ABSTRACT
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite aggressive therapy, patients with metastatic or relapsed disease experience dismal outcomes and novel therapies are urgently needed. In this study, we evaluated expression of disialoganglioside (GD2), a cell surface antigen with therapeutic implication, in 16 RMS patient samples. Scoring revealed GD2 positivity in 25% of the samples. These data suggest that a small subset of RMS tumors express GD2, which may be a therapeutic target in these patients.
Subject(s)
Antigens, Neoplasm/biosynthesis , Gangliosides/biosynthesis , Gene Expression Regulation, Neoplastic , Rhabdomyosarcoma/metabolism , Soft Tissue Neoplasms/metabolism , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Rhabdomyosarcoma/pathology , Rhabdomyosarcoma/therapy , Soft Tissue Neoplasms/therapyABSTRACT
Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities.
Subject(s)
Capillaries/abnormalities , Hemangioma, Capillary/pathology , Kidney Neoplasms/pathology , Kidney/blood supply , Neovascularization, Pathologic , Vascular Malformations/pathology , Adolescent , Age Factors , Antigens, CD34/analysis , Biomarkers/analysis , Biopsy , Capillaries/chemistry , Capillaries/surgery , Child , Child, Preschool , Female , Hemangioma, Capillary/chemistry , Hemangioma, Capillary/genetics , Hemangioma, Capillary/surgery , Humans , Immunohistochemistry , Infant , Infant, Newborn , Kidney Neoplasms/chemistry , Kidney Neoplasms/genetics , Kidney Neoplasms/surgery , Male , Nephrectomy , Vascular Malformations/genetics , Vascular Malformations/metabolism , Vascular Malformations/surgeryABSTRACT
Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined the association of mutations in MYO5B and disruption of microvillar assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2-BBE cells elicited loss of microvilli, alterations in junctional claudins, and disruption of apical and basolateral trafficking; however, no microvillus inclusions were observed in MYO5B-KD cells. Expression of WT MYO5B in MYO5B-KD cells restored microvilli; however, expression of MYO5B-P660L, a MVID-associated mutation found within Navajo populations, did not rescue the MYO5B-KD phenotype but induced formation of microvillus inclusions. Microvilli establishment required interaction between RAB8A and MYO5B, while loss of the interaction between RAB11A and MYO5B induced microvillus inclusions. Using surface biotinylation and dual immunofluorescence staining in MYO5B-KD cells expressing mutant forms of MYO5B, we observed that early microvillus inclusions were positive for the sorting marker SNX18 and derived from apical membrane internalization. In patients with MVID, MYO5B-P660L results in global changes in polarity at the villus tips that could account for deficits in apical absorption, loss of microvilli, aberrant junctions, and losses in transcellular ion transport pathways, likely leading to the MVID clinical phenotype of neonatal secretory diarrhea.
Subject(s)
Malabsorption Syndromes/etiology , Malabsorption Syndromes/metabolism , Microvilli/metabolism , Microvilli/pathology , Mucolipidoses/etiology , Mucolipidoses/metabolism , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Myosin Type V/genetics , Myosin Type V/metabolism , rab GTP-Binding Proteins/metabolism , Caco-2 Cells , Enterocytes/metabolism , Enterocytes/pathology , Gene Knockdown Techniques , Humans , Indians, North American/genetics , Infant , Malabsorption Syndromes/pathology , Mucolipidoses/pathology , Mutation , Myosin Heavy Chains/antagonists & inhibitors , Myosin Type V/antagonists & inhibitors , RNA, Small Interfering/geneticsABSTRACT
Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of bone is a rare childhood tumor most commonly located in the metadiaphysis. In skeletally immature patients, lesions of the epiphysis are rarely malignant, with the most common diagnosis being chondroblastoma. This article presents a case of ES/PNET of the proximal humeral epiphysis in a 12-year-old boy. To the authors' knowledge, this is the first reported case of epiphyseal ES/PNET confirmed with molecular testing. Radiographs of the patient's painful shoulder showed a well-defined lytic lesion within the humeral epiphysis. Magnetic resonance imaging suggested a chondroid tumor with surrounding edema. Based on the imaging characteristics, the patient's age, and the lesion's location, a preliminary diagnosis of chondroblastoma was made. A trochar biopsy of the lesion demonstrated a small, round, blue cell tumor on frozen section. Subsequently, immunohistochemical staining was uniformly positive in a membrane pattern for CD99, and molecular diagnostic testing demonstrated a EWSR1/FLI1 fusion transcript, confirming the pathologic diagnosis of ES/PNET. Although metadiaphyseal locations for ES/PNET are most common, this case adds to previously reported cases of epiphyseal ES/PNET, suggesting that the diagnosis be considered for pediatric epiphyseal tumors. This case also demonstrates why following rigorous oncologic treatment algorithms by obtaining a limited trochar biopsy, even in the case of a confident radiographic diagnosis, is critically important; the biopsy results can lead to a major change in treatment and avoid contamination of a larger area of soft tissue and bone.
