Survivors Of Childhood Medulloblastoma Research Articles

Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over 3 decades.

Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown. Adult survivors of childhood medulloblastoma (n = 505; median [minimum-maximum] age, 29 [18-46] years) and sibling controls (n = 727; 32 [18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI] ≥ 30 Gy, no chemotherapy), standard-risk (CSI > 0 to <30 Gy + chemotherapy) and high-risk (CSI ≥ 30 Gy + chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, and marital/partner status. Multivariable models estimated the risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence. Survivors in each treatment exposure group had a 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had a higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems, and seizures were associated with 33-34%, 25-26%, and 21-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with nonindependence. Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.

QOL-04.IN VIVO MODELLING RECAPITULATES RADIOTHERAPY DELIVERY AND LATE-EFFECT PROFILE FOR CHILDHOOD MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is the most common malignant paediatric brain tumour, with 5-year survival rates &amp;gt;70%. Survivors frequently suffer a wide-range of late-effects due to their tumour and its treatment. Cranial radiotherapy (CRT) to the whole-brain, with posterior fossa boost (PFB), underpins treatment for non-infants, however, radiotherapeutic insult to normal brain tissue has deleterious consequences to neurocognitive and physical functioning, and causes accelerated ageing/frailty. Unfortunately, approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development. METHODS We have developed a clinically-relevant in vivo model system that recapitulates the radiotherapy dose, delivery and late-effect profile of childhood medulloblastoma, at an equivalent developmental stage. Consistent with human regimens, age-equivalent (postnatal days 28-37) C57Bl/6J mice received targeted, CT image-guided, CRT (human-equivalent 38 Gy, n=12) or CRT with PFB (human-equivalent 49 Gy, n=12), via the small animal radiation research platform (SARRP) and were longitudinally assessed for over a year. Late-effects were compared to a sham-irradiated group (n=12). RESULTS CRT was well tolerated, independent of PFB receipt, and no mice suffered severe acute toxicity. Mice were significantly more frail following irradiation (frailty index; p=0.0002) and had reduced physical functioning; time to fall from a rotating rod and grip strength were significantly lower (rotarod; p=0.026 and grip strength; p=0.006, respectively). Neurocognitive deficits were consistent with those observed in childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; p=0.009) and exhibited spatial memory deficits (Barnes maze; p=0.029). Receipt of PFB did not induce a more severe late-effect profile. CONCLUSION We conclude that our in vivo model of childhood MB radiotherapy recapitulates the late-effect profile of MB survivors. Our clinically-relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late-effects and the development of novel interventions for their amelioration.

In vivo modeling recapitulates radiotherapy delivery and late-effect profile for childhood medulloblastoma.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with 5-year survival rates > 70%. Cranial radiotherapy (CRT) to the whole brain, with posterior fossa boost (PFB), underpins treatment for non-infants; however, radiotherapeutic insult to the normal brain has deleterious consequences to neurocognitive and physical functioning, and causes accelerated aging/frailty. Approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development. We have developed a clinically relevant in vivo model system that recapitulates the radiotherapy dose, targeting, and developmental stage of childhood medulloblastoma. Consistent with human regimens, age-equivalent (postnatal days 35-37) male C57Bl/6J mice received computerized tomography image-guided CRT (human-equivalent 37.5 Gy EQD2, n = 12) ± PFB (human-equivalent 48.7 Gy EQD2, n = 12), via the small animal radiation research platform and were longitudinally assessed for > 12 months. CRT was well tolerated, independent of PFB receipt. Compared to a sham-irradiated group (n = 12), irradiated mice were significantly frailer following irradiation (frailty index; P = .0002) and had reduced physical functioning; time to fall from a rotating rod (rotarod; P = .026) and grip strength (P = .006) were significantly lower. Neurocognitive deficits were consistent with childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; P = .009) and exhibited spatial memory deficits (Barnes maze; P = .029). Receipt of PFB did not induce a more severe late-effect profile. Our in vivo model mirrored childhood MB radiotherapy and recapitulated features observed in the late-effect profile of MB survivors. Our clinically relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late effects and the development of novel interventions for their amelioration.

