacks recurred lasting several hours at a time and later resolved without any residual deficits. Patient underwent MR imaging of the brain and cervical spine with and without gadolinium, a doppler of the left upper extremity, MR angiogram of the head and neck, electromyography and nerve conduction studies, hypercoagulable panel, lumbar puncture for cell count and differential, protein and glucose as well as CSF cytology. All the investigations were unremarkable. The patient was given sumatriptan and ibuprofen with significant relief. Our clinical impression was that the patient was suffering from SMART syndrome associated with complex regional pain syndrome a decade after craniospinal irradiation for the treatment of a medulloblastoma. To the best of our knowledge, the association of SMART syndrome with complex regional pain syndrome after craniospinal irradiation has never been described before. The long survival of some medulloblastoma patients following successful treatment may allow for the detection of previously undescribed complications of craniospinal irradiation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-08. RISK OF SECONDARY NEOPLAMS IN SURVIVORS OF CHILDHOOD BRAIN TUMORS

Stephanie Perkins ¹, Eric Shinohara ¹

Abstract

With the use of multi-modality therapy including surgery, chemotherapy and radiation therapy, the outcome for many childhood brain tumors has greatly improved. However, long term survivors are at risk for late effects from the therapy they receive during treatment. One of the most concerning long term risks is the development of secondary neoplasms. Although the risk is low, appearance of secondary neoplasms appears to increase with time. Using the surveillance, epidemiology, and end results (SEER) database between 1973-2003, we assessed the occurrence of secondary neoplasms in childhood brain tumor survivors. Patients diagnosed between the ages of 0-19 years that survived at least 5 years after diagnosis were included for analysis. A total of 5078 patients were identified. Median age was 8 years with a male to female ratio of 1.19. Initial diagnosis consisted of a wide variety of brain tumors including astrocytoma/glioma in 3298 (65%), oligodendroglial tumors in 218 (4%), embryonal/medulloblastoma/PNET in 921 (18%), ependymoma 331 (7%), and other 310 (6%). Median follow-up was 11.9 years. Among the 5078 5-year survivors, 159 (3.1%) patients developed 166 second neoplasms. Median time to subsequent neoplasm was 14 years. The most common secondary neoplasms included 15 thyroid cancers, 30 meningiomas, 61 malignant brain/spinal cord tumors and 13 cases of leukemia or myelodysplastic syndrome. Secondary neoplasm occurred in 5.3% of patients that received radiotherapy at initial diagnosis as compared to 1.5% of patients that received no radiotherapy. Risk of secondary neoplasm for patients that survived at least 30 years was 7.1%. Median survival after diagnosis of a secondary neoplasm was 28 months (range 0-298). Median survival after diagnosis of a secondary brain tumor was 18 months (range 0-218). Although the development of a secondary neoplasm after treatment for a childhood brain tumor is rare, the risk continues to increase with extended follow-up.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-09. BARRIERS TO PARTICIPATION IN A NEURO-ONCOLOGY EDUCATION AND SUPPORT GROUP

Debra Spoljaric ¹, Jill Isenberg ², Moroline Whittington ², Marnie Hauff ¹, Allison King ¹

Abstract

Support groups are an important resource for individuals with cancer and their families. Limited research exists to identify barriers that prevent individuals from participating. Identification of barriers is important, because some barriers may be amenable to change. The current study surveyed parents of patients who have been treated in a neuro-oncology program regarding barriers that prevent them from attending a support group for this population. The survey addressed a range of barriers that might prevent participation, including practical barriers, perception of need and efficacy, and preferences regarding group characteristics. Forty-nine parents (43 mothers, 5 fathers, 1 unknown) completed the survey. Parents were predominantly Caucasian (91.8%) and middle-aged (M = 39.43 years, SD = 7.02). Parents identified few barriers to participation. The primary barrier was practical in that families reported a busy schedule (63.2%). The pattern of responding suggested a limited perception of need, because parents felt their families were coping well (42.8%). Notably, parents indicated interest in meeting other parents who have had a similar experience (73.4%) and most parents felt that hearing about other's experiences would be helpful (63.3%). Parents supported the use of technology such as live streaming via the internet (63.3%) and viewing videos on the hospital's website (65.3%). Parents were less interested in financial assistance for transportation, greater frequency of meetings, or meeting outside the hospital. Parents of neuro-oncology patients value the opportunity to meet and share with others who have had similar experiences in a support group. The primary barrier was practical, which could be addressed through technology to allow virtual attendance. Families felt that they were coping well, but it may be helpful to encourage these families to attend to provide personal accounts of "how we made it through." Removing barriers to participation in the group will increase quality of life for neuro-oncology survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-10. SOCIOECONOMIC STATUS AND QUALITY OF LIFE IN CHILDREN WITH CANCER OR BRAIN TUMORS: THE MEDIATING ROLE OF FAMILY FACTORS

Kristin Litzelman ¹, Emily Barker ¹, Kristine Catrine ², Diane Puccetti ², Peggy Possin ², Whitney Witt ¹

Abstract

OBJECTIVE: This study aimed to determine if and to what extent: (1) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (2) family functioning and burden mediate the relationship between socioeconomic status and children's QOL. METHODS: In this cross-sectional study, parents of children with cancer (n = 46) or brain tumors (n = 25) and parents of healthy children (n = 135) completed in-person interviewer-assisted surveys assessing sociodemographics, child QOL, family functioning and burden. For children with cancer or brain tumors, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between socioeconomic demographics and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. RESULTS: Lower income was associated with worse child QOL. The effect of income differed by case status; income was more strongly associated with QOL in children with cancer or brain tumors than healthy children. Among children with cancer or brain tumors, log income was significantly associated with child QOL; this relationship was significantly attenuated by family functioning and family burden. Children with brain tumors had worse QOL than children with other types of cancer, but the effect of income did not differ by type of cancer. CONCLUSIONS: Significant socioeconomic disparities exist in the QOL of children with cancer or brain tumors. Family factors partially explain the relationship between low socioeconomic status and poor QOL outcomes among these children. Lower income families may have fewer resources to cope with their child's illness. Increased support, monitoring, and referrals to reduce burden for lower income families may lead to improved QOL in children with cancer or brain tumors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-11. POSTERIOR FOSSA TUMOUR SURGERY OUTCOMES: THE LIVERPOOL CAUSALITY COMPLICATIONS ASSESSMENT TOOL

Conor Mallucci ¹, Ram Kumar ¹, Barry Pizer ¹, Dawn Williams ¹, Benedetta Pettorini ¹

Abstract

INTRODUCTION: Complications following posterior fossa tumour surgery in children are reported between 32-62% of cases. Determining if an adverse event or adverse outcome after surgery is the result of surgery or some other factors (such as as the tumour itself or other treatments) is often difficult and may be controversial. In most of cases, the decision relies on judgement of the neurosurgeon or other component of the team, making reporting of complication rates unreliable and makes more difficult identifying predisposing risk factors and method able to reduce these risks. A method for improving this system is required. METHODS: The authors have developed a causality assessment tool for adverse events following posterior fossa tumour surgery in children. This tool is built around similar work in our institution on identifying adverse reactions to drugs in children. RESULTS: The causality tool has been tested and developed on a retrospective review of post-operative course in 67 children with posterior fossa tumours operated on in our centre with specific reference to suspected complications in surgery. The review of case notes has resulted in the development of proxy indicators of complications that may be useful in future routine monitoring from administrative data. CONCLUSION: The posterior fossa tumour surgery adverse event causality tool is necessary for future multicentre research studies on surgical complications and for comparative effectiveness studies. The proxy indicators of complications are necessary for quality improvement.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-12. PHYSICAL FUNCTIONING OF PEDIATRIC POSTERIOR FOSSA BRAIN TUMOUR SURVIVORS

Janine Piscione ¹, Eric Bouffet ¹, Iffat Shams ¹, Abhaya Kulkarni ¹

Abstract

PURPOSE: Children who survive posterior fossa brain tumours (PFBTs) are vulnerable to limitations in long-term physical functioning (PF); yet, a standardized approach for assessing PF in this population is not well-described. We used two standardized measures to describe PF in children with PFBTs and compared results to norms. METHODS: The self/parent-report Pediatric Outcomes Data Collection Instrument (PODCI) and the observational-based Bruininks-Oseretsky Test of Motor Performance, Second Edition (BOT2) were used in a cross-sectional study of 30 pediatric patients previously treated for PFBT. Adolescents (11-18.9years) completed the PODCI and parents of children (5-10.9years) completed the parent-report version. All participants were assessed with the BOT2. RESULTS: Mean age at diagnosis was 5.2 years. Mean time since last treatment for PFBT was 5.6 years. Seventeen adolescents and 13 parents completed the PODCI. Compared to norms (using t-test), parents reported worse upper extremity function (p = 0.03) and sports/physical functioning (SPF) (p = 0.02), while adolescents self-reported worse SPF only (p = 0.01). All participants completed the BOT2 and mean scores were significantly worse than norms (t-test) in: Balance (p < 0.0001); Bilateral Coordination (p = 0.02) and Running speed/agility (RSA) (p = 0.0050). Stratified by tumour type, participants with astrocytoma (N = 13) had lower scores than norms on balance (p = 0.004), whereas higher grade tumours (N = 17) were associated with lower scores in all subdomains (Bilateral Coordination, p = 0.02; Balance, p < 0.0001; RSA, p = 0.001; Strength, p = 0.043). Multivariate analyses revealed craniospinal radiation most strongly associated with decreased RSA and post-operative mutism and receipt of chemotherapy associated with decreased strength. There was poor correlation between the BOT2 and PODCI data except for between the RSA and SPF domains (r = 0.72). CONCLUSION: Significant PF limitations were observed using the BOT2, yet correlated poorly with PODCI self/parent-reporting. Notably, although skill proficiency is affected, activity participation continues. Consequently, combined use of observational and self/parent-reporting measures may provide a more comprehensive assessment of PF in PFBT patients.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-13. LATE-COMPLICATIONS IN IRRADIATED CHILDHOOD BRAIN TUMOR SURVIVORS

Tiina Remes ¹, Arja Harila-Saari ¹, Maria Suo-Palosaari ², Pekka Arikoski ³, Pekka Riikonen ³, Anna Sutela ⁴, Päivi Koskenkorva ⁴, Marja Ojaniemi ¹, Heikki Rantala ¹

Abstract

BACKGROUND: The treatment of childhood brain tumors has developed during the last four decades so that 70-74 % of children will become 5-year survivors of their primary CNS malignancy. This improved outcome has resulted in a new and growing population of childhood cancer survivors. METHODS: A total of 44 adults treated for childhood brain tumor in the Oulu and Kuopio University Hospitals were studied for secondary CNS tumors, osteoporosis, metabolic disease and hormonal dysfunction. All the patients had received CNS irradiation as part of their treatment and the follow-up time since cessation of therapy was more than 5 years. 68 patients were initially identified to be eligible, but 24 declined to participate or could not be contacted. Patients were examined with craniospinal MRI and dual X-ray absorptiometry (DEXA). Pituitary, thyroid and gonadal function were evaluated. RESULTS: Secondary CNS tumor was detected in 13,6 % of patients (6/44) with MRI. Four patients had meningioma, one patient suspected Schwannoma and one a tumor of unknown etiology. Osteoporosis (13,6 %) and osteopenia (52,3 %) were common. The bone mineral density correlated positively with body mass index and negatively with FSH levels. Hormonal dysfunction was found in 75,0 % of the patients with thyroidal dysfunction being the most common abnormality. Almost all (87,5%) of the survivors had findings requiring further investigations or treatment. CONCLUSIONS: Majority of the long-term survivors of childhood brain tumors treated with irradiation had untreated late-effects. The common complications were secondary brain tumors and reduced bone mineral density. On the basis of our studies, these patients are in urgent need for organized regular follow-up in clinics with expertise in late-effects of childhood cancer.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-14. PSYCHIATRIC SYMPTOMS IN CHILDREN WITH MEDULLOBLASTOMA

Cynthia J Campen ¹, Dejeunne Ashby ², Paul G Fisher ¹, Michelle Monje ¹

Abstract

BACKGROUND: Therapy for medulloblastoma (MB) influences neurodevelopmental processes thought to be important in the pathophysiology of depression, such as new hippocampal cell formation and maturation of the limbic system. Furthermore, children with MB must overcome significant challenges from extensive surgeries and a nearly year-long treatment course. We hypothesize that children with MB will have a high risk of mood and adjustment disorders. METHODS: Patients were identified via the LPCH Pediatric Brain Tumor Database and were included if they were aged birth to 30 years at the time of diagnosis of their incident brain tumor, diagnosed between 1/1/1997 - 6/1/2011, and treated at LPCH. RESULTS: Fifty-six patients with medulloblastoma were identified. The median age at diagnosis was 11.75 years, 36 (64.3%) were male, and median dose of radiation to the supratentorial deep gray and frontal lobes was 23.4 Gy. Median age at diagnosis was 11.75 years. Seventeen (30.4%) patients with psychiatric symptoms were identified, of whom 15 (88.2%) were male. This male predominance was significant (p = 0.04). There was a significant difference in age at diagnosis between those who developed psychiatric symptoms (median: 9.5 years [SD 2.78]), and those who did not (median: 5.9 years, [SD 4.4], p = 0.034). Psychiatric symptoms included: depression, anxiety, and adjustment disorder. Median time to first psychiatric symptom was seven months. There was no significant difference in median radiation dose or cycles of chemotherapy between the symptomatic and non-symptomatic patients (p = 0.91 and 0.35, respectively). CONCLUSIONS: We report a high rate of depression and adjustment disorders in children treated for medulloblastoma. Risk factors include older age and male gender. These patterns likely reflect psychiatric responses to life-threatening illness, although abnormal brain development may also play a role.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-15. LONG-TERM QUALITY OF LIFE IN CHILDREN TREATED FOR POSTERIOR FOSSA BRAIN TUMOURS

