Ependymal tumors in childhood

BACKGROUND: Ependymal tumors are classified as ependymoma (benign or low grade) versus anaplastic ependymoma (malignant or high grade). Ependymomas represent 5-10% of intracranial neoplasm in children. In this study, demographic data and the treatment results of pediatric patients with ependymal tumors, treated in a single institute, is reported. PATIENTS AND METHODS: Between 1989 and 2001, 40 (22 M/18 F) previously untreated patients with a median age of 5.5 years (3 months-15 years), of histologically proven ependymal tumors (except ependymoblastomas) were referred to the Institute of Oncology, University of Istanbul. The localization was supratentorial in 18, infratentorial in 20, both supra and infratentorial in two patients. Histologic subgroups were 18 ependymomas (43.6%), and 22 anaplastic ependymomas (56.4%). Total tumor resection was performed in 20 patients (50%), subtotal in 18 patients (45%), and biopsy only in 2 patients (5%). Postoperative treatment consisted of regional (8 patients) or craniospinal (CSI) (9 patients) radiotherapy (RT) in patients with ependymoma; regional (7 patients) or CSI RT (14 patients) with chemotherapy (ChT) in patients with anaplastic ependymoma; ChT only (1 patient) in patients less than 3 years of age. The standard technique for posterior fossa irradiation was parallel-opposed lateral fields and total dose was 45-54 Gy. Between September 1989 and May 1991 patients received regimen A, which consisted of RT followed by eight-in-one ChT, given every 4 weeks for eight courses. Patients who were treated between June 1991 and July 1994, received regimen B, which included two courses of postoperative "VEC" (vincristine, etoposide, cisplatin) ChT, administered every 3 weeks, followed by RT applied with low dose concomitant cisplatin used as a radiosensitizer. Patients with objective response to postoperative "VEC" continued to have "VEC" after completion of RT for six more courses. From August 1994 on, patients received regimen C, consisting of RT and concomitant infusion of cisplatin followed by "VCPCU" (vincristine, cyclophosphamide, procarbazine, lomustine) administered every 4 weeks for eight courses. RESULTS: A total of 40 patients were included in the outcome and survival data. The 5-year overall survival (OS) rate was 64.9%, and the 5-year progression-free survival rate was 50.8% for the whole series. Median time for progression or relapse was 24.3 months and there were 19 patients (43.6%) with relapse or progression. Non-metastatic patients (P = 0.0008, 5-year OS rate was 82% vs. 29%), and totally resected patients (P = 0.01, 5-year OS rate was 80% vs. 55%), and > or =3 years of age (P = 0.04, 5-year OS rate was 75% vs. 38%) had significantly better outcome. CONCLUSIONS: The majority of complete responders were patients who had total tumor removal. Treatment failure occurred mainly within the first 2 years, and outcome was dismal for patients who relapsed or had progressive disease. The median age at diagnosis is 6 years in our patient group; younger children (less than 3 years old) have less favorable outcome. There was no significant difference in survival or progression-free survival between the two histologic subtypes.     

CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN THE FIRST SIX MONTHS OF LIFE: The Childrens Hospital Los Angeles Experience, 1979–2005

Background: The authors report the experience at the Children's Hospital Los Angeles with brain tumors diagnosed before 6 months of age, describing the characteristics of the patients, their tumors, treatment strategies, and prognostic factors. Methods: Thirty-three children who were identified between 1979 and 2005 were included. Twelve were female (36%). There were 11 gliomas, 9 choroid plexus tumors, 8 medulloblastomas and supratentorial primitive neuroectodermal tumors (PNET), 2 atypical teratoid/rhabdoid tumors (ATRT), and 1 each of ependymoma, craniopharyngioma, and immature teratoma. Locations of primary tumors included 21 supratentorial (64%) and 7 posterior fossa, and 5 tumors involved both compartments. The treatment strategies included 5 patients with biopsy only, 18 less than gross total resections (<GTRx), and 9 GTRx. Fourteen children (42%) received chemotherapy. Three patients (9%) received irradiation, 1 at initial diagnosis and 2 at relapse. Nine patients (27%) demonstrated metastases, 6 at diagnosis and 3 at relapse. Results: The Kaplan Meier analysis of event-free survival (EFS) and overall survival (OS) for all patients is 21 ± 9% and 35 ± 9% at 5 years. For the glioma patients, the 4-year OS is 48 ± 17%, while the 5-year OS for the medulloblastoma/PNET/ATRT patients is 12 ± 11% (p = .39). The 5-year OS for children achieving a GTRx is 64 ± 21% and for those with <GTRx is 27 ± 10% (p = .08).     