A - 114 Long Term Cognitive Sequela of Intracranial Radiation Therapy in a Pediatric Cerebellar Medulloblastoma Survivor.

Intracranial radiation therapy (IRT) for pediatric brain tumors is associated with late delayed brain injury due to cerebrovascular abnormality, white matter necrosis, demyelination, and gliosis which are irreversible. As a result, persistent cognitive deficits in adulthood emerge which are aggravated by younger age at diagnosis, higher radiation dose, whole brain radiation (WBR), and concurrent chemotherapy. The case is a childhood brain tumor survivor seen 18years post treatment who displayed cognitive deficits reflecting the cognitive sequela of WBR that overlapped with the anatomical distribution of white matter damage sustained. 23-year-old Black male with a history of childhood cerebellar medulloblastoma diagnosed at age 4, tumor resection, WBR, chemotherapy, more recent seizure disorder and medullary stroke, diabetes, and hypertension was seen for a neuropsychological evaluation due to memory complaints. His neuroimaging showed white matter hyperintensities in bilateral temporal and occipital lobes, bilateral cerebellar hemispheres, bilateral frontal lobes, medial posterior right cerebellar cyst, and 10 x 5mm cyst in the left temporal lobe. Results showed FSIQ = 59 and deficits in language, processing speed, visuospatial abilities, executive functioning, and verbal memory. His auditory working memory and visual memory were preserved. Based on his numerous adaptive limitations, moderate intellectual development disorder diagnosis was given. Deficits across several cognitive domains were consistent with multi-focal white matter lesions seen in patient's neuroimaging which reflect radiographic findings related to long-term sequela of previous intracranial radiation. A unique finding was relatively preserved visual memory as findings related to asymmetrical memory dysfunction in childhood medulloblastoma survivors are scarce.

PO-1567 Health-related quality of life in survivors of childhood medulloblastoma: a systematic review

PO-1567 Health-related quality of life in survivors of childhood medulloblastoma: a systematic review

The Burden of Surviving Childhood Medulloblastoma: A Population-Based, Matched Cohort Study in Ontario, Canada.

Survivors of childhood medulloblastoma suffer from substantial late effects. We characterized these sequelae using real-world health services data in a population-based cohort of medulloblastoma survivors. All 5-year medulloblastoma survivors diagnosed age < 18 years between 1987 and 2015 in Ontario, Canada, were identified and matched 1:5 with population controls. Index date was 5 years from latest pediatric cancer event. Linkage to provincial administrative health data allowed for comparison of cumulative incidences of several adverse outcomes. Two hundred thirty survivors, 81.3% of whom had received craniospinal irradiation, were matched with 1,150 controls. The 10-year postindex cumulative incidence of all-cause mortality was 7.9% (95% CI, 3.9 to 11.8) in survivors versus 0.6% (95% CI, 0.1 to 1.1) in controls (hazard ratio [HR], 21.5; 95% CI, 9.8 to 54.0). The cumulative incidence of stroke was higher in survivors (4.8%; 95% CI, 2.2 to 9.0) compared with controls (0.1; 95% CI, 0.01 to 0.7; HR, 45.6; 95% CI, 12.8 to 289.8). Hearing loss requiring an amplification device was present in 24.9% (95% CI, 18.8 to 31.4) of survivors versus 0.3% (95% CI, 0.1 to 1.0) of controls (HR, 96.3; 95% CI, 39.7 to 317.3). Disability support prescription claims were submitted by 44.5% (95% CI, 37.1 to 51.6) of survivors versus 5.5% (95% CI, 4.2 to 7.1) of controls (HR, 10.0; 95% CI, 7.3 to 13.6). Female survivors were significantly less likely to deliver a liveborn child compared with controls (HR, 0.2; 95% CI, 0.1 to 0.7). Survivors of medulloblastoma have significant long-term medical sequelae, increased all-cause mortality, and are frequently dependent on disability supports. Efforts to reduce the toxicity of current therapy, specifically incorporating molecularly informed risk stratification to spare low- and intermediate-risk survivors the toxicity of treatment, are urgently needed. These findings should prompt a re-evaluation of our current treatment approaches where research focused on late-effect interventions should be prioritized.