Abhaya V Kulkarni ¹, Janine Piscione ¹, Iffat Shams ¹, Eric Bouffet ¹

Abstract

INTRODUCTION: In the face of increasing survival, quality of life (QOL) has become an important indicator of treatment success in children with posterior fossa brain tumours (PFBT). Our objective was to assess long-term quality in survivors of PFBT. METHODS: A cross-sectional study of children previously treated at our institution for PFBT was conducted. All participants had received standard treatment for PFBT, with treatment ending at least 6 months before assessment, and were under the age of 19 years at the time of assessment. Their current QOL was measured with the PedsQL Generic Core Scales (parent-completed version) and the Health Utilities Index-3. Several variables (patient-related, treatment-related, and socioeconomic), obtained mostly from retrospective chart review, were tested for association with QOL. RESULTS: A total of 62 children participated in the study (median age at assessment 11.9 years, interquartile range [IQR] 7.8-14.8 and median age at diagnosis 4.9 years IQR 2.5-6.9). They had last received active treatment for their PFBT a median 5.2 years ago (IQR 2.4-10.1). Tumour types included: pilocytic astrocytoma (45.2%), medulloblastoma (30.6%), ependymoma (11.3%), and brainstem astrocytoma (11.3%). Adjuvant therapy included chemotherapy (40.3%) and/or radiotherapy (14.5% focal and 21.0% craniospinal). Permanent treatment for hydrocephalus was required in 38.7%. Tumour recurrence occurred in 11.3% requiring repeat treatment. Median HUI-3 was 0.91 (IQR 0.71-1.00) and the median PedsQL Total score was 78.3 (IQR 64.1-92.4). Only the following variables were significantly associated with worse QOL in multivariable model testing (all p < 0.01): need for permanent hydrocephalus treatment, large ventricle size, and lower family income. CONCLUSIONS: As a group, long-term survivors of pediatric PFBT appear to have QOL indicators that are comparable to the general population, although a minority experience poor outcome. Although several confounding variables likely remain in this retrospective study, important associations with QOL include the presence of hydrocephalus and family income.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-16. EVALUATION OF THE THERAPEUTIC OUTCOME AND QOL IN THE PATIENTS WITH INTRACRANIAL GERMINOMA - A SINGLE INSTITUTION STUDY

Hideo Nakamura ¹, Keishi Makino ¹, Shigetoshi Yano ¹, Jun-ichi Kuratsu ¹

Abstract

PURPOSE: This study is to clarify the long-term subjective functional state and the therapeutic factors that may influence the outcome and ADL of patients with intracranial germinoma. PATIENTS AND METHODS: The therapeutic outcome and QOL were evaluated in 60 patients (46 males and 14 females) with an average age of 16 years treated at Kumamoto University Hospital from 1975 to 2011. Patients were treated with radiotherapy only from 1975 to1991 (1st period), they were treated with platinum-based chemotherapy and local radiotherapy from 1992 to 1998 (2nd period) and were treated with platinum based chemotherapy and extended local radiotherapy (whole ventricles were covered) from 1999 to 2011 (3rd period). Tumor recurrence rate and overall survival of the patients in these three periods were compared. In relation to QOL of the patients the highest formal education level, the employment rate and marital status were investigated. RESULTS: Tumor recurrence rate in the 1st, 2nd and 3rd period was 4/24 (17%), 6/14 (43%) and 2/22 (9%), respectively. Four patients in the 1st, 3 in the 2nd and 1 in the 3rd period were dead. Nineteen of 22 patients in the 3rd period graduated from normal high school, while less than half of the patients in both 1st and 2nd periods could graduate from the normal high school. The employment rate in each period was 63%, 80% and 78%, respectively. Three of 24 in the 1st period, 3 of 14 and 1 of 22 were married. Since almost of the patients in the 3rd period are not old enough to marry, there is only one married person. CONCLUSION: Our data suggested that current therapeutic modality of extended local radiotherapy combined with chemotherapy, should be sufficiently effective and be expected for an improvement of QOL in patients with intracranial germinoma.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-17. HYPERTENSION IN CHILDREN WITH MALIGNANT TUMORS

Filip Jadrijevic-Cvrlje ¹, Maja Batinica ¹

Abstract

The prevalence of hypertension in children with malignant tumors is 10-20%. In pediatric oncology, hypertension occurs mainly in children with Wilms tumor, neuroblastoma, phaeochromocytoma and with a brain tumor. Pathogenetic mechanisms are usually complex. OBJECTIVE: To describe the incidence of hypertension in children New cases of malignant disease, and to analyze the complications and procedures related to hypertension. METHODS: We conducted a retrospective descriptive study in children with newly diagnosed malignant disease in the Reference Centre for solid tumors in children Children's Hospital Zagreb during the period of five years (2005.-2009.). RESULTS: The Children's Hospital in Zagreb Oncology department treated about 40-60 new cases of children with malignant tumors. Groups have been formed due the histopathologic diagnosis of malignant disease. For each group we analyzed the median blood pressure; in the case of hypertension, it was analyzed for grade, the presumed etiology and pathogenesis, used antihypertensive therapy and complications of hypertension. IN SUMMARY: This paper presents the experience of pediatric oncology center in the process of hypertension. The etiology is multifactorial mainly. Although often asymptomatic, treatment of hypertension is essential to prevent complications and oncological therapy conducted according to protocol. Most frequently used antihypertensive medications were nifedipine, enalapril, and furosemide.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-18. FACTORS INFLUENCING PLACE OF DEATH IN TERMINALLY ILL CHILDREN WITH BRAIN TUMORS

Helen Toledano ¹, Tseela Hoffman ¹, Yifat Ezer-Cohen ², Shalom Michowiz ³, Isaac Yaniv ¹, Ian J Cohen ¹, Inna Adler ⁴

Abstract

Little is known about factors that influence where children with a brain tumor die. We sought to determine the features associated with home or hospital deaths. This was a retrospective study of deaths from a brain tumor in children aged 1-21 at our center from 2005 - 2011. We collected data regarding place of death, the family (socioeconomic status, religion, housing, country of origin and primary language and siblings), tumor type, symptoms, complexity of the care in the terminal period (NG feeding, catheter, IV etc), distance from our center and involvement of the community. We documented parent's wishes regarding place of death and whether this was achieved, the number and length of hospital admissions in the terminal period and continuation or not of chemotherapy. There were 43 deaths - two thirds in Jewish children and one third Arabs. The median age at death was 8.9 years. 36/43 deaths occurred in the hospital, 5 at home, 1 in the ambulance on the way home and 1 in a hospice. Of those dying in the hospital, 28/36 died in the oncology department, 1 in a pediatric ward and 7 in the ICU. In 100% of files we found documentation of the parents wishes regarding place of death - 30% wanted this to occur at home and 70% in the hospital. Chemotherapy was stopped on average 5 weeks before death. No association was found between the parents requests regarding place of death and the age of the child or his siblings or the length of the illness prior to death. We will present details on the influence of other factors on place of death. CONCLUSIONS: The majority of deaths are still occurring in the hospital. These findings have important implications for the provision of pediatric palliative care for children with brain tumors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-19. ADJUVANT CHEMOTHERAPY, NOT GROWTH HORMONE, INCREASES PREVALENCE AND GRADE OF SECOND PRIMARY TUMOURS (SPT) AFTER NEURAXIAL RADIATION FOR CHILDHOOD POSTERIOR FOSSA BRAIN TUMOURS (PFBT)

Samuel Mindel ¹, Mahalakshmi Gopalakrishnamoorthy ¹, Dawn Saunders ², Mark Gaze ¹, Helen Spoudeas ¹

Abstract

BACKGROUND: SPTs, such as surgically resectable meningiomas and thyroid tumours, are known late effects of PFBT attributed to high dose radiation scatter at the field's edge. However the effects of adjuvant chemotherapy, genetic cancer predisposition or growth hormone (GH) therapy on their prevalence, is unclear. METHODS AND AIMS: In a long term (>10yrs) evaluation of late functional, endocrine and cognitive outcomes, we performed surveillance MRI brain scans on 103 (65% M) PFBT survivors (68 PNET, 18 Astrocytomas, 17 Ependymomas) aged 21.8 (7-38) years transitioning to adult services. 54 (49%) had received childhood GH replacement, especially after PNET (80%). Non-CNS SPTs, prior oncological therapy and any known genetic cancer predisposition were noted. RESULTS: Over a median 14.4 (2.8-34.8) years, 20 SPTs occurred in 14 (29%M) neuraxially irradiated PFBT survivors, all excepting one (ependymoma), being PNET survivors. 11 had received prior GH therapy Two patients each had 2 and 3 SPT's respectively, one of whom was found to harbour a FAP gene mutation. 10 (50%) SPTs occurred in the 8 PNET patients given chemotherapy, occurring earlier (12.3 vs 19 years) and tending to higher grade (sarcoma, leukaemia) than in the 5 without chemotherapy CONCLUSION: All but one SPT occurred in PNET survivors, some 20% (1:5) developing at least one SPT over a median 14.4-years. Three had never received GH therapy. The average time to SPT is similar to that reported (13 vs15 years) but the 14% prevalence is significantly greater than (2-3%) expected. Chemotherapy doubled the risk of, and halved the time to SPT. These novel and preliminary data suggest that patients with PNET may be genetically predisposed to SPT and that adjuvant chemotherapy signifcantly increases the risk.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-20. NEUROCOGNITIVE OUTCOME AND ACADEMIC ACHIEVEMENT IN ADULT SURVIVORS OF CHILDHOOD MEDULLOBLASTOMA

Virginie Kieffer ¹, Georges Dellatolas ³, Mathilde Chevignard ¹, Stéphanie Puget ⁵, Frédéric Dhermain ², Jacques Grill ², Christelle Dufour ⁴

Abstract

PURPOSE: To investigate neurocognitive outcome and academic achievement in adult survivors of childhood medulloblastoma. PATIENTS AND METHODS: We assessed 51 adults (median age, 23.4, range 18-32 years) who were treated postoperatively for a medulloblastoma at Institute Gustave Roussy, with radiotherapy and/or chemotherapy between 1.4 and 15.3 years (median, 10.1). The last assessment was performed 2 to 17 years (median, 7.2) after radiotherapy. Clinical symptoms at diagnosis, postoperative neurological status, neuropsychological data, academic achievement and parental education were collected. RESULTS: Mean full scale Intellectual Quotient (FSIQ) at the last assessment was 81.6 (SD = 17.6); it was significantly lower in the 12 patients who experienced postoperative akinetic mutism (mean IQ = 69 vs 92, p< 0.001), but not related to the age at diagnosis (p = 0.09) nor the type of treatment they had received (p = 0.1). Moreover, the FSIQ was correlated to the parent's educational level (p = 0.02). Six survivors (11%) had severe intellectual disability, 20 (39.2%) were still studying, 14 (27.4%) had a regular employment and 11 (24.6%) were unemployed. Mean FSIQ for patients without any diploma, patients with National Vocational Qualification (NVQ) level 1,2, patients with NVQ level 3 and patients with upper level achievement were 70.8 (SD = 13.1), 83.1 (SD = 9.7), 82.9 (SD = 11.5) and 107.2 (SD = 18.0), respectively. CONCLUSION: We demonstrated that postoperative akinetic mutism and parental education were associated to the degree of cognitive impairment in adults treated for childhood medulloblastoma. The degree of academic achievement is strongly related to IQ scores.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-21. PARENTAL KNOWLEDGE AND HEALTH CARE SATISFACTION WITH NEUROFIBROMATOSIS TYPE 1

Ryan Muir ², Andrea Hunter ¹, Andrew Latchman ¹, Olaf de Camargo ³, Katrin Scheinemann ²

Abstract

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder with many health implications, including behavioral, social and emotional disabilities, skin changes, motor skills impairments, visual abnormalities, delayed puberty, cardiovascular abnormalities, skeletal deformations and tumor development. Addressing these health care needs is quite challenging in the current system. METHODS: After their first visit to the NF1 co-ordination of care clinic at McMaster Children's Hospital, caregivers completed a Likert-scale questionnaire adapted from the Multidimensional Assessment of Parental Satisfaction. This assessed caregiver understanding of the potential impact of NF1 on several dimensions of health as well as caregiver satisfaction with previous health care provider education of the complexity of NF1. RESULTS: Questionnaires were completed by 11 caregivers so far. Parental knowledge was highest for visual abnormalities and the risk of tumor development, especially optic pathway gliomas (OPGs), with scores of “Good” and “Excellent” reported by 91% of the study population. Similarly, parental satisfaction with previous health care addressing these domains achieved scores of “Good” and “Excellent” for 100% of the study population. In contrast, parental knowledge was especially limited - a score of “Fair”, “Very Poor” and “Poor” - in domains of bone and cardiovascular health, with nearly 50% of the study population reporting these scores. Importantly, scores of “Very Poor” or “Poor” were reported in 30% of the population with respect to their health care provider's interest in referring to specialized services to address their child's unique NF1 related health care needs. CONCLUSIONS: Though NF1 is a multisystem disorder healthcare providers appear to focus on the risk of development of OPGs and vision problems while some other dimensions of health are underemphasized. This may highlight the importance of the role of multidisciplinary health clinics and physicians with keen interests in NF1 in effectively addressing the unique health-care needs of these patients.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-22. CHRONIC MYELOID LEUKEMIA AS A SECOND MALIGNANT NEOPLASM IN A PATIENT WITH MEDULLOBLASTOMA AFTER TREATMENT WITH CHEMOTHERAPY AND IRRADIATION: A CASE REPORT AND REVIEW OF THE LITERATURE

