Somatic-type Malignancies in Testicular Germ Cell Tumors: A Clinicopathologic Study of 63 Cases.

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.

Clinical Features and Long-Term Outcome of Primary Intracranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors: 14 Cases From a Single Institution.

OBJECTIVE: Primary intracranial Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare, and only a few studies have reported >4 cases of this disease. The purpose of this study was to explore the clinical features, treatment, and outcome of primary intracranial ES/pPNETs. METHODS: The clinical data of 14 patients who had been surgically treated from February 2003 to November 2017 and in whom immunohistochemical staining results had confirmed the diagnosis of primary intracranial ES/pPNETs were retrospectively analyzed. Kaplan-Meier survival analysis was used to estimate the survival rate and the median survival time (MST). RESULTS: Gross total resection (GTR) was achieved in 7 cases, and subtotal resection was performed in 7 cases. During follow-up, 10 (71.4%) patients had local recurrence and 3 (21.4%) patients had distant metastasis. The overall 1-, 2-, and 5-year survival rates were 78.6%, 47.6%, and 19.0%, respectively. Kaplan-Meier survival analysis showed that postoperative radiotherapy was a significant prognostic factor for longer MST (P = 0.034). GTR and radiotherapy with or without adjuvant chemotherapy yielded the highest 2-year survival rate (100%). Three patients who underwent GTR, radiotherapy, and chemotherapy had the highest 2-year survival rates (100%) and the longest MST (48 months). CONCLUSIONS: Primary intracranial ES/pPNETs have an aggressive clinical course, with a high tendency for local recurrence and distant metastasis. Radiotherapy plays a significant role in improving the survival of patients. GTR combined with radiotherapy and chemotherapy may be the most beneficial treatment modality.

Multimodal treatment of pediatric patients with Askin's tumors: our experience.

BACKGROUND: We report our experience and outcomes about the management of Askin's tumors [AT], which are rare primitive neuroectodermal tumors (PNETs) that develop within the soft tissue of the thoracopulmonary region, typically in children and adolescents. METHODS: We retrospectively analyzed the charts of 9 patients affected by AT (aged 6-15 years), treated at the Paediatric Oncology Unit of Gemelli University Hospital in Rome between January 2001 and December 2016. RESULTS: All nine patients underwent to biopsy followed by neoadjuvant chemotherapy. At the end of the neoadjuvant chemotherapy, they underwent to surgical removal of the residual tumor. Five patients with positive tumor margins and/or necrosis< 90% received local radiotherapy. Two patients with metastasis received an intensified treatment, with the addition of high dose adjuvant chemotherapy followed by peripheral blood stem cells rescue. No statistically significant correlation was found between outcome and gender; the presence of any metastasis and the radiotherapy. The overall survival was 65.14 months (95% confidence interval [95%CI], 45.81-84.48), and the 5 years survival was 60%, at a median follow-up of 53.1 months. CONCLUSION: Our study confirms that a multimodal treatment with surgery, chemotherapy, and radiotherapy may increase the survival in AT pediatric patients.

[The treatment and prognosis of peripheral primitive neuroectodermal tumor].

Objective: To evaluate the treatment and prognosis of peripheral primitive neuroectodermal tumor (pPNET). Methods: From March 2006 to April 2015, 47 patients with pPNET who had undergone chemotherapy in our hospital were enrolled. The clinical data and survival information of these patients were collected and interpreted retrospectively to analyze the effect of each treatment on the survival of patients. Results: The median overall survival (OS) for whole group was 23.5 months, and 5-year survival rate was 33.8%. In the patients who underwent radical surgery, the median OS was 70.4 months, the 5-year survival rate was 54.4%, the median disease-free survival (DFS) was 23.1months, and 5-year DFS rate was 34.4%. Sixteen patients had recurrences or metastasis after surgery. Eighty-one percent of them (13/16) occurred within 2 years after surgery. The difference of median OS between patients who got adjuvant chemotherapy and those who did not was statistically significant (P=0.04). But the difference of median PFS between these two groups was not statistically significant (P=0.057). There was no statistically significant difference for median OS (P=0.619) and median DFS (P=0.191) between patients who got adjuvant radiotherapy and those who did not. The recurrence rate between these two groups was not statistically significant (P=0.40). The median OS and PFS for 34 patients who received first-line palliative chemotherapy was 10.7 months and 3.2 months. 1-year and 2-year survival rates were 48.0% and 17.8%. The response rate and clinical benefit rate for first-line chemotherapy was 53.1% and 75.0%. The median PFS and OS for patients who received platinum-based regimens were 3.3 months and 14.5 months. The median PFS and OS for patients who got non-platinum regimens were 2.7 months and 10.3 months. There was no significant difference of PFS and OS between platinum-based and non-platinum regimens. Palliative surgery and radiotherapy did not improve the OS of pPNET this cohort. Conclusions: Comprehensive treatment including chemotherapy, radiotherapy and surgery is the standard treatment model for early pPNET patients. Adjuvant chemotherapy significantly improved the overall survival of early pPNET patients. Chemotherapy is the main treatment for patients with advanced pPNET. Platinum-based chemotherapy seem to be a good option.