High dose craniospinal irradiation as independent risk factor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review

PurposeOur aim was to determine the main risk factors related to the occurrence of permanent alopecia in childhood medulloblastoma (MB) survivors.MethodsWe retrospectively analyzed the clinical features of all consecutive MB survivors treated at our institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole scalp and nape region), then on the basis of the toxicity degree (G). Any relationship between permanent alopecia and other characteristics was investigated by a univariate and multivariate analysis and Odds ratio (OR) with confidence interval (CI) was reported.ResultsWe included 41 patients with a mean10-year follow-up. High dose CSI resulted as an independent factor leading to permanent hair loss in both groups: alopecia of the whole scalp (G1 p-value 0.030, G2 p-value 0.003) and of the nape region (G1 p-value 0.038, G2 p-value 0.006). The posterior cranial fossa (PCF) boost volume and dose were not significant factors at multivariate analysis neither in permanent hair loss of the whole scalp nor only in the nuchal region.ConclusionIn pediatric patients with MB, the development of permanent alopecia seems to depend only on the CSI dose ≥ 36 Gy. Acute damage to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily irradiation of a large volume may have a stronger effect than a higher but focal dose of radiotherapy.

Bone mineral density and nutrition in long-term survivors of childhood brain tumors.

Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz-1 to-1.99 and very low BMDz ≤-2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. Fifty survivors with a median age of 25.5 years (5.5-51.9) and a median follow-up time of 19.5 years (3.2-40.5) were included. Mean BMDz lumbar spine was-0.8 (SD 1.1, 95% CI:-1.1 to-0.4), and BMDz total body was-0.6 (SD 1.1, 95% CI:-0.9 to-0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D<50nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D≤50nmol/L were detected.

MEDB-07. Long-term medical and functional outcomes of medulloblastoma survivors: a population-based, matched cohort study

BACKGROUND: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. METHODS: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse or subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse or new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. RESULTS: We identified 230 cases [65.7% female; median diagnostic age: 7y, interquartile range (IQR) 4-10; median attained age: 24y, IQR 18-31] and 1150 controls. One hundred eighty-seven (81.3%) received craniospinal irradiation. Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. CONCLUSIONS: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions in preventing neurovascular sequelae and hearing loss is warranted, as are dedicated supports for survivors.

MEDB-53. Incidence of Hearing impairment in childhood Medulloblastoma Survivors treated in King Fahad Medical City KFMC Saudi Arabia