Nitika Dhir ¹, Wafik Zaky ¹, Toska Zomorodian ², Kenneth Wong ¹, Girish Dhall ¹

Abstract

Medulloblastoma (MB) accounts for approximately 20% of all pediatric brain tumors. The survival rate of medulloblastoma patients has improved over the past three decades; however, at the expense of long-term toxicity, including second malignant neoplasm (SMN). Here, we report a case of chronic myeloid leukemia (CML) as a SMN in a patient with MB treated as per Children's Oncology Group (COG) study A9961, Regimen B. A 19-year old female was diagnosed with average-risk classic MB. She was treated as per COG study, A9961, with craniospinal irradiation and weekly vincristine followed by 8 consolidation cycles of cisplatin, cyclophosphamide and vincristine and was in continuous complete remission until nine months following completion of therapy when she presented with fever, chest pain, dyspnea and fatigue. Complete blood count showed pancytopenia and 88% blasts. Her CSF showed 26% blasts. Peripheral blood flow cytometry demonstrated Pre-B Cell ALL. She was diagnosed with Philadelphia Chromosome positive ALL as cytogenetic study revealed t(9;22). However, after performing a BCR-ABL length study, a diagnosis of CML with blast crisis was made. Treatment was started with multidrug induction chemotherapy and dasatinib. Unfortunately, the patient expired 3 months later from sepsis and multi-organ failure. Patient did not have any family history of cancer and work-up for constitutional p53 mutation was negative. Overall, there is a 5.4 x increased risk of SMN after medulloblastoma therapy. On COG study A9961, the largest prospective randomized trial performed in MB, 14 of 379 eligible patients developed a SMN at a median of 5.75 years (range, 3.2 - 10.1) from diagnosis (5 high-grade gliomas, 1 leukemia, 1 pilocytic astrocytoma, 2 myelodysplastic syndrome, 1 sarcoma, 3 carcinomas and 1 basal cell carcinoma). To the best of our knowledge, this is the first reported case of CML in a patient with MB treated with irradiation and chemotherapy.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-23. PRIMARY HYPOTHRYOIDISM IN PEDIATRIC PATIENTS RECEIVING CRANIOSPINAL IRRADIATION

Margaret Macy ¹, Christine Lauro ¹, Philip Zeitler ¹, Nicholas Foreman ¹, Arthur Liu ¹

Abstract

BACKGROUND: Endocrine abnormalities are well known sequelae of radiation for pediatric brain tumors. In particular, hypothyroidism either due to direct irradiation of the thyroid gland during craniospinal irradiation or due to irradiation of the hypothalamic-pituitary structures has been reported. MATERIALS AND METHODS: We performed a retrospective database review of all pediatric oncology patients diagnosed at our institution between 1994-2011 for patients who received craniospinal irradiation (CSI) and had thyroid function testing following radiation. RESULTS: We identified 86 patients who received CSI. Eighty three 83 (97%) had thyroid testing following CSI. Patients received 1800cGy to 3600cGy CSI with the majority receiving 2340 Gy (n = 53). Two patients had leukemia with CNS disease; the remaining 80 had primary brain tumors. The age range was 2-22.5 (median 8.9 years) at completion of radiation. Median follow-up time from radiation was 3.8 years. Fifty-eight patients (70.7%) developed hypothyroidism with primary hypothyroidism occurring more frequently than central hypothyroidism (57.3% and 10.9%, respectively). The mean time to develop primary hypothyroidism was 24.9 months (95% CI 21.1, 28.7) compared to 55.5 months (95% CI 40.0, 79.5) for central. There was no association between the rate of primary hypothyroidism and radiation dose (p = 0.43). The incidence was higher in younger children with 79% of patients less than 5 years developing primary hypothyroidism compared to 65% in those ages 5-10 and 43% in patients over 10 years. CONCLUSION: The incidence of hypothyroidism in our patient population following CSI was quite high with the majority being primary hypothyroid. While the radiation dose does not appear to influence the occurrence of primary hypothyroidism, younger age is associated with higher risk. Given the high incidence of hypothyroidism in this population, new strategies to protect the thyroid gland may be warranted.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-24. EFFICIENCY OF GROWTH HORMONE THERAPY IN CHILDREN TREATED FOR MEDULLOBLASTOMA OR POSTERIOR FOSSA EPENDYMOMA: EFFECTS ON HEIGHT, BODY PROPORTIONS AND IGF-I

Monika Chocholous ¹, Philippe Dodier ¹, Andreas Peyrl ¹, Karin Dieckmann ², Gabriele Häusler ¹, Irene Slavc ¹

Abstract

BACKGROUND: Most children treated for brain tumors with craniospinal irradiation and chemotherapy develop growth hormone deficiency (GHD). Despite GH-replacement therapy most patients fail to reach their genetically determined length. Possible explanations are impairment in responsiveness to growth hormone or tissue damage. We report on the auxological and endocrinological parameters of 23 patients with posterior fossa tumors treated in a similar way and receiving GH-replacement therapy for 12 months to 9 years. PATIENTS AND METHODS: Between 1991 and 2009 58 consecutive patients with medulloblastoma and posterior fossa ependymoma were treated according to the consecutive HIT protocols with craniospinal irradiation and chemotherapy. 23/58 patients (m:f = 11:12) received continuous GH-replacement therapy. Mean age at diagnosis was 7.0 ±3.48 years and at start of growth hormone treatment 11.4 ±2.98 years. RESULTS: Mean height at diagnosis was -0.06 SDS. During the first three years after diagnosis growth was reduced leading to a decrease of height of -1.83 SDS primarily due to a significant decrease in sitting height (-2.46 ±1.20 SDS) at the time of diagnosis of GHD. During growth hormone therapy (25 µg/kg/d) height (p = 0.004), IGF1 (p = 0.001), and leg length (p = 0.000) increased significantly. However, there was only a small increase in mean sitting height during therapy and disproportion increased with a difference of up to 3 SDS between sitting height and leg length. CONCLUSIONS: Growth hormone therapy using a standard substitution dose is efficient with respect to normalization of IGF1 and long bone growth. While catch-up growth occurs in non-irradiated bones this appears to be impossible in irradiated tissue such as the spine. While we do not recommend supraphysiological growth hormone doses in these patients, an earlier start of growth hormone treatment might help to counteract the adverse effect of irradiation by enabling at least physiological growth of the spine.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-25. INTRA-OPERATIVE MRI IN POSTERIOR FOSSA TUMOUR RESECTION- ABNORMALITIES OF DIFFUSION AND ASSOCIATED POSTOPERATIVE NEUROLOGICAL OUTCOME WITH AN EMPHASIS ON POSTERIOR FOSSA SYNDROME

Shivaram Avula ¹, Ram Kumar ¹, Connor Mallucci ¹, Benedetta Pettorini ¹, Deborah Garlick ¹, Barry Pizer ¹

Abstract

Posterior fossa syndrome (PFS) is a well recognized complication in children following posterior fossa tumour surgery. Among various factors that have been implicated in its aetiology, damage to structures including the dentate nucleus, superior cerebellar peduncle and the mesencephalic tegmentum has been described in literature. These abnormalities can be detected on the immediate postoperative MRI, which is usually performed 24 to 48 hours post surgery. This information can potentially help modify surgical techniques and minimise the risk of developing PFS. Diffusion weighted imaging is sensitive in identifying these post surgical changes but the appearances can vary depending on the timing of the scan and other post operative factors. Since the advent of Intra-operative MRI (IoMRI) at our institution, the final IoMRI has served as the immediate postoperative MR scan (which was traditionally performed within 48 hours). This gives an opportunity to evaluate all post operative imaging at a uniform time period (i.e. immediately post surgery). In the initial 2 year period Diffusion weighted imaging (DWI) or diffusion tensor imaging (DTI) was performed on the final IoMRI in 23 children during 25 tumour resections. All the diffusion imaging data were anonymised and retrospectively evaluated by a paediatric neuroradiologist for diffusion abnormalities. The patient's notes were evaluated independently by a paediatric neurologist for evidence of posterior fossa syndrome and associated neurological deficits. In this presentation we aim to present the imaging findings on diffusion weighted sequences in patients with PFS, the structures involved and pitfalls in image interpretation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-26. INCREASING RISK OF SEVERE, LIFE-THREATENING AND FATAL CHRONIC HEALTH CONDITIONS IN AGING SURVIVORS OF CHILDHOOD CNS TUMORS: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY

Gregory Armstrong ¹, Toana Kawashima ², Wendy Leisenring ², Marilyn Stovall ³, Charles Sklar ³, Leslie Robison ¹

Abstract

BACKGROUND: The incidence, severity, and spectrum of chronic health conditions in the third and fourth decades of life among survivors of childhood CNS tumors have not been well studied. METHODS: Analyses included 14,358 >5 yr survivors of childhood cancer including 1876 (13.1%) survivors of CNS tumors (median age at last follow-up 31.0 yrs, range 6.0-56.0; 45.8% >30 years) and a sibling comparison group (n = 4,023). Self-reported health conditions were classified using the NCI CTCAE 4.0 grading system. Analyses focused on serious conditions (SC) defined as severe/life-threatening/fatal, grades 3-5. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for gender and race, using age as the time scale. RESULTS: Among survivors of CNS tumors with no previous SC through age 25, the cumulative incidence for a new SC by age 40 compared to non-CNS tumor survivors and to siblings was 25.1% (95% CI 25.1-25.2) vs. 23.7% (95% CI 23.7-23.7) vs. 6.2%, (95% CI 6.2-6.3), respectively. Survivors of CNS tumors ≥30 yrs of age had a 6.1-fold (95% CI 5.4-6.8) increased risk of a SC compared to same age siblings, in contrast to non-CNS survivors (HR 4.3, 95% CI 3.9-4.7). Compared to siblings, CNS tumor survivors had a significantly increased risk for: stroke (HR 26.7, 95% CI 15.9-45.1), myocardial infarction (HR 2.1, 95% CI 1.1-4.2), hypothyroidism (HR 4.8, 95% CI 3.6-6.3), ovarian or testicular dysfunction (HR 4.5, 95% CI 3.0-6.9) and renal failure (HR 5.9, 95% CI 2.0-17.3) among other serious conditions. Compared to non-CNS survivors, CNS tumor survivors had significantly higher risks of stroke (p < 0.001), hypothyroidism (p = 0.004) and growth hormone deficiency (p < 0.001). CONCLUSIONS: As they age, adult survivors of childhood CNS tumors continue to develop new SC at overall rates that are comparable to non-CNS survivors, but at substantially higher rates than siblings.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-27. CHILDREN SURVIVING BRAIN TUMORS HAVE HIGH RATES OF OBESITY INDEPENDENT OF PUBERTY

Constantine Samaan ¹, JoAnn Duckworth ¹, Katrin Scheinemann ¹

Abstract

BACKGROUND: Over the past few decades, improvement in brain tumor therapies has enhanced the survival of an increasing number of children, but this has also resulted in larger number of survivors experiencing comorbidities related to the tumor or its treatment. One area of comorbidities that has received limited attention so far is the risk of obesity and cardiometabolic complications of the tumor or its treatment on the individual child. In the general population, obesity rates have tripled in children over the past three decades, and today 25% of Canadian children are overweight (BMI between 85-95^th percentile) or obese (BMI >95^th percentile). Understanding the causes for weight gain in children with brain tumors may help the development of treatment and preventive strategies that reduces the burden of complications to survivors. In this study, we investigated the rates of overweight and obesity in survivors of pediatric brain tumors and correlated this with a known risk factor of increased adiposity i.e. puberty. METHODS: Retrospective chart review of children with different brain tumors (gliomas, ependymomas, medulloblastomas, PNET, germ cell tumors) who are cared for at McMaster Children's Hospital. We included children who are 6 or more months post completion of therapy. RESULTS: The cohort included 50 children (32 boys), mean age 11.7 years (SD 5.3). Overall, 42% of subjects were overweight or obese, including 44% (N = 14) of boys and 39% (N = 7) of girls. Puberty had no effect on excess weight gain (P = 0.7). CONCLUSIONS: Survivors of brain tumors have higher rates of overweight and obesity than the general population. Obesity rates are not affected by puberty.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-28. SCREENING TOOL FOR LATE EFFECT PEDIATRIC NEURO-ONCOLOGICAL CLINICS: A TREATMENT ORIENTED QUESTIONNAIRE

Noa Greenberg-Kushnir ¹, Sigal Freedman ¹, Rina Eshel ¹, Nirit Zverling ¹, Ronit Elhasid ¹, Rina Dvir ¹, Michal Yalon ², Abhaya V Kulkarni ⁴, Shlomi Constantini ¹

Abstract

Many survivors of childhood brain tumor suffer from long-term late effects (LE). The aim of this study was to develop a treatment-oriented questionnaire that will serve as a screening toolfor possible LE and will improve the long-term follow up and patient-specific treatment and his/hers quality of life (QOL). The treatment-oriented screening questionnaire is composed of 12 Treatment Arms, and refers to the objective and the subjective aspects of the patients' needs. We used the Long Term Follow-Up Guidelines published by the Children's Oncology Group, pediatric hemato-oncology experts' experience, and the Health Utility Index 3 (HUI3) as guidelines for the compilation of the questionnaire. The 12 Treatment Arms Scores (12 TASs) are the sum of the relevant questions scores (presented as a percentage out of the maximal possible score). Data are presented from 41 childhood brain tumor survivors, undergone neurosurgical operation in Dana Children's Hospital, Tel-Aviv Medical Center. All Patients were younger than 20 years old, at least 2 years off treatment, and without evidence of recurrence or secondary malignancy. Both patients and their parents were asked to answer the questionnaire separately. Patients were also evaluated by a pediatric hemato-oncology expert. A significant correlation was found, when comparing the 12 TASs and HUI3 scores, between the patients', parents', and experts' questionnaires. It appears that the questionnaires provide a reliable evaluation of the patients' needs, and reflect the patients' QOL. Finding suggests that the screening questionnaire for LE in survivors of childhood brain tumors is a useful, easy to use and calculate tool for the LE clinics. A unique treatment program should be tailored for each patient according to his/hers special needs, presented by the 12 TASs. By using the questionnaire over a period of years, we can improve the individual's function abilities, and QOL, while saving important resources.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-29. THE UK “HEADSMART – BE BRAIN TUMOUR AWARE” CAMPAIGN

Sophie Wilne ¹, Jo-Fen Liu ¹, Julia Trusler ³, Sarah Lundsell ³, Colin Kennedy ⁴, Lucie Clough ², Neil Dickson ³, Monica Lakhanpaul ⁵, Maureen Baker ⁶, Jan Dudley ², Richard Grundy ¹, David Walker ¹