Muerte súbita por embolismo pulmonar metastásico de un tumor renal no diagnosticado en una niña de 11 años / Sudden death due to a metastatic pulmonary embolism due to an undiagnosed renal tumor in an 11 years old female

El tumor neuroectodérmico primitivo (PNET) es un tumor de células pequeñas, redondas y azules de rara presentación renal. La embolia pulmonar es excepcional en la edad pediátrica, no obstante, su presentación como embolismo masivo tiene como primera causa una neoplasia subyacente. Presentamos un caso de muerte súbita por embolismo pulmonar debido a un tumor no diagnosticado en una niña de 11 años. El estudio autópsico demostró la presencia de un tumor renal, que tras el estudio histopatológico, inmunohistoquímico y citogenético se diagnosticó como PNET (AU)

A primitive neuroectodermal tumor (PNET) is a small, round, blue cell, rare primary tumor in the kidney. Pulmonary embolism in children is uncommon, although an underlying malignancy is the leading cause of massive embolism. We present a case of sudden death due from metastatic pulmonary embolism due to an undiagnosed tumor in an 11-year-old female. The autopsy showed presence of a kidney tumor, which after histopathological, immunohistochemistry, and cytogenetic analyses, was diagnosed as a PNET (AU)

Circulating T-regulatory cells in PNET: a prospective study.

PURPOSE: Bone marrow regulatory T-cells (Tregs) have been evaluated in patients with peripheral neuroectodermal tumor (PNET); data on peripheral blood circulating Tregs are lacking. The objective of our study was to determine baseline Tregs (both Treg frequency and absolute number) in patients with PNET and correlate with patient characteristics, and observe their change with treatment and relapse. METHODS: Five milliliters blood was evaluated in de novo patients with PNET at diagnosis, post-neoadjuvant chemotherapy and at relapse/progression, along with nine healthy controls using flow-cytometric analysis for Treg cells (CD4+ CD25+ FoxP3+). RESULTS: Thirty-seven patients with median age 17 years; male/female ratio 5.1:1 had significantly higher baseline absolute Tregs than controls (mean 338.95 ± 264.63/mm(3) vs. 34.83 ± 24.90/mm(3); P < 0.001). Patients with fever had a significantly higher mean Treg frequency than those without fever (11.27 ± 8.36% vs. 8.40 ± 2.58%; P = 0.014). There was significant reduction in the circulating Tregs after neoadjuvant chemotherapy (mean 339.78 ± 294.31/mm(3) vs. 82.09 ± 91.25/mm(3), P < 0.001) and rise at progression (n = 13) as compared to values post-neoadjuvant chemotherapy (mean 240.92 ± 191.90/mm(3) vs. 57.67 ± 39.01/mm(3), P = 0.012). There was no significant difference in the event-free survival (EFS) or overall survival (OS) between the high and low Treg cell groups (2-year EFS 51.6% vs. 52.1%; P = 0.689 and OS 61.3% vs. 59.2%; P = 0.891). CONCLUSION: This study on circulating Tregs in PNET demonstrated that peripheral blood Tregs are higher in patients than healthy controls. There was significant reduction in Tregs with chemotherapy and rise at progression.

Treatment outcomes in 23 thoracic primitive neuroectodermal tumours: a retrospective study.

