Ewing Sarcoma: Current Management and Future Approaches Through Collaboration

2015 ◽  
Vol 33 (27) ◽  
pp. 3036-3046 ◽  
Author(s):  
Nathalie Gaspar ◽  
Douglas S. Hawkins ◽  
Uta Dirksen ◽  
Ian J. Lewis ◽  
Stefano Ferrari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
High Dose Chemotherapy ◽  
Therapeutic Strategies ◽  
High Dose ◽  
Dismal Prognosis ◽  
Medical Oncologists ◽  
Localized Disease ◽  
The Many ◽  
Novel Therapeutic Strategies

Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.

scholarly journals Recent advances in targeted therapy for Ewing sarcoma

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2077 ◽  
Author(s):  
Kathleen I. Pishas ◽  
Stephen L. Lessnick
Keyword(s):  
Signal Transduction ◽  
Overall Survival ◽  
Ewing Sarcoma ◽  
Therapeutic Strategies ◽  
Signal Transduction Pathways ◽  
Important Goal ◽  
Genetic Aberration ◽  
Poorly Differentiated ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal.

scholarly journals High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008

2019 ◽  
Vol 37 (34) ◽  
pp. 3192-3202 ◽  
Author(s):  
Uta Dirksen ◽  
Bernadette Brennan ◽  
Marie-Cécile Le Deley ◽  
Nathalie Cozic ◽  
Henk van den Berg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Event Free Survival ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Significant Difference ◽  
Pleural Metastases

PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

scholarly journals Osteosarcoma in Children: Not Only Chemotherapy

2021 ◽  
Vol 14 (9) ◽  
pp. 923
Author(s):  
Maura Argenziano ◽  
Chiara Tortora ◽  
Elvira Pota ◽  
Alessandra Di Paola ◽  
Martina Di Martino ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
High Dose Chemotherapy ◽  
Therapeutic Strategies ◽  
High Rate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Bone Microenvironment ◽  
Dose Methotrexate ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Osteosarcoma (OS) is the most severe bone malignant tumor, responsible for altered osteoid deposition and with a high rate of metastasis. It is characterized by heterogeneity, chemoresistance and its interaction with bone microenvironment. The 5-year survival rate is about 67% for patients with localized OS, while it remains at 20% in case of metastases. The standard therapy for OS patients is represented by neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The most used chemotherapy regimen for children is the combination of high-dose methotrexate, doxorubicin, and cisplatin. Considered that the necessary administration of high-dose chemotherapy is responsible for a lot of acute and chronic side effects, the identification of novel therapeutic strategies to ameliorate OS outcome and the patients’ life expectancy is necessary. In this review we provide an overview on new possible innovative therapeutic strategies in OS.

Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial

2005 ◽  
Vol 23 (3) ◽  
pp. 432-440 ◽  
Author(s):  
Peter Schmid ◽  
Walter Schippinger ◽  
Thorsten Nitsch ◽  
Gerdt Huebner ◽  
Volker Heilmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Dose Chemotherapy ◽  
Primary Objective ◽  
High Dose ◽  
Intent To Treat

Purpose The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. Patients and Methods Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. Results A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. Conclusion This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.

Impact of Consolidation Radiotherapy in Patients With Advanced Breast Cancer Treated With High-Dose Chemotherapy and Autologous Bone Marrow Rescue

1999 ◽  
Vol 17 (3) ◽  
pp. 887-887 ◽  
Author(s):  
Dennis L. Carter ◽  
Lawrence B. Marks ◽  
Joseph M. Bean ◽  
Gloria Broadwater ◽  
Atif Hussein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Advanced Breast Cancer ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Advanced Breast ◽  
High Dose ◽  
Autologous Bone ◽  
The Impact

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994, 425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT−). The assignment of RT was not randomized. The RT+ and RT− groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT− patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT− groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT− groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Autologous Transplant Event-Free Survival (EFS) Following Failure of CHOP-Rituximab (CHOP-R) for Diffuse Large B-Cell Lymphoma (DLBCL) Is the Same as the EFS Following Failure of CHOP Alone.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 890-890 ◽  
Author(s):  
Julie M. Vose ◽  
Philip J. Bierman ◽  
James C. Lynch ◽  
Gregory Bociek ◽  
James O. Armitage
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose

Abstract Several studies have now identified that the addition of rituximab (R) to CHOP chemotherapy has increased the complete response, EFS, and overall survival (OS) for patients with previously untreated DLBCL. However, concerns of increased resistance of DLBCL following failure of CHOP-R and the inability to salvage those patients with high-dose chemotherapy and autologous stem cell transplantation have been raised. In an attempt to address this issue, we evaluated 103 patients with high risk, relapsed, or refractory DLBCL receiving high-dose chemotherapy and autologous stem cell transplantation at our center between 1999 and 2003. Fifty-six (54%) of the patients received CHOP as their initial induction therapy and 47 (46%) received CHOP-R. The patients ranged in age from 20–73 years (median 50). Sixty patients were male and 43 female. Sixty two of the patients were transplanted < 12 months from diagnosis and 41 were transplanted ≥ 12 months from diagnosis. The patients had received a median of 2 prior therapies (range 1–4). The majority (81%) were chemotherapy sensitive at the time of transplantation. The median follow-up of surviving patients is 27 months ( range 3–74). All patients received a BEAM (C) - based regimen [carmustine, etoposide, cytarabine, melphalan or cycylophosphamide] +/− anti-CD20 monoclonal antibodies. There was no difference in the 2-year EFS for patients failing CHOP vs. CHOP-R (60% vs. 68%, p=0.49). In addition, there was no difference in the 2-year overall survival (OS) of patients failing CHOP vs. CHOP-R (72% vs. 68%, p=0.63). In a multivariate analysis, the only factor predicting for an event (relapse or death) post-transplant was having received ≥ 2 prior chemotherapies (Relative Risk (RR) 7.5, p=0.048) and predicting for death from any cause was chemotherapy resistance (RR 2.5, p=0.037) and an increased lactic dehydrogenase at transplant (RR 4.1, p=0.002). The additional use of a monoclonal antibody with the transplant regimen did not significantly impact outcome in this analysis. This study demonstrates that patients with DLBCL failing CHOP-R are able to be salvaged with high-dose chemotherapy and autologous stem cell transplantation and have a similar 2-year EFS and OS as patients being transplanted following CHOP failure.

Role of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Systemic Amyloidosis: A Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2872-2872
Author(s):  
Madhusmita Behera ◽  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy

Abstract Background: Primary systemic amyloidosis (AL) is a rare plasma cell clonal disorder(8/million) characterized by extracellular deposits of material composed mainly of fragments of light chain immunoglobulin throughout a body. Standard chemotherapy (e.g. melphalan and prednisone) is associated with poor outcomes (typical median survival is between 12–18 months with less than 5% survive 10 years). Autologous stem cell transplant (ASCT) has been increasingly advocated for treatment of AL. However, it is uncertain whether ASCT is better than standard chemotherapy. To address this uncertainty, we undertook a systematic review/meta-analysis to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with AL. Methods: Data search of published studies included Medline [all randomized controlled trials (RCTs)], Cochrane library and hand search of references. Studies were included if they were comparison trials of HSCT versus conventional chemotherapy, regardless if they were RCTs, prospective studies with historical control, or single arm studies. The studies were eligible if patients had biopsy proven AL with at least one major organ involved. Data were extracted on benefits as well as harms (overall survival, event-free survival, response, treatment related mortality, treatment-related morbidity). Results: Out of 34 identified studies only 13 met the inclusion criteria for the current systematic review (2 RCTs, 2 prospective non-randomized trials involving historical control, and 9 single arm trials). Altogether these trials enrolled 1056 patients. Pooled data from 4 trials with controls (RCT and non-RCT) found similar overall survival for ASCT and conventional therapy arms [hazard ratio (HR) of 1.10 (95% CI 0.88, 1.36, p=0.4); p= 0.6]. Analysis of data according to trial design also did not find any difference in survival [HR for RCTs was 1.10 (95% CI 0.88, 1.37) and for non RCTs HR was 0.98 (95% CI 0.29, 3.35)]. The complete hematological response was also similar in both arms in RCTs (Odds ratio [OR]=1.38, 95%CI 0.67, 2.85; p=0.4) and non RCTs (OR=1.78, 95%CI 0.22, 14.65; p=0.32). The pooled proportion of treatment-related deaths in the single arm studies for AHCT was 0.119 (95% CI = 0.09 to 0.14)]. Conclusion: The results from the meta-analysis indicate that there is no statistically significant difference between the treatment effects from high-dose chemotherapy with ASCT and conventional chemotherapy. Hence, the efficacy of ASCT in improving overall survival and complete hematological response remains to be proven.

Multiple Myeloma Profile In Latin America: Clinical and Epidemiological Observational Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5327-5327
Author(s):  
Vania T M Hungria ◽  
Angelo Maiolino ◽  
Gracia Aparecida Martinez ◽  
Carmino A De Souza ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Clinical Features ◽  
Median Overall Survival ◽  
High Dose Chemotherapy ◽  
Patterns Of Care ◽  
Disease Stage ◽  
High Dose

Abstract Introduction Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries. Objective To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America. Patients and Methods This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012). Results Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p<0.001). The multivariate prognostic model included patient baseline variables that were associated with mortality in the Kaplan-Meier univariate analyses. Only hypercalcemia, DSS II and III, ISS stage III andnon- high-dose chemotherapy were independent predictors of mortality. Conclusion This current study, which is the largest case series of MM patients in Latin America, recognizes the feasibility of large, collaborative, observational studies among various tertiary-care hematology centers in Latin America. Note We will present more details related to the demographic and most frequently used treatments in Latin America for newly diagnosed and relapsed patients in these LA countries. Disclosures: No relevant conflicts of interest to declare.

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