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.

Clinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India.

BACKGROUND: Embryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome. METHODS: Our cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed. RESULTS: Cohort included 15 patients with age range between 1 and 28 years and M:F ratio of 1.5:1. Supratentorial location predominated in comparison to tumors arising in posterior fossa. ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL + ETANTR), MEPL and embryonal tumor, unclassified. All tumors readily expressed LIN 28A and INI-1 was retained. Recurrence with evidence of glial and rhabdoid differentiation was noted in a single patient 9 months following resection. Follow-up period ranged from 1 to 31 months, with overall median survival of 6.4 months. Eight patients were planned for adjuvant treatment following surgery, of which only four could complete it. All patients, except for one, succumbed to the disease. CONCLUSIONS: ETMR have a heterogenous morphology and gathers ETANTR, EBL, MEPL within its spectrum. Following treatment, the recurrent tumor may feature glial/rhabdoid differentiation. LIN28A is expressed in all cases, however should be interpreted in context of histology. Prognosis of ETMR remains dismal despite multimodal therapy.

Embryonal tumors with multilayered rosettes: A tertiary care centre experience.

BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) is an extremely rare and highly aggressive tumor. It includes three distinct entities i.e, embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL). Here, we present our institutional experience of seven ETMR cases treated over a period of five years. MATERIALS AND METHODS: Patients' records from 2015 to 2019 were reviewed manually and electronically to retrieve the data. Clinicopathological and outcome details of ETMR cases were entered in a predesigned proforma. RESULTS: A total of seven cases of ETMR were registered from 2015 to 2019 with a median age at presentation of four years (range 3-7 years). All patients underwent surgery. However, only three patients completed the planned adjuvant treatment, comprising of focal radiotherapy (RT) alone, craniospinal irradiation (CSI) alone and CSI followed by six cycles of chemotherapy in one patient each respectively. Two patients commenced CSI but deteriorated during RT and thereafter needed best supportive care. Two patients could not be started on any adjuvant treatment. Unfortunately, six patients succumbed to their disease within one year of their diagnosis. Only one patient who received both CSI and adjuvant chemotherapy is alive at 15 months of diagnosis. CONCLUSION: ETMR is a rare and aggressive entity. Majority of the patients die within one year of the diagnosis despite multimodality treatment.

Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET.

PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells. EXPERIMENTAL DESIGN: Delta-24-RGD determinants for infection and replication were evaluated in patient expression datasets. Viral replication and cytotoxicity were assessed in vitro in a battery of CNS-PNET and AT/RT cell lines. In vivo, efficacy was determined in different orthotopic mouse models, including early and established tumor models, a disseminated AT/RT lesion model, and immunocompetent humanized mouse models (hCD34+-NSG-SGM3). RESULTS: Delta-24-RGD infected and replicated efficiently in all the cell lines tested. In addition, the virus induced dose-dependent cytotoxicity [IC50 value below 1 plaque-forming unit (PFU)/cell] and the release of immunogenic markers. In vivo, a single intratumoral Delta-24-RGD injection (107 or 108 PFU) significantly increased survival and led to long-term survival in AT/RT and PNET models. Delta-24-RGD hindered the dissemination of AT/RTs and increased survival, leading to 70% of long-term survivors. Of relevance, viral administration to established tumor masses (30 days after engraftment) showed therapeutic benefit. In humanized immunocompetent models, Delta-24-RGD significantly extended the survival of mice bearing AT/RTs or PNETs (ranging from 11 to 27 days) and did not display any toxicity associated with inflammation. Immunophenotyping of Delta-24-RGD-treated tumors revealed increased CD8+ T-cell infiltration. CONCLUSIONS: Delta-24-RGD is a feasible therapeutic option for AT/RTs and CNS-PNETs. This work constitutes the basis for potential translation to the clinical setting.

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.

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.

Post-treatment FDG PET/CT predicts progression-free survival in young patients with small round blue cell tumors: Ewing sarcoma and PNET.

