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Introduction/Background*Due to the rarity of cancer during pregnancy, physicians not always have up to date knowledge on all possibilities of treatment during pregnancy. To support physicians with decision on optimal cancer treatment for their pregnant patients, the Advisory Board on Cancer, Infertility and Pregnancy (ABCIP) was founded under the umbrella of the International Network for Cancer, Infertility and Pregnancy (INCIP).MethodologyMedical experts from a variety of disciplines and countries were informed on this new initiative, and asked whether they were interested in actively participating in the ABCIP. Several national advisory boards were founded, as well as an overarching international board. Funding was acquired to build a website to facilitate accessibility for physicians requesting advice and a forum for online discussions and communication between the board members. Based on available literature, default texts were drafted to use in the recommendation letters.Result(s)*An online platform was created at www.ab-cip.org, where physicians are able to submit questions regarding their pregnant patients with cancer, using only anonymous patient data. A total of 73 experts from a variety of disciplines and countries are joined in the national and international boards. Of this group, experts from eight countries already expressed their interest in setting up their own national advisory board. Incoming requests are discussed by the experts on a secure forum on the website. The website generates a recommendation letter, based on available literature and expert opinion of the board members, to send back to the requesting physician. In the first month after foundation, seven requests for advice were already submitted and discussed.Abstract 705 Figure 1Conclusion*The ABCIP provides easily accessible, free of charge recommendations to physicians from all over the world with questions regarding their pregnant patients with a cancer diagnosis or patients with a cancer diagnosis who wish to become pregnant in the future.

Introduction/Background*Physicians encounter pregnant women with cancer only incidentally, leading to lack of expertise or confidence to inform and treat these patients according to up to date guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumor board (MDT) for cancer and pregnancy was founded in 2012, and consists of 33 physicians from all over the country. Requests to discuss patients in the MDT were received by e-mail and a recommendation letter was generated based on available literature and expert opinion of the board members.MethodologyAll requests and recommendations were gathered in a database and analyzed for tumor type, stage, gestational age and recommendation given. A survey was sent out to 93 physicians who requested recommendations of the MDT, containing questions regarding the their experiences with the MDT and the impact on treatment decisions.Result(s)*From December 2012 to May 2021, 209 recommendations were formulated, mostly regarding pregnant patients with breast cancer (n=65), cervical cancer (n=32), haematological malignancies (n= 32), rare cancer types (n=30) and melanoma (n=21). Questions were asked regarding possibilities of ionized imaging, chemotherapy, hormonal therapy or immunotherapy during pregnancy and possible effects on the child, the sequence of the different treatment components and questions on fertility. Response rate of the questionnaire was 54%. Overall satisfaction with the recommendations of the MDT was high, and 94% of the respondents informed their patients about consulting the MDT and felt supported by the received recommendations.Abstract 290 Figure 1Conclusion*A national MDT for cancer and pregnancy is frequently consulted and highly appreciated by physicians. Next to that, it increases expertise of its members about this rare coincidence of cancer and pregnancy. We highly recommend to establish an (inter)national MDT in each country. Figure 1 shows the important steps necessary to establish an MDT for cancer in pregnancy based on our experience.

Introduction/Background*Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases.MethodologyUsing a large data set of 88,294 NIPT performed in our University Hospital Leuven, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumour biopsy.Result(s)*Fifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, a novel multidisciplinary care path for efficient clinical management of these cases was presented.Conclusion*The here presented approach for analysing NIPT results has an unparalleled high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the novel care model that we presented here.These findings have now been accepted for publication in eClinicalMedicine (online journal of The Lancet group), showing the importance of these data.

Introduction/BackgroundThe purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management.MethodologyClinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis.ResultsThe median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy.In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations.Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers.ConclusionSurvival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important.DisclosureThis project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.Abstract P95 Figure 1Distribution of birth weight expressed in customised percentile for gestational age (n=117)Abstract P95 Figure 2Progression-free (A) and overall (B) survival of early stage HL during pregnancy

