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TU_25_3116 - Ovarian Toxicity in Pediatric Cancer Survivors After Abdominopelvic Radiation Therapy: A Report From the PENTEC (Pediatric Normal Tissue Effects in the Clinic) Initiative

Tuesday, October 23
1:00 PM - 2:30 PM
Location: Innovation Hub, Exhibit Hall 3

Ovarian Toxicity in Pediatric Cancer Survivors After Abdominopelvic Radiation Therapy: A Report From the PENTEC (Pediatric Normal Tissue Effects in the Clinic) Initiative
C. E. Hill-Kayser1, C. H. Hua2, E. D. Yorke3, K. S. Keene4, C. M. Ronckers5, E. van Dulmen-den Broe6, L. Kremer7, C. R. Gracia MD8, J. Ginsberg9, M. L. Metzger2, and L. S. Constine10; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2St. Jude Children's Research Hospital, Memphis, TN, 3Memorial Sloan Kettering Cancer Center, New York, NY, 4University of Alabama at Birmingham, Birmingham, AL, 5Department of Pediatric Oncology, Emma Children’s Hospital / Academic Medical Center, Amsterdam, Netherlands, 6VU University Medical Center, Amsterdam, Netherlands, 7Princess Maxima Centre for Pediatric Oncology and the Amsterdam Medical Centre, Utrecht, Netherlands, 8University of Pennsylvania, Philadelphia, PA, 9Children's Hospital of Philadelphia, Philadelphia, PA, 10Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY

Purpose/Objective(s): Ovaries are recognized to be exquisitely radiosensitive; however, explicit risk of acute ovarian failure (AOF) and oocyte death are poorly understood in the pediatric population. The PENTEC female reproductive task force aims to quantify ovarian risk among children receiving abdominopelvic RT, particularly as related to age and RT dose.

Materials/Methods: A comprehensive search of PubMed database was performed using the terms “radiotherapy AND female AND cancer AND (oocyte OR premature menopause OR gonadotoxicity)” and revealed 2392 records. Of these 856 were relevant on initial review, and 42 on detailed review.

Results: Overall risk factors for infertility due to AOF and oocyte death include increasing RT dose to ovary, increasing cumulative alkylating agent dose, and increasing age at the time of RT1: in contrast to most pediatric organs, the pediatric ovary is less radiosensitive than the adult ovary, likely because children have the greatest overall numbers of oocytes. Doses of ≥20 Gy are expected to result in high risk (70-100%) of AOF and death of all oocytes in all female patients, regardless of age. Age appears to be a more important predictor at doses <20 Gy, with risk of AOF less in patients who are pre-menarchal (risk of ovarian failure 30% vs 70% in girls < 13y vs ≥13y receiving 10-19 Gy2). Although some ovarian resiliency is observed at younger ages, even doses of 10-20 Gy have been shown to result in need for hormonal supplementation3, and dose < 10 Gy can induce AOF in patients with additional risk factors (older age and alkylator exposure)2. Preservation of oocytes is also age dependent; unique published models suggest an effective sterilizing dose of 20 Gy at birth, 18 Gy at 10 y, and 16 Gy at 20 y; however, the dose required to destroy 50% is predicted to be much lower - < 2Gy in older girls and young adults4-5.

Conclusion: Ovarian tissue and oocytes are extremely sensitive to radiation. Maintaining ovarian dose of < 2Gy, when possible, is expected to best preserve oocytes and prevent ovarian failure. Surgical movement and/or marking of ovaries and use of proton therapy to eliminate exit dose may assist with reduction in ovarian dose depending on the radiation target. When elimination of dose is not possible, consultation with an oncologic fertility team is advised before radiotherapy, with possibility of oocyte or ovarian cryopreservation to be explored. Female cancer may benefit from reproductive endocrinology consultation after abdominopelvic radiation. Future goals of the PENTEC team include more detailed modeling of ovarian dose-volume relationships.

Author Disclosure: C.E. Hill-Kayser: Employee; University of Pennsylvania. C. Hua: None. E.D. Yorke: Co-chair of WGSBRT; AAPM. Vice-chair of Task Group 100; AAPM. K.S. Keene: None. C.M. Ronckers: None. E. van Dulmen-den Broe: None. L. Kremer: None. C.R. Gracia: Research Grant; NIH. Consultant; ASRM. J. Ginsberg: None. M.L. Metzger: None. L.S. Constine: Chair; American College of Radiology.

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TU_25_3116 - Ovarian Toxicity in Pediatric Cancer Survivors After Abdominopelvic Radiation Therapy: A Report From the PENTEC (Pediatric Normal Tissue Effects in the Clinic) Initiative



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