Research Outputs

See conference abstracts and Ewing sarcoma published papers in peer-reviewed journals.

Publications

The following academic papers on Ewing sarcoma have been published in peer-reviewed journals. Click on the links to read a summary of each paper.

  1. Li J, Ohmura S, Marchetto A, Orth MF, et al (2021). Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer. Nat Commun. 2021 Sep 16;12(1): 5356.
  2. Bierbaumer L, Katschnig AM, Radic-Sarikas B, et al (2021). YAP/TAZ inhibition reduces metastatic potential of Ewing sarcoma cells. Oncogenesis. 2021 Jan 8;10(1): 2.
  3. Zöllner SK, Amatruda JF, Bauer S, Collaud S, et al (2021). Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives. J Clin Med. 2021 Apr 14;10(8):1685.
  4. Peneder P, Stütz AM, Surdez D, Krumbholz M, et al (2021). Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Nat Commun. 2021 May 28;12(1): 3230.
  5. Gonzato O, Gronchi A. The evolving role of patient advocates in rare cancers: opportunities and challenges. Expert Rev Pharmacoecon Outcomes Res. 2019 Feb;19(1): 1-3.
  6. Selvanathan SP, Graham GT, Erkizan HV, Dirksen U, et al (2015). Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11): E1307-16.
  7. Kovar H (2014). Blocking the road, stopping the engine or killing the driver? Advances in targeting EWS/FLI-1 fusion in Ewing sarcoma as novel therapy. Expert Opin Ther Targets. 2014 Nov;18(11): 1315-28.
  1. Le Deley MC, Paulussen M, Lewis I, Brennan B, et al (2014). Cyclophosphamide compared with ifosfamide in consolidation treatment of standard-risk Ewing sarcoma: results of the randomized noninferiority Euro-EWING99-R1 trial. J Clin Oncol. 2014 Aug 10;32(23): 2440-8.
  2. Whelan J, Khan A, Sharma A, Rothermundt C, et al (2012). Interval compressed vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide in patients with advanced Ewing's and other Small Round Cell Sarcomas. Clin Sarcoma Res. 2012 Sep 21;2(1): 12.
  3. Womer RB, West DC, Krailo MD, Dickman PS, et al (2012). Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-54. Erratum in: J Clin Oncol. 2015 Mar 1;33(7):814.
  4. Ladenstein R, Pötschger U, Le Deley MC, Whelan J, et al (2010). Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol. 2010 Jul 10;28(20): 3284-91.
  5. Juergens C, Weston C, Lewis I, Whelan J, et al (2006). Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer. 2006 Jul;47(1): 22-9.
  6. Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, et al (2003). Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15): 2974-81.

American Society of Clinical Oncology (ASCO) Conference 2021 - Ewing Sarcoma Abstracts

GEIS 39: Phase II trial of nabpaclitaxel for the treatment of patient with multiply relapsed/refractory desmoplastic small round cell tumor (DSRCT) and Ewing sarcoma (EwS)

Conclusions: Single agent nab-paclitaxel in biomarker selected EwS patients, but not in DSRCT, provided clinically meaningful activity that deserves further development. Nab-paclitaxel had a manageable adverse event profile.

Genomic alterations and associated pathway abnormalities in Ewing sarcoma

Conclusions: Secondary GAs affecting major pathways were observed in high frequency, often co-occurring with the FGFR4 G388R SNP. Secondary alteration of known oncogenic pathways may contribute to sarcoma formation in ES potentially informing further therapeutic strategies in the future

TK216 for relapsed/refractory Ewing sarcoma: Interim phase 1/2 results

Conclusions: TK216 plus VCR was well tolerated and showed encouraging early evidence of anti-tumor activity in this heavily pre-treated/ high tumor burden ES pt population.

Phase 1 trial of seclidemstat (SP-2577) in patients with relapsed/refractory Ewing sarcoma

Conclusions: Seclidemstat has a manageable safety profile with proof-of-concept preliminary activity in heavily pretreated pts with relapsed/refractory ES. These data support the planned Phase 2 expansion of seclidemstat as single agent and in combination with chemotherapy in ES and other sarcomas that share similar translocations.

Comparison of treatment effect and long-term outcomes for pediatric and adult Ewing sarcoma patients in British Columbia, Canada

Conclusions: The treatment plans for paediatric patients (PP) with EWS were more often dose dense compared to the adult patients (AP). Outcomes for PP were vastly better than for APs, despite overall similarities in the number of lines of therapy and types of agents used. Given the lack of difference between dose dense and non-dose dense regimens for APs, this is not the likely cause of difference in survival between PPs and APs. Extrapolating pediatric protocols to the adult setting may not be appropriate given the differences in outcomes. Further work to identify effective therapies and predictive biomarkers in this disease are needed, and my further identify reasons for discrepant outcomes in pediatric and adult populations.