Subject(s)
Bone Neoplasms/diagnosis , Epiphyses/pathology , Humeral Head/pathology , Neuroectodermal Tumors, Primitive, Peripheral/diagnosis , Sarcoma, Ewing/diagnosis , Child , Humans , MaleABSTRACT
We report a case of a 2-year old boy with cervicothoracic deformity with vertebral rib anomalies, neurenteric cyst, separate thoracoabominal enteric duplication cyst, concurrent intestinal malrotation, and dextroposition of the heart. This combination of abnormalities is very rare. When these lesions are suspected, the patient must be investigated carefully. This case is presented to show the importance of cross-sectional imaging (MR and CT) for surgical planning.
ABSTRACT
PURPOSE: Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome. PATIENTS AND METHODS: This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750×10(6)/L and a platelet count greater than 75×10(9)/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P=.048). The toxicity of the regimens was similar. CONCLUSION: For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Neoplasms/drug therapy , Sarcoma, Ewing/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Neoplasms/pathology , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Etoposide/administration & dosage , Etoposide/adverse effects , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Infant , Middle Aged , Prospective Studies , Sarcoma, Ewing/pathology , Vincristine/administration & dosage , Vincristine/adverse effects , Young AdultABSTRACT
Ewing sarcoma/peripheral primitive neuroectodermal tumor (EWS/pPNET) and other tumors with EWS gene rearrangements encompass a malignant and intermediate neoplasm with a broad anatomic distribution and a wide age range but a predilection for soft tissue in children, adolescents, and young adults. The overlapping histologic, immunohistochemical and cytogenetic and molecular genetic features create diagnostic challenges despite significant clinical and prognostic differences. Ewing sarcoma is the 3rd most common sarcoma in children and adolescents, and desmoplastic small round cell tumor is a rare neoplasm that occurs more often in older children, adolescents, and young adults. Pathologic examination is complemented by immunohistochemistry, cytogenetics, and molecular genetics. This article reviews the clinicopathologic features of EWS/pPNET and desmoplastic small round cell tumor in the spectrum of tumors with EWS gene rearrangements. Other tumors with different histopathologic features and an EWS gene rearrangement are discussed elsewhere in this volume.
Subject(s)
Desmoplastic Small Round Cell Tumor , Neuroectodermal Tumors, Primitive, Peripheral , Sarcoma, Ewing , Adolescent , Child , Gene Rearrangement , Humans , RNA-Binding Protein EWS/genetics , Young AdultABSTRACT
BACKGROUND: The insulin-like growth factor-1 (IGF-1) signaling pathway plays an important role in the pathology of Ewing sarcoma (ES). Retrospective studies have suggested that levels of IGF-1 and IGF binding protein 3 (IGFBP-3) are correlated with the outcome of patients with ES. METHODS: The IGF-1 signaling pathway was investigated prospectively in 269 patients who had localized, previously untreated ES. Serum samples were obtained at diagnosis, and concentrations of IGF-1 and IGFBP-3 were determined by enzyme-linked immunosorbent assays. In addition, immunohistochemistry (IHC) was performed to assay for phosphorylated p70S6 kinase, protein kinase B (Akt), and forkhead box protein O1 (FOXO1) and to determine the presence of protein tyrosine phosphatase-L1 (PTPL1). IHC findings along with IGF-1 and IGFBP-3 concentrations were correlated with age, tumor location, sex, event-free survival, and overall survival. RESULTS: Patients aged >18 years tended to have higher levels of IGF-1 (P = .10), lower levels of IGFBP-3 (P = .16), and decreased IGFBP-3:IGF-1 ratios (P = .01). No correlations were observed between sex, tumor location, or outcomes and concentrations of IGF-1 or IGFBP-3. Phosphorylation of p70S6 kinase, Akt, and FOXO1 was detected in the majority of patient tissues but was not associated with age, sex, or tumor location. PTPL1 was present in >80% of tumors and also was not correlated with age, sex, or tumor location. There was no difference in survival with respect to the presence of phosphorylated p70S6 kinase, phosphorylated FOXO1, phosphorylated Akt, or PTPL1. CONCLUSIONS: The baseline IGFBP-3:IGF-1 ratio was correlated with age but did not affect the outcomes of patients with ES. The authors concluded that additional investigation of the IGF-1 pathway is warranted in patients with ES, and especially in those who have received treatment with IGF-1 receptor antibody inhibitors.
