scholarly journals BONE SARCOMAS IN CHILDREN: CLINICAL FEATURES

2018 ◽  
Vol 63 (4) ◽  
pp. 119-124
Author(s):  
M. Yu. Rykov ◽  
D. D. Sevryukov ◽  
E. R. Senzhapova ◽  
V. V. Hajrullova
Keyword(s):  
Solid Tumors ◽  
Clinical Features ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Clinical Observations ◽  
Bone Sarcomas

Solid tumors in children occupy the second place in the structure of morbidity, yielding to hemoblastosis. Among solid tumors, approximately 5% are bone sarcomas: osteosarcoma (3%) and Ewing’s sarcoma (2%). Atypicality of  the course of  these diseases makes it difficult to diagnose them early. The article describes a series of clinical observations of patients with bone sarcomas, which illustrate the complexity of diagnosing diseases of this group.

Experimental Therapies and Clinical Trials in Bone Sarcoma

2010 ◽  
Vol 8 (6) ◽  
pp. 715-725 ◽  
Author(s):  
Rashmi Chugh
Keyword(s):  
Clinical Trials ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Bone Sarcoma ◽  
Pediatric Malignancies ◽  
Experimental Therapies ◽  
Bone Sarcomas ◽  
Made In

Sarcomas originating in the bone represent a challenge for physicians and patients. Because they constitute only 0.2% of all adult malignancies and 6% of pediatric malignancies, resources for studying this disease are often limited.1,2 Nonetheless, significant advancements have been made in the treatment of this disease, and there are ongoing efforts toward improvement. This article discusses recently completed and currently enrolling clinical trials for the 3 most common bone sarcomas: osteosarcoma, Ewing's sarcoma family tumors, and chondrosarcoma.

Chemotherapy in the Management of Osteosarcoma and Ewing's Sarcoma

2007 ◽  
Vol 5 (4) ◽  
pp. 449-455 ◽  
Author(s):  
Scott M. Schuetze
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Disease Patient ◽  
Bone Sarcoma ◽  
The United States ◽  
High Grade ◽  
Medical Oncologists ◽  
Bone Sarcomas ◽  
Localized Disease ◽  
Relapsed Disease

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.

scholarly journals A DNA methylation-based classifier for accurate molecular diagnosis of bone sarcomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11034-11034
Author(s):  
Shengyang Wu ◽  
Benjamin Thomas Cooper ◽  
Fang Bu ◽  
Christopher Bowman ◽  
Keith Killian ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synovial Sarcoma ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Clinical Sample ◽  
Methylation Status ◽  
Accurate Diagnosis ◽  
Cpg Sites ◽  
Bone Sarcomas ◽  
Methylation Profiling

11034 Background: Bone sarcomas present a unique diagnostic challenge because of the considerable morphologic overlap between different entities. The choice of optimal treatment, however, is dependent upon accurate diagnosis. Genome-wide DNA methylation profiling has emerged as a new approach to aid in the diagnosis of brain tumors, with diagnostic accuracy exceeding standard histopathology. In this work we developed and validated a methylation based classifier to differentiate between osteosarcoma, Ewing’s sarcoma, and synovial sarcoma. Methods: DNA methylation status of 482,421 CpG sites in 15 osteosarcoma, 10 Ewing’s sarcoma, and 11 synovial sarcoma samples were measured using the Illumina HumanMethylation450 array. From this training set of 36 samples we developed a random forest classifier using the 400 most differentially methylated CpG sites (FDR q value < 0.001). This classifier was then validated on 10 synovial sarcoma samples from TCGA, 86 osteosarcoma samples from TARGET-OS, and 15 Ewing’s sarcoma from a recently published series (Huertas-Martinez et al., Cancer Letters 2016). Results: Methylation profiling revealed three distinct molecular clusters, each enriched with a single sarcoma subtype. Within the validation cohorts, all samples from TCGA were correctly classified as synovial sarcoma (10/10, sensitivity and specificity 100%). All but one sample from TARGET-OS were classified as osteosarcoma (85/86, sensitivity 98%, specificity 100%) and all but one sample from the Ewing’s sarcoma series was classified as Ewing’s sarcoma (14/15, sensitivity 93%, specificity 100%). The single misclassified osteosarcoma sample was classified as Ewing’s sarcoma, and was later determined to be a misdiagnosed Ewing’s sarcoma based on RNA-Seq demonstrating high EWRS1 and ETV1 expression. An additional clinical sample that was misdiagnosed as a synovial sarcoma by initial histolopathology, was accurately recognized as osteosarcoma by the methylation classifier. Conclusions: Osteosarcoma, Ewing’s sarcoma and synovial sarcoma have distinct epigenetic profiles. Our validated methylation-based classifier can be used to provide an accurate diagnosis when histological and standard techniques are inconclusive.

