Cancer in Pregnancy - all diagnoses and treatments Children born from mothers diagnosed with cancer during pregnancy

Ayaka Wakatsuki

Kristel Van Calsteren, MD PhD

Elyce Cardonick, MD

Mina Mhallem

Frederic Amant, MD, PhD

Kristel Van Calsteren, MD, PhD

Lieven Lagae, MD, PhD

Luc Mertens, MD, PhD

Kristel Van Calsteren, MD

Michael Halaska, MD

Monica Fumagalli, MD PhD

Maarten Lambrecht, MD PhD

Jaroslav Klát, MD

Lone Storgaard, MD

Berit Woetmann Pedersen, MD

Mona Aarenstrup, MD

Cristel Maria Soerensen-Hjortshoej, MD

Georeg-Marios Makris, MD

Fedro Peccatori, MD

Monica Fumagalli, MD

Giovanna Scarfone, MD

Giorgia Mangili, MD

Bianca Masturzo, MD

Álvaro Cabrera Garciá, MD

Ingrid Boere, MD PHD

Frédéric Amant, MD PHD

C.A.R. Lok, MD PHD

M.M. Van den Heuvel-Eibrink, MD PHD

C.J.M. De Groot, MD PHD

R.C. Painter, MD PHD

P.B. Ottevanger, MD PHD

P.O. Witteveen, MD PHD

C.P. Schröder, MD PHD

S.J. Gordijn, MD PHD

J. Kroep, MD PHD

R.L.M. Bekkers, MD PHD

A.M.J. Thijs, MD PHD

Line Bjorge

Kolawa Wojciech

Marta Balajewicz-Nowak, MD

Kazimierz Pitynski, MD

Stefan Sajdak, MD

Paula Duarte, MD

Anastasia Parokonnaya, MD

Roman Shmakov, MD

Vladim Bezrukikh

Kenny Rodriguez-Wallberg, MD

Amant Frederic, MD PhD

The researchers aim to investigate the outcome (overall survival) of mothers who are diagnosed and/or treated for cancer during pregnancy. Furthermore they want to test the hypothesis that children who were exposed to cancer or cancer treatment (cytotoxic drugs, radiation therapy, targeted therapy,...) develop normally (neurologic and cardiologic examination).

Study contains several study parts (protocol version 4.4):

\*\*\*\*\*\*\*\*\*\*Part I. Pregnancy, delivery and maternal health\*\*\*\*\*\*\*\*\*\* Part I.I.A. Registration study 'Cancer during pregnancy' mother and neonate None Part I.I.B. Effects of prenatal exposure to cancer treatment on fetal growth. The association between placental pathophysiologic mechanisms (histopathology and immunohistochemistry), circulating maternal factors and fetal growth.

From participating women, a maternal blood sample will be collected during or shortly after birth. Also, an umbilical cord blood sample and placental and umbilical cord biopsies will be drawn.

Part I.II. Measurement of maternal and paternal anxiety and emotional needs when confronted with a cancer diagnosis during pregnancy The participants will be asked to complete questionnaires.

\*\*\*\*\*\*\*\*\*\*Part II. Child\*\*\*\*\*\*\*\*\*\* Long term follow up of children and adolescents in utero exposed to chemotherapy and/or radiotherapy Regular check-ups of the child, at the age of 6 months, 18 months, 3y, 6y, 9y, 12y, 15y, and 18y, and after the age of 18 years: 5-yearly cardiologic assessment and questionnaires (23y, 28y, 33y, 38y, and 43y). Optional at the ages of 9y, 12y, 15y and 18y: MRI session.

Summary part I:

Prospectively the outcome of mothers diagnosed and/or treated for cancer during pregnancy will be registered and investigated.

Summary Part II:

In a prospective trial we invite children that were exposed to cytotoxic drugs or radiotherapy in utero for a standardized neurological and cardiological examination. The examinations will be done by qualified psychologists, neurological and cardiological pediatricians.

Maternal blood serum and sediment of blood; from 2010 on we collect umbilical cord blood.

Since new approval of protocol version 4.2 (08-02-2018) we collect samples of placental tissue, umbilical cord tissue and membranes.

Effects of Oncological Treatment During Pregnancy on Mother and Child

Oncological Treatment During Pregnancy: Pharmacokinetics of Chemotherapy and Long Term Follow up of the Offspring

treatment during pregnancy, obstetrical outcome, maternal survival

The Netherlands Cancer Institute

Erasmus Medical Center

San Gerardo Hospital

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Charles University, Czech Republic

University Hospital, Gasthuisberg

MD, PhD

Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Subjects exposed to I131 before the age of 18 years

Elizabeth K Cahoon

The nuclear power plant accident at Chornobyl released large quantities of Iodine-131 and other radioisotopes of iodine in the atmosphere, contaminating thousands of square kilometers and exposing millions of people. For this study, a well-defined subset of Ukrainian children aged 0-18 years or in utero at the time of the accident are being identified and examined by well-trained specialists for thyroid disease every two years for at least three cycles. The study is a collaborative effort of research in Ukraine and the United States.

