Vision-related quality-of-life in pediatric primary brain tumor patients.

PURPOSE: Brain tumors are the leading cause of death from childhood cancer. Although overall survival has improved due to earlier detection, better therapies, and improved surveillance, visual dysfunction and impaired vision-related quality-of-life (VR-QOL) are often unrecognized in children. This project investigated VR-QOL in pediatric brain tumor patients. METHODS: We evaluated visual impairment and quality-of-life (QOL) in a quality improvement project at one tertiary care center. Patients ≤ 18, greater than 6 months from diagnosis of brain tumor, excluding intrinsic anterior visual pathway tumors, underwent standardized neuro-ophthalmologic examination. Health-related QOL (HR-QOL) (PedsQL Brain Tumor Module) and VR-QOL questionnaires [CVFQ (Children's Visual Function Questionnaire) in children < 8, and EYE-Q in children 8-18] were obtained from patients and parents. RESULTS: Among 77 patients, craniopharyngiomas (n = 16, 21%) and astrocytomas (n = 15, 20%) were the most common tumors. Among 44/77 (57%) visually impaired children, 7 (16%) were legally blind. Eye-Q median score was 3.40 (interquartile range 3.00-3.75), worse than average scores for normal children. Eye-Q score decreased 0.12 with every 0.1 increase in logMAR visual acuity (p < 0.001). Patients who were legally blind had a significantly lower Eye-Q score than those who were not [0.70 vs. 3.44 (p < 0.001)]. Cognitive HR-QOL scores decreased 1.3 for every 0.1 increase in logMAR visual acuity (p = 0.02). CONCLUSIONS: Pediatric brain tumor patients' vision, HR-QOL, and VR-QOL were often severely affected even when tumors were considered cured. Visual acuity and legal blindness correlated with VR-QOL. Systematic neuro-ophthalmologic examinations in pediatric primary brain tumor patients are necessary to facilitate early preventative and corrective ophthalmologic interventions.

Impact of executive functioning on health-related quality of life of pediatric brain tumor survivors.

BACKGROUND: Brain tumor survivors are at risk for significant late effects following treatment completion that may adversely impact health-related quality of life (HRQOL). The current study examines the relationship between executive functioning (EF) and HRQOL in pediatric brain tumor survivors within a longitudinal framework. We hypothesized that early deficits in EF would be related to less optimal HRQOL in this population. PROCEDURE: The current study utilized retrospective medical chart review to identify neurocognitive correlates of HRQOL in 137 youth previously treated for a pediatric brain tumor. Participants completed the Pediatric Quality of Life Inventory (PedsQL) and neuropsychological assessment, including a well-validated measure of executive functioning (Behavior Rating Inventory of Executive Function; BRIEF). General linear regression and multivariate models were utilized to examine the relationship between child executive functioning and HRQOL. RESULTS: Multiple domains of child executive functioning, as reported by parents on the BRIEF, significantly predicted parent-proxy reported HRQOL after controlling for demographic and medical covariates, including child intellectual functioning (IF). Similarly, after controlling for covariates, the BRIEF Cognitive Regulation Index was a significant predictor of self-reported physical and school functioning domains of HRQOL. CONCLUSION: Current data demonstrate EF is a significant predictor of HRQOL during survivorship for youth previously diagnosed with a pediatric brain tumor. Results suggest that opportunities may exist to intervene and improve HRQOL of pediatric brain tumor survivors by targeting EF.

Guidelines for Treatment and Monitoring of Adult Survivors of Pediatric Brain Tumors.