Abstract

AIMS: To reduce the median symptom interval (SI) experienced by UK children and young people with brain tumours from three months to one month. METHODS: Quality improvement methodology was used to: Improve awareness among parents, carers, young people and healthcare professionals of symptoms potentially indicative of a brain tumour. Develop clinical decision support for healthcare professionals to assist then in selecting those children who require CNS imaging from those that require reassurance or scheduled review. SPECIFIC METHODS USED INCLUDED: Development of an evidenced based clinical guideline (published 2010). Media campaign. Development of the HeadSmart website. Survey of healthcare professionals' and the public's awareness of childhood brain tumours and the HeadSmart campaign. Recruitment of clinical champions to report symptom interval. RESULTS: Following campaign launch (June2011): 69% of surveyed healthcare professionals had heard of HeadSmart. 11% of the general public had heard of HeadSmart. The website had had 14,426 hits (to Feb 2012). 22 presentations on HeadSmart had been given (including 2 international and 5 national meetings). 19 clinical champions had been recruited and had provided data on time to diagnosis for 295 children newly diagnosed with a brain tumour. Before guideline publication the median SI experienced by UK children newly diagnosed with a brain tumour was 3.3 months (0-82.7). Before campaign launch (Jan to Jun 2011) the median SI for was 2.1 months (0-91.6), after campaign launch (Jun 2011 to Jan 2012) it was 1.7 months (0-83.6). CONCLUSIONS: Quality improvement methodology has resulted in widespread awareness of brain tumour symptoms and the HeadSmart campaign. Early results show a reduction in the SI experienced by UK children newly diagnosed with a brain tumour. Further data collection is required to determine whether this reduction is sustained and significant.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-30. LONG-TERM ENDOCRINOLOGICAL IMPAIRMENTS AND QUALITY OF LIFE OF PATIENTS WITH MEDULLOBLASTOMA TREATED WITHIN THE HIT'91 STUDY

Katja von Hoff ¹, Nadine Herzog ², Holger Ottensmeier ³, Desiree Grabow ⁴, Nicolas U Gerber ⁵, Carsten Friedrich ¹, André O von Bueren ¹, Anika Resch ¹, Rolf D Kortmann ⁶, Peter Kaatsch ⁴, Helmuth G Doerr ², Stefan Rutkowski ¹

Abstract

BACKROUND: Craniospinal radiotherapy followed by maintenance chemotherapy has been shown to be effective for disease control in the majority of medulloblastoma patients with clinical average risk. METHODS: To assess the long-term endocrinological outcome and quality of life (QoL), adult survivors of childhood medulloblastoma treated within the HIT'91 trial (randomisation maintenance chemotherapy with lomustine, cisplatin, vincristine versus sandwich chemotherapy with ifosfamide, etoposide, methotrexate, cisplatin, cytarabine, combined with 35.2 Gy craniospinal irradiation and 55.2 Gy posterior fossa boost) were interviewed using a QoL (EORTC-QLQ-C30 + brain tumor module: BN20), and an endocrinology questionnaire. RESULTS: Of 156 identified long-term survivors, 122 could be contacted and 65 replied (treatment: sandwich chemotherapy, 34, maintenance, 31; stage: M0, 40, M1, 7, M2/3, 6, insufficient staging, 12 with similar distribution in therapy groups). Mean time from diagnosis was 14.7 years (11.9-17.6). Height was below 2 standard deviations (SD) in 52% (34) of patients, and 53% (35) have received growth hormone treatment. 77% (49) have received any hormone treatment, 52% have received thyroxine (sandwich, 10; maintenance, 23, p < 0.001), 8% hydrocortisone (sandwich, 0; maintenance, 5, p = 0.016), and 11% of males have received testosterone treatment (sandwich, 0; maintenance, 5; p = 0.021) at any time after end of treatment. Relevant deficits in QoL scores were detected for physical functioning (10%, n = 6 patients below 2 SD of reference values), role functioning (20%, n = 13 <2 SD), social functioning (23%, n = 15 <2 SD). 22% (14) patients rated financial difficulties more severe than 2 SD of reference values. 30% (19) of patients had moderate or severe drowsiness. Impaired physical function, social function, motor dysfunction, and fatigue were more frequent in patients with maintenance chemotherapy (p < 0.05). CONCLUSION: A high rate of adult survivors has relevant deficits. Some of these deficits were more pronounced after maintenance chemotherapy. Modified maintenance regimen need to be investigated. Supported by Deutsche Kinderkrebsstiftung

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-31. HOME CARE IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS

Francesca del Bufalo ¹, Angela Mastronuzzi ¹, Annalisa Serra ¹, Luigi de Sio ¹, Franco Locatelli ¹

Abstract

The quality of life (QoL) of children and adolescents suffering for brain tumors is often affected by long hospitalization for chemotherapies and for the delicate management of end stage diseases. In order to improve the QoL of our patients and, secondly, to reduce the cost of assistance, a home-care (HC) service was activated in our Hematology-Oncology Unit in 2009. From 2009 until 2011, pediatric patients with brain tumors residing in Rome and with family compliance were enrolled in the HC program of the Ospedale Pediatrico Bambino Gesù. During 30 months of activity, 13 patients, aged 31 - 357 months (median age: 138 months), with controlled disease in 4/13 and advanced/terminal disease in 9/13, received HC. On the whole, 5 patients required procedures of maintenance of the central venous catheter, 4 children i.v. therapies, including chemotherapies, 1 patient needed transfusional and parenteral nutrition support, 2 children received rehydration therapies, pain-treatment was required in 2 patients. All of the children needed blood tests (233 procedures). Terminal palliation was required in 4 children, whilst 5 children died in hospital. Median assistance for patient was 20 days (range 2-388) with a total of 756 accesses (259/143 medical/psychologist accesses and 354 accesses of the nurses), replacing 312 days of hospitalization (181 out-patient and 131 in-patient days). The average daily cost for single patient resulted 170 € and was mainly related to the staff pay, compared with an average daily cost of 800 € for patients admitted to the hospital for the same procedures. HC assistance offers children and their families the opportunity of reducing hospitalizations and correlates costs thus allowing them to continue their daily lives and improving their ability to cope with the disease. This aspect gains a peculiar relevance for children with terminal disease who can spend their last days with their relatives.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-32. ENVIRONMENT DETERMINES DISABILITY OF CHILDREN WITH CANCER: FIRST APPLICATION OF WHO INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH FOR CHILDREN AND YOUNG PEOPLE (WHO ICF-CY) TO PEDIATRIC NEURO-ONCOLOGY

Veronica Biassoni ¹, Matilde Leonardi ², Daniela Ajovalasit ², Daria Riva ³, Chiara Vago ³, Arianna Usilla ³, Paola Fidani ⁴, Annalisa Serra ⁴, Elisabetta Schiavello ¹, Fulvia Gariboldi ⁵, Maura Massimino ¹

Abstract

INTRODUCTION: WHO's ICF-CY is a description/classification of health/health-related states. “Cure&Care” was a pilot project on children/adolescents with brain tumours funded by the Italian Health Ministry whose operative referral model was ICF-CY; its extensive results have already been published, here we will focus on the environmental factors. They include attitudes and social/physical background people live in; they positively/negatively influence the participation to society, the capacity of doing actions/tasks, the functioning and the body structures and so they contribute to determine disability. MATERIALS AND METHODS: Environmental factors have been evaluated in all 29 children (37.9% males, 62.1% females) enrolled in the project “Cure&Care” through the ICF-CY questionnaires (derived from ICF-CY) and the WHO-DAS II for children or proxy (ICF-related instrument that evaluates functioning and disability). Interviews were performed after surgery (T0), after 3 and 6 months (T1 and T2). To analyze the data, facilitators and barriers have been divided into “mild-moderate” and “substantial-complete” and then a count of them has been made for each domain. RESULTS: Barriers have been reported in < 10% at all time points; the emerged substantial facilitators are “relationships” (formal and informal, 45%), “attitudes of persons other than the relatives” (>50%), “technologies” (25%) including drugs, computers, aids for moving and “services, systems and policies” including exemption for tumors. At T2, i.e. when children return to society, facilitators are still the same but decribed as “mild/moderate” except for “family and friends attitudes” still reported as substantial facilitators. CONCLUSIONS: Our research underlines the importance of environment in reducing disability. All children/adolescents resulted strongly supported by the environment, with the unique exception in “school and related activities” where they are less supported. The role of environmental factors in determining disability, evaluated through ICF-CY, allows us to focus rehabilitation not only on the children but also on the background they live in.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-33. INJURY TO DENTATE NUCLEI AND EFFERENT FIBERS BY PEDIATRIC POSTERIOR FOSSA TUMORS

Robert Lober ¹, Sebastien Perrault ¹, Sonia Partap ¹, Michael Edwards ¹, Paul Fisher ¹, Kristen Yeom ¹

Abstract

BACKGROUND: Injury to the dentatorubrothalamic tract (DRTT) has been implicated in cognitive sequelae complicating the post-treatment course of some children with posterior fossa tumors. We sought to determine the impact of these tumors on the structural integrity of DRTT constituents, i.e., dentate nuclei, superior cerebellar peduncles, red nuclei, and ventrolateral thalamic nuclei. METHODS: Using diffusion tensor imaging (DTI), we evaluated the DRTT in 17 pediatric patients with posterior fossa tumors, selected from a consecutive series based on pairing with available age-matched controls. Imaging data were acquired using a 3T MRI with diffusion tensor echo planar imaging in 25 isotropic directions with b 1000 s/mm², slice thickness 3 mm. RESULTS: Median age at diagnosis was 6.7 (range 0.8 to 15.7) years, and median age at imaging was 10.7 (range 2 to 17) years. Diagnoses included 7 medulloblastoma, 6 pilocytic astrocytoma, 3 ependymoma, and 1 choroid plexus papilloma. All patients underwent surgical resection, 8 received radiotherapy, and 7 received chemotherapy, with a mean interval before imaging of 36, 27, and 26 months, respectively. Mean diffusivity of the superior cerebellar peduncles (SCP), but not the other constituent structures of the DRTT, was decreased in tumor patients compared to controls (868 ± 125 x 10^{− 6} mm²/s versus 953 ± 104 x 10^{− 6} mm²/s; p = 0.007). Fractional anisotropy of the SCP was not different between the groups. Combined bilateral dentate nuclei volumes were decreased in tumor patients relative to controls (1102 ± 455 mm³ versus 1512 ± 645 mm³; p = 0.003). There were no differences based on tumor pathology, radiation, or chemotherapy. CONCLUSION: Taken together, these data suggest injury to the dentate nuclei with Wallerian degeneration of efferent fibers from pediatric posterior fossa tumors, independent of pathology or treatment. Additional studies are required to determine the cognitive sequelae relevant to this phenomenon.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-34. THE FIRST HUNDRED REACHING ADULTHOOD: WHAT HAPPENS TO PEDIATRIC BRAIN TUMOR SURVIVORS AFTER 18 YEARS OF AGE

Duarte Salgado ¹, Sofia Nunes ¹, Sofia Vinhais ¹

Abstract

The study of survivors of pediatric brain tumor is revealing the late toxicities of our therapies and is also a stimulus for innovative and safer treatments in the future. METHODS: Retrospective study of patients followed in our unit since 1985 until December 2011. All patients with a diagnosis of a central nervous system tumor before the age of eighteen and alive after that age were included. Data was collected on gender, age, age of diagnosis, tumor pathology, type of treatment, response to treatment, neurological sequelae, functional status and survival. Variables were analysed using methods of descriptive statistics. RESULTS: One hundred and three patients were analysed (55,3% male, mean age at diagnosis 8,7 years) glial tumors being the majority (n = 41, 39,8%) followed by PNET/medulloblastoma (n = 28, 27%). Overall mean follow-up was 14.3 years and mortality rate was 6.8% (n = 7). Thirteen patients (12.6%) were lost to follow-up. The survivor group whose data was available included 83 patients with a mean age of 24 years (ranging between 18 and 38 years) and a mean follow-up of 15.4 ± 5,6 years. The majority had low grade gliomas (41%) and PNET/medulloblastoma (28.9%). After surgery the majority were treated with radiotherapy and chemotherapy (44.6%) or radiotherapy only (31.3%). Twenty three patients (27.7%) remain with a residual lesion and recurrence occurred in 9.6%. More than a third had late complications namely epilepsy, second tumors and vasculopathy related events. Although 87% were classified as independent for activities of daily living and 89% have some kind of school degree, the majority are unemployed. In the total group (n = 103), 81 patients were treated with radiotherapy and for 41 an MRI with T2* weighted images was available showing cavernomas and/or microbleeds in 31 patients. DISCUSSION: Our series is in line with other more extensive surveys, the high frequency of epilepsy and T2* findings have not been reported.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-35. SHOULD WE WORRY ABOUT MICROBLEEDS/CAVERNOMAS IN BRAIN TUMOR SURVIVORS?