Introduction/BackgroundThe International Network of Cancer, Infertility and Pregnancy was launched in order to register women of reproductive age with a cancer diagnosis. Over the years, the project has expanded with currently 2653 cases registered by 114 centres and an annual registration rate of 150 patients. The expected rising numbers of cancer diagnosis during pregnancy as a result of an increased age at first childbirth and the possibility of early cancer detection by the non-invasive prenatal testing calls for an ongoing evaluation of clinical practice. Moreover, women might become pregnant while exposed to new target therapies that are being introduced into oncological practice.MethodologyThe INCIP database consists of a secured on-line registration tool. Oncological, obstetric and neonatal data are registered by members. Annual scientific meetings give updates on the ongoing research projects.ResultsMost patients were registered in Belgium, the Netherlands, Italy and USA and one third of participating centres are non-European. Currently 2059 patients with a cancer diagnosis or treatment during pregnancy are registered, 395 women that received fertility preservation and 199 patients with a postnatal cancer diagnosis (figure 1). Breast cancer, lymphoma and cervical cancer are the most frequent registered cancer types and the majority of patients (67%) received antenatal cancer treatment (figure 2). Most women delivered a live born baby (88%), however 47% delivered preterm and 80% of preterm deliveries were medically induced. One-fifth of neonates (21%) were small for gestational age. Congenital malformations were reported in 3% of live births.Abstract – Figure 1Registered cases by INCIPAbstract – Figure 2Management of cancer during pregnancy according to trimester of diagnosisConclusionCancer occurring in women endangers obstetrical and neonatal outcome and potentially future fertility. The INCIP registry is open for further collection of data since for such a relatively rare situation, only a large scale project will provide better insights on maternal and foetal risks assessment, which is essential for optimal patient counselling and care.DisclosureThe INCIP network would not be able to operate without the ongoing support of ESGO. Furthermore the project is supported by the Research Foundation—Flanders (FWO) in Belgium (grant no G070514N) and the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. There are no conflicting interests to declare.

Although cervical carcinoma is among the most frequently encountered malignancies during pregnancy, only four cases of neoadjuvant chemotherapy during pregnancy have been reported. A 28-year-old A0P1G2M0 was diagnosed at 15 weeks with stage Ib1 invasive squamous cervical cancer. Because she strongly desired the continuation of this pregnancy, after extensive counseling she was treated with 75 mg/m2 cisplatin every 10 days starting at 17 weeks. After six cycles, clinically and radiologically stable disease with normalization of the squamous cell carcinoma tumor marker was obtained. An elective cesarean delivery followed by radical hysterectomy and lymphadenectomy was performed at 32 weeks gestation. The pathology report revealed a moderately differentiated squamous cell carcinoma of 3.5 cm, and all 33 lymph nodes were free of disease. Neonatal examination of the baby could not reveal any abnormalities, and this was confirmed at 6 months. The use of neoadjuvant chemotherapy enabled us to continue this pregnancy until the fetus was viable. Cisplatin did not influence the short-term outcome, but only a long-term follow-up will inform us on its safety during pregnancy.

Background and Objective As a result of changes in physiology during pregnancy, the pharmacokinetics (PK) of drugs can be altered. It is unclear whether under- or overexposure occurs in pregnant cancer patients and thus also whether adjustments in dosing regimens are required. Given the severity of the malignant disease and the potentially high impact on both the mother and child, there is a high unmet medical need for adequate and tolerable treatment of this patient population. We aimed to develop and evaluate a semi-physiological enriched model that incorporates physiological changes during pregnancy into available population PK models developed from non-pregnant patient data. Methods Gestational changes in plasma protein levels, renal function, hepatic function, plasma volume, extracellular water and total body water were implemented in existing empirical PK models for docetaxel, paclitaxel, epirubicin and doxorubicin. These models were used to predict PK profiles for pregnant patients, which were compared with observed data obtained from pregnant patients. Results The observed PK profiles were well described by the model. For docetaxel, paclitaxel and doxorubicin, an overprediction of the lower concentrations was observed, most likely as a result of a lack of data on the gestational changes in metabolizing enzymes. For paclitaxel, epirubicin and doxorubicin, the semi-physiological enriched model performed better in predicting PK in pregnant patients compared with a model that was not adjusted for pregnancy-induced changes. Conclusion By incorporating gestational changes into existing population pharmacokinetic models, it is possible to adequately predict plasma concentrations of drugs in pregnant patients which may inform dose adjustments in this population.