Association of treatment delays with an unfavorable outcome in patients with localized Ewing sarcoma: A retrospective analysis of data from the GPOH Euro-E.W.I.N.G.99 trial

Conclusions: Delays between induction chemotherapy and surgery and between surgery and consolidation chemotherapy are independently associated with a poor outcome in patients with localized EWS. Our results also underscore the need to treat EWS patients in larger and experienced sarcoma centers. The implementation of new and standardized methods in the operative strategy and optimized supportive care during systemic therapy are required to reduce perioperative morbidity and treatment delays.

Efficacy of dose intensification in induction therapy for localized Ewing sarcoma: Italian Sarcoma Group (ISG) and Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) ISG/AIEOP EW-1 study

Conclusions: Intense induction therapy with arm B did not improve 5-year EFS when compared with the standard arm A. The higher toxicity observed in arm B than in arm A was counterbalanced, in good responders, by a similar outcome with a shorter treatment plan. For poor responders, with almost 30 patients per arm event-free and with < 48-month FUP, better 5-year EFS in arm B than in arm A was observed but needs further observation.

Phase 1 expansion trial of the LSD1 inhibitor seclidemstat (SP-2577) with and without topotecan and cyclophosphamide (TC) in patients (pts) with relapsed or refractory Ewing sarcoma (ES) and select sarcomas

Methods: This dose expansion Phase 1 study (NCT03600649) assesses seclidemstat at 900 mg PO BID, the recommended Phase 2 dose, in two expansion cohorts: a single agent expansion in select sarcoma pts (n = 30) and a safety lead-in dose escalation and expansion (n = 24) of seclidemstat combined with TC in pts with ES. Pts must be ≥12 years old, have ECOG performance status of 0 or 1, with a life expectancy > 4 months. In the select sarcoma cohort, pts must have ML (n = 15) or other sarcomas with FET family translocations (n = 15) including DSRCT. One to 3 prior lines of therapy are allowed. In the ES combination cohort, up to 2 lines of prior therapy are allowed. Primary objective is safety/tolerability and secondary objective is efficacy. The trial is currently recruiting across 8 locations in the United States.

Efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic Ewing sarcoma

Conclusions: In this study, we showed real-life efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic osteosarcoma. Toxicities were concern about in these heavily pretreated patients. Treatment options of metastatic Ewing sarcoma are limited. VIT regimen may be considered in patients who have a good performance.

Impact of psychosocial factors on the receipt of guideline concordant care in adolescent and young adults with localized Ewing sarcoma and osteosarcoma

Conclusions: Given the occurrence of cancer during a complex developmental time, AYAs have a relatively high occurrence of psychosocial changes and needs, which we found to be associated with receipt of NCCN guideline concordant care in patients with localized ES and OS. While a limited sample size, as the first study to define specific psychosocial factors that affect receipt of guideline concordant care, these finding suggest the need to improve identification and support of these discrete patient factors.

The MGMT (O6-methylguanine–DNA methyltransferase) promotes methylation and clinical outcomes of salvage temozolomide and irinotecan chemotherapy in progressive Ewing sarcoma: A preliminary report

Conclusions: This preliminary data suggests a possible prognostic role for MGMT promoter methylation, with a markedly extended median OS for the methylated group. Nevertheless, the median OS difference did not reach statistical significance in this preliminary analysis. We plan to report data of the final analysis after finalizing MGMT testing for the rest of our study patients.

A pilot study of the feasibility and utility of a fitness tracker to correlate activity level with patient reported outcomes (PROs) in sarcoma patients undergoing systemic therapy

Conclusions: Incorporating a fitness tracker is feasible in sarcoma pts receiving systemic therapy. It provides longitudinal, objective evaluation of activity levels and sleep patterns. Correlation of activity level with sleep, body composition, and PROs was limited due to small numbers; however, a larger prospective pilot study is ongoing.

Testing of B7-H3 targeting antibody-drug conjugate (ADC) MGC018 in models of pediatric solid tumors by the Pediatric Preclinical Testing Consortium (PPTC)

Conclusions: B7-H3 is an important target for immuno-oncology agents for childhood cancers. Our results provide proof-of-principle for the ability of MGC018 to produce profound antitumor activity in select pediatric solid tumor models in a B7-H3 specific manner.

Phase 2 trial of cabozantinib in children and young adults with refractory sarcomas, Wilms tumor, and rare tumors: Children's Oncology Group Study (ADVL1622)

Conclusions: Cabozantinib is active in patients with relapsed refractory OS and deserves further study in this disease. PRs were also seen in select carcinomas. Activity is limited in other sarcomas and WT. 

Whole-genome sequencing to improve sarcoma diagnosis and patient care

Conclusions: WGS is an important extension of the diagnostic arsenal of pathologists and has contributed to change of care in 52% of patients with sarcomas. Given the diagnostic complexity and high unmet need for new treatment opportunities in sarcomas we advocate the use of WGS for sarcoma patients early in the disease course.

Methylation of MMP2 and MMP9 in patients with localized and generalized forms of Ewing's sarcoma

Conclusions: Specific methylation of the matrix metalloproteinases genes MMP2 and MMP9 identified in the groups of localized and generalized Ewing's sarcoma. At the same time, the group with generalized forms of ES was characterized by gene hypomethylation.