Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Primitive neuroectodermal tumor incidence, treatment patterns, and outcome: An analysis of the National Cancer Database.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS: The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS: White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P < .001), primary tumor resection (P < .001), and experienced increased 90-day mortality (P < .014). CONCLUSION: cPNET and pPNET are rare and aggressive malignancies that tend to arise in White males. Multimodal treatment including surgery, chemotherapy, and radiation is conventional. Patients with cPNET more often receive radiation and primary tumor resection with increased 90-day mortality.

Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes.

BACKGROUND: Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. METHODS: Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment). RESULTS: The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five- and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85-52.18) and 41.78% (95% CI 36.11-47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70-71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. CONCLUSIONS: The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Primary spinal primitive neuroectodermal tumor: A single center series with literature review.

Context: Primary spinal primitive neuroectodermal tumor (PNET) of the central nervous system has a low incidence. The intraspinal case is very rare. Around 30 cases have been reported so far. We summarized the cases of primary spinal PNET available in the database of our institute, either intramedullary or extramedullary cases. Then we did literature review of the same disease. Findings: There were eight cases of primary spinal PNET available in our database, with one intramedullary case and seven extramedullary cases. Surgical resection was performed. The histology diagnosis was PNET. Peri-operative image examinations of the whole central nervous system (CNS) were performed to exclude tumors other than spinal cord origin. Then during literature review, 33 reports of the disease were included. The pre-operative diagnosis rate was low. The disease had a high recurrence rate and poor prognosis given available treatment. Conclusion: Primary spinal primitive neuroectodermal tumor is of high malignancy. Little is known due to its quite low incidence. The prognosis is poor due to lacking of effective treatment strategy. Present treatment strategy is referred to other common CNS malignancies like glioma. Further investigation of the disease is necessary.

The incidence of brainstem primitive neuroectodermal tumors of childhood based on SEER data.

PURPOSE: Incidence of BS primitive neuroectodermal tumors (BS-PNET) in children is not reported to date. Our main objectives were to estimate the incidence and report the outcome of BS-PNET in children. METHODS: Data were collected using the Surveillance Epidemiology and End Results cancer registry. RESULTS: From 1973 to 2013, we identified 83 pediatric patients (aged 0-21 years). Patients were divided into two age groups (0-3 years and 4-21 years). Median overall survival was 53 months. Patients in the older age group had a significant survival advantage (P < 0.001), as did those who received three modalities of therapy (surgery, chemotherapy, and radiation therapy) (P < 0.001) and patients with gross or subtotal tumor resection (P < 0.001). CONCLUSIONS: This study presents the first estimate of incidence and the largest cohort of pediatric BS-PNETs to date. A high index of suspicion of BS-PNET in similar cases is crucial for diagnosis, treatment, and outcome.

Birth weight and subsequent risk of childhood primary brain tumors: An updated meta-analysis.

BACKGROUND: Primary brain tumors are common in childhood, but the etiology is largely unclear. As studies on birth weight as a risk factor for the occurrence of histologically specified tumors have been inconclusive, we decided to update a 2008 meta-analysis on the subject. METHODS: A search strategy was performed in Medline and EMBASE for the period 2007-2016. We included six new studies and performed further subgroup analyses for medulloblastoma and primitive neuroectodermal tumors (PNETs). Dichotomous analyses were performed for low (2,500 g) and high birth weight (4,000 g cutoff point). RESULTS: Our results confirmed that high birth weight increases the risk of astrocytoma (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.23-2.09) and medulloblastoma/PNET. However, subgroup analysis revealed an increased risk of medulloblastoma (OR = 1.31, 95% CI: 1.08-1.58) but not of PNET (OR = 1.16, 95% CI: 0.92-1.46). Low birth weight was associated with an increased risk of medulloblastoma/PNET. Subgroup analysis for medulloblastoma and PNET revealed increased risk but CIs included zero. Neither low nor high birth weight was associated with the risk of ependymoma. CONCLUSIONS: While an association between high birth weight and astrocytoma was confirmed, more studies are needed to investigate medulloblastoma and PNET risk in children with high and low birth weight.