OBJECTIVES: Thoracic primitive neuroectodermal tumour is an aggressive malignancy with poor survival despite multimodality treatment regimens. Early diagnosis of the tumour by histological, immunohistochemical, ultrastructural and cytogenetic techniques and early total surgical resection of the tumour with intensive chemoradiation may improve outcomes. METHODS: Over 30 years, 23 patients (median age 29.5) with primitive neuroectodermal tumours (15 chest wall, 4 lung, 3 costovertebral sulcus and 1 anterior mediastinum) were diagnosed by transthoracic needle biopsy (43%) or excisional biopsy (57%). Treatment of a localized disease (Stage I and II) in 19 patients included surgery (wide excision of chest lesions in 11, 4 lung resections, excision of 3 costovertebral sulcus and 1 anterior mediastinal tumours, and resection of adjacent tissues involved by tumour en bloc) with adjuvant chemoradiation. Four metastatic chest wall tumours (Stage III) had chemotherapy and radiation alone. RESULTS: Tumour recurred in 5 (2 chest wall, 2 costovertebral sulcus and 1 lung) requiring further chemotherapy, radiation and completion pneumonectomy for a lung recurrence. The incidence of recurrent tumour in 7 years for Stage I was 21 vs 40% (P=0.4) for Stage II lesions and 16% after the neoadjuvant chemotherapy vs 30% (P=0.4) after adjuvant chemoradiation. Four with recurrence, except one with a chest recurrence, succumbed to second relapse (78-96 months). All four Stage III chest tumours succumbed to advanced disease (30 months). The Kaplan-Meier disease-free survival of the overall group (23 patients) was 82±2% at 5 years and 64±3% at 10 years. The 10-year disease-free survival of 19 patients with localized tumours was 76%, but was high at 90% for chest wall tumours and low 33% for costovertebral sulcus tumours (P≤0.01). The 10-year disease-free survival was 86% for Stage I vs 60% (P=0.02) for Stage II tumours; and 83% for neoadjuvant vs 76% (P=0.06) for adjuvant chemotherapy and radiation. CONCLUSIONS: The primitive neuroectodermal tumours are aggressive neoplasms with poor prognosis. Early diagnosis and total surgical excision of localized tumours with neoadjuvant or adjuvant chemotherapy and radiation improved disease-free survival.

High burden of metastases and poor outcome in pelvic PNET.

Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty-eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5-33); 31 (65%) had metastases. After median follow-up of 20.4 months (range: 1.3-64.9), 3-year EFS, OS, and local-control-rate were 13.5 ± 5.5%, 15.4 ± 9%, and 41.3 ± 14.9%, respectively. Hypoalbuminemia (≤3.4 g/dl) predicted inferior EFS and OS for both entire cohort and metastatic group. All patients with hypoalbuminemia (n = 10) had low BMI as compared to 23/38 without hypoalbuminemia (P = 0.02).

Outcomes after interdisciplinary management of 7 patients with Askin tumor.

PURPOSE: Askin tumors are rare but highly malignant chest wall tumors, which require multimodal therapy including often extensive resection of the thoracic wall. This study evaluated the outcome of Askin tumor in seven patients with an interdisciplinary approach. METHODS: Patients' records, treated between 1994 and 2011, were reviewed retrospectively. Seven patients (three male, four female; mean age 12.3 years; range 2-21 years) were included. All patients received neoadjuvant chemotherapy. After reduction of initial tumor volume, radical tumor resection and thoracic wall reconstruction were performed. All survivors were evaluated in 2011 by clinical examination and lung function test. RESULTS: Five-year survival rate in our group of patients is 86 % and overall survival is 71 %. There were two mortalities. One patient passed away 7.5 years after the primary management, mainly attributed to tumor progression, which demanded aggressive surgical procedures and irradiation. Another patient died 18 months after the first diagnosis after several surgical interventions for recurrent multiple pulmonary metastases. Three years after the first diagnosis, one patient suffered from clear cell sarcoma of the contralateral kidney and developed a local recurrence of Askin 1 year later. The large chest wall defects arising after surgery have been successfully reconstructed using combination of latissimus dorsi muscle flaps and biomaterials. CONCLUSION: Data of pediatric patients with Askin tumor is scarce. Analysis of our seven patient series indicates that improved outcomes (71 % over all survival rate and 86 % 5-year survival rate) can be achieved by aggressive interdisciplinary management including radical surgery and chemotherapy. Chest wall stability can be achieved by utilization of local muscle flaps and biomaterials to cover surgical chest wall defects.

Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.

The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4 patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

Clinical features and outcomes in patients with Ewing sarcoma and regional lymph node involvement.