PURPOSE: To determine if post-treatment F-18 FDG PET/CT results (overall positive findings, specific localizations) are independent predictors of disease progression in young patients with Ewing sarcoma and Primitive neuroectodermal tumor. METHOD: A consecutive sample of 48 patients (age 14 ±â€¯5 years, 32 male) was referred to F-18 FDG PET/CT for the suspected progression of Ewing sarcoma (39 patients) and Primitive neuroectodermal tumor (PNET) (9 patients) and followed-up clinically for 4.3 ±â€¯2.3 years after F-18 FDG PET/CT (range 1-8 years). The diagnostic value of F-18 FDG PET/CT was determined in comparison to the biopsy. Kaplan-Meier analysis was used to compare progression-free survival between the groups with positive and negative F-18 FDG PET/CT findings. Variables included in the Cox regression for predicting the progression-free survival were sex, age, F-18 FDG PET/CT findings, MDCT findings, and MR ratio. RESULTS: F-18 FDG PET/CT findings were positive in 32 (67 %) patients (sensitivity 93.7 %, specificity 87.5 %, accuracy 91.7 %) with an average SUVmax of 5.8 ±â€¯3.2 (95 % CI 4.8-7.1). The progression-free survival was significantly lower (p = 0.001) in patients with positive F-18 FDG PET/CT findings (median 28 months) and when recurrence was located in bones, soft tissues, and muscles (p = 0.02, median 21 months). The significant predictors of the disease progression were the overall positive F-18 FDG PET/CT findings (HR 8.36, p = 0.004) and, specifically, the local recurrence in the bone with infiltration of soft tissue/muscles (HR 4.08, p = 0.003). CONCLUSION: Post-treatment F-18 FDG PET/CT findings are useful for predicting the progression of Ewing sarcoma and PNET and should be included in the clinical monitoring of these patients.

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Ovarian primary primitive neuroectodermal tumor: a review of cases at PUMCH and in the published literature.

BACKGROUND: The pathological characteristics, treatment strategies and prognosis of ovarian primary primitive neuroectodermal tumor (PNET) were unclear due to the rarity of PNET. All cases treated at Peking Union Medical College Hospital (PUMCH) between 1975 and 2016 and published in the English literature between 1980 to 2017 were reviewed. RESULTS: Finally four cases from PUMCH and 15 cases in the literature were included. The median age was 25 years (range 13-79), and the median diameter of the tumors was 13.4 cm (range 5.0-30.0). The most common initial symptoms were abdominal pain, bloating and a pelvic mass. Diagnosis primarily depended on immunohistochemical and fluorescence in situ hybridization data. Treatment consisted of surgery, various chemotherapy regimens and/or radiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 15 and 52%, respectively. For patients with OS and PFS > 12 months, the median ages were 21 years (range 13-35) and 17 years (range 13-35), respectively, while for patients with OS < 12 months and PFS < 12 months, the median ages were 48 years (range 14-79) and 25 years (range 18-79), respectively. CONCLUSIONS: No standard therapy for ovarian primary PNET exists, and an individualized strategy is recommended. Young patients seem to have better prognoses.

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.

[Survival and prognostic factors analysis of primitive neuroectodermal tumor].

Objective: To investigate the clinical features and prognosis of primitive neuroectodermal tumor (PNET). Methods: The clinical data of 99 patients with PNET from February 1, 1998 to February 1, 2017 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multiviate Cox regression was applied to analyzed independent prognostic factor for patient survival. Results: Among the 99 patients, 81 were peripheral PNET(pPNET) and 18 were central PNET (cPNET) . Biopsy was performed exclusively in 16 cases, with R0 resection in 61 cases, with R1 resection in 4 cases, and with R2 resection in 18 cases. Twelve patients underwent surgery only, nine had chemotherapy only, and one received radiotherapy only. There were 72 patients who had combined treatment including chemotherapy, and 48 patients had combined therapy including radiotherapy. The one-year, three-year and five-year overall survival(OS) rates of the 99 PNET patients were 79.2%, 63.9% and 56.1% respectively, and median OS time was 14.0 months. The one-year, three-year and five-year progression free survival (PFS) rates of these patients were 42.7%, 25.7% and 19.8% respectively, and median PFS time was 8.0 months. The univariate analysis revealed that lymph node metastasis, surgical resection, numbers of cycles of chemotherapy and radiotherapy dose were the main factors affecting the OS (all P<0.05). Gender, age, lymph node metastasis, staging, and chemotherapy cycles were related to PFS in PNET patients (P<0.05). Multivariate analysis showed that the degree of surgical resection, chemotherapy cycle, and radiotherapy dosage were independent influencing factors of OS in PNET patients (risk ratio=1.856, 0.398, and 0.408, respectively, all P<0.05), and gender was an independent factor influencing PFS in PNET patients (risk ratio=0.494, P<0.05). Conclusions: Comprehensive therapy is the main therapy for PNET patients. The surgical resection, cycles of chemotherapy and radiotherapy dosage are independent prognostic factors for patient's OS.