OPINION STATEMENT: Pathologies of pediatric brain tumors are more varied than those diagnosed in adults and survival outcomes more optimistic. Therapies for pediatric brain tumors are also diverse and treatment options are expanding. The growing number of adult survivors of childhood brain tumors is quite diverse. Medical management of these adults requires understanding the tumor diagnosis and location, the modalities used to treat the tumor, the age of the survivor at the time of diagnosis and treatment, any complications of treatment, and, most importantly, the baseline medical condition and neurological function of each adult survivor. A network of medical, neurological, and mental health providers is critical in the care of a child with a brain tumor. A comparable network should be available to survivors of these tumors since they may transition to adulthood with medical and neurological deficits and can acquire additional late effects of treatments as they age. Optimally, each survivor will have an individualized survivor health plan (SHP) that concisely summarizes the tumor, treatments, potential late effects, and screening that may identify evolving late effects before they impact mental, social or physical functioning. This plan helps patients, families, and the medical team advocate for surveillance aiming to optimize the survivor's quality of life. Failure to support the health and function of these heroic cancer survivors renders the medical advances, the courage, and the struggle that permitted survival meaningless.

Clinical responses of patients with diffuse leptomeningeal glioneuronal tumors to chemotherapy.

INTRODUCTION: Diffuse leptomeningeal glioneuronal tumors (DLGT) have been recognized in the most recent WHO classification as a distinct entity. OBJECTIVE: We describe seven pediatric cases of DLGT and the responses to therapy and outcome. METHODS: We conducted a retrospective review of charts from 1985 to 2013. RESULTS: DBS is an effective therapeutic modality for intractable TLE, particularly in patients with lateralized EEG A total of seven patients were identified. Median age at diagnosis was 3 years. Three months was the median time from symptom development to diagnosis. Common MRI findings included diffuse leptomeningeal thickening, nodularity, or coating of the subarachnoid or ependymal surfaces. The leptomeningeal lesions often appear cystic and contrast enhancement was variable. Six patients had leptomeningeal involvement of the brain and spine. All patients had a negative CSF cytology. Biopsies demonstrated thickened meninges infiltrated by a monotonous population of oligodendrocyte-like cells. Immunohistochemistry revealed variable features of neuronal and/or glial differentiation. All samples were negative for BRAF V600E mutation by immunohistochemistry. Therapy included one patient treated with craniospinal irradiation followed by vincristine, etoposide, cyclophosphamide, and cisplatin with stable disease for 164 months. Six patients received carboplatin and vincristine with a median duration of response of 20+ months (15-122+). Three patients received temozolomide upfront and progressed at 3, 4, and 27 months. No patients demonstrated complete or partial responses to any chemotherapy regimens. Progression-free survival ranged from 3 to 164+ months; 4/7 patients remained free of progression. All patients are alive. CONCLUSIONS: DLGT are rare tumors that lack imaging responses; however, there was clinical/ symptom improvement in 100% of the patients. A better understanding of the tumor biology is necessary to improve the diagnosis and treatment of this rare disease.

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib.

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E-positive residual tumor. Vemurafenib (660 mg/m(2) /dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy.

The feasibility of frameless stereotactic radiosurgery in the management of pediatric central nervous system tumors.

Recurrent malignant primary and metastatic central nervous system (CNS) tumors in pediatric patients are devastating, and efforts to improve outcomes for these patients have been disappointing. Conventional re-irradiation in these patients increases the risk of significant toxicity. We therefore evaluated feasibility and outcomes using frameless radiosurgery (FRS) in children with recurrent primary and metastatic brain tumors. We reviewed five cases of recurrent primary and metastatic brain tumors treated with frameless radiosurgery between 2008 and 2013. We analyzed safety and feasibility, dosimetric data, local control, and adverse effects. Five patients were treated with frameless radiosurgery for palliation. Fifteen target volumes were treated using our institutional FRS system. The volumes of targets ranged from 0.08 to 51.67 cm(3) with doses ranging from 15 to 21 Gy. Radiosurgery was well tolerated, decreased the need for large-volume CNS irradiation, and allowed for effective palliation in this small cohort. Frameless radiosurgery is feasible in this patient population. Frameless radiosurgery should be considered in management of select patients with recurrent primary or metastatic brain tumors.

Transient enlargement of craniopharyngioma after radiation therapy: pattern of magnetic resonance imaging response following radiation.