Survival and signals of response in advanced sarcoma patients enrolled on phase 1 trials in the era of precision oncology and novel immunotherapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11063-11063
Author(s):  
Shiraj Sen ◽  
Kenneth R. Hess ◽  
David S. Hong ◽  
Gerald Steven Falchook ◽  
Roberto Pestana ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Phase 1 ◽  
Phase 1 Trials ◽  
Best Response ◽  
Bone Sarcomas ◽  
Us Fda ◽  
Advanced Sarcoma

11063 Background: Few effective US FDA approved therapies exist for refractory, metastatic sarcomas. Many of these patients therefore enroll onto phase 1 clinical trials. Because tumor-specific outcomes are not always reported in less common cancers such as sarcomas, outcomes of sarcoma patients treated with novel immunotherapy and targeted therapy approaches remains unknown. Methods: We analyzed clinical and next generation sequencing data from all sarcoma patients treated on phase 1 trials at MD Anderson Cancer Center (MDACC) and performed logistic and Cox proportional hazards regression analyses to evaluate response rate (RR), median time to progression (mTTP), clinical benefit rate (CBR; defined as CR, PR, or SD > 6 months), and median overall survival (OS). Results: Among the 406 patients with advanced sarcomas (321 soft tissue sarcoma, 85 bone sarcomas) treated on phase 1 trials at MDACC from May 2006 to May 2018, median age was 53 (range 11-84), 48% were female, with a median 3 prior lines of therapy (range 0-9). The most commonly treated soft tissue sarcoma subtypes included leiomyosarcoma (n = 66; 16%), liposarcoma (n = 52; 13%), GIST (n = 44; 11%), UPS (n = 14; 3%), and synovial sarcoma (n = 11; 3%) and most commonly treated bone sarcomas included osteosarcoma (n = 34; 8%), chondrosarcoma (n = 28; 7%), and Ewing’s sarcoma (n = 25; 6%). RR was 7% (95% CI 5, 10), mTTP was 2.9 months (95%CI 2.6, 3.1), CBR was 24% (95% CI 20, 29), mOS was 17.2 months (95% CI 13.8, 20.8). 2 patients had a CR as best response, 1 chondrosarcoma patient treated with an anti-APO2L/Trail agent and 1 Ewing’s sarcoma patient treated with the combination of an IGF1R inhibitor plus mTOR inhibitor. 26 patients (6%) had a PR as best response using novel immunotherapies targeting PD1, PDL1 plus CCR4, CTLA4 plus KIT, and TLR7/8 and novel targeted therapies against TRK, LRRC15, cMET, mTOR, VEGF, MDM2, KIT/PDGFRA, and FGFR. Responses were seen across sarcoma subtypes - ASPS, UPS, myxoid sarcoma, liposarcoma, GIST, carcinosarcoma, clear cell sarcoma, embryonal rhabdomyosarcoma, epitheliod sarcoma, fibrious histiosarcoma, and Ewing’s sarcoma. Conclusions: Our analysis identifies a reasonable survival in heavily pretreated, metastatic refractory sarcoma patients with responses seen with novel targeted therapies and immunotherapies that are not yet US-FDA approved. Biomarker analysis is ongoing to help identify the subset of responders in our cohort. Advanced sarcoma patients should be considered for molecular profiling and early phase clinical trials.

scholarly journals Comparison of MRI and Histopathology with regard to Intramedullary Extent of Disease in Bone Sarcomas

Sarcoma ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Ashish Gulia ◽  
Ajay Puri ◽  
T. S. Subi ◽  
Srinath M. Gupta ◽  
S. L. Juvekar ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Correlation Analysis ◽  
Limb Salvage ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Salvage Surgery ◽  
Limb Salvage Surgery ◽  
Bone Sarcomas ◽  
The Mean ◽  
Extent Of Disease