Proton therapy for central nervous system tumors in children

Proton therapy is a form of particle therapy with physical properties that provide a superior dose distribution compared to photons. The ability to spare healthy, developing tissues from low dose radiation with proton therapy is well known. The capability to decrease radiation exposure for children has been lauded as an important advance in pediatric cancer care, particularly for central nervous system (CNS) tumors. Favorable clinical outcomes have been reported and justify the increased cost and burden of this therapy. In this review, we summarize the current literature for proton therapy for pediatric CNS malignancies, with a focus on clinical outcomes to date.     

Hearing loss in children with brain tumors treated with cisplatin and carboplatin-based high-dose chemotherapy with autologous bone marrow rescue

Carboplatin is less ototoxic than cisplatin, but ototoxicity may occur with carboplatin at higher doses. We evaluated hearing in children with brain tumors treated with conventional dose cisplatin followed by high-dose carboplatin. Children under 6 years of age, newly diagnosed with brain tumors, were treated after surgery with cisplatin, Etoposide, cyclophosphamide, and vincristine, followed by consolidation with carboplatin, ThioTEPA, Etoposide, and autologous bone marrow rescue. Hearing was assessed before and after consolidation, utilizing standard audiometric techniques. Seven of the 11 evaluable patients developed high-frequency sensorineural hearing loss after induction therapy. Hearing deteriorated after consolidation in five patients, with pure tone threshold shifts of up to 65 dB between 2,000 and 8,000 Hz. Of these five patients, audiological abnormalities were documented in four prior to consolidation, one received cranial irradiation after consolidation, and all five received aminoglycoside antibiotics for at least 2 weeks, with toxic drug levels in four. Three patients have subsequently required hearing aids. Significant ototoxicity is common in these patients. Ototoxicity related to consolidation therapy is likely due to the high dose of carboplatin used, prior cisplatin therapy, aminoglycosides, and, in one patient, cranial irradiation. Audiological assessment is essential in children treated with dose-intensive chemotherapy regimens containing cisplatin and carboplatin for identification and rehabilitation of ototoxicity. © 1996 Wiley-Liss, Inc.     

Successful Treatment of a Recurrent Choroid Plexus Carcinoma with Surgery Followed by High-Dose Chemotherapy and Stem Cell Rescue

Choroid plexus carcinoma (CPC) is a rare central nervous system malignant tumor with a dismal prognosis, especially in the case of incomplete resection or recurrence. The authors report long-term survival of a 1-year-old patient with recurrent CPC and Li-Fraumeni syndrome with surgical resection and high-dose chemotherapy (HDC) consisting of single cycle of Busulfan and Thiotepa followed by autologous stem cell rescue without the use of radiation therapy. Remarkably the patient remains without evidence of recurrence 5 years after completion of therapy. Additional studies are necessary to determine the role of HDC and stem cell rescue in patients with recurrent CPC.     

Neuropsychological status of children treated for brain tumors: A critical review and integrative analysis

The literature on the neuropsychological status of children with primary brain tumors was reviewed to identify English-language publications reporting the results of standardized, quantitative measures of patient function. The 22 studies that met these review criteria, representing 544 patients, were evaluated to assess the relationship between traditional risk factors (age at diagnosis, tumor location, radiation therapy, and time since completion of treatment), as well as subsequent intellectual development, academic achievement, psychosocial adjustment, and neuropsychological status. The impact of other potentially salient factors, such as seizures and sensory and motor deficits, was evaluated when possible. Despite inconsistent reporting of demographic and treatment-related effects across studies which precluded formal meta-analysis, we were able to confirm the primary importance of radiation therapy volume and age at treatment on IQ. No effects were detected for tumor location. Younger children treated with cranial (whole brain) irradiation showed a 14-point deficit in IQ as compared with their older counterparts. No significant differences were noted between older children receiving lòcal or cranial irradiation, although both groups had IQ levels 12–14 points lower than those not irradiated. The high-risk groups identified in this study require increased clinical surveillance. Definitive evaluation of potential risk factors for neuropsychological impairment will depend on more complete reporting of relevant patient characteristics and interinstitutional studies. © 1992 Wiley-Liss, Inc.     

Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children's Oncology Group

BACKGROUND: This Phase II study was designed to determine response to chemotherapy and survival after response-based radiation (RT) in children with CNS germ cell tumors. PROCEDURE: Children with germinomas and normal markers received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine + cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with nongerminomatous tumors or with abnormal markers received doubled doses of cisplatin and CPM. For germinoma patients in complete response (CR), RT was decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR. RESULTS: Of 12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma patients attained CR, six PR, one SD, one not evaluable after resection. Two nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable after resection; one inadequately treated patient had progressive disease (PD). Both PD patients died; one SD patient died during a seizure. Eleven germinoma patients are PF at median 66 months; one patient in CR refused RT, had PD at 10 months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous patients were PF at median 58 months. CONCLUSION: Response (germinoma, 91%; nongerminomatous, 55%) and survival are encouraging after this regimen plus response-based RT.     

Pediatric Neuroblastic Brain Tumors Containing Abundant Neuropil and True Rosettes

We have encountered a series of seven unusual neuroblastic pediatric central nervous system (CNS) neoplasms with a unique constellation of histologic, immunohistochemical, and ultrastructural features. The tumors presented in five girls and two boys, ages 1 to 3 years. In six cases the lesions involved the frontoparietal region, in one case the tectal plate. The tumors consisted of small to medium-sized, round to oval, hyperchromatic cells with poorly defined cytoplasmic borders. Cells were found in clusters and cords set in a paucicellular fibrillar neuropil matrix. Distinctive, virtually anuclear regions of neuropil were scattered throughout the lesions. True rosettes with well-formed central lumens often filled with granular debris were present, along with perivascular pseudorosettes and occasional Homer-Wright rosettes. Mitoses and apoptosis were frequent, but large regions of confluent necrosis were absent. Immunohistochemically, the neuropil-like areas as well as the perinuclear cytoplasm of many embryonal tumor cells were positive for synaptophysin and neurofilament protein. Ultrastructurally, the tumor cells showed microtubule-containing neuronal processes, some with neurosecretory granules. While the lesions were largely glial fibrillary acidic protein (GFAP) negative, there was focal GFAP positivity consistent with divergent differentiation in one case. The clinical outcome was poor, with five patients dead from their disease 5 to 14 months after initial presentation and one patient with recurrent disease 7 months after resection and chemotherapy. The final patient is alive without recurrent disease 30 months after initial presentation. These lesions present distinctive histological features within the group of primitive neuroectodermal tumors. Received November 2, 1998; accepted September 9, 1999.     

Muscle strength and quality of life in patients with childhood cancer at early phase of primary treatment

Cancer- and treatment-related side effects in patients with childhood cancer may cause limitations in motor performance affecting activities of daily living (ADLs). Data focusing on long-term effects are available, but little is known with regard to the short-term perspective. Therefore, the purpose of this study was to assess muscle strength performance and quality of life (QoL) in children and adolescents with cancer at the beginning of primary treatment. Forty children and adolescents aged 5–18 years (mean: 11.39 ± 4.08 years) with different types of childhood cancer were enrolled. On average 36 ± 20.5 days after diagnosis, strength performance in 7 muscle groups was assessed by handheld dynamometry. KINDL questionnaires were completed to evaluate QoL (children's self-report and parents' report). All parameters were compared with age- and gender-matched reference values. Patients with childhood cancer showed significantly lower strength values in all muscle groups (P < .01) compared with age- and gender-matched controls. Most affected were the lower extremities, with a ?57.1% ± 10.4%, median: ?59.2%, minimum: ?75.4%, maximum: ?41.4% percentage deviation in knee flexion from healthy peers. Children themselves and parents assessed total QoL significantly below age- and gender-matched reference values (P < .01). Correlation between elbow flexion and self-reported QoL was detected. Broader correlations were found for the parents' report. Muscle weakness and decreased QoL in children and adolescents seem to persist already at the beginning of anticancer treatment. This underlines the need of counteracting measures, such as exercise intervention programs, starting as early as possible during the treatment process. Efforts on this topic are currently being carried out by our group.