[Molecular methods in diagnosis of poorly differentiated malignant brain tumors in children].

The histological diagnosis of malignant brain tumors in children is a complex process. In some cases, glioblastoma, primitive neuroectodermal tumor of the central nervous system, and atypical teratoid/rhabdoid tumor have a histological type similar to that of small blue round cell malignant tumor. Despite the similar histology, biological properties and approaches to treatment, these neoplasms are completely different and require their own treatment protocols. We retrospectively reviewed the most malignant types of childhood tumors and analyzed our own experience to propose a diagnostic algorithm for intracerebral small blue round cell malignant tumors in children based on the use of immunohistochemistry and fluorescence in situ hybridization.

Traffic-related air pollution and the incidence of childhood central nervous system tumors: Texas, 2001-2009.

BACKGROUND: Due to increasing concerns regarding air pollution and childhood cancer, we conducted a population-based study evaluating the association between traffic-related hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter [DPM]) and the incidence of childhood central nervous system (CNS) tumors. PROCEDURE: Information on children diagnosed with a CNS tumor at <15 years of age, in Texas, for the period of 2001-2009 (n = 1,949) was obtained from the Texas Cancer Registry. Information on the corresponding at-risk population was obtained from the United States (U.S.) Census. Annual census tract-level pollutant concentrations, estimated by the U.S. Environmental Protection Agency, were categorized based on quartiles (low, medium, medium-high, and high) of the statewide distribution. Multivariable Poisson regression was used to calculate adjusted incidence rate ratios (aIRR). Juvenile pilocytic astrocytomas (JPAs) (n = 384), other astrocytomas (n = 372), ependymomas (n = 142), medulloblastomas (n = 235), and primitive neuroectodermal tumors (PNET) (n = 47) were evaluated. RESULTS: Census tracts with medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates (aIRR [95% confidence interval (CI)]: 1.46 [1.05-2.01] and 1.69 [1.22-2.33], respectively) compared with low concentrations. Census tracts with medium DPM concentrations had higher astrocytoma (aIRR [95%CI]: 1.42 [1.05-1.94]) and medulloblastoma (aIRR [95%CI]: 1.46 [1.01-2.12]) incidence rates compared with low concentrations. Increased concentrations of 1,3-butadiene and benzene were strongly associated with increased PNET incidence rates, but were not statistically significant. No associations were detected with JPA or ependymoma incidence. CONCLUSIONS: In one of the largest studies of its kind, our results suggest positive associations between hazardous air pollutants and incidence of astrocytoma (1,3-butadiene and DPM) and medulloblastoma (DPM).

[Ewing/PNET sarcoma family of tumors: towards a new paradigm?]. / Tumeurs de la famille Ewing/PNET : vers un nouveau paradigme ?

Ewing sarcoma family of tumors are mainly aggressive sarcomas of bone and also arising in soft tissues, which share common features: morphological features of basophilic round cell tumors, immunohistochemical features by expression of membrane CD99 protein, and genetic features with a translocation involving EWS and FLI1 in approximately 90% of cases. The discovery of this translocation has made it possible to unify in a single entity several lesions such as PNET, neuropitheliomas, Askin tumors, Ewing sarcomas… Since then, the extensive use of molecular/genetic methods has helped to identify an increasing number of molecular anomalies in unclassified round cell sarcomas, these sarcomas often harboring an atypical morphology and a less frequent CD99 positivity. Besides the rearrangements between the FET family of genes (EWS or FUS) and the wide ETS family of genes (FLI1, ERG, FEV, ETV…), new partner genes are gradually identified: cases with EWS-non ETS partners are extremely rare, but there are more important groups which are CIC-DUX4 and BCOR-CCNB3 translocation-positive sarcomas. These findings raise the problem of the nosological borders of the Ewing/PNET entity and its links with new "Ewing-like" groups of tumors, and raise the therapeutic problems. The forward-looking identification of new round cell sarcomas should enable studies of wider series to try to answer these questions.

Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy.

SUMMARY: PT promises to reduce side effects in children with brain tumors by sparing normal tissue compared with 3D conformal or intensity-modulated radiation therapy. Information is lacking about the combined effects of PT and chemotherapy in young children. We describe imaging changes in 8 very young children with localized brain tumors who received PT after chemotherapy. Mostly transient signal abnormalities and enhancement in brain parenchyma were observed by serial MR imaging, which were consistent with radiation-induced effects on normal-appearing tissue. Correlation with PT planning data revealed that the areas of imaging abnormality were located within or adjacent to the volume that received the highest radiation dose. Radiologists should be aware of these findings in children who receive PT after chemotherapy. In this report, we describe the time course of these PT-related imaging findings and correlate them with treatment and clinical outcomes.

The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children.

Medulloblastomas (MB) and primitive neurectodermal tumours (PNET) are known to affect children more than adults. To estimate the magnitude of the differences between the incidence of adults and children, the incidence rates, ratios and time trends of MB and PNET in children and adults are measured using data from the Surveillance, Epidemiology and End-Results (SEER) database. Between 1973 and 2007 in the SEER 9 registries, 1372 people were diagnosed with a MB and 530 with a PNET. The overall incidence rate of MB and PNET is approximately 1.5 and 0.62 per million population in the USA. Children (1-9 years of age) with MB had an incidence rate of 6.0, compared to 0.6 in adults, and therefore children are 10 times more likely to be affected by an MB than adults. Children are 4.6 times as likely to be afflicted by a PNET than adults. The difference in incidence rates based on sex existed only in children. Our study confirmed that the incidence rates of MB has not changed over time.

Overview of primary brain tumors: pathologic classification, epidemiology, molecular biology, and prognostic markers.

Contemporary neuropathology plays a key role in the multidisciplinary management of brain tumor patients, in part due to increased supplementation of histopathological assessments by molecular diagnostic tests involving brain tumor tissue. Several molecular tests have become routine for clinical practice, and not only contribute to a refinement of tumor classification, but also aid in improved prediction of prognosis and in development of a tailored approach to therapy. This review provides an overview of classification and grading of brain tumors, particularly neuroepithelial tumors, and describes genetic/epigenetic changes that have gained clinical significance for molecular diagnostic testing.

Medulloblastoma and primitive neuroectodermal tumors.

Medulloblastomas and sPNETs remain highly problematic tumors to treat. Prognosis has improved over the past two decades, but many children who survive treatment have significant long-term sequelae. The improvements in outcome have been due to advances in surgical techniques, the wider use of chemotherapy, and the more judicious use of radiotherapy. For further improvements,the recent impressive discoveries concerning molecular mechanisms of embryonal tumor origin, development,and growth will need to be translated into molecularly based, risk-adapted therapy.

Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data.

PURPOSE: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. RESULTS: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). CONCLUSION: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone.

Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs).

BACKGROUND: Medulloblastomas are 1 of the most common brain tumors in children but can affect individuals of all ages. For this report, the author investigated the impact of medulloblastomas/primitive neuroectodermal tumors (PNETs) on the US population with a focus on age differences. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were used to describe cumulative relative survival (CRS) using crude, period, and longitudinal period approaches for patients diagnosed with all medulloblastoma subtypes and PNETs. CRS estimates were obtained using SEER expected mortality data and the Ederer II method for expected survival estimation. These data were applied to the construction of rational follow-up scheduling protocols. RESULTS: The 5-year period CRS for all patients who were followed between 2001 and 2006 was 69%. Adults had a worse overall prognosis, but this difference in excess hazard rates appeared only after 4 years of follow-up. Furthermore, the 5-year and 10-year CRS has improved a minimum of 11% in children, adolescents, and adults over the past 25 years. CONCLUSIONS: The survival difference between children, adolescents, and adults with medulloblastomas and PNETs depended on the length of follow-up, which was described in this report as an age-by-follow-up interaction and observed as a "fork" on Kaplan-Meier curves. Differences in survival between children and adults emerged only 4 years after diagnosis, and adults fared worse. There has been significant improvement in survival from medulloblastomas/PNETs since the late 1970s and early 1980s.

