Pediatric Cancer

PD 04 - Pediatrics 1 - Poster Discussion

1033 - Risks of Breast Hypoplasia and Decreased Lactation from Radiation Therapy (RT) in Survivors of Pediatric Malignancy: Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Sunday, October 21
5:21 PM - 5:27 PM
Location: Room 217 C/D

Risks of Breast Hypoplasia and Decreased Lactation from Radiation Therapy (RT) in Survivors of Pediatric Malignancy: Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative
A. C. Lo1,2, C. M. Ronckers3, I. W. van Dijk4, T. Rancati5, M. Avanzo6, G. Gagliardi7, L. Kremer8, L. S. Constine9, and K. J. Marcus10; 1University of British Columbia, Vancouver, BC, Canada, 2BC Cancer, Vancouver, BC, Canada, 3Department of Pediatric Oncology, Emma Children’s Hospital / Academic Medical Center, Amsterdam, Netherlands, 4Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdam, Netherlands, 5Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 6Division of Medical Physics, Centro di Riferimento Oncologico Aviano IRCCS, Aviano, Italy, 7Karolinska University Hospital, Stockholm, Sweden, 8Emma Children’s Hospital / Academic Medical Center, Amsterdam, Netherlands, 9Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, 10Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA

Purpose/Objective(s): Breast hypoplasia and impaired lactation are poorly studied outcomes of chest RT in children. The PENTEC female breast task force aimed to quantitate the radiation dose-volume effects on these endpoints. The hypothesis is that there is an increased risk of breast hypoplasia and impaired lactation from chest RT in children.

Materials/Methods: PubMed searches were conducted of peer-reviewed manuscripts evaluating breast hypoplasia and lactation among young adults who received chest RT as children. The search yielded 789 abstracts. For the breast hypoplasia endpoint, no studies on childhood cancer survivors were identified, but two studies on children irradiated at <4 years of age for angioma did provide dosimetric data correlated with hypoplasia. We calculated relative risks (RR) and 95% confidence intervals (CI) for breast hypoplasia based on this data. Only one study from our literature search was relevant to the lactation endpoint, in which patients were given RT for Hodgkin lymphoma at age 14-40 years.

Results: The two studies regarding breast hypoplasia involved 153 subjects, and the one study regarding lactation involved 153 subjects (83 who received RT and 70 sibling controls). The dose/outcome data for breast hypoplasia after a single fraction of RT is summarized in the below table. The expected volume reduction in the treated breast is based on a simple linear regression (y=3.12+6.65x; where x=dose in Gy and y=% difference in breast volume) that modeled the dose-effect relationship with a correlation coefficient of 0.72 (p<0.001).
Patient-reported breast hypoplasia Expected difference in volume compared to untreated breast (%)
Dose to breast bud (Gy) Prevalence RR (95% CI) P-value
0 15% 1.0
0-1.0 38% 2.5 (1.3-4.6) 0.0045 <10%
1.0-2.5 61% 4.0 (2.1-7.4) <0.0001 10-20%
≥2.5 97% 6.3 (3.6-10.8) <0.0001 ≥20%
≥10 Not reported ≥70%
There was suggestion of lesser severity of breast hypoplasia when a total dose of >5Gy was given over multiple fractions compared to a single fraction; 2 patients who received 5.7-5.8 Gy over 3 weeks experienced <33% reduction in breast volume, compared to the expected 41% reduction if given in a single fraction; 2 patients who received total doses of 9.6-10.3 Gy, each in 2 multi-fraction courses separated by 4 months, experienced a breast volume reduction of 33-50%, compared to the expected 67-72% if in a single fraction. The risk of unsuccessful breastfeeding was 39% after a median mediastinal dose of 41Gy (range, 27-46Gy), compared to 21% in the control group (P=0.044). RT dose of ≥42Gy was not found to be associated with less success at breastfeeding.

Conclusion: Young adults exposed to thoracic RT as children are at significant risk of breast hypoplasia and decreased ability to breastfeed. The prevalence and severity of breast hypoplasia increases with increasing dose to the breast bud. To date, lactation outcomes have not been studied for those who received RT at age <14 years. Parents should be counseled accordingly about breast-related toxicities prior to RT.

Author Disclosure: A.C. Lo: None. C.M. Ronckers: Employee; Netherlands Cancer Institute. Research Grant; Dutch Cancer Society / KiKa Foundation, Dutch Cancer Society / European Union. Board Member DCOG LATER Study Group; Dutch Childhood Oncology Group - Late Effects after Childhood Cancer Consortium. Member of Scientific Review Board; Dutch Cancer Society. I.W. van Dijk: None. T. Rancati: None. M. Avanzo: None. G. Gagliardi: None. L.S. Constine: Chair; American College of Radiology. K.J. Marcus: Editorial Board Member; PDQ.

Karen Marcus, MD

Dana Farber

Disclosure:
Employment
Dana - Farber Cancer Institute: Associate Professor: Employee

Leadership
PDQ: Editorial Board Member; UpToDate: Contributor

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1033 - Risks of Breast Hypoplasia and Decreased Lactation from Radiation Therapy (RT) in Survivors of Pediatric Malignancy: Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative



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