BACKGROUND: Platina and taxanes are frequently used chemotherapeutic agents to treat cancer, also when diagnosed during pregnancy. This report presents an interim analysis of the largest series of children prenatally exposed to platinum and/or taxane agents and aims to determine their physical health and neurocognitive outcomes. METHODS: As part of a multicentre, prospective cohort study (ClinicalTrials.gov: NCT00330447), children born between 2000 and 2022 were assessed between 2005 and 2024 at ages 1.5-18 years (interim analysis; median length of follow-up, 3.2 years (IQR 3.0-6.4)) by a comprehensive neurocognitive test battery, parent-reported questionnaires, and a physical assessment. Mixed-effects regression and Type III Analysis of Variance models were used to investigate associations between these outcomes and platinum/taxane cumulative dose and agent type, with best-fit models corrected for age and covariates (gestational age at birth, chemotherapy timing, other chemotherapy, sex, parental education level, maternal death). FINDINGS: In total, 144 children were included (13% exposed to platinum, 62% to taxanes, 25% to both). Of these, 101 were assessed at age 1.5 years, 96 at age 3, 63 at age 6, 32 at age 9, 18 at age 12, 7 at age 15, and 2 at age 18 years. Neurocognitive outcomes were within normal ranges across all ages, compared with test-specific normative data. Eight children (6%) reported ototoxicity, seven (5%) reported chronic medical conditions, three (2%) had congenital malformations, and two (1%) were diagnosed with Attention-Deficit Hyperactivity Disorder. Thirty-three children (23%) needed extra neurocognitive support, of which 64% were born preterm. Children prenatally exposed to paclitaxel scored lower on visuospatial (β = 0.64 ± 0.21, p = 0.0052) and verbal memory (β = 0.68 ± 0.27, p = 0.015) than those exposed to docetaxel. INTERPRETATION: In this interim analysis, we found normal neurocognitive outcomes and no increase in congenital malformations nor medical conditions after prenatal exposure to platinum/taxane-based chemotherapy. However, owed to the limited number of older children, further investigation regarding their potential neurotoxicity and its long term effects is necessary in follow-up studies with larger samples. FUNDING: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Cooperatio program, Research Foundation Flanders.

• Klíčová slova
• Cancer during pregnancy, Child development, Platinum-based chemotherapy, Prenatal chemotherapy exposure, Taxane-based chemotherapy,
• Publikační typ
• časopisecké články MeSH

The incidence of cancer during pregnancy is steadily rising because of the postponement of plans for childbearing. One of the most common cancers diagnosed during pregnancy is cervical cancer. Diagnosis of most cases usually occurs in the early stages, but there are still cases of tumors staged IB2 and higher. In these cases, the treatment strategy entails administration of neoadjuvant chemotherapy. However, a universally recognized standardized regimen for neoadjuvant chemotherapy treatment of cervical cancer during pregnancy has yet to be established. The chemotherapy agents used during treatment are known for their fetal adverse effects. The aim of the therapy is to attain full-term pregnancy while minimizing fetal toxicity and decreasing tumor size. In this case report, we present a first-time sequential chemotherapy administration to minimize the cumulative toxicity of individual regimens and demonstrate the benefits for the patient and fetus.

• Klíčová slova
• Cervical cancer, Individualized therapy, Neoadjuvant chemotherapy, Pregnancy,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.

• MeSH
• dítě MeSH
• kognice MeSH
• kohortové studie MeSH
• lidé MeSH
• nádory * farmakoterapie   MeSH
• novorozenec MeSH
• předčasný porod * MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH