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      Dosimetric Evaluation of the Uterus in Patients Receiving Total Body Irradiation with Ovarian Shielding

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          Abstract

          Infertility is a well-known late complication in patients receiving hematopoietic stem cell transplantation (HSCT). We previously reported that total body irradiation (TBI) with ovarian shielding reduces the radiation dose to the ovaries to 2.4 Gy − one-fifth of the dose compared to conventional TBI − and preserves fertility without increasing the risk of relapse. Exposure to the uterus and ovaries can reportedly affect pregnancy and childbirth. However, the dose constraint of the uterus that causes infertility remains unknown. Herein, we report the pregnancy and birth outcomes of 2 patients who gave birth following TBI with ovarian shielding and evaluated the dose to the uterus using a dose-volume histogram. Case 1 involved a 30-year-old woman with acute myeloid leukemia who underwent HSCT at 21 years of age with a uterus mean dose ( D mean) of 7.0 Gy. She had a natural pregnancy and elective cesarean section at 38 weeks of gestation due to hypertensive disorders of pregnancy. She gave birth to a normal-birthweight infant. Case 2 involved a 32-year-old woman with T-cell acute lymphoblastic leukemia who underwent HSCT at 30 years of age with a uterus D mean of 7.6 Gy. Her baby was delivered at full term with normal birthweight. These results indicate that a uterus D mean between 7.0 and 7.6 Gy does not have a significant impact on pregnancy and delivery with the ovarian function being preserved for patients who received TBI with ovarian shielding after puberty.

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          Most cited references18

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          Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation.

          Patients successfully treated with a marrow transplant often have concerns about fertility and pregnancy. This study was performed to determine pregnancy outcome among patients who had received high-dose chemotherapy alone or with total-body irradiation (TBI) and marrow transplantation for aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal and 196 prepubertal patients currently more than 12 years of age after marrow transplant in Seattle from August 1971 to January 1992 were reviewed to determine the patients with normal gonadal function and pregnancies. Among 708 postpubertal women, 110 recovered normal ovarian function and 32 became pregnant. In addition, nine formerly prepubertal girls with normal gonadal function became pregnant. Among 618 postpubertal men, 157 recovered testicular function and partners of 33 became pregnant. An additional two formerly prepubertal men had partners who became pregnant. Forty-one female patients and partners of 35 male patients had 146 pregnancies after transplant. All 76 patients responded to a questionnaire requesting pregnancy history, outcome, infant birth weight, and congenital anomalies information for all clinically recognized pregnancies. There were 115 live births among 146 (79%) pregnancies. Spontaneous abortion terminated four of 56 (7%) pregnancies for 28 female cyclophosphamide (CY) recipients and six of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28 male CY recipients had four of 62 (6.4%) pregnancies terminate with spontaneous abortion, but there were no spontaneous abortions among eight pregnancies of five TBI recipients' partners. Preterm delivery occurred for eight of 44 (18%) and five of eight (63%) live births for 24 CY and eight TBI female recipients (P = .01). This 25% incidence among all female patient pregnancies is higher than the expected incidence of 8% to 10% (P = .0001). The 13 preterm deliveries resulted in 10 low birth weight ([LBW] 1.8 to 2.24 kg) and three very low birth weight ([VLBW] < or = 1.36 kg) infants, for an overall incidence of 25%, which is higher than the expected incidence of 6.5% for the general population (P = .0001). Twelve of the 13 premature infants survive. Congenital anomalies were seen among two of 52 (3.8%) live-born infants of female and six of 63 (9.5%) live-born infants of male patients, which is not different from the 13% of single congenital anomalies reported for the general population. These data demonstrate that clinically recognized pregnancies among women who have received a marrow transplant incorporating TBI are likely to be accompanied by an increased risk of spontaneous abortion. Pregnancies among all women who received a marrow transplant are likely to be accompanied by preterm labor and delivery of LBW or VLBW babies who do not seem to be at an increased risk of congenital anomalies. However, determination of possible adverse effects of parental exposure to high-dose alkylating agents with or without TBI on children born posttransplant requires longer, additional follow-up.
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            Female survivors of childhood cancer: preterm birth and low birth weight among their children.

            Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes. Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm ( 500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight). Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.
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              Nonmalignant late effects after allogeneic stem cell transplantation.

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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                Case Reports in Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-6575
                Sep-Dec 2022
                20 September 2022
                20 September 2022
                : 15
                : 3
                : 809-815
                Affiliations
                [1] aDepartment of Radiology, Jichi Medical University Saitama Medical Center, Saitama, Japan
                [2] bDivision of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
                [3] cDepartment of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
                [4] dDepartment of Radiology, Jichi Medical University, Tochigi, Japan
                [5] eDivision of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
                Author notes
                Article
                cro-0015-0809
                10.1159/000526536
                9941773
                4183f752-8a27-4433-b7f8-9d5904eb3802
                Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 12 July 2022
                : 29 July 2022
                : 2022
                Page count
                Figures: 2, References: 18, Pages: 7
                Funding
                This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
                Categories
                Case Report

                Oncology & Radiotherapy
                total body irradiation,ovarian shielding,fertility,uterus,radiation dose
                Oncology & Radiotherapy
                total body irradiation, ovarian shielding, fertility, uterus, radiation dose

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