Clinical experience suggests that craniopharyngiomas may temporarily increase in size after radiation therapy (RT). The study goal is to determine the incidence and natural history of this response in a cohort of patients managed at Children's Healthcare of Atlanta (CHOA) or Emory Healthcare (EHC). Between 08/1998 and 06/2009, 41 children and young adults were diagnosed with craniopharyngioma at CHOA and/or EHC. Of these, 21 received external-beam radiation and were included in our analysis. Serial magnetic resonance imaging (MRI) studies were evaluated volumetrically to assess response to RT. Median age at diagnosis was 8.2 years (range 3.2-23.5 years). Median radiation dose was 54.0 Gy using standard fractionation (1.8-2.0 Gy/day). With median follow-up of 41.3 months (range 7.2-121.8 months), actuarial local control and overall survival rates at 5 years were 78.7 % and 100 %, respectively. Of subjects, 52.4 % of subjects (11 of 21) were noted on serial MRI evaluation to have tumor enlargement (mostly cystic component) after radiation before eventual shrinkage without further intervention. For tumors that expanded, the median volume increase was 33.9 % (range 15.6-224.4 %). Median time to maximal tumor/cyst expansion was 1.5 months (range 1.0-5.0 months). Finally, nearly all patients (20 of 21) showed a measurable objective response to therapy by MRI regardless of ultimate disease control. Median time to maximal response post-radiation, as defined by MRI, was 9.5 months (range 3.5-39.9 months). In summary, RT is effective for managing craniopharyngioma. However, despite good ultimate responses, approximately 50 % of the patients show tumor/cyst expansion on MRI over the first few months post-radiation. Caution should be taken not to subject these patients to "salvage surgery" or cyst aspiration during this early time unless there are other overriding surgical indications. Understanding the natural history of this phenomenon could potentially help guide the management of these craniopharyngioma patients.

A phase II study of metronomic oral topotecan for recurrent childhood brain tumors.

BACKGROUND: The prognosis for recurrent or refractory brain tumors in children is poor with conventional therapies. Topotecan is a topoisomerase I inhibitor with good central nervous system (CNS) penetration following oral administration. Increased efficacy of topotecan has been demonstrated with prolonged low-dose daily treatment in pre-clinical models. To investigate further this drug delivered orally in pediatric CNS malignancies, a phase II study in children with recurrent or refractory brain tumors was performed. PROCEDURE: Patients ≤ 21 years of age at diagnosis with a recurrent, progressive, or refractory primary CNS malignancy and measurable disease, were eligible. Patients enrolled into four strata: ependymoma (N = 4), high-grade glioma (HGG) (N = 6), brainstem glioma (BSG) (N = 13), and primitive neuroectodermal tumor (PNET) (N = 8). Oral topotecan was administered once daily at a dose of 0.8 mg/m(2)/day for 21 consecutive days repeated every 28 days. Response and toxicity profiles were evaluated. RESULTS: Twenty-six patients were evaluable (median age 9.2 years; 10 males). Two objective responses were observed in PNET patients with disseminated tumor at study entry. These two patients remain alive and in remission 7 and 9.5 years off study. Four other patients (two BSG, one PNET, and one HGG) had stable disease (median 4.6 months). The most common toxicities were hematologic. CONCLUSIONS: Daily oral topotecan at a dose of 0.8 mg/m(2)/day can be safely administered to children with recurrent or refractory brain tumors. This regimen identified activity in recurrent PNET. The prolonged progression free survival (PFS) in two PNET patients justifies consideration of this regimen in more advanced clinical trials.

Seventeen-year-old adolescent with pituitary abscess.

Pituitary abscess is a rare but potentially life-threatening infectious process. Diagnosis is challenging as symptoms are non-specific and signs of infection may be absent. We report the case of a previously healthy 17-year-old male who presented with worsening headaches, polyuria, polydipsia and no clinical signs of infection. On evaluation, he was found to have hypopituitarism with diabetes insipidus, hypothyroidism and adrenal insufficiency. An imaging study revealed a pituitary mass. He underwent transsphenoidal biopsy to rule out tumor. The abscess was drained transsphenoidally and he was treated with parental antibiotics. Magnetic resonance imaging one year later revealed a normal pituitary without any evidence of abscess or mass. He continues to require thyroid, adrenal and anti-diuretic hormone replacements. As with any pituitary lesion, prompt complete hypothalamic pituitary evaluation is essential to avoid potentially life-threatening consequences.