Dysembryoplastic Neuroectodermal Tumor: An Analysis from the Surveillance, Epidemiology, and End Results Program, 2004-2013.

BACKGROUND: Dysembryoplastic neuroectodermal tumor (DNT) is a rare neoplasm. Though the pathology is commonly considered benign, there have been various reports documenting rapid growth, recurrence/progression, sudden death, and malignant transformation. Most studies have addressed outcomes regarding seizure control, but limited data exist regarding incidence and survival. Consequently, we explore the Surveillance, Epidemiology, and End Results (SEER) database to explore the epidemiology of DNT. METHODS: From the SEER-18 registry database, information from all patients diagnosed with intracranial DNT between 2004 and 2013 was extracted, including age, sex, race, marital status, tumor location, tumor size, receipt of surgery, extent of primary surgery, receipt of radiation, and follow-up data. Age-adjusted incidence rates and overall survival (OS) were calculated. A Cox proportional hazards model was used to assess relationships between various demographic/treatment variables and OS. RESULTS: A total of 381 cases were identified in the SEER-18 database. The incidence of DNT within the large subset of the United States population represented by SEER was 0.033 per 100,000 person-years (95% confidence interval [CI], 0.030-0.037). The median duration of follow-up was 50 months. The median OS was not attained. The 3-, 5-, and 9-year OS was 99.363% (95% CI, 97.428%-99.844%), 97.993% (95% CI, 95.168%-99.174%), and 96.296% (95% CI, 91.834%-98.341%), respectively. Seven of the 381 patients passed at their last follow up. Of all demographic/treatment factors, only receipt of radiation demonstrated a significant relationship with OS (hazard ratio, 0.051; 95% CI, 0.01-0.267; P < 0.01). CONCLUSIONS: Although the prognosis for DNT is generally favorable, the pathology can lead to poor outcomes in rare cases. Common demographic factors, treatment with surgery, and the extent of surgical resection did not show significant associations with OS. In contrast, treatment with radiation was associated with poorer OS.

Outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) - a retrospective analysis spanning 40 years of treatment.

BACKGROUND: Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described. MATERIAL AND METHODS: All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified. RESULTS: We found 175 patients. In 13 of them, the diagnosis was changed upon histopathological review and in 4 patients part of the treatment was administered at other hospitals. Thus, 158 patients were included for further analysis. Eight patients did not receive adjuvant therapy because of a dismal clinical condition. The overall 5-year survival rate for MB and CNS-PNET was 54%, for MB 57%, and for CNS-PNET 41%. Gross total resection (GTR) was achieved in 118 patients and 5-year overall survival for patients with GTR versus those with non-GTR differed significantly with 64% versus 22%. Cytological examination of the cerebrospinal fluid was performed in 52 patients. A total of 126 patients received radiotherapy as part of the primary treatment and 24 did not due to young age. Median time from surgery to start of radiotherapy was 33 days. Duration of radiotherapy was more than 48 days in 22% of patients. At the time of analysis, 63 patients were alive and disease-free, one alive with disease, and 94 patients were deceased; 84 of these due to MB/CNS-PNET and 10 due to supposed late effects from the treatment. CONCLUSIONS: Survival was comparable to data from other population-based studies. The importance of GTR for survival was corroborated. Reporting real-world data remains crucial to know the true outcome of patients treated outside clinical trials.

Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study.

OBJECTIVES: Dose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores. METHODS: Data of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses. RESULTS: Overall, 248 patients were evaluated: median age, 11.2 years (range 1.0-17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2-7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12-17 years), p = 0.002, but not in children (2-11 years). CONCLUSIONS: Performance status of 90-100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.

Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: a report from the Children's Oncology Group.

