Study finds strong pregnancy outcomes for survivors of childhood cancer

(Press-News.org) BOSTON -- Although women who survived childhood cancer face an increased risk of infertility, nearly two-thirds of those who tried unsuccessfully to become pregnant for at least a year eventually conceived, according to clinical researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Brigham and Women's Hospital. This is comparable to the rate of eventual pregnancy among all clinically infertile women.

"Most women think that if they had cancer as a child, then they'll never have children. It turns out that many of them can get pregnant. It just might be a little harder," said senior author Lisa Diller, MD, chief medical officer of Dana-Farber/Boston Children's and medical director of the David B. Perini, Jr. Quality of Life Clinic at Dana-Farber Cancer Institute.

The paper, published July 13 in Lancet Oncology, is the first large-scale study of female childhood cancer survivors that examines outcomes for those who experienced infertility, as defined by the typical clinical definition of infertility (attempting to conceive for a year or more without success).

Overall, 15.9 percent of women who survived childhood cancer were affected by infertility, with 12.9 percent trying to conceive for at least one year without success. The remainder of survivors included in the infertile group had ovarian failure and may not have even attempted pregnancy. In a comparison group comprised of sisters of childhood cancer survivors, 10.8 percent experienced infertility. This translates to a roughly 50 percent higher risk of infertility among the survivors of childhood cancer.

The new study is based on data from the Childhood Cancer Survivor Study, a cohort study of five-year survivors from 26 institutions who were under 21 when diagnosed with cancer between 1970 and 1986. Researchers studied 3,531 sexually active female survivors, age 18-39, and a control group of 1,366 female siblings of participants in the large-scale survivor study.

"This is the first study to examine direct questions about infertility and the use of infertility services," said lead author Sara Barton, MD, a clinical fellow of reproduction and infertility at Brigham and Women's Hospital at the time of the research. "Previous studies used surrogate markers. Parenthood. Pregnancy. Births. These don't take into account people's intent. They don't take into account how long it took to achieve pregnancy."

Among survivors of childhood cancer who had been trying unsuccessfully to get pregnant for at least a year, 64 percent conceived after, on average, another six months, compared with an average of five months for clinically infertile women in the control group who eventually conceived.

Women whose cancer was treated with alkylating agent chemotherapy or high-dose radiation to the abdomen or pelvis were most at risk of infertility. Although pediatric oncologists have changed a number of treatment protocols over the last several decades to reduce late effects, alkylating agents and radiation continue to be used.

"Women getting alkylating agents or radiation to the pelvis or abdomen should be triaged for fertility preservation. In addition to being at highest risk to report infertility, female cancer survivors who received those cancer therapies were the least likely to conceive once they had infertility," said Barton, who is now a staff physician at the Heartland Center for Reproductive Medicine and clinical professor at the University of Nebraska Medical School. The new research, she added, will help clinicians offer guidance to current patients based on the treatment protocol for their cancer. "If you're newly diagnosed with Hodgkin's lymphoma, for instance, you may be slightly more likely to experience infertility, but I don't necessarily think you need to delay your therapy to freeze your eggs."

The researchers also found that only 42 percent of cancer survivors who sought treatment for infertility were prescribed medication, compared with 75 percent in the control group. Both groups – 69 percent of survivors and 73 percent in the control group – were similarly likely to seek medical help for their infertility.

Prior research has found that survivors of childhood cancer face a greater risk of infertility but, once pregnant, are not at greater risk for miscarriage or stillbirth.

"What we found delivers a really nice message to clinicians," Diller said. "If you have a patient who is a childhood cancer survivor and is self-reporting clinical infertility, the chances are good that she will become pregnant. Women who have a history of childhood cancer treatment should consider themselves likely to be fertile. However, it might be important to see an expert sooner rather than later if a desired pregnancy doesn't happen within the first six months."

### Additional coauthors are Julie S. Najita, Ph.D. of Dana-Farber; Elizabeth S. Ginsburg, M.D., of Brigham and Women's; Wendy M. Leisenring, Sc.D., of Fred Hutchinson Cancer Institute; Marilyn Stovall, Ph.D., and Rita E. Weathers, M.S. of University of Texas M.D. Anderson Center; Charles A. Sklar, M.D., of Sloan-Kettering Cancer Center; and Leslie L. Robison, Ph.D. of St. Jude Children's Hospital. The study was funded by the National Cancer Institute (Grant U24 CA55727) and Swim Across America, Inc.

The Dana-Farber/Boston Children's Cancer and Blood Disorders Center brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's Hospital and outpatient care at the Dana-Farber Cancer Institute's Jimmy Fund Clinic. Dana-Farber/Boston Children's brings the results of its pioneering research and clinical trials to patients' bedsides through five clinical centers: the Blood Disorders Center, the Brain Tumor Center, the Hematologic Malignancies Center, the Solid Tumors Center, and the Stem Cell Transplant Center.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by $640 million in funding. For the last 19 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.

CONTACT: Irene Sege
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
617-919-7379
irene.sege@childrens.harvard.edu
(On July 12, contact Anne Doerr, 617-632-5665, anne_doerr@dfci.harvard.edu)

Marjorie Montemayor-Quellenberg
Brigham and Women's Hospital
617-534-2208
mmontemayor-quellenberg@partners.org