The cohort will include approximately 13,000 persons who were children in 1986, all or most of whom have had their thyroids measured for radioactivity during the weeks immediately following the accident (or whose mothers had measurements taken while the child was in utero). Under a rigid research protocol these subjects will receive diagnostic thyroid examinations, including palpation, ultrasound scanning, thyroid hormone and other laboratory tests, and, if indicated, fine-needle aspiration biopsy. Interview information regarding residential, health, diet and lifestyle history will also be collected. All subjects will be followed for thyroid cancer morbidity and mortality. Thyroid cancers will be confirmed by expert pathology examination of tissue.

In addition to the analysis of thyroid radiation measurements made in May-June, 1986, efforts will be made to reconstruct each person's exposure and to estimate the radiation dose to the thyroid. This will involve the reconstruction of deposition patterns and environmental pathways of the radioiodines, and of the location, dietary characteristics, and lifestyle of each person throughout the exposure period.

The aim of the study is to carry out valid and credible assessments of the early and late morphologic and functional changes in the thyroid glands of persons exposed to radiation from radioactive materials released as a consequence of the Chornobyl nuclear power plant accident. The emphasis is on dose- and time-specific changes.

In the course of the study other possible risk factors will be examined including dietary iodine intake during and after 1986, and the ingestion of potassium iodide for thyroid protection shortly after the accident.

The nuclear power plant accident at Chornobyl released large quantities of Iodine-131 and other radioisotopes of iodine into the atmosphere, contaminating thousands of square kilometers and exposing millions of people. For this study, a well-defined subset of Ukrainian children aged less than 18 years or in utero at the time of the accident were identified and have been followed up. The main cohort was screened for thyroid disease every two years for 4 cycles from 1998 through 2007, with another cycle resumed in 2011(fifth cycle), which is now underway. The in utero cohort was screened between 2003-2006 and has also been screened since 2011. The study is a collaborative effort of researchers in Ukraine and the United States.

The main cohort includes approximately 13,000 persons who were children in 1986, all or most of whom had their thyroids measured for radioactivity during the weeks immediately following the accident. Under a rigid research protocol, these subjects receive diagnostic thyroid examinations, including palpation, ultrasound scanning, thyroid hormone and other laboratory tests (only in the first four cycles). If indicated, they are referred for a fine-needle aspiration biopsy. Interview information regarding residential, health, diet and lifestyle history has also been collected. All subjects are followed for thyroid cancer morbidity. Thyroid cancers are confirmed by expert pathology examination of tissue obtained during surgery. The in utero cohort includes a total of 2,582 individuals. In addition starting in 2003, \~ 7,000 parents of members of the main cohort who were under age 10 y at the time of the accident were interviewed in order to increase the accuracy of recall. These individuals were listed as new subjects. Altogether, 23,143 individuals have been accrued in this study.

In addition to the analysis of thyroid radiation measurements made in May-June, 1986, radiation dose to the thyroid was estimated drawing on such data as the reconstruction of deposition patterns and environmental pathways of the radioiodines, and of the location, dietary characteristics, and lifestyle of each person throughout the exposure period. For in utero subjects, fetal dose has been estimated based on the mother s thyroid dose.

The aim of the study is to assess the early and late morphologic and functional changes in the thyroid glands of persons exposed at young ages to radiation from radioactive materials released as a consequence of the Chernobyl nuclear power plant accident, with emphasis on dose-and time-specific changes.

There have been several amendments to the protocol: transition in 2008 to cancer case ascertainment using a passive form of follow-up based on linkage to the National Cancer Registry of Ukraine (NCRU) which still continues during thefifth cycle of screening; a sub-study involving an additional follow-up examination of those cohort members who were diagnosed with benign nodular thyroid pathology during one of the earlier four active screening cycles; and genetic studies (gene expression and germline SNP studies) of thyroid cancer in this Ukrainian cohort exposed to radioiodines from Chernobyl fallout as children or adolescents; and most recently, a pilot study of genomic characterization of thyroid cancers (2013).

Scientific Protocol for the Study of Thyroid Cancer and Other Thyroid Disease in Ukraine Following the Chernobyl Accident

Scientific Protocol for the Study of Thyroid Cancer and Other Thyroid Diseases in Ukraine Following the Chernobyl Accident

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Autoimmune Diseases

Endometrial Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Endocrine Disruptors

DES-exposed mothers, daughters and sons, and identified subjects

DES-unexposed mothers, daughters and sons, and identified subjects

Rebecca Troisi, D.Sc.