BACKGROUND: Supratentorial PNETs (sPNET) are uncommon embryonal malignancies of the central nervous system whose prognosis has historically been poor. We evaluated the outcome and prognostic factors of children with sPNET treated prospectively on a Children's Oncology Group trial. PROCEDURE: Following surgery, patients received craniospinal radiotherapy with concurrent carboplatin followed by six months of maintenance chemotherapy with cyclophosphamide and vincristine. RESULTS: Five-year overall survival (OS) and progression-free survival (PFS) for all patients was 58 ± 7% and 48 ± 7%. For patients with pineoblastoma (n = 23), five-year OS and PFS was 81 ± 9% and 62 ± 11%. Extent of resection but not M-stage was prognostic. Five-year OS and PFS for 37 patients with non-pineal tumors (NPsPNET) was 44 ± 8% and 39 ± 8%, significantly worse than for PB (P = 0.055 and 0.009 respectively). Extent of resection and major radiotherapy deviations were prognostic. Five year OS was 59 +/- 11.4% for those undergoing complete resection versus 10.4 +/- 7% for those who did not (P = 0.017). Central pathologic review called 14 (38%) "classic" sPNET, 8 (22%) "undifferentiated" and 13 (35%) "malignant gliomas." There was no significant difference between the subgroups, although survival distributions approached significance when the combined "classic" and "undifferentiated" group was compared to the "malignant gliomas." CONCLUSIONS: Carboplatin during RT followed by 6 months of non-intensive chemotherapy is a feasible treatment strategy for patients with sPNET. Aggressive surgical resection should be attempted if feasible. The classification of supratentorial small cell malignancies can be difficult.

Receiver operating characteristic curve analysis of SEER medulloblastoma and primitive neuroectodermal tumor (PNET) outcome data: identification and optimization of predictive models.

PURPOSE: This study used receiver operating characteristic curves to analyze Surveillance, Epidemiology and End RESULTS (SEER) medulloblastoma (MB) and primitive neuroectodermal tumor (PNET) outcome data. The aim of this study was to identify and optimize predictive outcome models. MATERIALS AND METHODS: Patients diagnosed from 1973 to 2009 were selected for analysis of socio-economic, staging and treatment factors available in the SEER database for MB and PNET. For the risk modeling, each factor was fitted by a generalized linear model to predict the outcome (brain cancer specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A Monte Carlo algorithm was used to estimate the modeling errors. RESULTS: There were 3,702 patients included in this study. The mean follow up time (S.D.) was 73.7 (86.2) months. Some 40% of the patients were female and the mean (S.D.) age was 16.5 (16.6) years. There were more adult MB/PNET patients listed from SEER data than pediatric and young adult patients. Only 12% of patients were staged. The SEER staging has the highest ROC (S.D.) area of 0.55 (0.05) among the factors tested. We simplified the 3-layered risk levels (local, regional, distant) to a simpler non-metastatic (I and II) versus metastatic (III) model. The ROC area (S.D.) of the 2-tiered model was 0.57 (0.04). CONCLUSIONS: ROC analysis optimized the most predictive SEER staging model. The high under staging rate may have prevented patients from selecting definitive radiotherapy after surgery.

Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor.

Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages.

Survival of patients with Ewing's sarcoma in Yazd-Iran.

BACKGROUND: The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. MATERIALS AND METHODS: All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. RESULTS: Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. CONCLUSIONS: Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

A prognostic analysis of pediatrics central nervous system small cell tumors: evaluation of EGFR family gene amplification and overexpression.

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors that occur in children, however there were few big-data follow-up analysis published in China. Overexpression of epidermal growth factor receptor (EGFR) family members was reported on glioblastoma (GBM) and medulloblastoma (MB) before. However, the correlation between EGFR family members expression with prognosis of MB, supratentorial primitive neuroectodermal tumor (PNET) and small cell GBM is unclear in Chinese children. METHODS: A retrospective and survival analysis was performed on children (age ≤ 16 years) diagnosed as CNS primary small cell tumors in the Affiliated Provincial Hospital, Shandong University from 2000 to 2012, including MB (n = 44), PNET (n = 8) and small cell GBM (n = 19). The expression of EGFR, ERBB-2, ERBB-3 and ERBB-4 were detected by immunohistochemistry (IHC). The fluorescence in situ hybridization (FISH) was used to observe the amplification of EGFR and ERBB-2 gene. RESULTS: Median survival times of MBs, small GBMs and PNETs were 23 ± 6.7 months, 8 ± 4.7 months and 10 ± 1.4 months. Expression and amplification of ERBB-2, ERBB-3 and ERBB-4 were not observed in all tumor samples. The multiply Cox regression suggested the overexpression and amplification of EGFR were negative prognostic factors for MB. Radiotherapy had the positive function for all pediatric patients. CONCLUSION: Overexpression of EGFR predicts poor outcomes of MBs, small cell GBMs and PNETs, suggesting those three CNS tumor subtypes can be considered as one group for the potential common mechanism. The current individual treatment and big data analysis of pediatric CNS embryonal tumors and GBM continues to be very challenging in China. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7649640001237474.

Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.

PURPOSE: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. METHODS AND MATERIALS: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). RESULTS: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively). CONCLUSIONS: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.