Duarte Salgado ¹, Sofia Nunes ¹, Sofia Vinhais ¹

Abstract

Brain microbleeds and cavernomas are increasingly described in survivors of brain tumors and leukemia, the risk factor being exposure to radiation therapy. The clinical relevance of these lesions, specially microbleeds is based on studies of adults harboring other pathologies: hypertension, diabetes and amyloid angiopathy, that have shown the possibility of cognitive decline, focal deficits, epilepsy and brain hemorraghe. We present four patients (2 female, 2 male) being followed in our institution after therapy for a medulloblastoma who present microbleeds and cavernomas. Age of diagnosis was at 4, 5, 7 and 14 years of age respectively. All were treated with surgery (gross total ressection) followed by radiochemotherapy (whole brain-spine-posterior fossa boost + 8 cycles of CCNU, cisplatin and vincristine). Three patients are asymptomatic, one has a refractory epilepsy with an EEG focus localising to a right occipital cavernoma. In three patients we document new lesions over a period of years. The patient with longer follow-up, 18 years has the heavyest microbleed burden. We conclude that maybe radiation brain microbleeds/cavernomas are a progressive condition although more studies are in order. We should worry that a growing lesion burden over time correlates with new neurological symptoms and signs.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-36. NEUROLOGIC SEQUELAE IN LONG-TERM SURVIVORS OF CHILDHOOD BRAIN TUMORS: A CHILDHOOD CANCER SURVIVOR STUDY (CCSS) UPDATE AND EXPANDED RISK FACTOR ANALYSIS

Elizabeth M Wells ¹, Kristy Seidel ², Nicole J Ullrich ³, Wendy Leisenring ², Greg Armstrong ⁴, Lisa Diller ⁵, Allison King ⁶, Kevin R Krull ⁴, Joseph Neglia ⁷, Leslie L Robison ⁴, Marilyn Stovall ⁸, Kimberly Whelan ⁹, Charles Sklar ¹⁰

Abstract

PURPOSE: The current study was undertaken to determine incidence of adverse neurologic outcomes and treatment-related risk factors in survivors of childhood brain tumors up to 30 years after diagnosis. PATIENTS AND METHODS: 1,876 survivors of childhood brain tumors diagnosed between 1970 and 1986 were evaluated for self-reported auditory, visual and focal neurologic deficits, and seizures using the 1994, 2000, and 2007 CCSS questionnaires. Of survivors, 34% were diagnosed when < 5, 30% when5-9, and 36% when > 9 years. Tumors were 66% astroglial, 20% primitive neuroectodermal, 9% ependymoma, and 5% other. Treatments included 23% surgery, 37% surgery + radiation, 25% surgery + radiation + chemotherapy. Median follow-up was 23 years (range 5-39 years). RESULTS: Cumulative incidence curves continued to increase with 5/15/30 year percentages of 50/57/61 for coordination/balance problems, 27/35/41 seizures, 21/28/35 motor problems, 9/15/23 hearing loss, 14/16/18 for legal blindness. In multivariable analyses, relapse increased risk of all neurologic sequelae (RRs 2.2-4.8, all p-values < 0.001). Risk of hearing loss was increased by radiation to posterior fossa (RR 2.1, p < 0.01 for <50Gy; RR 2.9, p < 0.0001 for 50 + Gy) and temporal lobe (RR 2.8, p < 0.0001 50 + Gy) in a dose-dependent fashion. Likelihood of seizures increased with radiation to temporal (RR 1.8, p < 0.05 <50Gy; RR 2.1, p < 0.005 50 + Gy) and frontal (RR 1.8, p < 0.05 50 + Gy) lobes and was also increased with concurrent secondary malignancies (RR 2.9, p < 0.05). Coordination or balance problems increased with brain radiation regardless of location or dose (RR 1.9, p < 0.01) and with secondary malignancies (RR 4.4, p < 0.005). Motor problems increased with high-dose radiation to temporal (RR 1.6, p < 0.05) and parietal (RR 2.0, p < 0.01) lobes. CONCLUSION: Extended cumulative incidence curves demonstrate continuing risk of new onset neurologic deficits in survivors of childhood brain tumors up to 30 years after diagnosis. Cranial radiation and tumor relapse are the strongest predictors of increased risk for late-onset neurologic sequelae.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-37. STAYING CONNECTED: A GUIDE FOR FAMILIES WHEN A SICK CHILD HAS TROUBLE COMMUNICATING

Ceilidh Eaton Russell ¹, Eric Bouffet ², David Brownstone ², Caelyn Kaise ²

Abstract

The majority of children with brain tumors that are resistant to treatment rapidly lose their ability to speak and write due to progressive neurological impairment and/or fatigue. It becomes increasingly difficult for caregivers to decipher the child's wants and needs, and for the child to interact meaningfully with loved ones, causing significant distress for the child and family. To support families through this critical time, our research team interviewed bereaved parents of 14 children about their communication experiences when their dying child had compromised abilities to speak because of a brain tumor. These retrospective interviews elicited parents' perspectives of: communicative needs and abilities of dying children; creative strategies to facilitate meaningful communication; and the most important issues for families to discuss with their children. Beyond the practical and functional aspects of communication, parents' responses illuminated the critical role of communication in maintaining relationships and intimate connections during the end of their children's lives. Ultimately our team compiled the wealth of information, experience and wisdom from these parents into a handbook, including chapters describing: preparing for the future; important topics to discuss; practical strategies and tools; and suggestions for exploring and supporting children through complex emotional, spiritual and end-of-life issues. Sample tools and a list of resources are included in the printed and electronic versions of this 70 page handbook. This evidence-based tool provides important new support for children and their caregivers during a unique and challenging experience. The presentation will highlight the key issues and strategies and provide the opportunity to discuss the handbook and obtain a copy of this exciting new resource. The application of the handbook is for any paediatric patient who has communication limitations but retains cognitive function. While the handbook is in English, the illustrated tools are not language dependant.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-38. QUALITY OF SURVIVAL (QOS) OF CHILDREN TREATED FOR STANDARD RISK MEDULLOBLASTOMA IN THE RANDOMISED EUROPEAN PNET4 STUDY OF HYPERFRACTIONATED (HFRT) VERSUS STANDARD RADIOTHERAPY (STRT)

Colin Kennedy ¹, Kim Bull ¹, David Culliford ¹, Mathilde Chevignard ², Helen Spoudeas ³, Gabriele Calaminus ⁴

Abstract

OBJECTIVES: To compare QoS following HFRT with that following STRT for medulloblastoma. METHODS: Follow-up study of children randomly allocated to HFRT (1.0 Gy bd; total dose 36 Gy; 24 Gy post fossa boost; 32 Gy residual tumour boost) or STRT (1.8 Gy od; total dose 23.4 Gy; 30.6 Gy post fossa boost) in the HIT-SIOP PNET4 study. To date no inter-group difference in event free survival has been observed. All participants received Vincrstine, CisPlatin and CCNU. Participants and parents/carers completed standardised questionnaires on executive function, health status and growth, behavioural problems and quality of life (QoL). Treatment allocation, sex, age at diagnosis, time from diagnosis and post-operative complications were included in a regression model. RESULTS: 151/244 (62%) eligible survivors from 7 countries participated at a mean of 6.1 years post diagnosis. Compared to those allocated to STRT, participants aged > 18.0 years allocated to HFRT had lower (superior) executive functioning z-scores (self-report group means 0.42, -0.44, difference 0.87, 95%CI 0.28 to 1.45, p = 0.005); those aged <18.0 years showed a similar trend (proxy-report group means 0.17, -0.16, difference 0.33, 95%CI -0.06 to 0.72, p = 0.098). Combining these sets of scores confirmed an overall difference, before and after adjustment in the multivariate regression model (adjusted inter-group difference 0.42 SDs, 95% CI 0.08 to 0.76, p = 0.017). More participants had abnormally elevated executive functioning scores after STRT (16/71 (23%) vs 7/68 (10%), p = 0.052). STRT and HFRT group mean scores were similar with respect to weight, health status, behavioural difficulties and QoL. Compared to those after STRT, height z-scores after HFRT showed a greater decrement relative to height at diagnosis (group mean decrement -0.85, -1.27, mean inter-group difference -0.43, 95%CI -0.76 to -0.10, p = 0.01). CONCLUSIONS: Allocation to HFRT was associated with superior questionnaire scores on executive functioning in everyday life but greater decrements in height.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-39. SECOND CANCER IN PATIENTS PREVIOUSLY TREATED FOR CENTRAL NERVOUS SYSTEM (CNS) TUMORS: A 10-YEARS REPORT FROM A SINGLE INSTITUTION

Daniele Bertin ¹, Stefano Vallero ¹, Erica Romano ¹, Maria Eleonora Basso ¹, Eleonora Biasin ¹, Franca Fagioli ¹

Abstract

From 1996 to 2005, 286 patients were diagnosed with a CNS tumor at our institution, and 191 received chemotherapy and/or radiotherapy. Among those patients, 4 developed a second tumor. Patient 1 developed a posterior fossa ependimoma at the age of 2, treated with surgery, chemotherapy and local radiotherapy according to the Italian “AIEOP-SNC95” infants protocol. Sixty months later she developed gliomatosis cerebri starting from cerebellar region and she died of disease 1 year later despite intensive chemotherapy with autologous hematopoietic stem cell transplantation (HSCT). Patient 2 was diagnosed at the age of 5 with an intramedullary anaplastic astrocytoma treated with surgery, intensive chemotherapy, auto-HSCT and local radiotherapy. After 34 months off-therapy, he developed myelodysplastic syndrome and underwent allogenic-HSCT. He is currently alive, 90 months after HSCT. Patient 3 was treated at the age of 3 for a posterior fossa ependimoma; after incomplete surgical resection, he was treated with chemotherapy and local radiotherapy according to “AIEOP-SNC91”. Due to 2 subsequent local relapses at 37 and 44 months he underwent surgery twice and received 6 courses of oral etoposide and 6 courses of temozolomide. Ten years after the end of radiotherapy, a papillary carcinoma of the thyroid was diagnosed, and treated with total thyroidectomy. The patient is currently alive 2 years after thyroidectomy. Patient 4 developed at the age of 16 a temporo-parietal glioblastoma, treated with surgery, chemotherapy, auto-HSCT and local radiotherapy, followed by maintenance with temozolomide (24 courses) and radiometabolic therapy with Y90-labeled somatostatin analog (8 courses). Forty-eight months after diagnosis he developed myelodysplastic syndrome and died 5 months after allogeneic-HSCT. Therapy-related malignancies are rare but possible late complications of the treatment of pediatric patients with CNS tumors: so we recommend a long-term follow-up with CNS imaging and blood samples analysis for the early diagnosis of secondary tumors including hematologic malignancies.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-40. EXECUTIVE FUNCTION DEFICITS IMPACT THE DAILY LIFE OF SURVIVORS OF CHILDHOOD BRAIN TUMORS

Kristen Ziara ¹, Allison L'Hotta ¹, Abigail Williams ¹, Rosie Thede ¹, Kara Moore ¹, Aimee James ¹, Allison King ¹

Abstract

OBJECTIVE: Executive function (EF) deficits are prevalent in survivors of childhood brain tumors. To our knowledge, no researchers have interviewed survivors and their parents to determine how these deficits affect survivors' daily functioning. Our goal was to gather qualitative data about how EF changes impact survivors at school and at home. METHODS: We conducted semi-structured telephone interviews with parents of children with brain tumors, brain tumor survivors, and siblings of survivors. Interviews were transcribed. Members of the research team read the transcripts, identified common themes, and defined the themes in a codebook. A primary and secondary coder assigned codes to meaningful text. We used Cohen's Kappa to assess inter-rater reliability. RESULTS: We interviewed 25 parents of survivors; 14 parents were also interviewed about a sibling of the survivor. Seven survivors > 13 years of age and four siblings >13 years of age completed telephone interviews. Reduced inhibition, difficulty concentrating, and slowed processing speed were all reported more frequently in interviews with or about survivors when compared to interviews with or about siblings. Difficulty concentrating was the most common survivor-reported EF deficit (57%). Reduced inhibition was the most common parent-reported EF deficit in survivors (40%). Reduced inhibition was associated with impulsive behaviors, poor decision-making, and frequent interrupting. Kappa was.74, indicating good agreement between coders. CONCLUSIONS: EF deficits are common among pediatric brain tumor survivors. Understanding the impact of EF deficits will guide the development of interventions to address impulse control, increase mental stamina, and improve processing speed of survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-41. SEX AND RELATIONSHIPS IN ADOLESCENTS WITH CANCER DIAGNOSIS

Elisabeth Björn ¹, Pernilla Franzén ¹, Annika Haag ¹, Ann-Kristian Lax ¹, Ilda Moreno ¹

Abstract

To be a teenager means having a lot of feelings, many expectations and new experiences like finding out about and exploring sexuality before growing up. Being ill with a serious disease during this period influences and compounds difficulties in the teenager's development. When serious disease requires long periods in a hospital ward the teenager misses the chance to develop in the same way as their peers. The purpose of this study is to answer the questions that teenagers ponder over about sexuality during cancer treatment. Literature surveys, existing ward programmes, brochures and interviews with experienced paediatricians were used in data collection. There are many thoughts that the teenagers have regarding their own sexuality but the subject feels taboo. Ward staff rarely bring this matter up with patients because it feels uncomfortable and they can be ignorant about the issue. It's a case-by-case matter but this need exists and should be taken seriously. That's why the authors recommend further studies and research to be done on the subject, as there remains a lot to find out.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-42. FITNESS, PHYSICAL ACTIVITY AND BODY COMPOSITION FOLLOWING TREATMENT FOR A CNS TUMOUR

Katrin Scheinemann ¹, Joyce Obeid ¹, Brian W Timmons ¹

Abstract

The physical activity and fitness of adolescents following treatment of a central nervous system (CNS) tumour is not well studied. We compared fitness, physical activity and body composition in adolescents following treatment for a CNS tumour and healthy controls. Fourteen adolescents between 1.1 and 7.9 years (mean ± SD, 3.4 ± 2.5 y) after final treatment for a CNS tumour (ST, age: 14.7 ± 2.6 y) and 14 age- and gender-matched healthy controls (HC, age: 13.9 ± 2.7 y) participated in one session. Height, weight and body composition as assessed by dual energy x-ray absorptiometry were determined. Aerobic fitness (VO_2peak) was assessed using the McMaster All-Out Continuous cycling test. Habitual physical activity was examined by accelerometry over 7 consecutive days; time spent in light, moderate, and vigorous intensities was determined along with time spent sedentary. Accelerometry variables were expressed as min/h of monitoring time. No differences were seen in height or weight between ST and HC (p > 0.2). Lean mass as a percentage of total mass was lower in ST compared with HC (69.7 ± 10.3 vs. 78.9 ± 4.7%, p = 0.01). VO_2peak was lower in ST (p < 0.05); this difference remained significant when values were normalized to lean body mass (VO_2peak: 41.6 ± 6.6 vs. 61.5 ± 6.8 mL/kg Lean/min, p < 0.01). Light activity (p < 0.01) and moderate-to-vigorous physical activity (3.1 ± 1.6 vs. 4.6 ± 1.7 min/hr, p = 0.03) were lower while time spent sedentary was higher (48.7 ± 3.5 vs. 43.9 ± 4.0 min/hr) in ST vs. HC. Within the ST group, children with the most MVPA also demonstrated the highest levels of aerobic fitness (r = 0.60, p = 0.02). Both fitness and physical activity are lower in adolescents following treatment for a CNS tumour, compared with healthy peers. The health-related consequences of these impairments require further investigation. This study has been supported by b.r.a.i.n.child.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-43. CREATING COMMUNITY: THE VALUE OF TRAINED PEER MENTORS

