Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.

Type, intensity, and duration of chemotherapy (CHT) and their correlation with prognosis of localized soft tissue Ewing tumors (STET): Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS).

10527 Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.

Vaginal Ewing Sarcoma: An Uncommon Clinical Entity in Pediatric Patients

Ewing sarcoma, including classical Ewing sarcoma of the bone and primitive neuroectodermal tumors arising in bone or extraosseous primary sites, is a highly aggressive childhood neoplasm. We present two cases of Ewing sarcoma arising from the vagina in young girls. Previously reported cases in literature focused on their pathologic rather than radiographic features. We describe the spectrum of multimodality imaging appearances of Ewing sarcoma at this unusual primary site. Awareness of vaginal Ewing tumors may facilitate prompt diagnosis and lead to a different surgical approach than the more commonly encountered vaginal rhabdomyosarcoma.

The importance of PET/CT in the evaluation of patients with Ewing tumors

The effective evaluation for the treatment of patients with Ewing tumors depends on the accuracy in the determination of the primary tumor extent and the presence of metastatic disease. Currently, no universally accepted staging system is available to assess Ewing tumors. The present study aimed at discussing the use of PET/CT as a tool for staging, restaging and assessment of therapeutic response in patients with Ewing tumors. In spite of some limitations of PET/CT as compared with anatomical imaging methods, its relevance in the assessment of these patients is related to the capacity of the method to provide further physiological information, which often generates important clinical implications. Currently, the assessment of patients with Ewing tumor should comprise a study with PET/CT combined with other anatomical imaging modalities, such as radiography, computed tomography and magnetic resonance imaging.

Time to Diagnosis of Ewing Tumors in Children and Adolescents Is Not Associated With Metastasis or Survival: A Prospective Multicenter Study of 436 Patients

Purpose The time to diagnosis (TtD) of Ewing tumors is one of the longest among pediatric tumors. Its precise consequences, however, have not been studied well. We analyzed the distribution of TtD for Ewing tumors in children and adolescents and its association with clinical features, tumor characteristics, surgical outcome, and long-term survival. Patients and Methods We analyzed prospectively collected data from two multicenter clinical trials of patients younger than 21 years old who had Ewing bone tumors treated in France between 1988 and 2000. Clinical and tumoral features, TtD, and outcome associations were studied by univariable and multivariable analyses. Results The median TtD for the 436 patients was 70 days (interquartile range, 27 to 146 days), with no significant decrease during the study period (P > .2). The factors associated with long TtD were older age and some tumor sites (pelvis, extremities of limbs). Increased tumor volume and decreased histologic response to chemotherapy were associated with long TtD on univariable analysis (P < .05) but not after adjustment. Presence of a nerve or spinal-cord compression at diagnosis, presence or site of metastasis, surgical treatment, mutilating surgery, complete resection, or survival were not associated with TtD. Conclusion TtD of Ewing tumors was long, especially for adolescents and for certain tumor sites, and did not improve over time. But TtD was not associated with metastasis, surgical outcome, or survival. These findings could be used to comfort parents at diagnosis and in expert testimony produced for malpractice claims.