Offspring Of Cancer Survivors Research Articles

Pediatric and Adolescent Oncofertility in Male Patients-From Alpha to Omega.

This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and adolescents aged 0–19 years will be diagnosed with cancer each year. Fertility is compromised in one-third of adult male survivors of childhood cancer. We present the latest approaches and techniques for fertility preservation, starting with fertility preservation counselling, a clinical practice guideline used around the world and finishing with recent advances in basic science and translational research. Improving strategies for the maturation of germ cells in vitro combined with new molecular techniques for gene editing could be the next scientific keystone to eradicate genetic diseases such as cancer related mutations in the offspring of cancer survivors.

Risk of Being Born Preterm in Offspring of Cancer Survivors: A National Cohort Study.

Background: With the increased number of cancer survivors, it is necessary to explore the effect of cancer and its treatments on pregnancy outcomes, such as preterm birth, which seriously endangers the health of offspring. We aimed to explore the risk of being born preterm among offspring of cancer survivors.Materials and Methods: This is a retrospective cohort study. All singleton live births between 1973 and 2014 in Sweden with information of birth outcomes were retrieved from the Swedish Medical Birth Register. By linking to several Swedish registers, we identified all parents of children and parental cancer diagnosis. Logistic regression was used to estimate odds ratios and 95% confidence intervals.Results: As compared to the children without parental cancer, the risk of being born preterm was significantly higher among children of overall female cancer survivors born after cancer diagnosis with an adjusted OR of 1.48 (95 CI% = 1.39–1.59), in particular those diagnosed with childhood cancer and cancer in female genital organs. Besides, the risk might continuously decline with time at the first 8 years after maternal diagnosis. A higher risk of being born preterm was found among offspring of male survivors diagnosed with central nervous system cancer (Adjusted OR = 1.26, 95% CI = 1.04–1.53).Conclusions: Our study provides evidence for a higher risk of being born preterm among children of female cancer survivors and male survivors with central nervous system tumor, as well as indicates that the effect on female reproductive system from cancer and related-treatments might decline with time.

Perinatal complications in female survivors of cancer: a systematic review and meta-analysis

BackgroundObservational studies have suggested that perinatal outcomes are worse in offspring of cancer survivors. We conducted a systematic review and meta-analysis to examine the risks of perinatal complications in female cancer survivors diagnosed before the age of 40 years. MethodsAll published articles on pregnancy, perinatal or congenital risks in female cancer survivors were screened for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. ResultsTwenty-two studies met the inclusion criteria. Meta-analysis indicates that offspring of cancer survivors are at increased risk of prematurity (relative risk [RR]: 1.56; 95% confidence interval [CI] 1.37–1.77) and low birth weight (RR 1.47; 95% CI 1.24–1.73) but not of being small for gestational age (RR 0.99; 95% CI 0.81–1.22). Cancer survivors have higher rates of elective (RR: 1.38; 95% CI 1.13–1.70) and emergency caesarean section (RR: 1.22; 95% CI 1.15–1.30) as well as assisted vaginal delivery (RR: 1.10; 95% CI 1.02–1.18) and are at increased risk of postpartum haemorrhage (RR: 1.18; 95% CI 1.02–1.36). The risk of congenital abnormalities also appears increased (RR 1.10; 95% CI 1.02–1.20), but this is likely to be an artefact of analysis. Although meta-analysis of the effects of radiotherapy was not possible for all outcomes, there was an increased risk of prematurity (RR 2.27; 95% CI 1.34–3.82) and consistent findings of low birth weight (RR 1.38–2.31). Risk of being small for gestational age was increased only after high uterine radiotherapy dosage. ConclusionThe increased perinatal risks warrant a proactive approach from healthcare providers in both counselling and management of perinatal care for cancer survivors.