In today’s era, limb salvage surgery is the procedure of choice and current standard of care in appropriately selected patients of bone sarcomas. For adequate oncologic clearance, preoperative evaluation of the extent of tumor is mandatory. The present study was done to compare measurements of bone sarcomas (osteosarcoma, Ewing’s sarcoma, and chondrosarcoma) as determined by magnetic resonance imaging (MRI) with the histopathological extent seen on resected specimens. We prospectively evaluated 100 consecutive patients with a diagnosis of bone sarcoma who underwent limb salvage surgery between May 2014 and December 2014. The maximum longitudinal (cranio-caudal) dimension of tumor on the noncontrast T1-WI sequence of MRI (irrespective of whether it was pre/postchemotherapy) was compared with the gross dimensions of the tumor on histopathology. The arithmetic mean difference, Wilcoxon signed-rank test, and Spearman’s correlation analysis were used to test the differences and correlation between groups. Mean tumor size on MRI based on the largest extent on MRI was 12.1 ± 4.85 cm (mean ± standard deviation), while it was 10.77 ± 4.6 cm (mean ± standard deviation) on histopathology. In 79 cases, MRI overestimated the extent of disease; the mean was 1.79 cm with a standard deviation of 1.56 cm. When the disease extent was underestimated on MRI (13 cases), the mean was 0.58 cm with a standard deviation of 0.43 cm. In 8 cases (osteosarcoma (7), Ewing’s sarcoma (1)), MRI measurement was equal to histopathology. The Spearman correlation analysis showed a high correlation of tumor length on histopathology with the MRI for all patients (R = 0.948, P<0.0001). We thus conclude that MRI is accurate in delineating the extent of bone sarcomas. A margin of 2 cm from the maximum tumor extent is adequate to ensure appropriate surgical resection.

scholarly journals Primary Ewing’s Sarcoma of the Spine in a Two-Year-Old Boy

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ali J. Electricwala ◽  
Jaffer T. Electricwala
Keyword(s):  
Spinal Canal ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Cauda Equina ◽  
Bone Tumour ◽  
Tracer Uptake ◽  
Tumour Mass ◽  
Gene Testing ◽  
Bone Sarcomas ◽  
Good Improvement

Ewing’s Sarcoma (ES) is a highly malignant bone tumour. It may involve any part of the skeleton but the most frequent parts are the ilium and diaphysis of femur and tibia (Alfeeli et al., 2005; Zhu et al., 2012). Primary ES of the spine is extremely rare (Yan et al., 2011). It accounts for only 3.5 to 14.9 percent of all primary bone sarcomas. The age of presentation ranges from 12 to 24 years (median 21 years) (Ferguson, 1999; Sharafuddin et al., 1992; Klimo Jr. et al., 2009). We report an unusual case of primary ES of the spine in a two-year-old boy, who presented to us with paraparesis and features of cauda equina syndrome. MRI scan showed a tumour mass arising from the pedicle of L4 vertebra invading the spinal canal. Tc-99 bone scan showed increased tracer uptake in L4 vertebra and normal tracer uptake elsewhere in the skeleton. After reaching the diagnosis of a space occupying lesion invading the lumber spinal canal, we performed a decompressive laminectomy and a biopsy was sent which confirmed the diagnosis of ES. Immunohistochemistry showed tumour cells staining positive for CD-99 (specific stain for ES). Gene testing showed an EWS-FLI 1 chimera. Surgery was followed by good improvement in motor signs. The child was then referred to a specialized oncotherapy centre for further treatment, radiation, and chemotherapy. To the best of our knowledge, we are the first to report primary ES of the spine at the age of two years.

scholarly journals Impact of ABC Transporters in Osteosarcoma and Ewing’s Sarcoma: Which Are Involved in Chemoresistance and Which Are Not?

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2461
Author(s):  
Massimo Serra ◽  
Claudia Maria Hattinger ◽  
Michela Pasello ◽  
Chiara Casotti ◽  
Leonardo Fantoni ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Chemotherapeutic Drugs ◽  
Future Perspectives ◽  
First Line ◽  
Physiological Conditions ◽  
The Past ◽  
Biological Impacts ◽  
Bone Sarcomas

The ATP-binding cassette (ABC) transporter superfamily consists of several proteins with a wide repertoire of functions. Under physiological conditions, ABC transporters are involved in cellular trafficking of hormones, lipids, ions, xenobiotics, and several other molecules, including a broad spectrum of chemical substrates and chemotherapeutic drugs. In cancers, ABC transporters have been intensely studied over the past decades, mostly for their involvement in the multidrug resistance (MDR) phenotype. This review provides an overview of ABC transporters, both related and unrelated to MDR, which have been studied in osteosarcoma and Ewing’s sarcoma. Since different backbone drugs used in first-line or rescue chemotherapy for these two rare bone sarcomas are substrates of ABC transporters, this review particularly focused on studies that have provided findings that have been either translated to clinical practice or have indicated new candidate therapeutic targets; however, findings obtained from ABC transporters that were not directly involved in drug resistance were also discussed, in order to provide a more complete overview of the biological impacts of these molecules in osteosarcoma and Ewing’s sarcoma. Finally, therapeutic strategies and agents aimed to circumvent ABC-mediated chemoresistance were discussed to provide future perspectives about possible treatment improvements of these neoplasms.