Wade Iwata ¹

Abstract

Peer support programs are an important resource for people affected by cancer as indicated in the Institute of Medicine's report Cancer Care For The Whole Patient (IOM, 2008). The report includes these programs in their standards of care recommendations and encourages professionals to offer patients and families these types of programs. Hoey et al. (2007) state there is a high level of satisfaction for people who participate in peer support programs. For families facing a pediatric brain tumor diagnosis, finding these types of services can be difficult. Due to the rarity of pediatric brain tumors, (4150 annually, according to the Central Brain Tumor Registry of the United States) families often struggle to meet others who have been through a pediatric brain tumor as well. Children's Brain Tumor Foundation (CBTF) offers families the opportunity to meet trained parent mentors through our Family to Family (F2F) Network. A critical analysis of our F2F program will look at our criteria for matching families, follow-up on matches, and professional support provided throughout the match process. Furthermore, an overview of our training procedures will be examined through surveys of current mentors to ensure mentors feel equipped to provide mentorship. Testimonials from both mentors and mentees about their experiences involved in the mentor relationship will be reviewed. Finally, the effectiveness of the program will be examined through community integration screening of both mentors and mentees and data from research on the effectiveness of peer support. The F2F program demonstrates the importance of these relationships and the mutual benefits each member receives.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-44. UTILIZING A CAMP ENVIRONMENT AND COMMUNITY SERVICE PROJECTS TO INCREASE SOCIAL SKILLS, TEAM BUILDING, SELF-ESTEEM AND COMMUNITY IN TEEN BRAIN TUMOR SURVIVORS

Stacia Wagner ¹

Abstract

Current evidence indicates childhood brain tumor survivors experience decreased social adjustment following treatment. They experience deficits in social competence at the level of social adjustment which worsens over time (Schulte, 2010). Previous social skill development programs for adolescent brain tumor survivors have demonstrated positive results and demonstrated effectiveness in reducing depression and improving social skills (Barrerea, 2009). The implementation of social skill training was incorporated into a six day retreat for adolescent brain tumor survivors between the ages of 13-18. Discussion topics and role plays were based on previous social skill programs. To enhance team building skills, the program also included the development and implementation of a community service project by the group. Session topics included known behavioral and cognitive challenges faced by brain tumor survivors (Barrera, 2009) and used information and role-play to improve social skills. The program addressed practical tips in relationship building such as establishing eye contact, perceiving and expressing emotions, interpreting body language and non-verbal cues and how to demonstrate empathy. Each session included information on the effect a brain tumor may have on these areas. After the informational session a following discussion allowed survivors to begin to understand their own attributions or their personal interpretations of their behavior. Role play included social initiation and development of peer relationships, demonstrating and reading social cues and self-advocacy, managing peer perceptions, demonstration of empathy and handling teasing/bullying. During the recruitment phase, parents reported on their perception of their child's peer involvement and support. Qualitative data was gathered on barriers and challenges to peer support. Participants with severe cognitive deficits were not included. Information on changes in peer support was gathered 30 days after participation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-45. SYMPTOM MONITORING AND PATIENT-REPORTED OUTCOMES (SyMonSAYS) IN PEDIATRIC PATIENTS WITH BRAIN TUMORS AND OTHER CANCERS

Jin-Shei Lai ¹, Kristi Waddell ¹, Sandra VanLeeuwen ¹, Monica Newmark ¹, Jessica Noonan ¹, Katie O'Connell ¹, Megan Urban ¹, Susan Yount ¹, Stewart Goldman ¹

Abstract

BACKGROUND: Effectively identifying and managing symptoms related to multi-modal therapy for children with cancer is fundamental to the overall success of cancer treatment. A system that allows capturing symptoms by patients in real-time is lacking, further preventing prompt intervention. Previous studies assessed symptoms utilizing patient-reported outcomes for adults. We developed a pediatric patient-oriented, technology-based, symptom monitoring and reporting system: Symptom Monitoring and Symptomatic Assessment in Young Survivors (SyMon-SAYS). The purpose of this study is to evaluate the feasibility of implementing SyMon-SAYS, its acceptability (defined as perceived usefulness) by satisfaction of parents, clinicians, and patients/ parents with the tool. METHODS & GOALS: Patients with a diagnosis of brain tumor or cancer who are receiving or have completed treatment within 6 months are eligible and will be recruited from Children's Memorial Hospital, Chicago. Patients and parents complete weekly fatigue assessment over eight weeks via internet accessible devices or interactive voice response by phone. Responses are stored in a central database and an alert e-mail is automatically generated to clinicians when criteria are met which include: changes which exceed significant difference-1 SD below the US general population norm. Clinicians will speak to parents to determine appropriate management. Clinicians and parents/patients will receive graphic reports summarizing fatigue scores at weeks -4 and -8, which we hope will improve communication between clinicians and parents/patients. This objective will be evaluated using an 8-item Client Satisfaction Questionnaire SyMon-SAYS evaluation by patients, parents, and clinicians. CONCLUSION: We anticipate that SyMon-Peds will be feasible, acceptable and well-received by parents and providers. Recruitment is ongoing. Fatigue scores reported by this system have prompted clinical intervention prior to previously scheduled clinical evaluation. We anticipate completing enrollment by February 2013. Preliminary findings will be presented.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-46. IMPROVED LONG-TERM PHYSICAL FUNCTIONING OF PEDIATRIC BRAIN TUMOUR SURVIVORS FOLLOWING AN INTENSIVE EXERCISE PROGRAM

Janine Piscione ¹, Deirdre Igoe ¹, Todd Cunningham ¹, Melanie Orfus ¹, Eric Bouffet ¹, Donald Mabbott ¹

Abstract

PURPOSE: Children who survive brain tumours are particularly vulnerable to a range of limitations in their long-term physical functioning. There are many services and supports for patients during the acute period; however, community resources to address functioning deficits in the long-term are significantly lacking. This paucity of services may result from a knowledge gap in whether interventions targeting long-term physical limitations have any benefit. To address this gap, we explored the effects of an intensive exercise program on the physical functioning of pediatric brain tumour survivors. METHODS: Participants were between 8.0 and 16.4 years old with a prior diagnosis of a hemispheric or posterior fossa brain tumour and treated with cranial spinal or focal radiation. The exercise program consisted of a 1.5 hour session, 3 times per week, for 12 weeks. Each session consisted of a warm-up, high-intensity games, sporting activities, a cool-down and stretching period. Physical functioning was assessed pre- and post-intervention using the Gross Motor Composite of the Bruininks-Oseretsky Test of Motor Performance, Second Edition (BOT2). RESULTS: Seven participants (one female, six male) completed the 12-week intervention. Median time since diagnosis was 6.0 years (range 2.3-8.6 years). Four participants were previously diagnosed with medulloblastoma, and three with ependymoma. Changes in standardized scores for each subdomain on the BOT2 were calculated for the difference in pre- and post-intervention data. Six of seven participants showed either improvement or no decline in bilateral coordination and strength. Similarly, five of seven participants showed either improvement or no decline in running speed/agility and balance. CONCLUSION: Notwithstanding small sample size, our results suggest 8 years post brain tumour diagnosis, physical functioning may be improved with an intensive exercise program. These data support the need for ongoing research with larger samples to determine the need for programs targeting long-term physical functioning in pediatric brain tumour survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-47. THE FEASIBILITY OF A PSYCHOSOCIAL SCREENING PROGRAM FOR SURVIVORS OF PEDIATRIC BRAIN TUMORS

Cori Liptak ¹, Peter Manley ¹, Christopher Recklitis ¹

Abstract

BACKGROUND: Survivors of pediatric brain tumors are at-risk for psychosocial difficulties. Psychosocial screening in childhood cancer survivors has been widely used, but not with pediatric brain tumor survivors. This study examined the feasibility of psychological screening with survivors of pediatric brain tumors and how self-report could enhance assessment. METHODS: 84 adolescents (age 12-18) completed the Beck Youth Inventory-II (BYI-II) and 79 young adults (age 19-30) completed the Brief Symptom Inventory-18 (BSI-18). Semi-structured clinical interviews were conducted and clinicians provided a Global Assessment of Functioning (GAF) score. Previously established cut-off scores were used to identify clinical cases. RESULTS: 84% of participants completed measures in <30 minutes, 90% reported no distress with participation, and 98% found measures easy to understand. For the adolescents, 17% (n = 14) were identified as clinical cases by self-report and 24% (n = 20) were identified by clinicians. Agreement between self-report and clinician rating was low (Kappa = .19, p = .077). 27% (n = 21) of young adults were identified by self-report as clinical cases and 32% (n = 25) were classified by clinicians. Agreement was moderate (Kappa = .34, p = .003). Analysis of discrepancies between self-report and clinician case identification demonstrated for adolescents, elevations on the Self-Concept scale accounted for half of the discrepancies, a domain not assessed by clinicians. Clinicians were more likely to identify young adults as cases based on deficits in social and vocational functioning, areas minimized by survivors. CONCLUSIONS: Pediatric brain tumor survivors are capable of completing self-report psychological measures without distress or burden. There is a value to self-report, particularly for adolescents, who may provide information not assessed or revealed in a clinical interview. However, self-report should not be used as a ‘stand-alone' assessment as certain aspects of psychological adaptation may be minimized by survivors. Screening studies should further investigate validity of measures and the impact of cognitive functioning on agreement with other reporters.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-48. SLEEP PROBLEMS IN CHILDREN WITH LOW-GRADE GLIOMAS OF THE BRAINSTEM

Phil Zhang ¹, Furqan Shaikh ², Indra Narang ², Eric Bouffet ²

Abstract

BACKGROUND: Low-grade gliomas (LGG) may confer chronic or life-long symptoms upon patients. Thus, concerns for supportive care and optimizing quality of life take on paramount importance. Children with brainstem low-grade gliomas (BS-LGG) may be expected to have sleep disturbances due to the central role of the brainstem in sleep and respiratory regulation. However, the characterization of sleep disturbance in children with BS-LGG has not been previously investigated. METHODS: We identified children diagnosed with a BS-LGG at our institution using a prospectively-maintained neuro-oncology database between 1986 and 2010 inclusive. Detailed data was collected retrospectively from the patient health records. RESULTS: Twenty-five children with BS-LGG were identified. There were 15 female and 10 male patients. The median age at diagnosis was 4.5 years (range 1.0 to 13.6 years) and the median duration of follow-up was 6.3 years. Eight children (32%) had a sleep diagnosis confirmed by polysomnography (PSG). Among these 8 children, 2 had no prior sleep complaints and 1 had sleep complaints first disclosed during the sleep consultation. Four children were prescribed BiPAP. The most common diagnosis was concurrent central and obstructive sleep apnea. Other diagnoses included hypoxemia, hypoventilation, and periodic limb movement disorder. All 8 children had tumour involvement of the medulla. In contrast, six children without medullary involvement had no sleep diagnosis. A sleep diagnosis was more common in children with more recently-diagnosed BS-LGG (6 of 12) compared to those with an earlier diagnosis (2 of 13). In addition, 2 children had sleep or respiratory complaints that were not further evaluated. Both these findings suggest that some sleep disorders may be overlooked. CONCLUSIONS: Sleep disorders are common among children with BS-LGG. Physicians should perform a detailed sleep history and consider a formal sleep evaluation in all affected children.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-49. THE IMPORTANCE OF MAINTAINING PEER SUPPORT AT END-OF-LIFE FOR SCHOOL AGE PATIENTS WITH POOR PROGNOSIS BRAIN TUMORS

Kazuko Matsumoto ¹, Kai Yamasaki ², Keiko Okada ², Hiroyuki Fujisaki ², Yuko Osugi ², Junichi Hara ²

Abstract

BACKGROUND: To establish a peer relationship for school age children is important. Patients with poor prognosis brain tumors once resolve, but relapse in the not-so-distant future. In many cases, general motor nerves will be gradually paralyzed and disturbance of consciousness will progress. Eventually, communication with patients becomes impossible. In this study, we aimed to identify the effect of peer support for end-of-life patients with brain tumors. METHODS: We conducted retrospective review of records of 7 patients (aged from 6 to 15) who diagnosed with poor prognosis brain tumors (including 4 with brain stem glioma) and a clinical psychologist intervened at our institute from 2010 to 2012. RESULTS: 1. Presence of ataxia without communication problem; this led patients to a crisis of growing apart from the local peer relationship (ex. school) even as their condition was all right. Also, not telling their limited life expectancy, parents tried to cheer on children and avoid letting them pour out their fears. Therefore, patients apply for support from other patients with parallel circumstances. 2. Progression of ataxia and communication problem; patients became less able to tell their will and their activities of daily living were limited. Therefore, parents hesitate to let children attend the peer activity. However, patients told us their will to attend by nodding or handclasp, and showed good responses (ex. roll their gaze). This improved parents' self-confidence and encouraged them to contact with other families. 3. Deterioration of consciousness; unfortunately, we couldn't confirm the patients' will, but parents kept on dealing their children in the communication loop among other children based on their experience that their children had enjoyed before. Seeing their children were accepted made parents feel supported. CONCLUSION: To maintain peer support at end-of-life care for patients with brain tumors is important to avoid isolation at dismal situation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-50. NEUROPSYCHOLOGICAL AND SURVIVAL OUTCOMES OF 31 CHILDREN UNDER 36 MONTHS AT DIAGNOSIS WITH CENTRAL NERVOUS SYSTEM PRIMITIVE NEUROECTODERMAL TUMOURS TREATED WITH DOSE INTENSIVE CHEMOTHERAPY AND IRRADIATION AT A SINGLE CENTRE

Kim Phipps ¹, Dianne Gumley ¹, Thomas Jacques ¹, Darren Hargrave ¹, Dawn Saunders ¹, Antony Michalski ¹