A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma.

PURPOSE: Medulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma. METHODS: We performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy. RESULTS: Twenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities. CONCLUSIONS: Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00031590.

Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma.

PURPOSE: Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment. Efforts to mitigate these effects include deintensification of craniospinal irradiation (CSI) dose and volume. METHODS: ACNS0331 (ClinicalTrials.gov identifier: NCT00085735) randomly assigned patients age 3-21 years with average-risk MB to receive posterior fossa radiation therapy (PFRT) or involved field radiation therapy (IFRT) following CSI. Young children (3-7 years) were also randomly assigned to receive standard-dose CSI (SDCSI; 23.4 Gy) or low-dose CSI (LDCSI; 18 Gy). Post hoc molecular classification and mutational analysis contextualized outcomes according to known biologic subgroups (Wingless, Sonic Hedgehog, group 3, and group 4) and genetic biomarkers. Neurocognitive changes and ototoxicity were monitored over time. RESULTS: Five hundred forty-nine patients were enrolled on study, of which 464 were eligible and evaluable to compare PFRT versus IFRT and 226 for SDCSI versus LDCSI. The five-year event-free survival (EFS) was 82.5% (95% CI, 77.2 to 87.8) and 80.5% (95% CI, 75.2 to 85.8) for the IFRT and PFRT regimens, respectively, and 71.4% (95% CI, 62.8 to 80) and 82.9% (95% CI, 75.6 to 90.2) for the LDCSI and SDCSI regimens, respectively. IFRT was not inferior to PFRT (hazard ratio, 0.97; 94% upper CI, 1.32). LDCSI was inferior to SDCSI (hazard ratio, 1.67%; 80% upper CI, 2.10). Improved EFS was observed in patients with Sonic Hedgehog MB who were randomly assigned to the IFRT arm (P = .018). Patients with group 4 MB receiving LDCSI exhibited inferior EFS (P = .047). Children receiving SDCSI exhibited greater late declines in IQ (estimate = 5.87; P = .021). CONCLUSION: Reducing the radiation boost volume in average-risk MB is safe and does not compromise survival. Reducing CSI dose in young children with average-risk MB results in inferior outcomes, possibly in a subgroup-dependent manner, but is associated with better neurocognitive outcome. Molecularly informed patient selection warrants further exploration for children with MB to be considered for late-effect sparing approaches.

De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system.

We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma. Identification of synchronous brain tumors prompted genetic testing for predisposition to malignancy. Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma. Patient DNA sequencing showed a TP53 allele with a premature stop codon in the oligomerization/nuclear export signal (NES) domain (R342ter). The child's parents, younger brother, paternal grandparents, and maternal grandmother, are without history of malignancy. The patient's brother tested negative for TP53 mutations. This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.

Congenital glioblastoma: a clinicopathologic and genetic analysis.

Congenital central nervous system (CNS) tumors are uncommon, accounting for 1% of all childhood brain tumors. They present clinically either at birth or within the first 3 months. Glioblastoma (GBM) only rarely occurs congenitally and has not been fully characterized. We examined clinicopathologic features and genetic alterations of six congenital GBMs. Tumors were seen by neuroimaging as large, complex cerebral hemispheric masses. All showed classic GBM histopathology, including diffuse infiltration, dense cellularity, GFAP-positivity, high mitotic activity, endothelial proliferation and pseudopalisading necrosis. Neurosurgical procedures and adjuvant therapies varied. Survivals ranged from 4 days to 7.5 years; two of the three long-term survivors received chemotherapy, whereas the three short-term survivors did not. Paraffin-embedded tissue sections were used for FISH analysis of EGFR, chromosomes 9p21 (p16/CDKN2A) and 10q ( PTEN/DMBT1); sequencing of PTEN and TP53; and immunohistochemistry for EGFR and p53. We uncovered 10q deletions in two cases. No EGFR amplifications, 9p21 deletions, or mutations of TP53 or PTEN were noted; however, nuclear p53 immunoreactivity was strong in 5/6 cases. Tumors were either minimally immunoreactive (n = 3) or negative (n = 3) for EGFR. We conclude that congenital GBMs show highly variable survivals. They are genetically distinct from their adult counterparts and show a low frequency of known genetic alterations. Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis.