Diethylstilbestrol (DES), a drug first synthesized in 1938, was administered to several million pregnant women in the U.S. and Europe for the prevention of spontaneous abortion and premature delivery. In 1971, Herbst reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancers in males and females. In the mid-1970's, several separate cohorts of DES-exposed daughters and unexposed comparison groups were followed for the occurrence of cancer, precursor lesions, and reproductive effects, but systematic follow-up of these cohorts had ceased by 1990. In 1992, Congress passed a bill (H;.R. 4178) mandating the continued follow-up of DES-exposed cohorts. The National Cancer Institute, in collaboration with five field centers, reassembled previously studied cohorts of DES-exposed and unexposed mothers, daughters and sons, and identified subjects with documented exposure status who had not been studied previously, through familial links within the cohorts. Standardized baseline questionnaires were mailed to cohort members to ascertain the risk of cancer and other disorders. Pathology reports were collected for reported cancers and preneoplastic conditions. Two separate rounds of follow up have been conducted and a third is almost complete. Patients from the Registry for Research on Hormonal Transplacental Carcinogenesis (the Registry) will be added to the follow-up effort in the third phase. The purpose of this study is to continue the follow-up, by means of mail questionnaires and medical record collection, which was begun during the first phase of the study. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer. Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer and DES is a potent estrogen. Cancer risk in the sons will also continue to be assessed, especially for increased risks of prostate cancer. Since the offspring who were exposed to DES in utero are currently reaching their late forties, when cancer rates begin to rise, it is important to continue the follow-up of these cohorts to determine if there are long-term increases in cancer risk.

Diethylstilbestrol (DES), a drug first synthesized in 1938, was administered to several million pregnant women in the U.S. and Europe for the prevention of spontaneous abortion and premature delivery. In 1971, Herbst reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancers in males and females. In the mid-1970's, several separate cohorts of DES-exposed daughters and unexposed comparison groups were followed for the occurrence of cancer, precursor lesions, and reproductive effects, but systematic follow-up of these cohorts had ceased by 1990. In 1992, Congress passed a bill (H;.R. 4178) mandating the continued follow-up of DES-exposed cohorts of mothers, daughters, sons and grandchildren. The National Cancer Institute, in collaboration with five field centers, reassembled previously studied cohorts of DES-exposed and unexposed mothers, daughters and sons, and identified subjects with documented exposure status who had not been studied previously, through familial links within the cohorts. Standardized baseline questionnaires were mailed to cohort members to ascertain the risk of cancer and other disorders. Pathology reports were collected for reported cancers and preneoplastic conditions. Three separate phases of follow up have been conducted. Patients from the Registry for Research on Hormonal Transplacental Carcinogenesis at the University of Chicago will be added to the follow-up effort and mailed the questionaire used in the third phase of follow-up. A cohort of daughters of women exposed and not exposed to DES in utero have been added to the study to assess the effects of DES on third generation women.

The purpose of this study as a whole is to continue the follow-up, by means of mailed questionnaires and medical record collection, which was begun during the first phase of the study. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer. Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer and DES is a potent estrogen. Cancer risk in the sons will also continue to be assessed, especially for increased risks of prostate cancer. Since the offspring who were exposed to DES in utero are currently reaching their late forties, when cancer rates begin to rise, it is important to continue the follow-up of these cohorts to determine if there are long-term increases in cancer risk.

We are planning to add a biospecimen collection component to the study. We propose to conduct a pilot study, nested within our ongoing combined cohort of DES-daughters, at Boston University to determine the feasibility of recruiting women participating in our study for phlebotomy and to investigate potential differences in the hormone metabolites and methylation patterns of germline DNA in 60 of these samples representing three groups of women: those exposed to high doses of DES prenatally, those exposed to low-doses of DES prenatally, and unexposed. Hormone metabolites and DNA methylation will be assessed in relation to DES exposure. Hormone metabolites will be measured at NCI s Frederick laboratory. DNA methylation will be assessed by Dr. Shuk-Mei Ho, the Jacob G. Schmidlapp Chair of the Department of Environmental Health, Director of the Center for Environmental Genetics, and Co-Leader of the Hormonal Malignancies Program in the Joint Cancer Center, at the College of Medicine in the University of Cincinnati, OH, and at Stephen Chanock s laboratory at NCI. The findings of this pilot study may have profound implications for the mechanisms by which endocrine disruption in the fetus influences human health. IRB approval of the data collection protocol has been received from Boston University.

Continuation of Follow-up of DES-Exposed Cohorts

Study title	NCT ID	Conditions	Eligibility	Organization
Effects of Oncological Treatment During Pregnancy on Mother and Child	NCT00330447	Cancer Pregnancy	18 Years -	University Hospital, Gasthuisberg
Scientific Protocol for the Study of Thyroid Cancer and Other Thyroid Disease in Ukraine Following the Chernobyl Accident	NCT00341094	Thyroid Cancer Non-Cancer Thyr... Non Thyroid Can...	18 Years - 48 Years	National Institutes of Health Clinical Center (CC)
Continuation of Follow-up of DES-Exposed Cohorts	NCT00340600	Breast Cancer Autoimmune Dise... Prostate Cancer Ovarian Cancer Endometrial Can...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for in utero

Every month we try and update this database with for in utero cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for in utero

Every month we try and update this database with for in utero cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for in utero cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.