BACKGROUND: A minority of patients with Ewing sarcoma present with regional lymph node involvement. We investigated if patient characteristics and outcomes differ between patients with Ewing sarcoma with and without regional node involvement. PROCEDURE: Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) reported to the SEER database from 1973 to 2008 were evaluated based on the presence (n = 91) or absence (n = 1,361) of regional node involvement. Patient characteristics were analyzed using Fisher exact tests. Overall survival was estimated by Kaplan-Meier methods and evaluated using log-rank tests and Cox models. RESULTS: Patients with regional node involvement were more likely to have extraskeletal primary tumors (65.9% vs. 31.2%; P < 0.001) and axial tumors (71.1% vs. 59.6%; P = 0.03) compared to patients without regional node involvement. The incidence of regional node involvement was 12.4% for patients with extraskeletal primary tumors compared to 3.2% for patients with skeletal tumors. Five-year overall survival from diagnosis was inferior for patients with regional node involvement compared to those without regional node involvement (45.9% vs. 60.3%; P < 0.001). On multivariate analysis, regional node involvement was predictive of inferior overall survival independent of age, metastatic status, tumor site, and soft tissue origin (hazard ratio 1.59; 95% CI 1.16-2.19). CONCLUSIONS: Patients with extraskeletal Ewing sarcoma should undergo evaluation for regional node involvement. If validated, our findings indicate that regional node involvement may be an independent adverse prognostic factor in Ewing sarcoma, and potentially useful in risk-stratifying patients with otherwise localized disease.

Prognostic factors and outcome in Askin-Rosai tumor: a review of 104 patients.

PURPOSE: To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS: Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS: One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION: Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Surgical treatment of malignant mediastinal neurogenic tumors in children.

INTRODUCTION: The aim of this study was to identify the role of surgical resection in the treatment of malignant mediastinal neurogenic tumors in children. MATERIALS AND METHODS: Thirty-eight consecutive children, who underwent surgical resection of a malignant mediastinal neurogenic tumor between 1986 and 2004, were included in this study. The tumor cell types were neuroblastoma in 23 patients (60.5%), ganglioneuroblastoma in 14 (36.8%), and malignant neuroepithelioma in 1 (2.6%). Surgery was performed for curative resection in localized tumors and salvage resection of residual mediastinal masses after chemotherapy in stage IV tumors. Of the 16 patients (42.1%) who underwent salvage resection, 14 had neuroblastoma and 2 ganglioneuroblastoma. RESULTS: Mean patient age was 3.4+/-3.0 years (1 month-13 years) and 26 patients (68.4%) were symptomatic at presentation. Adjacent structure invasion was found in eight patients (21.1%), invasion of chest wall in four, heart and vena cava in two, lung in one, and chest wall and lung in one. Complete gross resection was possible in 30 patients (78.9%) and there was no surgical mortality. Surgical morbidity occurred in 10 patients (26.3%) and Horner's syndrome was the most frequent complication (n=7). The 5-year survival was 95.2% for a localized tumor and 52.5% for a stage IV tumor (p=0.004). The significant risk factors of long-term survival were adjacent structure invasion (p=0.002) and a stage IV tumor (p=0.002) by multivariate Cox regression analysis. CONCLUSIONS: Surgical resection of localized malignant mediastinal neurogenic tumor in children showed good long-term survival, and salvage operations after chemotherapy showed acceptable long-term survival.

Favorable outcome of Ewing sarcoma family tumors to multiagent intensive preoperative chemotherapy: a single institution experience.

BACKGROUND: Aim of our study was to evaluate the efficacy of multiagent intensive preoperative chemotherapy in patients with Ewing sarcoma family tumors (ESFT), in order to succeed a better percentage of necrosis before surgical resection. PROCEDURE: Eighteen patients with ESFT were treated with the same multiagent intensive preoperative protocol. 5/18 patients had bone Ewings sarcoma (EWS) and 13/18 had peripheral primitive neuroectodermal tumor (PNET). None had metastases at diagnosis. Chemotherapy consisted of 5 or 6 cycles with vincristine, cisplatin, cyclophosphamide, and Adriamycin, followed by 12 cycles of vincristine, cyclophosphamide, and actinomycin-D. Five patients with EWS underwent total resection after 5-6 cycles of preoperative chemotherapy and prosthetic replacement was performed in two of them. In 3/13 patients with PNET the tumor was resected at diagnosis and in 1/13 after 5 cycles of chemotherapy, while 9/13 patients received chemotherapy only and/or radiotherapy. RESULTS: In patients with EWS, the histologic specimens of the resected tumors showed that tissue necrosis was 100% in four patients and 95% in one patient. The good histologic response reflects the effectiveness of this regimen in all ESFT. No patient had topical recurrence or developed metastatic disease during follow-up period (2-13 years, mean time 7.4 years). All patients had the scheduled cycles without delays or dose reductions. There were no major side effects of chemotherapy. CONCLUSIONS: The intensive chemotherapy schedule, comprising of 5-6 cycles preoperatively, seems to maximize the percentage of tumor necrosis, thus improving outcome. Our study implies that this combined therapy may improve the prognosis of ESFT.