Cyclophosphamide Plus Topotecan in Children With Recurrent or Refractory Solid Tumors: A Pediatric Oncology Group Phase II Study

2001 ◽  
Vol 19 (15) ◽  
pp. 3463-3469 ◽  
Author(s):  
Robert L. Saylors ◽  
Kimo C. Stine ◽  
Jim Sullivan ◽  
James L. Kepner ◽  
Donna A. Wall ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Stable Disease ◽  
Pediatric Patients ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Complete Response ◽  
Median Number ◽  
Pediatric Oncology Group ◽  
Hematopoietic Toxicity ◽  
Grade 3

PURPOSE: To determine the response rate of the combination of cyclophosphamide and topotecan in pediatric patients with recurrent or refractory malignant solid tumors. PATIENTS AND METHODS: A total of 91 pediatric patients, 83 of whom were fully assessable for response and toxicity, received cyclophosphamide (250 mg/m2/dose) followed by topotecan (0.75 mg/m2/dose), each given as a 30-minute infusion daily for 5 days. All patients received filgrastim (5 mcg/kg) daily until the absolute neutrophil count (ANC) was ≥ 1,500 μL after the time of the expected ANC nadir. RESULTS: A total of 307 treatment courses were given to the 83 fully assessable patients. Responses (complete response plus partial response) were seen in rhabdomyosarcoma (10 of 15 patients), Ewing’s sarcoma (six of 17 patients), and neuroblastoma (six of 13 patients). Partial responses were seen in two of 18 patients with osteosarcoma and in one patient with a Sertoli-Leydig cell tumor. Twenty-three patients had either minor responses (n = 6) or stable disease (n = 17); the median number of courses administered to patients with partial or complete response was six (range, two to 13 courses), and the median administered to those with stable disease was three (range, one to 11 courses). The toxicity of the combination was limited principally to the hematopoietic system. Of 307 courses, 163 (53%) were associated with grade 3 or 4 neutropenia, 84 (27%) with grade 3 or 4 anemia, and 136 (44%) with grade 3 or 4 thrombocytopenia. Despite the severe myelosuppression, only 34 (11%) of 307 courses were associated with grade 3 or 4 infection. Nonhematopoietic toxicity of grades ≥ 3 was rare and consisted of nausea and vomiting (two courses), perirectal mucositis (one course), transaminase elevation (one course), and hematuria (two courses). CONCLUSION: The combination of cyclophosphamide and topotecan is active in rhabdomyosarcoma, neuroblastoma, and Ewing’s sarcoma. Stabilization of disease was seen in osteosarcoma, although objective responses were rare in this disease. The therapy can be given with acceptable hematopoietic toxicity with the use of filgrastim support.

scholarly journals Vascularized Fibula Grafts for Reconstruction of Bone Defects after Resection of Bone Sarcomas

Sarcoma ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Michael Mørk Petersen ◽  
Dorrit Hovgaard ◽  
Jens Jørgen Elberg ◽  
Catherine Rechnitzer ◽  
Søren Daugaard ◽  
...  
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Hip Dislocation ◽  
Clinical Results ◽  
Bone Defects ◽  
Femoral Diaphysis ◽  
Vascularized Fibula ◽  
Multiple Metastases ◽  
Bone Sarcomas ◽  
Reconstruction Of Bone Defects

We evaluated the results of limb-sparing surgery and reconstruction of bone defects with vascularized fibula grafts in 8 consecutive patients (mean age at operation 13.6 years (range 4.1–24.2 years), female/male = 6/2) with bone sarcomas (BS) (osteosarcoma/Ewing's sarcoma/chondrosarcoma= 4/3/1) operated on form 2000 to 2006. The bone defects reconstructed were proximal femoral diaphysis and epiphysis (n=2), humeral diaphysis (n=2), humeral proximal diaphysis and epiphysis (n=1), femoral diaphysis (n=1), ulnar diaphysis (n=1), and tibial diaphysis (n=1). One patient with Ewing's sarcoma had an early hip disarticulation, developed multiple metastases, and died 9 months after the operation. The remaining patients (n=7) are all alive 50 months (range 26–75 months) after surgery. During the follow-up the following major complications were seen: 1-2 fractures (n=4), pseudarthrosis (n=2), and hip dislocation (n=1). Limb-sparing surgery with reconstruction of bone defects using vascularized fibular grafts in BS cases is feasible with acceptable clinical results, but fractures should be expected in many patients.

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