Medulloblastoma MB is the most common childhood CNS tumor treated with intensive multimodalities therapy Surgery, Radiation and Cisplatin chemotherapy which causing significant Hearing impairment (HI) with profound impact on child’s quality of life. METHOD: Retrospective study evaluating risk factors & (HI) incidence in childhood MB survivors treated in KFMC between 2010 and 2020. (HI) was graded using the National Cancer Institute (NCI) Grades (1-4) ALL patients received 6 weeks of Risk adapted CSI radiotherapy concurrent with daily oral Etoposide. patients were treated with 2 different Maintenance chemotherapy German HIT-MED MB protocol 8 Maintenance cycles (Cisplatin 70 mg/m² x 1d /lomustine/VCR) Cumulative dose of Cisplatin 560 mg/m2 KFMC MB SAPHOS protocol 6 Maintenance cycle alternating A&B. cycle A: Cisplatin 90 mg/m² x 1d & 3 weeks of daily oral Etoposide. cycle B: Cyclophosphamide x 2 d & Vincristine Cumulative dose of Cisplatin 270 mg/m2. RESULTS: At Median follow-up of 5 years total of 78 MB survivors, male predominance 66.7% Median age at diagnosis 82 months post end of therapy 28.2% maintain normal hearing while 71.8% had hearing decline compared with baseline audiology Median time of onset of hearing decline was 7 months after start of radiation therapy Significant (HI) (NCI grade 3/4) in 26.9% of patients, and 23.1% required hearing aid use NO statistically difference in incidence of significant (HI) in patients treated with HIT-MED protocol (26.7%) & patients treated with KFMC MB-SAPHOS protocol (27.1%) OR those treated as Average-Risk CSI radiotherapy 22.9% Vs High-Risk CSI radiotherapy (30.2%), patients age at diagnosis (< or > 5 years) does not affects HI incidence. CONCLUSIONS: significant hearing impairment incidence was not affected by Radiation doses OR cumulative Cisplatin dose. Our study will form base line for future studies to modify therapy related Toxicity and improve outcome of childhood MB in Saudi Arabia.

Long-term medical and functional outcomes of medulloblastoma survivors: A population-based, matched cohort study.

10053 Background: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. Methods: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 at &lt;18 years of age in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse/subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse/new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate the cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. We evaluated demographic, disease, and treatment predictors of mortality using Cox proportional hazards models. Results: Of 389 medulloblastoma diagnoses in the study period, 159 (40.9%) were excluded, most commonly due to early death prior to the index date. Two hundred thirty cases were matched to 1150 controls (Table). Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. None of the candidate predictors were significantly associated with mortality on univariate analyses. Conclusions: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions for preventing neurovascular sequelae and hearing loss is warranted, as is dedicated supports for survivors. [Table: see text]

Neuroimaging Biomarkers and Neurocognitive Outcomes in Pediatric Medulloblastoma Patients: a Systematic Review.

Medulloblastoma is a malign posterior fossa brain tumor, mostly occurring in childhood. The CNS-directed chemoradiotherapy treatment can be very harmful to the developing brain and functional outcomes of these patients. However, what the underlying neurotoxic mechanisms are remain inconclusive. Hence, this review summarizes the existing literature on the association between advanced neuroimaging and neurocognitive changes in patients that were treated for pediatric medulloblastoma. The PubMed/Medline database was extensively screened for studies investigating the link between cognitive outcomes and multimodal magnetic resonance (MR) imaging in childhood medulloblastoma survivors. A behavioral meta-analysis was performed on the available IQ scores. A total of 649 studies were screened, of which 22 studies were included. Based on this literature review, we conclude medulloblastoma patients to be at risk for white matter volume loss, more frequent white matter lesions, and changes in white matter microstructure. Such microstructural alterations were associated with lower IQ, which reached the clinical cut-off in survivors across studies. Using functional MR scans, changes in activity were observed in cerebellar areas, associated with working memory and processing speed. Finally, cerebral microbleeds were encountered more often, but these were not associated with cognitive outcomes. Regarding intervention studies, computerized cognitive training was associated with changes in prefrontal and cerebellar activation and physical training might result in microstructural and cortical alterations. Hence, to better define the neural targets for interventions in pediatric medulloblastoma patients, this review suggests working towards neuroimaging-based predictions of cognitive outcomes. To reach this goal, large multimodal prospective imaging studies are highly recommended.