Abstract

We report the results of 31 consecutive children with primitive neuro-ectodermal tumours of the central nervous system who presented to our institution at under 36 months of age between 1999 and 2010. All children were fully staged and were treated with a dose intensive induction regimen comprising 6 courses of vincristine (0.05mg/kg weekly), cyclophosphamide (90mg/kg) and carboplatin (AUC 6.6) given every 14 days or on recovery of blood counts. Children were treated with focal irradiation unless parents refused radiotherapy (2/31) or requested neuraxis irradiation to try and improve the chances of survival (3/31). Radiotherapy was followed by consolidation chemotherapy comprising 4 courses of cisplatin (70mg/m2), lomustine (75mg/m2) and vincristine (0.05mg/kg) unless the patients had been treated with craniospinal irradiation. 4/4 children with primary disease outside the posterior fossa died of disease. Of the remaining 27 patients 12 have died 10/12 died of disease 2/12 died of second primary tumours (glioblastoma, gliosarcoma) in the irradiated field. We present the results of detailed neuropsychological analysis of survivors. The survival results are presented stratified by disease stage and centrally reviewed histology. Dose intensive chemotherapy and focal irradiation is an acceptable strategy for a cohort of young children with PNET of the posterior fossa and results in children with neuropsychological function similar to that achieved with strategies that utilize intravenous and intrathecal chemotherapy. The incidence of second malignancies in the irradiated field is a cause for concern.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-51. ACUTE LATE ONSET HEARING LOSS IN SURVIVORS OF MEDULLOBLASTOMA GREATER THAN 10 YEARS AFTER TREATMENT

Peter Manley ¹, Christine Chordas ¹, Susan Chi ¹, Nathan Robison ¹, Pratiti Bandopadhayay ¹, Karen Marcus ², Mary Ann Zimmerman ¹, Liliana Goumnerova ², Mark Kieran ¹

Abstract

INTRODUCTION: Cisplatin is a known ototoxin associated with late onset hearing loss beyond completion of treatment and continued worsening of hearing over time. Cranial irradiation can affect central auditory pathways causing sensorineural hearing loss (SNHL). Patients with medulloblastoma treated with cisplatin and cranial radiation are at high risk for SNHL. However, we have now documented acute late onset hearing loss (ALOHL) ten or more years after treatment in patients with medulloblastoma. METHOD: A retrospective chart review was conducted of 5 patients treated for medulloblastoma between 2006 and 2012 at Dana-Farber Children's Hospital Cancer Center who reported acute hearing loss greater than ten years off treatment. ALOHL was defined as subjective reports of a sudden loss of hearing in one or both ears. RESULTS: The median age at diagnosis of medulloblastoma was 6.5years (range 3.0-13.3) with median time from diagnosis to most recent hearing assessment 16.8years (range 11-25). 4/5 patients received cisplatin, cumulative dose range 300-600mg/m². All patients had cranial radiation dose 23.4-40Gy; posterior fossa dose >/= 54Gy. At completion of initial treatment, 5 had mild to moderate SNHL with slight worsening over time. Patient's then reported subjective ALOHL. 4/5 had concurrent viral symptoms or physical findings. Audiometry findings varied: >45dB unilateral loss (n = 2), and >20 dB decrease at two or more frequencies in both ears (n = 3). There was also decreased speech discrimination thresholds (n = 2), or air and bone conduction changes (n = 1). Three patients reported subjective improvement with minimal corresponding audiometric improvement. CONCLUSIONS: The effects of hearing loss after cisplatin and cranial radiation are significant after treatment for medulloblastoma. We report ALOHL in survivors with known SNHL from treatment exposures. Concurrent viral symptoms may further impair existing hearing loss and may or may not be reversible. ALOHL is a complication seen in this group and requires prompt referral to otolaryngology.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-52. CHANGES IN PSYCHOLOGICAL FUNCTIONING IN PEDIATRIC BRAIN TUMOR SURVIVORS

Sarah Brand ¹, Tara Brinkman ³, Christine Chordas ¹, Brian Delaney ¹, Tanya Diver ², Celiane Rey ², Peter Manley ¹, Cori Liptak ¹

Abstract

BACKGROUND: Tumors of the central nervous system are the most common solid tumor diagnosed in childhood and account for approximately 22% of all childhood cancers. Treatment for pediatric brain tumors (PBT) consists of a combination of surgery, radiation, and chemotherapy. PBT survivors are at high risk for a complex array of late-effects spanning multiple functional domains, including medical, neurocognitive and psychosocial. Many late-effects can be attributed not only to the neurologic damage caused by the tumor but also to the effects of treatment. Late-effects can be cumulative and the complex interactions of medical/psychosocial late-effects are not well understood. OBJECTIVE: To describe psychosocial outcomes for survivors of PBT and examine medical variables in relation to psychosocial functioning to determine potential factors contributing to difficulties within this population. METHOD: After IRB approval, a medical record review of patients followed by the Pediatric Neuro-Oncology Outcomes Program at Dana-Farber Cancer Institute was completed, including information regarding current and past psychological functioning obtained during routine psychological screenings. RESULTS: 364 patient's medical records were reviewed. Regression analyses indicated current anxiety was associated with female gender (β = .82, pppppppppp < .01). DISCUSSION: A significant proportion of PBT survivors reported current and past psychological problems. Psychological functioning was associated with a variety of demographic and medical variables. These findings may be helpful in the development of intervention programs, targeting psychosocial distress in PBT survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-53. PILOT STUDY OF NUTRITIONAL DATA IN PEDIATRIC BRAIN TUMORS

Jennifer R Madden ¹, Molly S Hemenway ¹, Laura Dorneman ¹, Debra Stiller ¹, Arthur K Liu ¹, Nicholas K Foreman ¹, Rajeev Vibhakar ¹

Abstract

BACKGROUND: Pediatric neuro-oncology patients are known to have poor nutrition while treated with radiation and chemotherapy. There is little data comparing nutritional status with quality of life, tolerance of therapy, and survival. METHODS: In order to estimate the scope of the problem, as a prelude to a prospective study, we performed a retrospective chart review of all patients between the ages of 3 and 21with a diagnosis of medulloblastoma. We collected hospital presenting weight, total amount of weight lost, nutritional supplementation (enteral or parenteral), and any delays in therapy or dose reductions. RESULTS: Twenty-three of 31 children with medulloblastoma were evaluated. Eight patients were excluded due to insufficient data. The percentage of weight loss during therapy ranged from 6% to 35% with a mean of 17.3%. Three of 23 patients received enteral feeds with percentage of weight loss of 10, 18, and 33%. Two patients received parental feeds (TPN +/- Lipids) and both had a percentage of weight loss of 18%. Eleven of 23 patients had delays of therapy for any reason. Of the 11 patients with treatment delays, only 2 also received enteral nutrition. No patients who experienced treatment delays received parental nutrition. CONCLUSION: Although our survival data is equivalent to the national outcomes for medulloblastoma, there is little data comparing survival to nutritional status. Therefore, a prospective study is warranted to collect biophysical measurements including body mass index, mid-arm circumference, and pre-albumin serum levels. These measurements should be correlated with quality of life, dose-limiting toxicities, number of hospitalizations, event free survival (EFS), and overall survival (OS). We postulate that poor nutrition may affect quality of life and possibly OS.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-54. PALLIATIVE CARE ASSESSMENT IN PEDIATRIC BRAIN TUMORS

Michele Mitchell ¹, Molly Hemenway ¹, Nicholas Foreman ¹, Jennifer Madden ¹

Abstract

BACKGROUND: Although the survival rate for pediatric brain tumors is increasing, attention must still be focused on palliative care for this population. In spite of a well-established end-of-life care program, it was felt that services for children dying with brain tumors were receiving different levels of care. METHOD: A retrospective chart review was completed of the patients who died of a brain tumor over the previous 2 years. Date of tumor progression, date of palliative care referral, type of hospice, route of medications prescribed, and date of death were all recorded. RESULTS: During the 2 year time period, 33 patients died. Twenty of those patients were referred to hospice and 15 received intravenous medications at home for palliation. The range of time on hospice was from 5 days to 22 months. Of the 13 patients not referred to hospice, 4 did not die of the original brain tumor (suicide, thyroid cancer, multi-system organ failure, and motor vehicle accident). Three other patients not on hospice died catastrophically at presentation due to rapid tumor progression or intravenous fluids causing brainstem herniation. The final 6 patients not on hospice died out of state. CONCLUSION: Consistent palliative care with hospice is difficult to provide for patients that live outside of our metro area. Some rural areas do not even have hospice services available. Also, there is considerable variation in the amount of time children dying of brain tumors are receiving hospice services. Therefore, these patients require early referral to hospice and intensive intervention by the primary neuro-oncology team before and during the palliative care phase. The social worker and nurse practitioner of our multi-disciplinary team make routine phone calls and home visits to help support local hospices that may not have the expertise to care for this unique population.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-55. LONGITUDINAL TRACT-BASED WHITE MATTER CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA

Wilburn Reddick ¹, John Glass ¹, Yimei Li ¹, Robert Ogg ¹, Amar Gajjar ¹

Abstract

INTRODUCTION: Survivors treated for medulloblastoma exhibit damage to white matter tracts associated with neurocognitive deficits. This study explores longitudinal changes in white matter microstructure, fractional anisotropy (FA), using tract-based spatial statistics. METHODS: Eighty patients (6.1-20.3 years; 48 male) with medulloblastoma were imaged at baseline, 12 and 24 months and 53 age and gender similar controls (6.0-20.7 years; 31 male) were imaged three times 12 months apart. Diffusion tensor imaging was acquired and then processed following the TBSS pipeline. Two sets of analyses were performed using simple group-wise Student's T-tests between patients and controls controlling for family-wise error rates: 1) FA different between groups at each time point, and 2) FA change from baseline between groups at 12 and 24 months. RESULTS: FA throughout most fiber tracts was greater in controls than patients at baseline, 12 months, and 24 months. Test of the change in FA from baseline revealed significant increases in FA of the patients in the: 1) commissural fibers of the corpus callosum (predominantly in the splenium), 2) projection fibers of the corona radiata and the posterior thalamic radiation, and 3) associational fibers of the superior longitudinal fasciculus. Generally, the proportion of voxels with significant increases in FA within these fiber bundles grew with time. CONCLUSIONS: Children treated for medulloblastoma have lower FA compared to their peers even before therapy. This decreased FA can be attributed to disease, hydrocephalus, steroids, or surgery but is present before radiation or chemotherapy. Furthermore, FA in select regions increase with time relative to baseline, more than can be attributed to normal maturation. However, even with this significant increase, FA within all of these fibers was still significantly below healthy controls. Assuming a constant rate of change, extrapolating these longitudinal changes suggest the patients would reach age appropriate FA values in approximately 8 years.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-56. SHORT (30 DAY) AND LONG TERM (1-, 5- AND 10-YEAR) SURVIVAL OF PAEDIATRIC CNS TUMOURS IN THE UK

Mathew Ryan ¹, Roddy O'Kane ¹, Susan Picton ¹, Tom Kenny ¹, Charles Stiller ¹, Paul Chumas ¹

Abstract

INTRODUCTION: Regulatory bodies, peers and patients alike expect objective evidence of performance in order to make informed decisions. Our objectives were to examine early and long term outcomes by reporting a population-based study looking at 30 day, 1-, 5- and 10-year survival in the UK for common paediatric CNS tumours. No such national study has previously been reported. Results have been compared to the literature and to those recorded by the Surveillance Epidemiology and End Result (SEER) data set. METHODS: Data from the National Registry of Childhood Tumours (NRCT) between 1996-2005 and SEER registry between 1995-2006 were analysed. Only first tumours microscopically confirmed as malignant neoplasms (as defined by ICD 0-3) with mortality as any cause of death within 30 day 1-, 5- or 10-years of the diagnosis were included. A literature review between 1995-2011 was performed to provide a comparison. Kaplan-Meier estimation was used to calculate the survival rates. Log-rank testing was used to calculate differences between tumour subtype survival. RESULTS: The UK's 30-day post-operative mortality of >3% appears higher than that seen in most modern series (approximately 1%). Furthermore for most paediatric CNS tumour types the survival at 1-, 5- and 10-years is lower in the UK than in the US, and of that published in the literature. CONCLUSION: Despite the limitations of comparing differing healthcare models and also the changes in coding over time, analysing data from large, well recognised and validated registries reduces bias associated with institutional studies. Causes of the difference in survival might include: delay in initial diagnosis, rates of tumour resection, inclusion into clinical trials, types of adjuvant therapy administered, and aggressiveness at time of relapse. Future studies need to look at morbidity and investigate the causes for the discrepancy in outcome.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-57. RADIATION-INDUCED CAVERNOUS MALFORMATIONS IN SURVIVORS OF MEDULLOBLASTOMA

Anne Bendel ¹, Richard Patterson ¹

Abstract

The incidence, timing, and clinical significance of radiation-induced cavernous malformations (CMs) are not well defined. The purpose of this study was to determine the natural history of radiation-induced CMs in survivors of medulloblastoma. METHODS: A retrospective chart and MRI review was performed on all patients with medulloblastoma treated with cranial radiation between 2004-present. Patients > 6 months from completing radiation therapy were included. Gradient echo images (GRE) and diffusion-weighted images (DWI) were used to identify CMs. For the purposes of this study, CMs were defined as acquired low signal foci on GRE images and/or DWI (B = 0 s/mm²) that persisted on serial examinations. RESULTS: 23 patients with medulloblastoma were studied. Age at diagnosis was 2.5-17.5 years. No patient had CMs identified on MRI at the time of tumor diagnosis. 48 CMs developed in 12/23 (52%) patients. The number of CMs per patient varied: 4 patients had 1 CM, 3 patients had 3 CMs, and 1 patient each had 4, 5, 7, 8 & 11 CMs. The time interval between diagnosis and development of CMs was 22 months to 7 years. CM location included the following: cerebellar hemisphere 9 (19%), vermis 1(2%), occipital lobe 16(33%), corpus callosum 3(6%), thalamus 2(4%), parietal lobe 2(4%), temporal lobe 4(8%), and frontal lobe 11(23%). Age range at detection of CMs was 26 months-15 years. CMs developed in 6/9(67%) following 3600 cGy craniospinal radiation, 5/13(38%) following 2340 cGy radiation and 1/1 following isolated 5400 cGy focal radiation. There was no correlation between the number of CMs and age, gender, or craniospinal radiation dose. GRE was more sensitive than DWI (B = 0 s/mm²) at detecting CMs. No CM bled or required intervention. SUMMARY: CMs are frequently found following radiation therapy, and appear more common following 3600 cGy craniospinal radiation. GRE holds promise in identifying and following radiation-induced CMs.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-58. A RANDOMIZED CONTROL TRIAL TO EVALUATE THE EFFICACY OF A GROUP SOCIAL SKILLS INTERVENTION FOR CHILDHOOD SURVIVORS OF BRAIN TUMOURS

