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.

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.

Ewing's Sarcoma: An Approach to Radiological Diagnosis

1979 ◽  
Vol 65 (3) ◽  
pp. 389-399 ◽  
Author(s):  
Fabrizio Lombardi ◽  
Marco Gasparini ◽  
Cristina Gianni ◽  
Raffaele Petrillo ◽  
John David Tesoro-Tess ◽  
...  
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Primary Site ◽  
Long Bones ◽  
Age Group ◽  
Pediatric Age Group ◽  
Localized Disease ◽  
The Mean ◽  
Small Bones

All the pertinent radiographs of 83 patients with histologically proven Ewing's sarcoma were reviewed. Forty-nine patients were in the pediatric age group, and 34 were adults. The mean age, the symptoms and time from symptoms to diagnosis were evaluated in the 2 groups. The site of primary involvement was in 54 % the long bones, 35 % the flat bones, 8 % the small bones and 3 % extraosseous. For the primary site we considered the diagnostic results of the standard radiographic investigations and in some cases the usefulness of angiography, xeroradiography and telethermography. At presentation we also evaluated the possible diffusion of the disease with standard radiographic surveys (chest and skeletal, including limbs) and with foot lymphography in selected cases. In this way, 57 patients (69 %) were considered to have localized disease. In this group, we also considered the value of the periodic radiographic follow-up, which enabled us to disclose the appearance of metastases (chest 64 %, bone 54 %, lymph nodes 11 %) in 28 cases (49 %). Finally, we made a comparison of the different radiologic and epidemiologic findings between children and adults.

Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor.

1997 ◽  
Vol 15 (2) ◽  
pp. 583-588 ◽  
Author(s):  
D C West ◽  
H E Grier ◽  
M M Swallow ◽  
G D Demetri ◽  
L Granowetter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Primitive Neuroectodermal Tumor ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Residual Disease ◽  
Neuroectodermal Tumor ◽  
Peripheral Primitive Neuroectodermal Tumor ◽  
Rt Pcr ◽  
Relapsed Disease

PURPOSE To determine the feasibility of detecting Ewing's sarcoma (ES) or peripheral primitive neuroectodermal tumor (PNET) through a reverse-transcriptase polymerase chain reaction (RT-PCR) of the t(11;22)(q24;q12) fusion transcript in blood and bone marrow samples from patients with these neoplasms. PATIENTS AND METHODS Peripheral-blood (PB) and/or bone marrow aspirate (BM) samples were obtained from 28 patients with ES or PNET at initial presentation or at relapse. Patients were divided into two groups: newly diagnosed patients with nonmetastatic disease and those with metastatic/relapsed disease. RNA was extracted from fractionated BM and PB samples, and RT-PCR was performed for the EWS/HumFLI1 fusion mRNA was transcribed across the t(11;22) breakpoint. RESULTS Among the 16 patients with nonmetastatic disease, three of 16 were RT-PCR positive for EWS/HumFLI1 RNA in BM and three of 10 were positive in PB. The total number of nonmetastatic patients who were positive in either PB or BM was four of 16 (25%). Among patients with metastatic/relapsed disease, two of six were positive in BM and five of 10 were positive in PB. The total fraction of patients with metastatic/relapsed disease that was positive in either BM or PB was six of 12 (50%). CONCLUSION In this study, we show that it is possible to amplify the EWS/HumFLI1 RNA by RT-PCR from the BM and PB of a subset of patients with both nonmetastatic and metastatic ES or PNET, which implies that occult tumor cells are present at these sites. The true biologic and clinical meaning of this information is unknown. However, it does suggest a possible application of RT-PCR for the monitoring of residual disease in patients who are undergoing therapy for ES or PNET. This approach may permit early identification of patients who may benefit from alternative therapy or who may be spared possible overtreatment.

scholarly journals An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing’s Sarcoma Cells Using Physical Gas Plasma

2020 ◽  
Vol 21 (12) ◽  
pp. 4460 ◽  
Author(s):  
Josephine M. Jacoby ◽  
Silas Strakeljahn ◽  
Andreas Nitsch ◽  
Sander Bekeschus ◽  
Peter Hinz ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
Bone Sarcoma ◽  
Atmospheric Plasma ◽  
Local Surgery ◽  
Release Assay ◽  
Sarcoma Cells

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.

scholarly journals Pneumocystis jirovecii prophylaxis in patients treated for high-grade gliomas: a survey among neuro-oncologists

2018 ◽  
Vol 6 (4) ◽  
pp. 321-326
Author(s):  
Nebojša Skorupan ◽  
Surabhi Ranjan ◽  
Seema Mehta ◽  
Olga Yankulina ◽  
Nathan Nenortas ◽  
...  
Keyword(s):  
Online Survey ◽  
Practice Patterns ◽  
The United States ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
High Grade ◽  
Cancer Centers ◽  
Medical Oncologists ◽  
High Grade Gliomas ◽  
Cd4 Lymphocyte

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is a known complication in patients with high-grade gliomas (HGGs) who are treated with radiation and chemotherapy. PJP prophylaxis is commonly recommended, but there are currently no clear guidelines regarding duration of treatment and choice of drugs. This study aimed to assess current practice patterns of PJP prophylaxis among neuro-oncologists. Methods An online survey of 14 multiple choice questions was sent to 207 neuro-oncologists and medical oncologists treating brain cancers at all National Cancer Institute-designated cancer centers in the United States. Recipients were identified via a search of the cancer centers’ websites. Results Sixty-one invited experts completed the survey (response rate 29%; of these, 72% were neuro-oncologists, 18% were medical oncologists, and 10% were pediatric neuro- or medical oncologists). Seventy percent of respondents stated that they routinely prescribe PJP prophylaxis, while 7% do not provide prophylaxis. Eighty-one percent of respondents use absolute lymphocyte count (ALC) to assess lymphopenia and 13% also monitor CD4 lymphocyte counts during prophylaxis. The most commonly used first-line agent is trimethoprim-sulfamethoxazole (88% of respondents), followed by pentamidine (6%). Discontinuation of PJP prophylaxis is determined by the following: count recovery (33% by ALC; 18% by CD4 lymphocyte counts), radiation completion (23%), and chemotherapy completion (7%). Glucose-6-phosphate dehydrogenase levels were routinely checked by only 13% of respondents. Conclusions PJP prophylaxis is commonly used in HGG patients, but there are large variations in practice patterns, including the duration of prophylaxis. As consideration for PJP prophylaxis affects all patients with HGG, standardization of prophylaxis should be formally addressed.

scholarly journals Aggressive high-grade Ewing's sarcoma of maxilla: A rare case report

2018 ◽  
Vol 22 (4) ◽  
pp. 48
Author(s):  
Hema Keswani ◽  
TL Yogesh ◽  
Akshay Shetty ◽  
Diljith Rishi
Keyword(s):  
Case Report ◽  
Rare Case ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
High Grade ◽  
Rare Case Report

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.

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