Subject(s)
Insulin-Like Growth Factor I/metabolism , Sarcoma, Ewing/blood , Adolescent , Adult , Age Factors , Child , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/blood , Male , Sarcoma, Ewing/mortality , Signal TransductionABSTRACT
Astrocytomas are the most common brain tumors of childhood and adolescence. Low-grade astrocytomas (LGAs), in general, have favorable prognosis, but recurrence or progressive disease with dissemination, malignant transformation, and death occur in some cases. Current clinical and pathological measures including age, sex, imaging characteristics, location and size of the tumor, histopathology, and degree of resection cannot predict with certainty which tumors will demonstrate aggressive behavior. The objective of the study is to determine the predictive value of positron emission tomography (PET) and a proliferation index (PI) in identifying high risk LGAs. We reviewed 46 cases ages 5 months to 17 years with low-grade (WHO I-II) astrocytomas. All patients had PET scans utilizing [(18)F] fluorodeoxyglucose (FDG) and 24 cases had measurements with Ki-67/MIB-1 immunohistochemistry. Review of our data confirmed progressive disease (PD) in 18/46 (39%) of cases with 9/21 (42%) occurring after subtotal resection and 9/25 (36%) after gross total resection. The mortality rate was 5/46 (10.8%). Tumors with FDG hypermetabolism were significantly more likely to demonstrate aggressive behavior and PD. Increased PI values also suggested PD. Progression-free survival and time to progression were significantly longer for patients with hypometabolic scans. Time to progression was significantly longer with lower PI values. Results demonstrate that PET and PI are useful measures in the identification and stratification of high risk LGAs. The ability to identify a subset of progressive LGAs earlier may suggest the need for second-look neurosurgical procedures or more intensified adjuvant treatment that may ultimately improve outcome and survival.
Subject(s)
Astrocytoma/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Radiopharmaceuticals , Adolescent , Astrocytoma/metabolism , Brain Neoplasms/metabolism , Cell Proliferation , Child , Child, Preschool , Disease Progression , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Ki-67 Antigen/metabolism , Magnetic Resonance Imaging , Male , Prognosis , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , Survival Rate , Tissue DistributionABSTRACT
BACKGROUND: The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose-intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis. METHODS: We entered 60 patients with metastatic ESFTs of bone onto a single arm trial of a new intensive therapy. Treatment consisted of 51-weeks of chemotherapy and local control of the primary with radiation, surgery, or both. The chemotherapeutic protocol included two alternating blocks: one with vincristine (2 mg/m(2)), doxorubicin (90 mg/m(2)), and cyclophosphamide (2,200 mg/m(2)); and the second with ifosfamide (2,800 mg/m(2)/day x 5 days) and etoposide (100 mg/m(2)/day x 5 days). RESULTS: Of the 60 patients with metastatic ESFTs of bone enrolled onto this single arm trial, 12 had metastasis to lung only, 7 to bone marrow or bone only, 38 to multiple sites, 2 in other sites and 3 not specified. There were three toxic deaths. Six patients (6-year cumulative incidence: 9%) developed second malignant neoplasms and died. The 6-year overall event-free survival (EFS) was 28% (standard error (SE) 6%) and survival (S) was 29% (SE 6%). CONCLUSION: An intensified treatment regimen using higher doses of cyclophosphamide, ifosfamide, and doxorubicin increased toxicity and risk of second malignancy without improving EFS and S.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Neoplasms, Second Primary/chemically induced , Neuroectodermal Tumors, Primitive/therapy , Sarcoma, Ewing/therapy , Adolescent , Adult , Bone Neoplasms/diagnosis , Child , Child, Preschool , Critical Care , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infant , Injections, Subcutaneous , Male , Neoplasm Recurrence, Local/diagnosis , Neoplasms, Second Primary/diagnosis , Neuroectodermal Tumors, Primitive/diagnosis , Neuroectodermal Tumors, Primitive/secondary , Risk Factors , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/secondary , Survival Rate , Treatment OutcomeABSTRACT
This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Neoplasms/drug therapy , Leukemia, Myeloid/chemically induced , Neoplasms, Second Primary/chemically induced , Neural Tube Defects/chemically induced , Neuroectodermal Tumors, Primitive/drug therapy , Sarcoma, Ewing/drug therapy , Acute Disease , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dactinomycin/administration & dosage , Dactinomycin/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Follow-Up Studies , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Incidence , Infant , Leukemia, Myeloid/epidemiology , Male , Neoplasms, Second Primary/epidemiology , Neural Tube Defects/epidemiology , Proportional Hazards Models , Risk , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
PURPOSE: Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy. A randomly assigned proportion of patients received amifostine as a cytoprotective agent. PATIENTS AND METHODS: Eligible patients were < or = 30 years old and had histologically proven Ewing sarcoma or primitive neuroectodermal tumor (PNET) and metastasis at diagnosis. Chemotherapeutic cycles began every 21 days, after recovery from toxicities. RESULTS: One hundred ten of the 117 patients enrolled were eligible. Thirty-six patients received initial topotecan. Three had partial responses (PRs), and 17 had progressive disease (PD). Thirty-seven patients were administered topotecan and cyclophosphamide; 21 of these patients achieved PR, and one patient had PD. In a randomly assigned group of 69 patients, amifostine did not provide myeloprotection, which was measured by absolute neutrophil count, platelet count, or cycle intervals. The best responses to the overall therapy included 45 complete responses, 41 PRs, stable disease in 14 patients, and PD in five patients. For all patients, the 2-year event-free survival (EFS) rate was 24% (+/- 4%), and the overall survival rate was 46% (+/- 5%). For the 39 patients with isolated pulmonary metastases, the 2-year EFS rate was 31% (+/- 7%) compared with 20% (+/- 5%) for patients with more widespread disease. CONCLUSION: Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Amifostine was not myeloprotective. Overall results showed no improvement compared with previous studies.