Hospitalization rate in offspring of cancer survivors: a national cohort study

PurposeThe number of childbirths among cancer survivors continues to increase, but it is still largely unknown whether the children of cancer survivors might experience adverse health outcomes during the process of growing up.MethodsWe identified all individuals diagnosed with cancer between 1958 and 2015 from the Swedish Cancer Registry and linked them to the Swedish Medical Birth Register to identify their offspring born between 1997 and 2015. Up to 10 children, whose parents did not have a diagnosis of cancer, were matched with the study population according to date of birth and gender.ResultsBy linking with the Swedish Hospital Discharge Register, we found that the hospitalization rate was 15% higher in offspring of female cancer survivors, and 16% higher in offspring of male cancer survivors as compared to matched controls. Besides an increased risk of hospitalization due to malignant neoplasms (relative risk (RR) = 1.86, 99% CI 1.70–2.04) and benign neoplasms (RR = 1.48, 99% CI 1.18–1.86), a non-significant increased risk was found for hospitalization due to infectious and parasitic disease (RR = 1.09, 99% CI 0.98–1.21), diseases of the blood and blood-forming organs and certain disorders involving the immune mechanisms (RR = 1.33, 99% CI 0.98–1.80), and diseases of the circulatory system (RR = 1.05, 99% CI 0.98–1.12).ConclusionOur study suggests that children of cancer survivors might experience a significantly increased rate of hospitalization, which calls for further studies.Implications for Cancer SurvivorsCancer survivors might be aware that the risk of hospitalization due to various diseases might be higher in their children as compared to the normal population.

Congenital malformation in offspring of female cancer survivors: a national cohort study.

Current evidence on congenital malformations in the offspring of cancer survivors is largely inconsistent. Therefore, through this study we aimed to explore the prevalence of congenital malformations in the offspring of cancer survivors. To this end, female cancer survivors were identified from the Swedish Cancer Register and were further linked to the Swedish Medical Birth Register and Hospital Discharge Register to identify congenital malformation in their children at birth or during adulthood between 1987 and 2010. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between congenital malformation and maternal cancer diagnosis. A total of 816 congenital malformations were noted among 9266 children of maternal cancer survivors, and the rate was 8.8%, whereas the rate in the general population was 7.7%. After adjusting for some confounding factors, we found that the risk for congenital malformation in children of cancer survivors was significantly increased with an odds ratio of 1.11 and 95% confidence interval of 1.04-1.20 as compared with that in controls. The increased risk was largely consistent irrespective of maternal age at diagnosis of cancer. The risk for congenital malformation was increased among offspring of female cancer survivors, which calls for further attention directed toward those cancer survivors who plan to have children.

Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors.

Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades.

Young adult female cancer survivors’ concerns about genetic cancer risk in offspring.

121 Background: More than 362,000 female cancer survivors under 40 years old live in the US. Research consistently shows no increased cancer risk among offspring of cancer survivors in the absence of a hereditary cancer. Still survivors voice concerns over the health of future children. This analysis explores young adult female cancer survivors’ (YAFCS) perceptions of genetic cancer risk and related reproductive concerns. Methods: Eligible females were aged 18-35, at least one year post-treatment. Participants were recruited using social media posts from 17 young adult cancer advocacy groups and directed to an anonymous web-based survey that included the Reproductive Concerns after Cancer Scale (RCACS), with a 3-item “Concerns about Future Child Health” subscale. Results: 346 YAFCS completed the full survey, and based on logic-based branching, 192 respondents could have completed the RCACS: 177 (92%) completed the entire scale and 187 (97%) completed the child’s health subscale. Mean RCACS score was 58.5 (sd = 11.6; range 22-86); mean child’s health score was 11.3 (sd = 3.3; range 3-15), with a negative skew. At the item-level, 65% of the sample worried about passing along cancer risk to offspring; 71% worried about family health history affecting future children; and 60% were afraid their children would have a high chance of getting cancer. RCACS and child’s health subscale scores did not vary by age, race, education, income, or diagnosis. Further, mean scores did not vary between survivors of family cancer syndromes (breast, ovarian, colorectal) and those with other diagnoses (RCACS: t = 1.4, df = 175, p = .14; child’s health: t = 0.02, df = 185, p = .99). Conclusions: Despite studies showing minimal genetic cancer risk in offspring of survivors, many YAFCS have concerns about the health of future children. This may be related to mistaken beliefs that genetic mutations within tumor cells are transmissible or unawareness of availability of pre-implantation genetic diagnosis for embryo selection in those with transmissible genetic mutations. There is a need to educate patients about these issues to enable them to make family building choices based on accurate information about genetic risk.