Anesthesia Exposure during Therapy Predicts Neurocognitive Outcomes in Survivors of Childhood Medulloblastoma

To examine the contribution of anesthesia exposure during treatment for childhood medulloblastoma to neurocognitive outcomes 3years after tumor diagnosis. In this retrospective study, anesthesia data were abstracted from medical records for 111 patients treated with risk-adapted protocol therapy at St Jude Children's Research Hospital. Neurocognitive testing data were obtained for 90.9% of patients. For the 101 patients (62.4% male) who completed testing, mean age at diagnosis was 10.1years, and 74.3% were staged to have average-risk disease. Anesthesia exposure during treatment ranged from 1 to 52 events (mean=19.9); mean cumulative duration per patient was 21.1hours (range 0.7-59.7). Compared with normative expectations (16%), the group had a significantly greater frequency of at-risk scores (<1 SD) on measures of intelligence (28.7%), attention (35.2%), working memory (26.6%), processing speed (46.7%), and reading (25.8%). Including anesthesia exposure duration to linear regression models accounting for age at diagnosis, treatment intensity, and baseline IQ significantly increased the predicted variance for intelligence (r2=0.59), attention (r2=0.29), working memory (r2=0.31), processing speed (r2=0.44), and reading (r2=0.25; all P values <.001). In survivors of childhood medulloblastoma, a neurodevelopmentally vulnerable population, greater exposure to anesthesia significantly and independently predicts deficits in neurocognitive and academic functioning. When feasible, anesthesia exposure during treatment should be reduced.

MON-458 Radiological Alterations Of The Hypothalamic-pituitary Region After Craniospinal Irradiation For Medulloblastoma During Childhood.

Background Hypothalamic-pituitary (HP) dysfunction after craniospinal irradiation (CSI) is frequently observed in childhood brain tumor survivors (CBTS). The risk increases with higher dose and younger age at time of radiation exposure. Whether radiological alterations of the HP-region or alterations in brain volume are predictive of HP dysfunction remains unknown. Aim The aim of this (retrospective) study was to quantify radiological alterations of the HP-region in time in CBTS after CSI and to correlate these alterations to the occurrence of HP dysfunction. Methods Ninety survivors of childhood medulloblastoma (mean age at diagnosis: 8.3 years) from a previously reported nationwide cohort, treated with CSI between 2002-2012, were included. Sixty CBTS (67%) were diagnosed with HP dysfunction during follow-up (FU). All MRI scans were collected from time of diagnosis, post-neurosurgical intervention, post-radiation and 3 and 5 years of FU. Pituitary height (PH) and width (PW) were measured on mid-sagittal images. The pituitary stalk (PS) width was assessed by measuring the ratio of the PS to basilar artery (BA) on axial images on the same plane in the middle of the PS. Volume measurements of the PG (PGV) were performed. Observers were blinded for outcome of HP function. Separate analyses were performed for children < 6 years at time of CSI. All measurements were corrected for age and gender using Z-scores. Statistical analyses were performed by SPSS (General Linear Model repeated measures with Bonferroni correction). Results Mean PH (p<0.01, 95% CI [0.25, 1.27], PW (p<0.01, 95% CI [0.85-2.32], width of the PS (p<0.01, 95% CI [0.38-3.0] and PGV (p<0.05, 95% CI [0.12-1.29] declined during FU. No correlation was observed between radiological alterations in time and the presence of HP dysfunction. On a marginal trend level, an interaction effect was seen for PS/BA ratio and the presence of HP dysfunction (p= 0.097, F= 2.44). HP dysfunction occurred more frequently in CBTS treated with CSI < 6 years (71% vs 58%). Radiological alterations in this age group could also not be related to occurrence of HP dysfunction. Conclusion When compared to age and gender reference values, CBTS treated with CSI show radiological alterations of the HP region in time. Exposure to cranial irradiation in childhood seems to have a negative effect on PH, PW, width of PS and PGV. However, these effects cannot be related to the development of HP dysfunction or age at time of CRT. Prospective studies are needed to confirm these results, with systematic evaluation of the HP function in time.