Low-grade bone lesions in survivors of childhood medulloblastoma/primitive neuroectodermal tumor.

OBJECTIVES AND RATIONALE: Medulloblastoma/primitive neuroectodermal tumor (MB/PNET) is the most common malignant tumor of the central nervous system (CNS) in children. MB/PNET survivors are at an increased risk for developing second malignancies. Little has been reported on development of low-grade lesions of the calvarium in the radiation field in MB/PNET survivors. The purpose of this study was to assess the frequency of the low-grade bone lesion development in the radiotherapy field in pediatric MB/PNET survivors and describe the imaging characteristics of these lesions. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective review which was compliant with Health Insurance Portability and Accountability Act. Forty-one MB/PNET patients (29 male) who survived for at least 2 years after initiation of radiation therapy were included. The medical records were reviewed. The most recent available brain magnetic resonance imaging studies were evaluated. RESULTS: Three patients (7.3%) developed low-grade calvarial lesions and underwent resection and/or biopsy of the lesions. There were one Langerhans cell histiocytosis, one benign spindle cell lesion with myxoid change, and one fibrous dysplasia. CONCLUSION: Development of low-grade bone lesions of calvarium is not very rare in pediatric PNET/MB survivors. Bones in the radiation therapy field need to be carefully examined for assessment of secondary lesions.

Birth anomalies and obstetric history as risks for childhood tumors of the central nervous system.

OBJECTIVE: The causes of childhood central nervous system (CNS) tumors are largely unknown. Birth characteristics have been examined as possible risk factors for childhood CNS tumors, although the studies have been underpowered and inconclusive. We hypothesized that birth anomalies and a mother's history of previous pregnancy losses, as a proxy for genetic defects, increase the risk for CNS tumors. METHODS: From the California Cancer Registry, we identified 3733 patients aged 0 to 14 years with CNS tumors, diagnosed from 1988 through 2006 and linked to a California birth certificate. Four controls were matched to each patient. We calculated odds ratios (ORs) for the reported presence of a birth defect and for history of pregnancy losses by using logistic regression, adjusted for race, Hispanic ethnicity, maternal age, birth weight, and birth order. RESULTS: Offspring from mothers who had ≥ 2 fetal losses after 20 weeks' gestation had a threefold risk for CNS tumors (OR: 3.13 [95% confidence interval (CI): 1.32-7.41]) and a 14-fold risk for high-grade glioma (OR: 14.28 [95% CI: 1.56-130.65]). Birth defects increased risk for the CNS cancers medulloblastoma (OR: 1.70 [95% CI: 1.12-2.57]), primitive neuroectodermal tumor (OR: 3.64 [95% CI: 1.54-8.56]), and germ cell tumors (OR: 6.40 [95% CI: 2.09-19.56]). CONCLUSIONS: Multiple pregnancy losses after 20 weeks' gestation and birth defects increase the risk of a childhood CNS tumor. Previous pregnancy losses and birth defects may be surrogate markers for gene defects in developmental pathways that lead to CNS tumorigenesis.

Genomic aberrations in pediatric gliomas and embryonal tumors.

