A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

AIM: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. METHODS: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. RESULTS: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. CONCLUSION: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature.

INTRODUCTION: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. METHODS: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. RESULTS: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. DISCUSSION/CONCLUSION: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.

Prolongation of radiotherapy duration is associated with inferior overall survival in patients with pediatric medulloblastoma and central nervous system primitive neuroectodermal tumors.

BACKGROUND: The importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs). METHODS: The National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan-Meier estimator was used to estimate the association between RT duration (≤45 days or >45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS. RESULTS: Six-hundred twenty-five patients met inclusion criteria, of which 181 were assigned to the "RT long" (>45 days) cohort (29.0%) and 444 (71.0%) to the "RT short" group (≤45 days). The five-year OS for the "RT short" compared with "RT long" cohort was 82.2% versus 70.9%, respectively (log-rank, P < 0.0037). For average risk patients, the five-year OS was 84.6% versus 86.4% for "RT short" and "RT long," respectively (log-rank, P = 0.40). However, for high-risk patients, five-year OS was 77.7% versus 51.0% (log-rank, P < 0.0001) in the "RT short" and "RT long" cohorts. CONCLUSION: For patients with high-risk medulloblastoma and CNS PNETs, RT duration >45 days was associated with inferior OS.

Primitive Neuroectodermal Tumor as the Second Malignant Neoplasm in a Long-Term Survivor Child of Acute Lymphoblastic Leukemia: A Case Report.

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

A dedicated cloud system for real-time upfront quality assurance in pediatric radiation therapy.

PURPOSE: Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. METHODS: Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch ), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. RESULTS: All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. CONCLUSION: The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.

Radiosurgery or hypofractionated stereotactic radiotherapy after craniospinal irradiation in children and adults with medulloblastoma and ependymoma.

PURPOSE: To assess the results and tolerance of radiosurgery/hypofractionated stereotactic radiotherapy performed after craniospinal irradiation for recurrent tumor. METHODS: Fourteen patients aged 3-46 years, diagnosed with medulloblastoma (10), anaplastic ependymoma (3), and primitive neuroectodermal tumor (1). All patients had craniospinal irradiation (CSI) with the total dose of 30.6-36 Gy and boost to 53.9-60 Gy either during primary or during second-line treatment. Twelve patients were irradiated with a single dose of 6-15 Gy (median 14.5 Gy). One received three fractions of 5 Gy and one six fractions of 5 Gy. In statistical analysis, the Kaplan-Meier method and log-rank test were used. The overall survival was calculated from the date of the end of stereotactic radiosurgery to the date of death or last contact. RESULTS: Recurrences were diagnosed after the median time of 16 months after the end of primary treatment. Eleven patients died during the follow-up. The follow-up for the 3 patients still alive was 6.7, 40.5, and 41.4 months, respectively. One- and 2-year overall survival (OS) was 70% and 39%. Patients who had ECOG performance status of 0 at the time of diagnosis of the disease trended to have better 2-year OS compared to those evaluated as ECOG 1 (p = 0.057). Treatment results were evaluable in 12 patients. Local control (stabilization or regression of the lesion) was achieved in 9 (75%). Overall disease progression was 67%. No patient developed radiation-induced necrosis. The treatment was well tolerated and no serious adverse effects were observed. Eleven patients were given steroids as a prevention of brain edema and four of them needed continuation of this treatment afterwards. In 7 patients, symptoms of brain edema were observed during the first weeks after reirradiation. CONCLUSIONS: Stereotactic radiosurgery or hypofractionated stereotactic radiotherapy is an effective treatment method of the local recurrence after CSI and can be performed safely in heavily pre-treated patients.

Detection of cavernous malformations after whole-brain radiotherapy in primitive neuroectodermal tumor patients-comparing susceptibility-weighted imaging and T2 gradient-echo sequences.

PURPOSE: The aim of this retrospective study is to investigate the value of the susceptibility-weighted imaging (SWI) sequence compared to gradient echo (GRE) in the detection and follow-up of cavernous malformations in patients who underwent whole-brain irradiation as part of their medulloblastoma treatment. METHODS: We retrospectively examined MRI studies of 28 subjects (16 males, 12 females) who received whole-brain irradiation as part of their treatment. Ages at irradiation ranged from 2 to 38 years. All patients were periodically followed up with MR imaging (ranging from 9 to 336 months). Two neuroradiologists reviewed studies of the same patients, comparing the number of suspected cavernomas detected on GRE and SWI sequences performed at different times (median time between studies, 10 months). RESULTS: Hypointense lesions were detected in 24 subjects on SWI sequences and in 19 subjects on GRE sequences. More lesions were seen on SWI than on GRE (p = 0.006). Four patients had no detectable lesions. The minimal period from irradiation to first lesion detection was 14 months. Cavernomas larger than 3 mm were detected in 14 subjects by both GRE and SWI. None of the subjects had symptoms related to cavernomas. CONCLUSIONS: The sensitivity of SWI in the detection of hypointense lesions in patients after whole-brain irradiation is significantly higher than that of the GRE sequence. It appears that almost all subjects eventually develop small hypointense lesions after radiotherapy, and some of them progress to cavernous malformations. The clinical significance of the increased sensitivity of SWI in this group of patients is not entirely certain.