Ewing sarcoma: favourable results with combined modality therapy and conservative use of radiotherapy.

BACKGROUND: At the Hospital for Sick Children (HSC), we have treated Ewing sarcoma (ES) with multi-agent chemotherapy, surgery and conservative use of radiotherapy for local control. Our objective was to describe the outcome and prognostic factors associated with this strategy. PROCEDURE: We performed a retrospective chart review of children diagnosed with ES at HSC from Feb 1984 to June 1999. RESULTS: Seventy-two evaluable children were identified. All received chemotherapy. Local control administered was surgery (n = 37), radiation (n = 23), both (n = 10) or neither (n = 2). The 7-year EFS was 66.4%. Recurrence occurred in 23 patients, 7 locally and 16 distantly. Better EFS was associated with male gender (78.5% vs. 52.1%; P = 0.007), localised disease (77.0% vs. 39.4%; P = 0.0004), extremity primary (88.2% vs. 52.8%; P = 0.005) and non-pelvic primary (75.7% vs. 18.2%; P < 0.0001). CONCLUSIONS: Favourable outcomes were seen for patients treated with multi-agent chemotherapy, surgery and conservative use of radiotherapy. Metastatic disease rather than local control was the major cause of failure.

Adult soft tissue Ewing sarcoma or primitive neuroectodermal tumors: predictors of survival?

BACKGROUND: Ewing sarcoma (ES) is the second most common primary osseous malignancy in childhood and adolescence. The improvement in survival is primarily associated with the combination of surgery and chemotherapy. HYPOTHESIS: Little is known about the outcome of adults with soft tissue ES or primitive neuroectodermal tumors (PNET). Certain prognostic factors from soft tissue sarcomas (tumor size, tumor location, margin status, and initial presentation) in adults (>16 years) with ES/PNET will help to identify factors associated with outcome. METHODS: Between July 1, 1982, and June 30, 2000, we identified 59 adult patients with primary soft tissue ES/PNET. Clinicopathologic factors were correlated with the end points studied: patient factors, tumor factors, pathologic factors, status of surgical margins, adjuvant chemotherapy, and radiation therapy. RESULTS: There were 41 male and 18 female patients, with a median age of 27 years (range, 16-72 years). Median tumor size was 8 cm, with all lesions being high grade. The most common site was the trunk (n = 22), with an even distribution of retroperitoneal, pelvis, buttock, and lower extremity (all n = 5). The median follow-up was 29 months (range, 6-222 months), with local recurrence identified in 13 patients (22%), with a median time to recurrence of 15 months (range, 5-200 months). Overall 5-year survival was 60%. Initial presentation was the only predictor of long-term survival, with primary tumor-only presentation having a 5-year survival of 60% (median not reached) compared with primary tumor plus metastatic disease having a 5-year survival of 33% (median, 17 months) (P =.02). CONCLUSION: Initial presentation of disease represents the only predictor of survival identified in this small group of adult patients with ES/PNET.

Prognostic factors and survival in late adolescent and adult patients with small round cell tumors.

The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1-14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 +/- 10.8% at 1 year and 30.5 +/- 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for a better eval-uation of the nonpediatric age group with small round cell tumors.

Comparison of soft tissue Ewing's sarcoma and peripheral neuroectodermal tumor.

Thirty-four cases with either extraskeletal Ewing's sarcoma (21 patients) or malignant peripheral neuroectodermal tumor of the soft tissues (13 patients) were reviewed retrospectively. The patients were treated between 1964 and 1991. Followup periods averaged 7.2 years for patients with peripheral neuroectodermal tumors and 10.4 years for patients with Ewing's sarcoma (minimal followup of 2 years). There were no significant differences in patient's age, gender, tumor location, and stages on presentation between patients with Ewing's sarcoma and those with malignant peripheral neuroectodermal tumor of the soft tissue. All but 2 patients underwent surgery for tumor resection. Adjunctive therapy (radiation or chemotherapy or both) was administered in 95% of the patients with Ewing's sarcoma and in 85% of the patients with peripheral neuroectodermal tumors. The 5-year overall survival was 50% for Ewing's sarcoma and 44% for peripheral neuroectodermal tumor. The 5-year disease free survival was 33% for both types of tumors. Survival rates were higher for Stage III compared with Stage IV disease for both types of tumors. There was a tendency for better outcome after complete surgical tumor resection. Survivors tended to be of a younger age at the time of tumor diagnosis. The results suggest that from a clinical perspective, these 2 tumors are quite similar.