The pathogenesis of pediatric central nervous system tumors is poorly understood. To increase knowledge about the genetic mechanisms underlying these tumors, we performed genome-wide screening of 17 pediatric gliomas and embryonal tumors combining G-band karyotyping and array comparative genomic hybridization (aCGH). G-banding revealed abnormal karyotypes in 56% of tumor samples (9 of 16; one failed in culture), whereas aCGH found copy number aberrations in all 13 tumors examined. Pilocytic astrocytomas (n = 3) showed normal karyotypes or nonrecurrent translocations by karyotyping but the well-established recurrent gain of 7q34 and 19p13.3 by aCGH. Our series included one anaplastic oligoastrocytoma, a tumor type not previously characterized genomically in children, and one anaplastic neuroepithelial tumor (probably an oligoastrocytoma); both showed loss of chromosome 14 by G-banding and structural aberrations of 6q and loss of 14q, 17p, and 22q by aCGH. Three of five supratentorial primitive neuroectodermal tumors showed aberrant karyotypes: two were near-diploid with mainly structural changes and one was near-triploid with several trisomies. aCGH confirmed these findings and revealed additional recurrent gains of 1q21-44 and losses of 3p21, 3q26, and 8p23. We describe cytogenetically for the first time a cribriform neuroepithelial tumor, a recently identified variant of atypical teratoid/rhabdoid tumor with a favorable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and 22q by aCGH. This study indicates the existence of distinct cytogenetic patterns in pediatric gliomas and embryonal tumors; however, further studies of these rare tumors using a multimodal approach are required before their true genomic aberration pattern can be finally established.

Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma--a report from the International Pleuropulmonary Blastoma Registry.

BACKGROUND AND AIMS: Ciliary body medulloepithelioma (CBME) is a rare embryonal ocular tumour of children under age 10 years. Pleuropulmonary blastoma (PPB) is a rare embryonal lung tumour in young children and the sentinel disease of the PPB Family Tumour and Dysplasia Syndrome, a distinctive predisposition leading to unusual dysontogenetic-dysplastic and neoplastic conditions in PPB patients and their relatives. Germline mutations of DICER1 gene, a key regulator of gene silencing, underlie this syndrome. CBME occurs with PPB. The authors' aim was to identify CBME cases associated with PPB. METHODS: The authors evaluated International PPB Registry and literature PPB cases for CBME, including review of pathologic specimens. RESULTS: Four CBME were observed among 550-600 PPB cases; three in patients and one in a parent. One CBME was clinically diagnosed; three were confirmed pathologically (one benign teratoid CBME; one benign non-teratoid CBME; one case, details not available). CONCLUSIONS: These observations suggest that CBME is a manifestation of the tumour predisposition associated with PPB. Paediatric oncologists and ophthalmologists should be aware that CBME can occur in PPB patients or their relatives and that CBME may indicate a hereditable tumour predisposition for a child or family.

Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of the spinal cord in children: four cases from the German HIT database with a critical review of the literature.

Approximately 30-50% of patients with intracranial primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT 2000 were retrospectively reviewed to describe clinical features, treatment modalities, and outcome of children with primary CNS-PNETs of the spinal cord who were registered as observational patients. Out of 1,248 patients with medulloblastomas or CNS-PNETs registered in the HIT database four patients (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at diagnosis. Complete and incomplete resection was performed in one patient each, whereas two patients underwent a biopsy only. Two patients received chemotherapy only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They developed disease progression and died six months after diagnosis. One patient was given chemotherapy in accordance with the HIT 2000 trial followed by craniospinal radiotherapy and four courses of maintenance chemotherapy. The patient is in complete remission almost four years after diagnosis. The fourth patient developed disease progression while receiving induction chemotherapy. Hence, chemotherapy was switched to a modified Head Start protocol. After three cycles he underwent double autologous stem cell transplantation and craniospinal irradiation. Forty months after diagnosis the patient is alive and well, but surveillance MRIs still show nodular enhancing lesions in the area of the primary tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal cord probably require multimodal treatment including radiotherapy to achieve sustained tumor control.