Radiation therapy for stage IIA and IIB testicular seminoma: peripheral dose calculations and risk assessments

This study was conducted to calculate the peripheral dose to critical structures and assess the radiation risks from modern radiotherapy for stage IIA/IIB testicular seminoma. A Monte Carlo code was used for treatment simulation on a computational phantom representing an average adult. The initial treatment phase involved anteroposterior and posteroanaterior modified dog-leg fields exposing para-aortic and ipsilateral iliac lymph nodes followed by a cone-down phase for nodal mass irradiation. Peripheral doses were calculated using different modified dog-leg field dimensions and an extended conventional dog-leg portal. The risk models of the BEIR-VII report and ICRP-103 were combined with dosimetric calculations to estimate the probability of developing stochastic effects. Radiotherapy for stage IIA seminoma with a target dose of 30 Gy resulted in a range of 23.0–603.7 mGy to non-targeted peripheral tissues and organs. The corresponding range for treatment of stage IIB disease to a cumulative dose of 36 Gy was 24.2–633.9 mGy. A dose variation of less than 13% was found by altering the field dimensions. Radiotherapy with the conventional instead of the modern modified dog-leg field increased the peripheral dose up to 8.2 times. The calculated heart doses of 589.0–632.9 mGy may increase the risk for developing cardiovascular diseases whereas the testicular dose of more than 231.9 mGy may lead to a temporary infertility. The probability of birth abnormalities in the offspring of cancer survivors was below 0.13% which is much lower than the spontaneous mutation rate. Abdominoplevic irradiation may increase the lifetime intrinsic risk for the induction of secondary malignancies by 0.6–3.9% depending upon the site of interest, patient’s age and tumor dose. Radiotherapy for stage IIA/IIB seminoma with restricted fields and low doses is associated with an increased morbidity. These data may allow the definition of a risk-adapted follow-up scheme for long-term testicular cancer survivors.

Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors

Background. Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. Material and methods. We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0–34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. Results. The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58–3.18, within 28 days 1.40, 95% CI 0.46–4.24 and within the first year of life 1.11, 95% CI 0.64–1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35–1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. Conclusion. Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.

Birth defects in offspring of cancer survivors investigated

Survivors of childhood cancer treated with radiotherapy or chemotherapy with alkylating agents are not more likely to have children with birth defects, according to a large study by scientists working with the US-based Childhood Cancer Survivor Study. Drawing from the Childhood Cancer Survivor Study—a repository of medical information for more than 20 000 patients diagnosed with the disease between 1970 and 1986—the investigators analysed data for the children of 2755 men and women who had been treated for cancer before adulthood. They compared the results for the children of patients who had been treated with radiation or chemotherapy with alkylating agents with those who had not undergone such treatment. Genetic birth defects occurred in 3·0% of children whose mothers had previously had radiotherapy or chemotherapy with alkylating agents versus 3·5% in those whose mothers had not. For those whose fathers had previously been treated with radiotherapy or chemotherapy with alkylating agents, the prevalence of birth defects was 1·9% (compared with 1·7% in children whose fathers had not received such treatments). These percentages match the general population. “Our fi ndings off er strong evidence that the children of cancer survivors are not at signifi cantly increased risk for congenital anomalies stemming from their parent’s exposure to mutagenic cancer treatment”, the investigators concluded. “This information is important for counselling cancer survivors planning to have children”, they added. The study used patient medical records to identify radiation doses to the ovaries and testes and analogous information for doses of chemotherapy (previous studies had not included such detailed exposure information). “When you’re looking at the possibility of inheriting defects, it’s essential to have these kinds of data”, lead author Lisa Signorello (International Epidemiology Institute, Rockville, MD, USA) told The Lancet Oncology. Cancer Research UK’s Martin Ledwick welcomed the study. “This is a question that adult survivors of childhood cancer actually ask”, he pointed out. “To have robust data showing that they probably don’t need to worry too much will give a lot of reassurance.” The next step, Signorello said, is to study survivors of childhood cancer and their children in more detail, using DNA sequencing to further assess the possible crossgenerational consequences of radiotherapy and chemotherapy.

Does Cancer Treatment in Childhood Induce Transgenerational Genetic Damage?

Does Cancer Treatment in Childhood Induce Transgenerational Genetic Damage?

Reproductive outcomes in male childhood cancer survivors: a linked cancer-birth registry analysis.

To compare the risk of reproductive and infant outcomes between male childhood cancer survivors and a population-based comparison group. Retrospective cohort study. Four US regions. Cancer registries identified males younger than 20 years diagnosed with cancer from 1973 to 2000. Linked birth certificates identified first subsequent live offspring (N = 470). Comparison subjects were identified from remaining birth certificates, frequency-matched on year and age at fatherhood, and race/ethnicity (N = 4150). Cancer diagnosis before age 20 years. Pregnancy and infant outcomes identified from birth certificates. Compared with infants born to unaffected males, offspring of cancer survivors had a borderline risk of having a birth weight less than 2500 g (relative risk, 1.43 [95% confidence interval, 0.99-2.05]) that was associated most strongly with younger age at cancer diagnosis and exposure to any chemotherapy (1.96 [1.22-3.17]) or radiotherapy (1.95 [1.14-3.35]). However, they were not at risk of being born prematurely, being small for gestational age, having malformations, or having an altered male to female ratio. Overall, female partners of male survivors were not more likely to have maternal complications recorded on birth records vs the comparison group. However, preeclampsia was associated with some cancers, especially central nervous system tumors (relative risk, 3.36 [95% confidence interval, 1.63-6.90]). Most pregnancies resulting in live births among partners of male childhood cancer survivors were not at significantly greater risk of complications vs comparison subjects. However, there remains the possibility that prior cancer therapy may affect male germ cells with some effects on progeny and on female partners.

Parenthood in Survivors After Adulthood Cancer and Perinatal Health in Their Offspring: A Preliminary Report

Cancer survivors may fear infertility, obstetric problems, and genetic alterations in their offspring. After linkage of three registries the probability of post-treatment parenthood and the risk of obstetric and perinatal problems were estimated in cancer survivors compared to individuals without a cancer diagnosis. A total of 1531 of 13,817 patients had 2307 children after one parent's cancer diagnosis: 972 males had 1479 children and 559 females had 828. A total of 1217 patients (784 males and 433 females) became parents > or =9 months after the diagnosis (1899 births: 1221 to male cancer patients and 678 to female patients). The post-diagnosis parenthood probability was 8% at 5 years, and 14% at 10 years without further increase. Female cancer survivors gave birth to post-diagnosis infants with on average 130 grams lower birth weight and 6 days shorter gestations compared with infants in the non-cancer population. Infants fathered by male cancer survivors did not differ from control infants with respect to birth weight or gestational age. There was no increase in the prevalence of major congenital malformations in the offspring of cancer survivors as compared with the offspring of the non-cancer population. Multiple births and deliveries by cesarean sections were increased. Parenthood after cancer is possible in a significant number of patients, more so for males than females. The risk of major congenital malformations was not increased relative to the non-cancer population, nor was perinatal mortality increased. However, female cancer survivors delivered more preterm births and low-birth-weight infants than what was found in the non-cancer population.

Relative Susceptibilities of Male Germ Cells to Genetic Defects Induced by Cancer Chemotherapies

Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors who were treated before or during their reproductive years may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time to pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, end point, and germ cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm fluorescent in situ hybridization have corroborated the differences in germ cell susceptibilities. The available evidence indicates that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.

Psychosocial aspects of infertility and decisions about reproduction in young cancer survivors: a review.

Several types of cancer treatment interfere with male and female fertility or can complicate pregnancy. Rates of birth defects and cancer have also been studied in the offspring of cancer survivors. Little is known, however, about the impact of a history of cancer on survivors' attitudes, anxieties, and choices about having children of their own. We review the relevant literature on cancer survivor's concerns about infertility and childbearing and propose areas for future research. We generate several hypotheses, including that cancer survivors will be more distressed than infertility patients without a major medical disorder, that survivors diagnosed in adolescence will have the most anxieties about parenthood, that women will be more distressed over infertility and more concerned about their children's health than men, that survivors who rate their overall quality of life more negatively will be less concerned about infertility and more apt to decide to forego parenthood, that survivors of inheritable cancer syndromes will have more distress about childbearing issues than other survivors, and that survivors who do have children after treatment will perceive them more positively than do parents who have not confronted cancer. Research on the emotional aspects of infertility after cancer and on the factors that influence survivors' decisions about having children assumes increasing importance with the growth in number of survivors of reproductive age.

Desire for children in tumor patients

After a chemo- and/or radiotherapy not only acute side effects but also longterm side effects do occur. The following longterm side effects are observed: irregularities in the menstrual cycle, early onset of menopause and infertility. They are of special importance to children, teenagers and young adults having survived a malignancy. For young women experiencing a premature menopause a hormone replacement therapy is indicated. The degree of gonadal failure depends on the total dose of cytotoxics, radiation or the combination of both. Alkylating substances are responsible for gonadal failure whereas other cytotoxic agents lead to reversible gonadal dysfunction. An important risk factor for the development of ovarian failure is the woman's age at the time of treatment. A pregnancy in patients with a history of malignancy always is a high risk pregnancy and needs a close follow up. The offspring of cancer survivors do not show a higher rate of chromosomal abnormalities or neoplasms. Before starting a chemo- and/or radiotherapy the patient should be informed about acute and late effects. Men and adolescent boys should be given the opportunity for sperm cryopreservation. It is unclear whether a fertility reserve can be achieved by cryopreservation also in women.