Resection of pulmonary metastases in pediatric patients with Ewing sarcoma improves survival

Background: Interval compression (IC), defined as 2 week-long cycles of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide, improves survival for localized Ewing sarcoma. The outcomes of patients with metastatic disease treated with IC are uncertain. Methods: We retrospectively reviewed the charts of pediatric patients with metastatic Ewing sarcoma treated with IC at our center between January-2013 and March-2020. We calculated event-free survival and overall survival and used log rank tests for univariate comparisons. Results: We identified 34 patients aged 2.7–17.1 years (median,11.6 years). Twenty-six patients (76%) had pulmonary metastases, and 14 (41%) had extra-pulmonary metastases in the bone (n = 11), lymph nodes (n = 2), and intraspinal tissue (n = 1). All patients received local control therapy: surgery only (n = 7, 21%), radiotherapy only (n = 18, 53%), or both (n = 9, 26%). The estimated 3-year OS and EFS were 62%±9% and 39%±9%, respectively. Patients with pulmonary only metastasis had a 3-year OS of 88%±8% in comparison to those with extra-pulmonary metastasis of 27%±13% (P=0.0074). Survival did not differ according to age group (> vs < 12 years), metastasis site, or primary tumor site, but 3-year event-free survival significantly differed according to local control therapy (surgery only, 83% ± 15%; combined surgery and radiation, 30% ± 18%; radiation only, 15% ± 10%; P = .048). Conclusion: IC yielded similar outcomes for patients with metastatic Ewing sarcoma to that reported in the literature using other regimens. We suggest including this approach to other blocks of therapy

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Faculty Opinions recommendation of Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733242040.793558290 ◽

2019 ◽

Author(s):

Stephen Lessnick

Keyword(s):

Ewing Sarcoma ◽

Pediatric Patients

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Understanding of Pulmonary Metastases in Pediatric Patients with Differentiated Thyroid Cancer Is Evolving

Clinical Thyroidology ◽

10.1089/ct.2021;33.217-220 ◽

2021 ◽

Vol 33 (5) ◽

pp. 217-220

Author(s):

Kara D. Meister ◽

Lisa A. Orloff

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Pediatric Patients ◽

Pulmonary Metastases

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Once Per Cycle Pegfilgrastim Versus Daily Filgrastim in Pediatric Patients with Ewing Sarcoma.

Blood ◽

10.1182/blood.v104.11.2919.2919 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2919-2919

Author(s):

Gerald Wendelin ◽

Herwig Lackner ◽

Wolfgang Schwinger ◽

Petra Sovinz ◽

Christian Urban

Keyword(s):

Ewing Sarcoma ◽

Pediatric Patients ◽

Actinomycin D ◽

Single Injection ◽

Severe Neutropenia ◽

Granulocyte Colony Stimulating Factor ◽

Subcutaneous Injections ◽

Comparable Effect ◽

Chemotherapy Patients ◽

Stimulating Factor

Abstract The administration of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) Filgrastim for reducing the duration of severe neutropenia after cytotoxic chemotherapy has become an important part of oncologic supportive care. Due to the short serum half-life Filgrastim has to be administrated daily by subcutaneous injections. Frequent injections however mark a problem in pediatric patients. Studies in adult patients have shown a comparable effect of the new long lasting rhG-CSF Pegfilgrastim which has to be administrated only once per cycle. In the current study the effects of Pegfilgrastim in pediatric patients were analysed. Five patients (10–16 years) with Ewing sarcoma were treated in a cross over study design alternately with Pegfilgrastim and Filgrastim following the EURO E.W.I.N.G. 99 protocol. Starting on day 4 after chemotherapy patients received Filgrastim 10μg/kg daily by subcutaneous injection until an absolute neutrophil count (ANC) >1000/μl after the expected nadir. Pegfilgrastim 100μg/kg was administrated on day 4 once per cycle subcutaneously. In 3 patients the stimulation with rhG-CSF was performed after each of the 6 preoperative VIDE-(Vincristin, Ifosfamide, Doxorubicin, Etoposide) cycles, in 2 patients after 8 postoperative VAI-(Vincristin, Actinomycin D, Ifosfamide), and in 2 patients after 7 postoperative VAC-(Vincristin, Actinomycin D, Cyclophosphamide) cycles of the EURO-E.W.I.N.G. 99 protocol. The duration of grade 4 neutropenia after single administration of Pegfilgrastim was 2,8 ±3,1 (0–10) days, after daily administration of Filgrastim 3,1 ± 2,7 (0–8) days. The number of days with a body temperature over 38 degrees and grade 4 neutropenia at the same time was 0,9 ±1,5 (0–6) after Pegfilgrastim and 0,9± 1,4 (0–4) after Filgrastim. Filgrastim had to be injected 6,7 ± 1,8 (3–10) times per cycle. Bone pain associated with Pegfilgrastim was noted in only one patient. Costs for Pegfilgrastim were 16% lower than for Filgrastim. We conclude that in pediatric patients with Ewing sarcoma the duration of severe neutropenia and number of days with febrile neutropenia after once per cycle Pegfilgrastim and daily Filgrastim are comparable. By using Pegfilgrastim the number of subcutaneous injections can be reduced to one single injection and costs can be lowered.

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Multimodality treatment of pediatric and adult patients with Ewing sarcoma: A single-institution experience.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10082 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10082-10082

Author(s):

David Lorente ◽

Robert Diaz ◽

Barbara Torres ◽

Adela Cañete ◽

Jorge Aparicio ◽

...

Keyword(s):

Prognostic Factors ◽

Ewing Sarcoma ◽

Cox Regression ◽

Pulmonary Metastases ◽

Univariate Analysis ◽

Local Treatment ◽

High Dose ◽

Cox Regression Analysis ◽

Increased Risk ◽

Treatment Surgery

10082 Background: Treatment of Ewing sarcoma pts. usually follows pediatric protocols, both in children and in adults. However, older patients fare poorly in most series. We analyze our experience with the 2001 protocol of the Spanish Society of Pediatric Oncology. Methods: Retrospective analysis. Schema: 6 cycles (cy) of VIDE chemotherapy (CT: vincristine, ifosfamide, etoposide, doxorrubicin). If no progression, local treatment (surgery or RT) and consolidation adjusted to risk: VACx8 (vincristine, dactinomycin, ciclophosphamyde) in standard-risk pts; if increased risk (axial, complete response in lung metastases or non-pulmonary metastases) VACx1, high-dose CT (busulphan-melphalan) and autologous transplant (ATSP). Analysis: induction CT toxicity, pathological response rates, consolidation treatment, disease-free (DFS) and overall survival (OS) (Kaplan- Meier). Log-rank and Cox regression analysis of prognostic factors in OS. Results: 35 patients (01.2003-05.2011). 60% male. Median age 16 y (r 7-57). Axial (43%), extremities (34%), extra-osseous (18%) and ribs (9%). Metastases: 54% (lung 58%, bone 26%, others 12%). > 1 location: 29%. Induction CT: 83% received 6 cy. 6% early progressions and 3% toxic deaths. 196 cycles of CT. Dose reduction (etoposide) in 60%. Grade 3-4 toxicity: neutropenia 13%, anemia 14%, neutropenic fever 13%, diarrhoea-stomatitis 7%.Local treatment: surgery (49%), radiotherapy (29%), none (22%). In 17 resections, > 90% necrosis in 53%. Consolidation: VACx8 29%; VACx1-ATSP in 34%; 37% other treatments (progression). No ATSP-related mortality. Median follow-up: 36 m ( 5-101 m). Median DFS 25 m (16-34 m). Median OS 28 m (15-41 m), 3-year OS 40%. Median time to progression 7 m (0.4-15 m). Median OS from progression 7 m (0.4-15 m). Age < 15 years, a non-axial primary and no extra-pulmonary metastases were favourable prognostic factors in the univariate analysis. Conclusions: Induction CT with the VIDE regimen is feasible in most patients, with a low risk of early progression. Hematological toxicity is substantial but manageable. Adults patients have a worse prognosis compared to pediatric patients. Unfortunately, survival after progression is dismal.

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Phase I study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10507 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10507-10507

Author(s):

Michela Casanova ◽

Francisco Bautista ◽

Quentin Campbell Hewson ◽

Guy Makin ◽

Lynley V. Marshall ◽

...

Keyword(s):

Solid Tumors ◽

Ewing Sarcoma ◽

Pediatric Patients ◽

Wilms Tumor ◽

Standard Dose ◽

Phase 1 ◽

Single Agent ◽

Maximum Tolerated Dose ◽

Clinical Activity ◽

Grade 3

10507 Background: In pediatric patients with solid tumors, regorafenib demonstrated acceptable tolerability and preliminary anti-tumor activity. This phase 1 study evaluated regorafenib in combination with vincristine/irinotecan in pediatric patients with rhabdomyosarcoma (RMS) and other solid tumors. Methods: Patients with relapsed/refractory tumors received intravenous vincristine (1.5 mg/m2, Days 1 and 8) and irinotecan (50 mg/m2/day, Days 1–5) plus once-daily oral regorafenib (patients 6– < 24 months: 60 mg/m2 escalating to 65 mg/m2; patients 2– < 18 years: 72 mg/m2 escalating to 82 mg/m2) on either Days 1–14 (concomitant dosing) or Days 8–21 (sequential dosing) during each 21-day cycle. As per protocol, at least 50% of patients were required to have RMS. Results: At the time of the cut-off, of 21 treated patients (RMS, n = 12; Ewing sarcoma, n = 5; neuroblastoma, n = 3; Wilms tumor, n = 1), two had concomitant (72 mg/m2) and 19 had sequential (72 mg/m2, n = 6; 82 mg/m2, n = 13) dosing. Median age was 10 years (1.5–17.0). Patients received a median of 3 cycles (1–17); dose reductions of irinotecan occurred in 62% of patients. Grade 3 dose-limiting toxicities were reported in both patients receiving concomitant dosing (peripheral neuropathy and liver injury; pain, vomiting, febrile aplasia) and one patient each in the sequential groups (rash and elevated AST; thrombocytopenia). Concomitant dosing was discontinued. The maximum tolerated dose and recommended phase 2 dose (RP2D) of regorafenib in the sequential combination was 82 mg/m2. The most common grade ≥3 treatment-emergent adverse events were neutropenia (71%), thrombocytopenia (33%), leukopenia (29%), anemia (24%), and ALT increased (24%). The response rate was 38%, including 1 complete (RMS) and 7 partial responders (5 RMS, 2 Ewing sarcoma); 3 of whom had prior irinotecan. Six (4 with alveolar subtype) of 12 patients with RMS had a response. Nine patients (43%) had stable disease (maximum duration 17 cycles). After the cut-off, partial response was reported for two additional patients (1 RMS, 1 Ewing sarcoma). Conclusions: Regorafenib can be combined at its single agent RP2D of 82 mg/m2 with standard-dose vincristine/irinotecan (with appropriate dose modifications) in pediatric patients with refractory/relapsed solid tumors in a sequential dosing schedule. Clinical activity was observed in patients with sarcoma. Clinical trial information: NCT02085148.

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