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma (MB) patients in LMICs if proton therapy were made available to them. For nine children of ages 2–14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37–0.75) and 0.64 (95% CI, 0.45–0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood MB in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

Intellectual, educational, and situation-based social outcome in adult survivors of childhood medulloblastoma

ABSTRACTPurpose: To investigate intellectual and situation-based social outcome and educational achievement in adult survivors of childhood medulloblastoma and analyse factors influencing outcomeMethods: We collected demographic, medical and cognitive data, and social and educational outcome at a mean time since the end of treatments of 14.9 years in 58 adults, aged 19–35 years, consecutively treated in a single cancer center between 1989 and 2005.Results: Ten survivors had severe intellectual disability, 12 were still studying, 23 had a regular employment and 13 were unemployed. Full Scale Intellectual Quotient, assessed 6.6 years after the end of treatments, ranged from 46 to 131. It was strongly associated with educational achievement and significantly lower in patients who experienced postoperative cerebellar mutism, and when parental education level was low.Conclusion: These factors should be systematically considered at diagnosis in order to offer adequate and timely assessments and interventions.

Metabolic late effects among young adult survivors of childhood medulloblastoma and acute lymphoblastic leukemia

Aim: Pediatric cancer survivors are at higher risk of metabolic late effects compared to the general population. We aimed to determine the prevalence of metabolic late effects among young adult survivors (YAS) of childhood medulloblastoma (cMB) and acute lymphoblastic leukemia (cALL).

Neurocognitive Function and Health-Related Quality of Life in Pediatric Korean Survivors of Medulloblastoma.

The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ) score was 86.78, which was within 1 standard deviation of the average score of 100. Processing speed, attention, and executive function showed mild to moderate deficits. Intelligence, memory, executive function, visuospatial function, and simple motor function were significantly lower in the patients diagnosed before 8 years of age compared with those diagnosed after 8. The cognitive deficits in the patients diagnosed at younger ages might be related to earlier exposure to craniospinal irradiation and chemotherapy. The patient and parent proxy evaluations of attention, fine motor function, and quality of life did not differ. We found significant neurocognitive changes in a wide range of neurocognitive functional domains in Korean survivors of childhood medulloblastoma. Long-term follow-up studies of survivors of childhood medulloblastoma beginning at the time of their first diagnosis are required to better understand the deficits exhibited by survivors of childhood medulloblastoma, so that intervention strategies and treatment refinements that reduce the long-term neurocognitive decline can be developed.

Endocrine complications in survivors of childhood medulloblastoma

Medulloblastoma is the most common malignancy of the central nervous system in childhood. With the current combined treatment with surgery, chemotherapy and radiotherapy, the survival rates had improved dramatically in recent years. However, these survivors are prone to develop various late sequelae secondary to treatment.

Effect of motivation on academic fluency performance in survivors of pediatric medulloblastoma

It has been proposed previously that extrinsic motivation may enable survivors of childhood medulloblastoma to significantly improve aspects of neurocognitive performance. In healthy populations, enhanced motivation has been shown to promote academic fluency, a domain likely more relevant to the educational outcomes of pediatric medulloblastoma survivors than academic skill development. The present study investigates the effect of enhanced extrinsic motivation on fluent (i.e., accurate and efficient) academic performance in pediatric medulloblastoma survivors. Participants were 36 children, ages 7–18, who had completed treatment for medulloblastoma. Participants completed a neuropsychological battery that included administration of equivalent tasks on Forms A and B of the Woodcock-Johnson III Tests of Achievement. Half were randomly assigned to an incentive condition prior to the administration of Form B. Provision of a performance-based incentive resulted in statistically significant improvement, but not normalization of function, in performance on measures of academic fluency. No demographic, treatment-related, academic, neuropsychological, or self-perception variables predicted response to incentive. Findings suggest that academic performance of survivors may significantly improve under highly motivating conditions. In addition to implications for educational services, this finding raises the novel possibility that decreased motivation represents an inherent neuropsychological deficit in this population and provides a rationale for further investigation of factors affecting individual differences in motivational processes. Further, by examining effort in a context where effort is not inherently suspect, present findings also significantly contribute to the debate regarding the effects of effort and motivation on neuropsychological performance.