Maru Barrera ¹, Fiona Schulte ², Ute Bartels ¹, Laura Janzen ¹, Donna Johnston ³, Danielle Cataudella ⁴, Joanna Chung ⁵, Lillian Sung ¹, Kelly Hancock ¹, Juliet Hukin ⁵, Sheyna Zelcer ⁴, Sarah Brandon ³, Isabelle Montour-Proulx ³, Doug Strother ²

Abstract

BACKGROUND: Many child and adolescent survivors of brain tumours experience neurocognitive functioning and social competence deficits. Unlike neurocognitive functioning, treatment for social competence deficits of these survivors has received little attention. This multi-site randomized control trial (RCT) aims to test the efficacy of a manualized group social skills training intervention program (SSIP) in pediatric brain tumor survivors. We hypothesized that survivors in SSIP group (Experimental Group; EG) will improve their social skills, reported by parents, teachers, peers, and survivors, compared to an attention Control Group (CG) at the end of intervention and 6 months later. METHODS: RCT design with repeated measures. Inclusion criteria: patients who are 8 to 16 years of age, who are in stable condition on brain tumour therapy or in follow-up, who attend school regularly. Following baseline assessment, participants will be randomized to either the EG or CG. 160 patients will be recruited from five pediatric cancer centres across Canada (Vancouver, Calgary, Ottawa, London, Toronto). Both groups will have 8 two-hour weekly group sessions and two post intervention assessments: at the end of intervention and 6 months later. In the EG the critical ingredient is structured social skills training through games and crafts, based on the manual. The CG will have games and crafts but no social skills training. The outcome measures will be parent, teacher and self-rated Social Skills Rating System (SSRS) and peer's social ratings (Revised Class Play). RESULTS: Data will be analyzed using linear mixed models with maximum likelihood estimation for repeated measures (SAS Proc Mixed). Currently we are recruiting participants across sites. DISCUSSION: Rigorous testing of the efficacy of an intervention program is a critical step for validating evidence-based treatments. SSIP has the potential to maximize survivors' social competence and their long-term social re-integration into their community, thereby improving quality of life.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-59. METABOLIC SYNDROME, CARDIOVASCULAR RISK AND INSULIN RESISTANCE IN PEDIATRIC SURVIVORS OF BRAIN TUMORS TREATED WITH RADIATION.

Raven Cooksey ¹, Daniel Bowers ¹, Lynn Gargan ², Amit Gode ¹, Laura Klesse ¹, Jon Oden ², Gloria Vega ¹

Abstract

BACKGROUND: The aim of this study is to examine the prevalence of metabolic syndrome (obesity, dyslipidemia, hypertension, and insulin resistance) in childhood brain tumor survivors. Metabolic syndrome may represent the connection between childhood cancer survivorship and increased long-term risk of cardiovascular disease, particularly in brain tumor survivors. METHODS: Participants underwent evaluation for metabolic syndrome (fasting lipid panel and glucose, blood pressure and waist circumference measurement) and have additional metabolic evaluation (C-peptide, insulin, DXA body composition scan). C-peptide and insulin levels are utilized to calculate the HOMA-IR, validated as an indicator of insulin resistance in pediatric patients. RESULTS: 38 survivors have been evaluated (28 radiated, 10 not radiated; 20 males, 18 females). Median age of enrolled patients is 14 years (range 10-20), median interval since diagnosis is 68 months (range 14-178). Obesity, based on waist circumference, was found in 39% of radiated patients and 70% of non-radiated patients. Obesity, based on DXA body fat, was similarly found in 29% of radiated and 60% non-radiated survivors. Hypertension prevalence was 18% in radiated patients, 30% in non-radiated. Dyslipidemia was identified in 50% of radiated patients, 40% non-radiated. No study participants had frank fasting hyperglycemia, though 18% of radiated patients met criteria for insulin resistance based on HOMA-IR (none in the non-radiated group). Eight patients have been identified to meet diagnostic criteria for metabolic syndrome, seven in the radiated group (25%) and one not radiated (10%). In all patients with metabolic syndrome, none had frank hyperglycemia; rather, all patients had evidence of dyslipidemia and insulin resistance based on HOMA-IR. DISCUSSION: Metabolic syndrome is a common source of long term morbidity for childhood brain tumor survivors. These preliminary results support the hypothesis that radiation increases the risk for metabolic syndrome in survivors, and that effects can be seen in early adolescence and young adulthood.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-60. LONG-TERM OUTCOME AFTER SURGERY FOR BRAINSTEM TUMORS IN CHILDREN

Francesco Sala ¹, Daniele Nuzzi ¹, Miriam Mulino ¹, Barbara Masotto ¹, Carlo Mazza ¹, Albino Bricolo ¹, Massimo Gerosa ¹

Abstract

INTRODUCTION: Brainstem tumors represent a heterogeneous group of neoplasms with different prognosis. Except for diffuse gliomas, focal lesions are amenable to surgical treatment. Yet the long-term follow-up of surgical series is rarely reported. We reviewed long-term results in 51 children (mean age 10 years, range 1-17) operated on for brainstem tumors between 1994 and 2007. MATERIALS AND METHODS: Reviews of clinical charts and outpatient clinic reports as well as phone interviews were used to collect clinical, neuroradiological, and quality of life data. Based on the pre-operative MRI, tumors were classified as focal (n = 20), exophytic(n = 23), diffuse(n = 6) or cervicomedullary (n = 2). Since 2000 surgery was performed under multimodality intraoperative neurophysiological monitoring (n = 29). Tumor removal was classified as total (n = 16), subtotal (n = 32) or partial/biopsy (n = 3); thirteen patients had two (n = 10) or more (n = 3) surgeries. Pilocytic astrocytomas were the most common histological diagnosis (n = 29). Radiotherapy (RT) and/or chemotherapy (CHT) were used in 16 patients. RESULTS: On February 2012, 7 patients are lost to follow-up, 13 are dead (all malignancies except 2), while 31 are alive at a mean follow-up of 125 months (range 52-207). Of these 31 patients, 8 have no evidence of disease, 21 have stable disease, 2 have small progression, and only two received adjuvant therapies following surgery. Eight patients are cognitively impaired and overall neurological impairment is absent/mild in 12, moderate in 7, while 5 are fully dependent on external support for daily activities. Currently, 9 patients are attending school (5 high, 2 middle, 2 elementary), 12 are employed, 10 unemployed (4 middle school, 4 high school, 2 academic degree). CONCLUSION: While the prognosis of diffuse and/or malignant brainstem tumors remains dismal, surgery alone warrants long-term survival in the majority of low grade tumors, especially pilocytic astrocytomas. Among survivors who became adults, about half are employed, and half are unemployed, in spite of higher education.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-61. RADIATION-INDUCED CAVERNOMA IN PEDIATRIC SURVIVORS OF MEDULLOBLASTOMA

Michael Tong ¹, Eric Bouffet ¹, Suzanne Laughlin ¹

Abstract

PURPOSE: The objectives of this study were to examine the incidence of cavernoma development in pediatric patients treated for medulloblastoma, further evaluate the association between radiotherapy and cavernoma development in the pediatric brain, and determine the most favourable magnetic resonance (MR) imaging technique to detect cavernoma. METHODS: This retrospective study involved 98 consecutive pediatric patients (73 male, 25 female) treated for medulloblastoma that presented to The Hospital for Sick Children between June 1996 and April 2008. The treatment protocols of the participating patients were reviewed with a neuro-oncologist, and the radiological studies up to each patient's most recent available MRI were examined with a neuro-radiologist for radiation-induced changes, including cavernoma. RESULTS: Of the participating patients, 40 (41%) were identified as having developed radiation-induced cavernoma. Of these, 25 (63%) had asymptomatic lesions, while 13 (33%) had hemorrhagic lesions and 2 (5%) presented with seizures during the follow-up period. The median age at first report of radiation-induced cavernoma was 12.1 years (range 4.7 to 17.5 years). The median latency period between the end of radiotherapy and first reported lesion was 2.8 years (range 6 months to 9.1 years). Additionally, 33 (83%) patients had their lesions first reported by a neuro-radiologist exclusively through findings from MPGR sequences. CONCLUSIONS: At 41%, this study found a significantly high incidence of radiation-induced cavernoma in pediatric survivors of medulloblastoma. As radiotherapy is common in treating pediatric brain tumors, radiation-induced cavernoma should be considered a potential treatment-related side effect, and patients and parents should be informed about their risks. Due to their higher conspicuity on gradient MR imaging, it is essential to include these sequences, particularly MPGR, on all imaging studies of patients that have undergone radiotherapy. Given their common latency period of a few years post-radiotherapy, a longer follow-up period is needed for patients treated with radiation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i125–i139.

QL-62. A QUALITATIVE INVESTIGATION INTO THE EARLY DELAYED SIDE EFFECT OF "SOMNOLENCE SYNDROME" FOLLOWING CRANIAL IRRADIATION IN PAEDIATRIC PATIENTS

Shona Mackie ¹, Lesley Taylor ¹, Geoff Sharpe ¹, Omar Al-Salihi ¹, Gary Nicolin ¹

Abstract

Somnolence syndrome is a side effect of cranial radiotherapy typically characterised by a transient period of exhaustion, drowsiness and anorexia, first described by Druckman in 1929. Despite recent advances in radiotherapy techniques there is almost no contemporary research describing the phenomenon. This study aims to update the literature regarding the incidence and clinical features of somnolence. Findings from the first ten patients are presented. RESULTS : Data on ten patients, treated at Southampton General Hospital Oncology Centre was collected from daily diaries (recording symptoms and hours of sleep) kept by patients/parents and from medical records. Patients were aged 3yrs 10mo to 18yrs (mean 11yrs 7mo). Five were male and five female with a diagnosis of medulloblastoma (2), pineal germinoma (2) ependymoma (2), low-grade glioma (3) and high-grade glioma (1). Radiotherapy was whole brain plus tumour boost in 4 and subtotal brain radiotherapy in 6. During treatment 2 patients had no change in their sleep pattern (both subtotal brain radiotherapy). Eight patients had an increase in average sleep per day (5% increase in four and 10% in four), occurring from 3 weeks of treatment onwards. Eating patterns fluctuated on treatment with 9 patients eating less than normal and 1 patient's appetite remaining unchanged. Post treatment 1 patient had no change in their sleeping pattern (focal cerebellum treatment). Seven patients had an increase in their sleep of >10% and 2 patients had a >25% increase in sleep. All the increases in sleep occurred after week 5 and lasted at least 2 weeks. Six of these patients ate less than normal during this time. CONCLUSION: Additional patients are being recruited to further explore the relationship between cerebral irradiation and somnolence syndrome. Further analysis is planned to investigate the relationship between age, treatment dosimetry, tumour location, time of onset and duration of somnolence.

PERMALINK

QUALITY OF LIFE/AFTERCARE

QL-01. GLUTATHIONE S-TRANSFERASE P1 SINGLE NUCLEOTIDE POLYMORPHISM PREDICTS PERMANENT OTOTOXICITY IN CHILDREN WITH MEDULLOBLASTOMA

Surya Rednam

Michael Scheurer

Adekunle Adesina

Ching Lau

Mehmet Okcu

Abstract

QL-02. COMPETENCE OF MOTHERS AS CAREGIVERS: ADOLESCENT AND YOUNG ADULT BRAIN TUMOR SURVIVORS LIVING AT HOME

Janet Deatrick

Sue Ogle

Michael Fisher

Lamia Barakat

Thomas Hardie

Yimei Li

Jill Ginsberg

Abstract

QL-03. S0CIAL REINTEGRATION AFTER CENTRAL NERVOUS SYSTEM TUMORS IN CHILDHOOD

Myriam Ben-Arush

Elena Krivoy

Rivka Rosenkranz

Monique Peretz-Nahum

Abstract

QL-04. MAGNETIC RESONANCE SPECTROSCOPY FOR EVALUATION OF IRRADIATION-INDUCED BRAIN INJURY IN A JUVENILE MOUSE MODEL

Robert J Brown

Joanne Love

David Warburton

William H McBride

Stefan Bluml

Abstract

QL-05. RISK OF FIRST AND RECURRENT STROKE IN PEDIATRIC CANCER SURVIVORS TREATED WITH CRANIAL RADIATION THERAPY

Sabine Mueller

Katherine Sear

Nancy Hills

Nassim Chettout

Shervin Afghani

Leanne Lew

Erica Tolentino

Daphne Haas-Kogan

Heather Fullerton

Abstract

QL-06. PROCESSING SPEED AND WHITE MATTER ASSOCIATION IN CHILDREN THREE YEARS POST TREATMENT FOR MEDULLOBLASTOMA

Wilburn Reddick

Shawna Palmer

John Glass

Yimei Li

Robert Ogg

Amar Gajjar

Abstract

QL-07. COMPLICATED MIGRAINE WITH COMPLEX REGIONAL PAIN SYNDROME AFTER CRANIOSPINAL IRRADIATION FOR MEDULLOBLASTOMA: A POSSIBLE SMART VARIANT

Ayman Omar

Abstract

QL-08. RISK OF SECONDARY NEOPLAMS IN SURVIVORS OF CHILDHOOD BRAIN TUMORS

Stephanie Perkins

Eric Shinohara

Abstract

QL-09. BARRIERS TO PARTICIPATION IN A NEURO-ONCOLOGY EDUCATION AND SUPPORT GROUP

Debra Spoljaric

Jill Isenberg

Moroline Whittington

Marnie Hauff

Allison King

Abstract

QL-10. SOCIOECONOMIC STATUS AND QUALITY OF LIFE IN CHILDREN WITH CANCER OR BRAIN TUMORS: THE MEDIATING ROLE OF FAMILY FACTORS

Kristin Litzelman

Emily Barker

Kristine Catrine

Diane Puccetti

Peggy Possin

Whitney Witt

Abstract

QL-11. POSTERIOR FOSSA TUMOUR SURGERY OUTCOMES: THE LIVERPOOL CAUSALITY COMPLICATIONS ASSESSMENT TOOL

Conor Mallucci

Ram Kumar

Barry Pizer

Dawn Williams

Benedetta Pettorini

Abstract

QL-12. PHYSICAL FUNCTIONING OF PEDIATRIC POSTERIOR FOSSA BRAIN TUMOUR SURVIVORS