Is there an increased risk of spinal relapse in standard-risk medulloblastoma/primitive neuroectodermal tumor patients who receive only a reduced dose of craniospinal radiotherapy?

PURPOSE: Medulloblastoma (MBL) is the most common pediatric brain malignancy. Postoperative radiotherapy to the entire craniospinal axis is the standard-of-care but has linked to long-term morbidity. In this study, we analyzed the implication of reduced dose craniospinal radiotherapy (RT) for survival and pattern of relapse in MBL patients. MATERIAL AND METHODS: The clinical characteristics of 32 consecutively diagnosed medulloblastoma/primitive neuroectodermal tumor patients were analyzed. After surgical resection, a dose of 23.4 Gy of spinal RT with a posterior fossa boost of 30.6 Gy was prescribed to standard-risk patients, whereas high-risk patients received 36 Gy spinal RT with additional boosts to the posterior fossa up to 54 Gy. Then, both groups received the same chemotherapy protocol. RESULTS: Five-year OS for standard and high-risk patients was 94 and 50%, respectively. When analyzing prognostic factors, postoperative tumor size is the most important one which affects the OS. Ten patients relapsed during follow-up, and there was no isolated spinal relapse in either group. CONCLUSION: The risk of isolated spinal relapse does not increase with reduced-dose craniospinal RT, since there is no isolated relapse in either the standard or high-risk groups of patients.

Adjuvant chemotherapy for a primitive neuroectodermal tumor of the uterine corpus: A case report and literature review.

A primitive neuroectodermal tumor (PENT) belongs to the category of a Ewing sarcoma. A PENT of the uterus is rare and has been known to be very aggressive by nature. Owing to the rarity of the tumor, there is no optimal treatment at present. In many cases, after hysterectomy, chemotherapy or radiation therapy has been performed. However, an effective chemotherapy regimen was unclear. In the soft tissue sarcoma area, the chemotherapy approach has recently greatly improved. Vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) therapy has improved the survival rate of patients with Ewing sarcoma/PENT. Thus, VDC-IE therapy may be used for a uterine PENT. Here, we report a case of a uterine PENT in a premenopausal woman successfully treated with multimodality treatment including VDC-IE therapy and discuss the optimal chemotherapy for a uterine PENT through a literature review.

A Rare Initial Presentation of Primary Diffuse Leptomeningeal PNET in a 10-Year-Old-Male.

Primary leptomeningeal primitive neuroectodermal tumors (PNETs) are extremely rare childhood central nervous system malignancies harboring a very poor prognosis. There is no consensus treatment for these tumors to date. We report a case of a 10-year-old male who presented with mental status change, hydrocephalus, intracranial and spinal diffuse leptomeningeal enhancement without a primary mass upon cranial imaging and a negative initial biopsy until five months into his presentation. He responded significantly well to initial chemotherapy and radiotherapy.

Gamma Knife Surgery for Recurrent or Residual Supratentorial Primitive Neuroectodermal Tumors.

BACKGROUND: Supratentorial primitive neuroectodermal tumors (PNETs) are highly malignant and rare tumors of the central nervous system. OBJECTIVES: The aim of this study was to determine the role of Gamma Knife surgery (GKS) as a salvage treatment option for patients with recurrent or residual supratentorial PNETs. METHODS: Between 1998 and 2014, 11 patients with supratentorial PNETs were retrospectively analyzed. This series consisted of 7 male and 4 female patients. The median age was 17 years. All patients received surgical resection followed by adjuvant therapy. The median time from operation to the first GKS treatment was 72.5 months. The median tumor volume was 17.5 cm3, and the median marginal dose was 11.5 Gy. RESULTS: 15 (65%) of the 23 tumors had been controlled. The actuarial local tumor control rate was 91% at 3 months, 73% at 6 months, and 44% at 12 months. At the time of analysis, 9 (82%) of the patients had died. The median survival time after the first GKS session was 17 months. The median survival time from the initial diagnosis was 65 months. No adverse radiation effect after GKS treatment occurred in any patient. CONCLUSIONS: GKS treatment might be an effective salvage treatment option for recurrent or residual supratentorial PNETs after multimodal treatment.