BackgroundLittle is known about the pharmacokinetics (PK) of acetaminophen during different stages of pregnancy. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict acetaminophen PK throughout pregnancy.MethodsPBPK models for acetaminophen and its metabolites were developed in non-pregnant and pregnant women. Physiological and enzymatic changes in pregnant women expected to impact acetaminophen PK were considered. The models were evaluated using goodness-of-fit-plots and through comparison of predicted PK profiles with in-vivo PK data. Predictions were performed to illustrate the concentrations at steady state (Css-mean), used as indicator for efficacy of acetaminophen achieved following 1000 mg q6h. Furthermore, as measurement for potential hepatotoxicity, the molar dose fraction of acetaminophen converted to NAPQI was estimated.ResultsPBPK models successfully predicted the PK of acetaminophen and its metabolites in populations of non-pregnant and pregnant women. Predictions resulted in lowest Css-mean in the third trimester (4.5 mg/L), while Css-mean was 6.7, 5.6 and 4.9 mg/L in non-pregnant, first and second trimester populations, respectively. Assuming a constant increased activity of CYP2E1 throughout pregnancy, the molar dose fraction of acetaminophen converted to NAPQI was highest during the first (11.0%), followed by second (9.0%) and third trimester (8.2%), compared to non-pregnant women (7.1%).ConclusionRisk for drug related hepatotoxicity in pregnant women might be increased as more NAPQI is produced during pregnancy compared to non-pregnant women, especially during the first trimester. However, lack of information on the detoxifying capacity precludes any strong conclusions.Disclosure(s)Paola Mian received a Short term Minor (STM-2017) grant from the Stichting Sophia Kinderziekenhuis fonds to conduct this research.

BackgroundLittle is known about fetal acetaminophen (paracetamol) pharmacokinetics and its potential for toxicity, despite the frequent use of acetaminophen during pregnancy. The aim of this study was to develop a feto-maternal physiologically based pharmacokinetic model (f-m PBPK) to predict placental transfer and PK of acetaminophen and its metabolites in fetus at term pregnancy.MethodsPreviously, a pregnancy PBPK model was developed for prediction of maternal PK of acetaminophen and its metabolites. This model was structurally extended with the fetal liver, and quantitative information on the maturation of relevant enzymes was integrated. Three different approaches (ex vivo placenta perfusion experiments, scaling of passive diffusion transfer rates, and the Mobi® default method) to describe placental drug transfer were tested. Predicted maternal and fetal acetaminophen concentrations were compared with those observed in the literature. umbilical cord data at birth.ResultsThe 3 different approaches to predicted acetaminophen PK in the umiblical vein were found to yield broadly similar results. Acetaminophen exposure was similar in maternal blood compared to venous umbilical cord blood. Prediction of the median dose fraction of acetaminophen converted to its metabolites (fm) revealed higher maternal acetaminophen-glucuronide formation clearance and sulphate formation compared to that in the fetal liver (fm_glucuronide52.2 vs 0% and fm_sulphate30.4 vs 0.8%, respectively) and higher fraction of acetaminophen converted to the reactive metabolite N-acetyl-p-benzoquinone-imine (fm_NAPQI, 6.5 vs 0.06%) in pregnant women compared to their fetus.ConclusionNo differences were observed in the 3 approaches for integration of placental drug transfer. Differences in acetaminophen biotransformation to its metabolites between pregnant women and their fetuses were quantitatively predicted.Disclosure(s)Paola Mian received a Short term Minor (STM-2017) grant from the Stichting Sophia Kinderziekenhuis fonds to conduct this research.

Fetal exposure to maternal cancer during pregnancy with or without treatment did not have an adverse effect on cognitive, cardiac, or general development in early childhood. Fetal development is a complex process. At different stages of development, different aspects can be influenced by external factors (e.g., teratogenic drugs, alcohol, smoking, maternal stress, and altered nutrition). Among women in whom cancer is diagnosed during pregnancy, factors such as maternal illness, diagnostic tests, cancer treatment, and increased levels of maternal stress can negatively influence fetal development. Cancer treatment during pregnancy exposes the fetus to potentially toxic substances that influence cell division. Chemotherapeutic drugs can cross the placenta in varying amounts. 1 , 2 Data on fetal effects of maternal cancer treatment are based mainly on retrospective cohort studies. 3 – 6 From . . .