Subject(s)
Amifostine/therapeutic use , Bone Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Sarcoma, Ewing/drug therapy , Topotecan/therapeutic use , Adolescent , Adult , Amifostine/adverse effects , Bone Neoplasms/mortality , Child , Child, Preschool , Cyclophosphamide/adverse effects , Female , Humans , Male , Sarcoma, Ewing/mortality , Topotecan/administration & dosage , Topotecan/adverse effectsSubject(s)
Bone Neoplasms/classification , Clinical Protocols , Neuroectodermal Tumors, Primitive, Peripheral/classification , Neuroectodermal Tumors, Primitive, Peripheral/pathology , Sarcoma, Ewing/classification , Sarcoma, Ewing/pathology , Soft Tissue Neoplasms/classification , Adult , Child , HumansABSTRACT
PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS: Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. RESULTS: Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Neuroectodermal Tumors, Primitive/drug therapy , Sarcoma, Ewing/drug therapy , Adolescent , Adult , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Child , Child, Preschool , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dactinomycin/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Humans , Ifosfamide/administration & dosage , Neoplasm Metastasis , Neuroectodermal Tumors, Primitive/pathology , Neuroectodermal Tumors, Primitive/therapy , Sarcoma, Ewing/pathology , Sarcoma, Ewing/therapy , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageSubject(s)
Biopsy , Endocardium/pathology , Graft Rejection/diagnosis , Heart Transplantation , Child , Humans , Transplantation, HomologousABSTRACT
OBJECTIVE: To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. METHODS: Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. RESULTS: Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). CONCLUSION: The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.
Subject(s)
Bone Neoplasms/drug therapy , Bone Neoplasms/surgery , Neuroectodermal Tumors, Primitive/drug therapy , Neuroectodermal Tumors, Primitive/surgery , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/surgery , Adult , Bone Neoplasms/mortality , Bone Neoplasms/radiotherapy , Chemotherapy, Adjuvant , Disease-Free Survival , Humans , Neuroectodermal Tumors, Primitive/mortality , Neuroectodermal Tumors, Primitive/radiotherapy , Randomized Controlled Trials as Topic , Ribs , Sarcoma, Ewing/mortality , Sarcoma, Ewing/radiotherapy , Time FactorsABSTRACT
Rhabdoid tumor of the kidney (RTK) has mimicked other renal tumors histologically, but there has been only one previous report of neuroblastoma mimicking RTK. The authors present the case of a 17-month-old boy who presented with a large left renal mass that was diagnosed as RTK. At the completion of therapy he was found to have residual masses. They were biopsied and found to be viable neuroblastoma.
Subject(s)
Kidney Neoplasms/diagnostic imaging , Neuroblastoma/diagnostic imaging , Rhabdoid Tumor/diagnostic imaging , Wilms Tumor/diagnostic imaging , Biopsy , Combined Modality Therapy , Diagnosis, Differential , Humans , Infant , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Male , Neuroblastoma/pathology , Radiography , Rhabdoid Tumor/pathology , Rhabdoid Tumor/therapy , Stem Cell Transplantation , Transplantation, Autologous , Treatment Outcome , Wilms Tumor/pathology , Wilms Tumor/therapySubject(s)
Gastrointestinal Neoplasms/pathology , Neuroectodermal Tumors, Primitive/pathology , Pelvic Neoplasms/pathology , Stromal Cells/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Child , Combined Modality Therapy , Diagnosis, Differential , Female , Gastrointestinal Neoplasms/chemistry , Gastrointestinal Neoplasms/therapy , Humans , Neoplasm Recurrence, Local , Neoplasms, Multiple Primary/chemistry , Neoplasms, Multiple Primary/pathology , Neuroectodermal Tumors, Primitive/chemistry , Neuroectodermal Tumors, Primitive/therapy , Pelvic Neoplasms/chemistry , Pelvic Neoplasms/therapyABSTRACT
BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. METHODS: Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. RESULTS: A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01). CONCLUSIONS: The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.