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

BACKGROUND: Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. CASE PRESENTATION: In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. CONCLUSIONS: Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

Renal Ewing tumors.

BACKGROUND: Renal Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is extremely rare. Clinical symptoms are nonspecific presenting abdominal pain, palpable mass, and hematuria. Owing to advanced technology demonstrating the ES-specific EWS/ETS translocation, this differential diagnosis has become feasible. PATIENTS AND METHODS: The German database of GPOH Ewing's sarcoma trials from 1980 to 2009 was searched for kidney as primary site. Twenty-four patients were identified and analyzed. The median time of observation was 3.71 years (range 0.27-8.75 years). Additionally, we carried out a Medline search for renal ES/PNET. RESULTS: The median age was 24.9 years (range 11-60 years). In 37.5%, patients presented with primary metastases. Tumor thrombi in the adjacent renal vessels occurred in 56.2%. In 90.9%, rearrangements of t(11;22) were found. All patients received a combined chemotherapy according to the EURO-E.W.I.N.G.99 protocol. In accordance, local control consisted predominantly of combined modality surgery and radiation (47%). At 3 years, overall survival (OS) was 0.80 (SE = 0.09), and event-free survival (EFS) 0.66 (SE = 0.11). CONCLUSIONS: ES/PNET should be considered in the differential diagnosis of renal tumors. Patients with renal ES/PNET respond to and benefit from conventional ES treatment according to ES study protocols. Therefore, an accurate diagnostic approach and a guideline-adapted therapy should be facilitated.

Glutathione S-transferase P1 single nucleotide polymorphism predicts permanent ototoxicity in children with medulloblastoma.

BACKGROUND: Glutathione S-transferase (GST) enzymes are involved in detoxifying chemotherapy and clearing reactive oxygen species formed by radiation. We explored the relationship between the host GSTP1 105 A > G polymorphism (rs1695), tumor GSTpi protein expression, and clinical outcomes in pediatric medulloblastoma. We hypothesized that the GSTP1 105 G-allele and increased tumor GSTpi expression would be associated with lower progression-free survival and fewer adverse events. PROCEDURE: The study included 106 medulloblastoma/primitive neuroectodermal tumor (PNET) patients seen at Texas Children's Cancer Center. Genotyping was performed using an Illumina HumanOmni1-Quad BeadChip and GSTpi expression was assessed using immunohistochemistry. We used the Kaplan-Meier method for survival analyses and logistic regression for toxicity comparisons. RESULTS: Patients with a GSTP1 105 AG/GG genotype (vs. AA) or who had received high dose craniospinal radiation (≥34 Gy vs. <26 Gy) had a greater risk of requiring hearing aids than their counterparts (OR 4.0, 95% CI 1.2-13.6, and OR 3.1, 95% CI 1.1-8.8, respectively, n = 69). Additionally, there was a statistically significant interaction between these variables. Compared with the lowest risk group (GSTP1 105 AA-low dose radiation), patients with a GSTP1 105 AG/GG genotype who received high dose radiation were 8.4 times more likely to require hearing aids (95% CI 1.4-49.9, p-trend = 0.005, n = 69). When adjusted for age, cumulative cisplatin dose, and amifostine use, the association remained. CONCLUSIONS: The GSTP1 105 G-allele is associated with permanent ototoxicity in pediatric medulloblastoma/PNET and strongly interacts with radiation dose. Patients with this allele should be considered for clinical trials employing radiation dose modifications and cytoprotectant strategies.

Review of spinal neuroectodermal tumor.

Primary spinal primitive neuroectodermal tumors (PNETs) are rare tumors. Most of these tumors occur in children and young adults. To date, 47 cases of primary spinal PNET have been reported in the literature. These tumors are highly aggressive with rapid growth. Review of the literature shows that the overall prognosis of PNETs of spinal cord is very poor even with adequate surgery, radiotherapy and chemotherapy. All the cases reported to date are reviewed in terms of surgical treatment, adjuvant therapy and outcome and the experience with two of these cases are described. Both cases were thoracic extradural ones with intrathoracic extension through intervertebral foramina resembling neurofibroma. Both cases underwent gross total removal of intraspinal and thoracic component. Post-operatively both underwent cranio-spinal radiotherapy. One patient died after a post-operative period of 4 months and the other one is still alive 8 months after surgery, radiotherapy and chemotherapy.

