Microscopic Infiltration of Cryopreserved Ovarian Tissue in 2 Patients With Ewing Sarcoma

Schifflers, Stefan; Delbecque, Katty; Galant, Christine; Francotte, Nadine; Philippet, Pierre; Chantrain, Christophe

doi:10.1097/mph.0000000000000928

Cited by 6 publications

(10 citation statements)

References 13 publications

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“…Abir et al [ 27 ] analyzed the ovarian tissue from eight Ewing’s sarcoma patients and found evidence of ovarian involvement in one patient by RT-PCR amplification of the ES specific translocation transcript. Infiltration of ovarian tissue cryopreserved for fertility preservation purposes with ES was also described in two young patients, based on the presence of CD99 positive tumor cells harboring the EWS-FLI1 translocation [ 28 ]. Although these studies suggest that ovarian involvement in ES is relatively rare, the frequency at which ovarian tissue fragments are contaminated with ES cells might be underestimated.…”

Section: Discussionmentioning

confidence: 99%

“…In a study by Greve et al [ 21 ] malignant cells were not detected in ovarian tissue stored for fertility preservation of nine surviving ES patients. Despite that metastatic involvement of the ovaries is not common, infiltration of ovarian tissue with ES has been reported by several authors [ 22 , 23 , 24 , 25 , 26 ], also in the context of OTC [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

Peek

Eijkenboom

Braat

et al. 2021

JCM

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Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

Peek

Eijkenboom

Braat

et al. 2021

JCM

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“…Cases of metastatic ovarian involvement in EWS patients have been described in the literature [3,24]. Microscopic ovarian infiltration could be present in non-metastatic EWS [14]. No metastasis in TT has been described [25].…”

Section: Discussionmentioning

confidence: 99%

“…EWS MRD detection by RT-PCR has been performed in OT. Schifflers et al [14] studied MRD in OT from patients with non-metastatic EWS. Abir et al described EWS MRD detection of cryopreserved ovarian samples by snap freezing [15].…”

Section: Introductionmentioning

confidence: 99%

Sensitive and Specific Detection of Ewing Sarcoma Minimal Residual Disease in Ovarian and Testicular Tissues in an In Vitro Model

Chaput

Grèze

Hallé

et al. 2019

Cancers

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Ewing sarcoma (EWS) is a common pediatric solid tumor with high metastatic potential. Due to toxic effects of treatments on reproductive functions, the cryopreservation of ovarian tissue (OT) or testicular tissue (TT) is recommended to preserve fertility. However, the risk of reintroducing residual metastatic tumor cells should be evaluated before fertility restoration. Our goal was to validate a sensitive and specific approach for EWS minimal residual disease (MRD) detection in frozen germinal tissues. Thawed OT (n = 12) and TT (n = 14) were contaminated with tumor RD-ES cells (10, 100, and 1000 cells) and EWS-FLI1 tumor-specific transcript was quantified with RT-qPCR. All contaminated samples were found to be positive, with a strong correlation between RD-ES cell numbers and EWS-FLI1 levels in OT (r = 0.93) and TT (r = 0.96) (p < 0.001). No transcript was detected in uncontaminated control samples. The invasive potential of Ewing cells was evaluated using co-culture techniques. After co-culturing, tumor cells were detected in OT/TT with histology, FISH, and RT-qPCR. In addition, four OT and four TT samples from children with metastatic EWS were tested, and no MRD was found using RT-qPCR and histology. We demonstrated the high sensitivity and specificity of RT-qPCR to detect EWS MRD in OT/TT samples. Clinical trial: NCT 02400970.

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“…The family understood that prognosis for survival was poor 17,18 . Furthermore, they understood the risk of reintroducing cancer cells with autotransplantation 19 . However, this risk is thought to be low for rhabdomyosarcoma, and better methods of screening ovarian tissue for residual disease as well as in vitro maturation and fertilization technology may be available in the future 20 .…”

Section: Casementioning

confidence: 99%

Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer

Schermerhorn

Rosen

Blevins

et al. 2021

Pediatric Blood & Cancer

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Ovarian tissue cryopreservation is the only fertility preservation (FP) option available to prepubescent females receiving gonadotoxic therapy, but it has limited availability. A 6-year-old female was diagnosed with high-risk rhabdomyosarcoma, and the planned treatment carried an 80% risk of ovarian failure. Her parents desired FP, but the nearest center was 500 miles away. The patient underwent oophorectomy at the cancer center with air transport of the tissue to the oncofertility center, where it was successfully cryopreserved. Formation of networks between full-service and limited oncofertility centers in a hub-and-spoke model would increase access to FP services, particularly in children. K E Y W O R D Sfertility preservation, oncofertility, ovarian tissue cryopreservation INTRODUCTIONAs survival in pediatric oncology has improved, greater emphasis has been placed on survivorship, including fertility preservation (FP)for those undergoing gonadotoxic therapies. 1,2 Discussion of fertility prognosis and preservation is the standard of care. [3][4][5] Risk prediction models for ovarian failure in children with cancer exist. 6,7 Historically, FP for females has been limited to oocyte and embryo cryopreservation, which is impossible before puberty. The only FP option for prepubertal females is ovarian tissue cryopreservation (OTC), which involves harvesting ovarian tissue for future autotransplantation or in Abbreviations: FP, fertility preservation; OTC, ovarian tissue cryopreservation.vitro maturation and fertilization. This technique has been trialed over the past two decades, resulting in 130 live births and touting pregnancy rates of 29-41% after autotransplantation, 2,8 at least two of which occurred after prepubertal OTC. 9,10 It is expected that more pregnancies after prepubertal OTC will soon occur, as these women are now reaching the age of desired fertility, and work on in vitro maturation and fertilization continues to progress. The American Society for Reproductive Medicine recently designated OTC as standard rather than experimental therapy 8,11 ; however, other groups continue to advocate that OTC in children should remain under institutional review board oversight. 12 Although the majority of survivors of childhood cancer desire fertility, FP services are underutilized due to multiple barriers, including

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Microscopic Infiltration of Cryopreserved Ovarian Tissue in 2 Patients With Ewing Sarcoma

Cited by 6 publications

References 13 publications

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

Sensitive and Specific Detection of Ewing Sarcoma Minimal Residual Disease in Ovarian and Testicular Tissues in an In Vitro Model

Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer

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