Successful treatment of a child with a prolactin secreting macroadenoma with temozolomide.

Prolactinomas are a rare subset of brain tumors in pediatrics. We report a child with a prolactin secreting macroadenoma which was refractory to initial treatment with a dopamine antagonist. Given the location of her tumor she was ineligible for surgical resection. Temozolomide (200 mg/m2×5 days each month) was administered with a dramatic and prolonged response in tumor size, prolactin level, and symptoms, with no side effects from treatment. We demonstrate the benefit of temozolomide in the treatment of a pediatric patient with prolactinoma.

Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor. MATERIALS AND METHODS: A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly. RESULTS: Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months. CONCLUSION: Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.

Loss of caspase-8 protein expression correlates with unfavorable survival outcome in childhood medulloblastoma.

PURPOSE: Escaping apoptosis is a hallmark of cancer. In medulloblastoma (MB) cell lines, resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis was recently shown to correlate with loss of caspase-8 mRNA expression, because of aberrant gene methylation (M. A. Grotzer et al., Oncogene, 19: 4604-4610, 2000). Loss of caspase-8 mRNA expression has been demonstrated in a subset of primary MB (T. J. Zuzak et al., Eur. J. Cancer, 38: 83-91, 2002). In this study, we analyzed primary MB samples to test whether loss of caspases correlates with survival outcome. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the protein expression of the key initiator caspase-8 and caspase-9 in paraffin-embedded tumor samples from 77 well characterized MB patients and compared the expression levels of caspase-8 and caspase-9 with apoptosis indices, clinical variables, and survival outcomes. RESULTS: Weak expression of caspase-8 and caspase-9 was found in 16 and 24% of the MB samples evaluated, respectively. Weak expression of caspase-8 was an independent significant prognostic factor for unfavorable progression-free survival outcome and was more predictive than standard clinical factors. In contrast, caspase-9 expression was not a prognostic factor. Treatment of caspase-8-deficient MB cells with IFN-gamma resulted in dose-dependent restoration of caspase-8 mRNA and protein expression and restoration of tumor necrosis factor-related apoptosis-inducing ligand sensitivity. CONCLUSIONS: Loss of initiator caspase-8 is associated with an unfavorable survival outcome. Restoration of caspase-8 (e.g., by treatment with IFN-gamma) might, therefore, represent a novel experimental therapy in childhood MB.

Adult height and adult sitting height in childhood medulloblastoma survivors.

Outcome in adult height and sitting height is poor in children surviving medulloblastoma due to craniospinal irradiation (CSRT) and chemotherapy. We evaluated adult height and sitting height in 51 medulloblastoma patients stratified into four groups: G1, GH-deficient (GHD) patients treated with 23-39 Gy CSRT but not treated with GH [recombinant human (rh)GH]; G2, patients treated with rhGH; G3, patients who were not GHD; and G4, patients treated with 18 Gy CSRT and rhGH. Standing/sitting height of each group was compared with parental height and previously reported outcome studies. The rhGH dose was 0.3 mg/kg.wk, a higher dose compared with other reports of adult heights. The adult heights were significantly taller in group G2 [mean height SD score (SDS) = -1.86] than that achieved in previous studies (P < 0.0001), but not different from group G3, non-GHD (mean SDS = -1.55). The tallest stature achieved was in group G4 (18 Gy CSRT), a height SDS of -1.01. Sitting heights were significantly less than the normal population, with mean SDS of -2.96 but -1.62 in group G4. We conclude that adult heights but not sitting heights in medulloblastoma survivors are significantly improved with the higher dose of rhGH. The lower dose of CSRT further improves not only adult height but also sitting height.

Adult heights attained by children with hypothalamic/chiasmatic glioma treated with growth hormone.

