We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers ( supplementary Box S1, available at Annals of Oncology online) is encouraged.

Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. The study is registered at ClinicalTrials.gov, NCT00330447.

The diagnosis of cancer during pregnancy imposes a medical-ethical dilemma in weighing the risks of both mother and child. Increasing awareness of the feasibility of chemotherapy during pregnancy results in more pregnant patients receiving treatment for cancer. Information on obstetric and pediatric outcome of these high-risk pregnancies is greatly needed to guide physicians in patient counseling. In this review we present reported evidence for the incidence, diagnostic options, therapeutic management, obstetric risks, and neonatal outcome when cancer treatment is initiated during pregnancy. Decision-making when a cancer is diagnosed in a pregnant patient should be multidisciplinary, always taking the patient’s perspective into account. Cancer treatment during pregnancy is associated with low birth weight and preterm delivery, therefore frequent obstetric follow-up during oncological treatment in a specialized center is mandatory. Short-term clinical, cardiac, and cognitive outcome of children pre-natally exposed to cancer treatment is overall reassuring. Long-term follow-up of children is warranted to define the possible effect of pre-natal cancer treatment on general health, fertility outcome, and the risk of secondary cancers.

Targeted therapies have drastically changed the management of metastatic melanoma and have shown encouraging results on tumour progression but are also known for their high rates of adverse reactions. In general, targeted therapies are contraindicated during pregnancy due to concerns about teratogenesis. For the BRAF V600 inhibitor vemurafenib, the available literature about the effects on human pregnancy is limited to a single case report. In patients with metastatic melanoma that wish to continue their pregnancy, targeted therapies like vemurafenib offer the only possibility of improving maternal outcome. In this article, we report on a pregnant woman with metastatic melanoma who was treated with vemurafenib during pregnancy and experienced a fatal adverse reaction.

Introduction: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer.Material and methods: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed.Results: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6‐30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported.Conclusions: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account.

Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the following indications: recent chemotherapy induced febrile neutropenia (5; 12%), dose dense chemotherapy (28, 67%), poly chemotherapy (7, 17%), or prevention of neutropenia at delivery (2; 5%). Among 24 women receiving dose dense chemotherapy, three (13%) patients recovered from asymptomatic neutropenia within 5 days. One patient developed pancytopenia following polychemotherapy after which the pregnancy was complicated by chorioamnionitis and intrauterine death. Nineteen singleton livebirths (49%) were born preterm. Sixteen neonates (41%) were admitted to the Neonatal Intensive care Unit (NICU). No neonatal neutropenia occurred. Two neonates had congenital malformations. Out of 21 children in follow-up, there were four children with a motor development delay and two premature infants had a delay in cognitive development. In conclusion, the rate of maternal and neonatal complications are similar to those described in (pregnant) women treated with chemotherapy. Due to small numbers and limited follow-up, rare or delayed effects among offspring exposed to G-CSF in utero cannot be ruled out yet.