Intensive Therapy With Growth Factor Support for Patients With Ewing Tumor Metastatic at Diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457—A Report From the Children's Oncology Group

Bernstein, Mark L.; Devidas, Meenakshi; Lafreniere, Dominique; Souid, Abdul Kader; Meyers, Paul A.; Gebhardt, Mark C.; Stine, Kimo C.; Nicholas, Richard W.; Perlman, Elizabeth J.; Dubowy, Ronald L.; Wainer, Irving W.; Dickman, Paul S.; Link, Michael P.; Goorin, Allen M.; Grier, Holcombe E.

doi:10.1200/jco.2005.02.1717

Cited by 131 publications

(92 citation statements)

References 17 publications

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“…), whereas all recurrences were fatal by 5 years in nonimmunotherapy recipients (28.6% OS vs. 28.6% PFS at 5 years.). Together, the data demonstrate favorable OS in participants who initiated immunotherapy on this trial compared with outcomes previously been reported in this population, raising the prospect that immunotherapy provided benefit (6)(7)(8)(9)(10)(11)(12)(13)17).…”

Section: Clinical Outcomesmentioning

confidence: 53%

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Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Merchant

Bernstein

Amoako

et al. 2016

Clinical Cancer Research

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Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations AE recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/ rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P ¼ 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. Ó2016 AACR.

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Section: Clinical Outcomesmentioning

confidence: 53%

“…1-3) and rhabdomyosarcoma (RMS; ref. 4,5), but patients presenting with metastatic disease experience dismal survival, despite high response rates (6)(7)(8)(9)(10)(11)(12). Survival also remains poor for patients with recurrent pediatric sarcomas (13,14).…”

Section: Introductionmentioning

confidence: 99%

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Merchant

Bernstein

Amoako

et al. 2016

Clinical Cancer Research

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“…59,62 Non-ifosfamidebased chemotherapy regimens have also demonstrated activity and good tolerability in patients with relapsed or refractory bone sarcomas. Regimens that appear to be active in this patient group include docetaxel and gemcitabine 63 ; topoisomerase I inhibitors (topotecan, irinotecan) with cyclophosphamide and temozolomide [64][65][66][67][68][69][70] ; cyclophosphamide and topotecan 65 ; irinotecan and temozolomide 68 ; and vincristine, irinotecan, and temozolomide. 71 A review of 107 patients with relapsed or refractory Ewing sarcoma examined the combination of etoposide with a platinum agent (ie, cisplatin or carboplatin), suggesting that further study of etoposide/carboplatin may be warranted.…”

Section: Treating Relapsed/refractory Diseasementioning

confidence: 99%

NCCN Guidelines Insights: Bone Cancer, Version 2.2017

Biermann

Chow

Reed

et al. 2017

J Natl Compr Canc Netw

223

187

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“…Primary multifocal Ewing's sarcoma has been associated with an unfavorable prognosis, as evidenced by a 2-year event-free survival of 15% to 31% [3,19,26]. When compared to other patients with advanced Ewing's tumors (ie, those relapsing within 2 years of chemotherapy or suffering multiple relapses), patients with primary multifocal disease treated with contemporary chemotherapy and myeloablative therapy showed a trend toward lower rates of event-free survival at 5 years (0% to 25% versus 24% to 28% for all advanced Ewing's tumors) [5-8, 20, 24, 26].…”

Section: Discussion and Treatmentmentioning

confidence: 99%

“…Overall, the results for myeloablative therapy with melphalan have been equivocal in patients with primary multifocal disease [17,23,24]. Other therapeutic approaches under investigation include growth factor support, interleukin therapy, and immunotherapy with tumor-specific dendritic cells cultured from CD34+ progenitors [1,3,23].…”

Section: Discussion and Treatmentmentioning

confidence: 99%

Chronic Bilateral Thigh and Knee Discomfort in an 18-year-old Man

Templeton

Bauer

Lietman

2008

Clinical Orthopaedics &Amp; Related Research

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An 18-year-old man presented with severe, intermittent bilateral thigh and knee pain of approximately 6 months' duration. His symptoms had initially manifested as localized anterior left knee pain 2 years earlier, and he had been treated with high-dose ibuprofen and physical therapy for the presumptive diagnosis of patellofemoral syndrome. Despite attempts at nonoperative management, he had experienced progressive discomfort involving the left thigh, right knee, and right thigh. At the time of presentation, he described pain principally in the left thigh, characterized as self-remitting and without clear antecedent. He also noted long-standing night pain interfering with sleep but denied any fevers, chills, rigors, weight loss, or other constitutional symptoms. A review of systems was otherwise negative, and medical history was unremarkable.Physical examination revealed mildly shortened stance phase with respect to the left lower extremity; the patient noted his limp had been more pronounced during the preceding month. Pelvic compression and palpation along the spinal column and long bones of the lower extremities elicited no focal tenderness. No visible lesions or palpable masses were observed in the trunk or upper or lower extremities. Active and passive range of motion of the hips and knees were full and well tolerated. The patient was neurologically intact with normal sensation to light touch and full motor strength in all muscle groups.Laboratory studies revealed normal white blood cell count Plain radiographs of the left femur (Fig. 1), computerized tomography (CT) scan of the pelvis and bilateral femora, radionuclide scan (Fig. 2), and magnetic resonance imaging (MRI) of the right acetabulum and bilateral femora (Fig. 3) were obtained.Based on the history, physical examination, and imaging studies, what is the differential diagnosis? Imaging InterpretationRadiographs of the left femur (Fig. 1) revealed an osteolytic lesion extending from the intertrochanteric region to the middiaphysis. The lesion demonstrated mild bony remodeling and cortical thickening most evident in the diaphysis with a well-defined proximal margin.A noncontrast CT scan performed through the pelvis and bilateral femora demonstrated multifocal osteolytic lesions in the left femur, right femur, and superior right Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved or waived approval for the reporting of this case and that all investigations were conducted in conformity with ethical principles of research.

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Intensive Therapy With Growth Factor Support for Patients With Ewing Tumor Metastatic at Diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457—A Report From the Children's Oncology Group

Abstract: 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.

Cited by 131 publications

References 17 publications

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

NCCN Guidelines Insights: Bone Cancer, Version 2.2017

Chronic Bilateral Thigh and Knee Discomfort in an 18-year-old Man

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