Hypothalamic/chiasmatic gliomas (H/CG) in children are commonly accompanied by endocrine dysfunction due to mass effects of the tumor itself or as a consequence of tumor therapy, with GH deficiency (GHD) being the most common disorder. We report the height outcomes of GH-treated H/CG patients with GHD. We reviewed the records of 14 GHD patients with H/CG who were treated with human GH. A comparison group of non-GH-treated H/CG patients was also identified. Heights were expressed as sd scores (SDS). For GH-treated patients, the mean initial height was -0.7 +/- 0.3 (+/-se). Their mean final height was -0.3 +/- 0.3. The mean change in height SDS for the GH-treated group was +0.4. The mean initial and final height SDS for the non-GHD patients were 0.6 (se = 0.4) and 0.0 (se = 0.4), respectively. The mean change in height SDS was -0.6. The GHD patients had significantly lower initial height SDS compared with the non-GHD patients (P = 0.01) and had a significantly greater change in their height SDS (P = 0.04). GH treatment for H/CG patients restores much of their growth potential and improves adult height to within normal limits.

Endocrine outcome in children with medulloblastoma treated with 18 Gy of craniospinal radiation therapy.

Craniospinal radiation therapy (CSRT) combined with chemotherapy results in significant endocrine morbidity. Between 1987 and 1990, a trial using 18 Gy was conducted to treat 10 young children with medulloblastoma. There were 7 survivors. We compared the endocrine outcome in these children (group 18 Gy) to that of a comparable group treated with conventional doses of CSRT that ranged from 23 to 39 Gy (group CD). Both groups had an identical history of chemotherapy and tumor stage and were treated with recombinant growth hormone therapy (rhGH). The mean age of group 18 Gy at diagnosis was 4.0 years, and rhGH treatment was initiated in 6 children at age 9.2 years. Group CD (12 children) was diagnosed at a mean age of 5.8 years and rhGH started in 11 children at a mean age of 9.6 years. The dose of rhGH used in both groups was identical (0.3 mg/kg/wk). For group 18 Gy, adult heights and sitting heights (a mean standard deviation score of -1.01 +/- 1.11 and -1.62 +/- 1.16, respectively) were statistically greater (P < 0.05) than those for group CD (mean standard deviation score of -2.04 +/- 0.83 and -3.16 +/- 1.43, respectively). Moreover, adult heights of group 18 Gy were not different from midparental heights, unlike group CD, whose adult heights were less than midparental heights (P < 0.0001). Of other endocrine sequelae, 10 patients of the CD group were hypothyroid, 3 had adrenal insufficiency, 3 had hypogonadism, and 2 had early puberty. In contrast, within group 18 Gy, only 1 was hypothyroid (P = 0.006) and 1 had early puberty. We conclude that endocrine morbidity was significantly reduced with 18 Gy CSRT in young children with medulloblastoma.

Craniospinal radiation in the treatment of biopsy-proven intracranial germinomas: twenty-five years' experience in a single center.

PURPOSE: The optimal treatment for intracranial germinomas remains controversial. We report on our 25-year experience using craniospinal irradiation (CSI) for this disease. METHODS AND MATERIALS: Between September 1976 and May 2001, 39 patients with biopsy-proven intracranial germinomas seen at the Children's Hospital of Philadelphia/Hospital of the University of Pennsylvania received CSI. Thirteen of 36 patients (36%) had evidence of spinal dissemination. Median doses to the whole brain, primary site, and spine were 36 Gy (range, 18-44.2 Gy), 50.4 Gy (range, 44-55.8 Gy), and 30.6 Gy (range, 18-40 Gy), respectively. RESULTS: With a median follow-up of 7.1 years (range: 1.5-20.2 years), there have been no documented relapses. This includes 5 patients without spinal dissemination who received 18-19.8 Gy to the craniospinal axis; for these patients, the median length of follow-up was 5.5 years (range, 1.3-6.8 years). One patient, who had no evidence of disease 12.9 years after CSI, died of unknown causes 4 months later. CONCLUSIONS: Our treatment of intracranial germinomas with CSI has yielded outstanding results with no known relapses during a long follow-up period. These results must be considered when evaluating other approaches, such as chemotherapy only or local field irradiation.