[A case of adult primitive neuroectodermal tumor(PNET)with multiple lung metastases effectively treated with ADM, IFM(AI)regimen].

The patient was a 48-year-old male with a right subclavicular tumor. The pathological diagnosis showed primitive neuroectodermal tumor(PNET)because of the rosette formation and the positive neurogenic marker.Radiation was administered at a total dose of 50 Gy, because surgical resection would induce the loss of right arm function. CT examination demonstrated a reduction of the primary tumor and new multiple lung metastases. The patient received intravenous AI regimen(ADM and IFM). After the 7th course, both the primary tumor and multiple lung metastases decreased. AI regimen might be effective for PNET.

A rare radiotherapy-sensitive primitive neuroectodermal tumor with APC gene amplification in an adult: a case report and literature review.

Primitive neuroectodermal tumor (PNET) of the lung is rare in adults, and treatment options vary. We herein describe the disease course and follow-up of PNET in an adult. A 27-year-old man was admitted to our hospital because of cough and headache, and whole-exome sequencing revealed positive expression of the EWSR1-FLI1 fusion gene and amplification of the APC gene. Although the patient received multidisciplinary treatment including chemotherapy regimens of etoposide plus cisplatin; focal radiotherapy focusing on the cerebrum, lung, and kidneys; and a subsequent palliative gastrointestinal operation, he eventually died of multiple organ functional failure. His overall survival period was 18 months, and his progression-free survival period was 4 months. During the treatment, the patient showed remarkable sensitivity to radiotherapy. In conclusion, PNET of the lung in adult patients is extremely rare, and the prognosis is very poor. Involvement of a multidisciplinary team in the development of personalized therapeutic strategies is essential. This patient with APC gene amplification showed excellent sensitivity to radiotherapy for intrapulmonary and intracranial lesions, suggesting that APC gene amplification may be related to radiotherapy sensitivity. However, further clinical research is needed.

Challenging case of a re-irradiation in a dorsal spine primitive neuroectodermal tumor: Role of modern image-guided pencil beam proton therapy.

Extradural primary primitive neuroectodermal tumor (PNET) is a rare aggressive disease mostly occurring in young adults. We present a locally recurrent case of dorsal PNET in the fifth decade of life after a prolonged disease-free interval of 10 years. The patient received radiation therapy in fairly large fields twice in his lifetime and was planned for third-time radiation to a few overlapping paraspinal areas over a period of three decades. Keeping in mind previous irradiations, possible target volume in proximity to organs at risk (OARs) patient was planned for consolidtive radiation using the most conformal technique available, which is proton beam therapy with image guided pencil beam scanning technique. Special dose constraints for the spinal cord and other OARs were set, and proton therapy plan was generated at our institute. When compared with parallelly generated intensity-modulated radiation therapy plan with the same dose prescription and dose constraints using helical tomotherapy, intensity-modulated proton therapy plan showed superior dosimetric benefit in terms of coverage and significant sparing of OARs.

Clinical features and outcomes in patients with extraskeletal Ewing sarcoma.

BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. The purpose of this study was to investigate whether patient characteristics, treatment strategies, and outcomes differ between skeletal Ewing sarcoma and extraskeletal Ewing sarcoma (EES). METHODS: Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor reported to the United States Surveillance, Epidemiology, and End Results Program database from 1973 to 2007 were evaluated based on skeletal (n = 1519) versus extraskeletal (n = 683) site of origin. Patient characteristics were compared using Fisher exact tests. Overall survival was estimated via the Kaplan-Meier method and compared using log-rank tests and Cox proportional hazard models. RESULTS: Patients with EES had a higher mean age (19.5 vs 16.3 years; P < .001) and were less likely to be male (53.4% vs 63.3%; P < .001) or white (84.8% vs 92.5%; P < .001) compared with patients with skeletal tumors. Extraskeletal tumors were more likely to arise in axial locations (72.9% vs 54.2%; P = .001) but were less likely to arise specifically in the pelvis (19.8% vs 26.6%; P < .001). Metastatic status or tumor size did not differ by group. Five-year overall survival was superior for localized EES compared with localized skeletal tumors (69.7% vs 62.6%; P = .02). The hazard ratio for death in patients with localized skeletal tumors compared with localized EES was 2.36 (95% confidence interval, 1.61-3.44) beyond 24 months from initial diagnosis. CONCLUSIONS: Patient characteristics and outcomes differ among patients with EES compared with patients with skeletal Ewing sarcoma. These findings may have important implications for patient care.

Curative treatment for central nervous system medulloepithelioma despite residual disease after resection. Report of two cases treated according to the GPHO Protocol HIT 2000 and review of the literature.

Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis.The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors.