A pregnant patient with ALK-positive non-small cell lung cancer treated with alectinib: A case report and review of the literature.

Oncogenic rearrangements in the anaplastic lymphoma kinase (ALK) gene account for 5% of non-small cell lung cancer (NSCLC) cases. ALK inhibitors have markedly improved the outcome of metastatic ALK-positive NSCLC (ALK+ mNSCLC) by increasing long-term overall survival. Although a diagnosis of NSCLC during pregnancy or the peripartum period is rare, ALK+ NSCLC accounts for 38% of NSCLC cases in women of childbearing age (18-45 years old). The younger age and prolonged survival of patients with ALK+ mNSCLC bring new challenges for lung cancer and obstetrics research, and raises questions related to pregnancy and family planning. The present study described normal fetal development and no obstetric complications in a patient infected with HIV diagnosed with ALK+ mNSCLC, who became pregnant during treatment with alectinib, a third-generation ALK inhibitor.

Impact of chemotherapy during pregnancy on fetal growth.

BACKGROUND: Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. OBJECTIVE: This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. STUDY DESIGN: All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016); (2) "low risk SGA" (birth weight below the 10th percentile), but an estimated growth above the 10th percentile; (3) "fetal growth disturbance", which did not meet all FGR criteria; (4) "non-FGR". Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlock's formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. RESULTS: We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer (n = 132, 66%). Regimens included anthracyclines (n = 121, 60%), (anthracyclines and) taxanes (n = 45, 22%) and platinum (n = 35, 17%). Fetal growth abnormalities were detected in 75 pregnancies: 43 (21%) FGR, 10 (5%) low risk SGA and 22 (8.5%) fetal growth disturbance. Chemotherapy prior to 20 weeks of gestation (47% vs. 25%, p = .04) and poor maternal gestational weight gain (median percentile 15 (range 0-97) vs. 8 (0-84), p = .03) were more frequent in the FGR group compared to the non-FGR group, whereas no difference was seen for specific chemotherapy or cancer types. Univariable regression identified gestational weight gain, hypertension, systemic disease, parity, neonatal sex and maternal BMI as confounders for birth weight percentiles. Multivariable regression revealed that each additional week of chemotherapy was associated with lower birth weight percentiles (-1.06; 95%CI -2.01; -0.04; p = .04), and that later initiation of chemotherapy was associated with an increase in birth weight percentile (1.10 per week; 95%CI 0.26; 1.95; p = .01). Each additional week of chemotherapy was associated with lower EFW and abdominal circumference (AC) percentiles (-1.77; 95%CI -2.21; -1.34, p < .001; -1.64; 95%CI -1.96; -1.32, p < .001, respectively). CONCLUSIONS: This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.

Severe Gestational Gigantomastia: from Mastectomy to Staged Autologous Breast Reconstruction. A Case Report.

Gestational gigantomastia (GGM) is a rare condition characterized by a massive overgrowth of breast tissue during pregnancy. Surgical sanction may be required when conservative measures fail. In this study, we report the case of a 29-year-old woman who presented with an evolutive GGM responsible for physical and emotional distress, despite medical treatment. A multidisciplinary decision was made to induce delivery at 32 weeks. In the postdelivery period, the patient developed breast wounds, complicated with septic cardiomyopathy. An emergency bilateral mastectomy was then carried out, together with banking of both nipple-areola complexes. Thereafter, delayed bilateral 2-stage breast reconstruction was started at 12 months with subcutaneous tissue expanders, later on followed by implants removal and autologous reconstruction with bilateral deep inferior epigastric artery perforator flaps and bilateral nipple replantation.

A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.

INTRODUCTION: Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. MATERIAL AND METHODS: Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. RESULTS: In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. CONCLUSIONS: In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy.

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients.

Prenatal Care during and after Breast Cancer Treatment.

Cancer associated with pregnancy is defined by diagnosis during pregnancy, lactation, or the first year after delivery. The decision about type of treatment depends on the cancer stage and gestational age. Termination of pregnancy does not seem to modify the maternal prognosis for breast cancers. Interdisciplinary meetings and discussions are needed to evaluate and balance the maternal and fetal risks. In this chapter, we discuss about how to prevent or treat maternal and fetal complications of surgery and chemotherapy in pregnancy-associated breast cancer.

Effects of chemotherapy on placental development and function using in vitro culture of human primary cytotrophoblasts.

Introduction Cancers during pregnancy can be treated with chemotherapy after the first trimester but the treatment is associated with smaller placentas and an increased risk of stillbirth, fetal growth retardation and preterm delivery. We decided to assess the effect of several chemotherapeutic agents on placental development by using in vitro culture of human term cytotrophoblasts. Methods Cytotrophoblasts isolated from term placentas were cultured for 48 h and treated for 24 h with epirubicin, docetaxel, vinblastine, methotrexate, tamoxifen, 4-hydroxytamoxifen, and endoxifen. First, cell viability was assessed. Then, the effect of the treatment on trophoblast differentiation and placental angiogenesis was assessed by quantifying hCG and PlGF mRNA and protein expression. Finally, the expression of two efflux transporters, BCRP and MDR1 was investigated. Results Epirubicin only strongly decreased cell viability. Epirubicin, docetaxel, and vinblastine inhibited HCGB and PlGF expression while methotrexate, tamoxifen and its two metabolites increased it. BCRP was essentially expressed in syncytiotrophoblasts and MDR1 in undifferentiated cytotrophoblasts. Their expression was not affected by the drugs but vinblastine increased BCRP mRNA expression by 2.8-fold. Discussion The most commonly used chemotherapeutic drugs are well supported in vitro by syncytiotrophoblasts, except for epirubicin, which was very cytotoxic. Chemotherapy perturbed the expression of genes normally upregulated during placental differentiation and angiogenesis but not the expression of the drug transporters. Further studies looking at the effect of combination therapy and the transporter capacities to reject the drugs will be needed to better define the effects of chemotherapy on placental development and function.

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.

Gynecologic cancers in pregnancy: guidelines of a second international consensus meeting.

OBJECTIVES: This study aimed to provide timely and effective guidance for pregnant women and health care providers to optimize maternal treatment and fetal protection and to promote effective management of the mother, fetus, and neonate when administering potentially teratogenic medications. New insights and more experience were gained since the first consensus meeting 5 years ago. METHODS: Members of the European Society of Gynecological Oncology task force "Cancer in Pregnancy" in concert with other international experts reviewed the existing literature on their respective areas of expertise. The summaries were subsequently merged into a complete article that served as a basis for discussion during the consensus meeting. All participants approved the final article. RESULTS: In the experts' view, cancer can be successfully treated during pregnancy in collaboration with a multidisciplinary team, optimizing maternal treatment while considering fetal safety. To maximize the maternal outcome, cancer treatment should follow a standard treatment protocol as for nonpregnant patients. Iatrogenic prematurity should be avoided. Individualization of treatment and effective psychologic support is imperative to provide throughout the pregnancy period. Diagnostic procedures, including staging examinations and imaging, such as magnetic resonance imaging and sonography, are preferable. Pelvic surgery, either open or laparoscopic, as part of a treatment protocol, may reveal beneficial outcomes and is preferably performed by experts. Most standard regimens of chemotherapy can be administered from 14 weeks gestational age onward. Apart from cervical and vulvar cancer, as well as important vulvar scarring, the mode of delivery is determined by the obstetrician. Term delivery is aimed for. Breast-feeding should be considered based on individual drug safety and neonatologist-breast-feeding expert's consult. CONCLUSIONS: Despite limited evidence-based information, cancer treatment during pregnancy can succeed. State-of-the-art treatment should be provided for this vulnerable population to preserve maternal and fetal prognosis. SUPPLEMENTARY INFORMATION: Supplementary data on teratogenic effects, ionizing examinations, sentinel lymph node biopsy, tumor markers during pregnancy, as well as additional references and tables are available at the extended online version of this consensus article, go to http://links.lww.com/IGC/A197.

Cervical cancer in pregnant women: treat, wait or interrupt? Assessment of current clinical guidelines, innovations and controversies.

Cervical cancer during pregnancy is relatively uncommon. However, the incidence is expected to increase as more women delay childbearing. When preservation of the pregnancy is desired, optimal treatment is a major challenge to all. Whereas delay of treatment is an option for pre-invasive disease, and also small invasive carcinomas without lymph node involvement, management of tumours >2 cm remains experimental. Type of treatment needs to be individualized and depends mainly on gestational age, disease stage, and histology. Extensive counselling regarding the maternal and foetal risks is required. In this current review, we aim to summarize available data and treatment guidelines concerning cervical cancer in pregnancy. Controversies and research priorities are also identified.

Tongue cancers during pregnancy: Case reports and review of literature.

BACKGROUND: Due to its rarity, there is no standard treatment for tongue cancers that concur with pregnancy. Treatment depends on the stage of cancer, gestational age of the pregnancy, and the wish of the mother to maintain the pregnancy. The purpose of this study was to review the literature and to report 5 new cases. METHODS: Twelve cases of tongue cancer during pregnancy were already reported between 1987 and 2009. We report 5 new cases and first administration of concomitant radiochemotherapy for tongue cancer. RESULTS: Median age of the patients was 29 years, 65% of diagnoses were made after the first trimester of pregnancy. Different treatment modalities are used to treat tongue cancer during pregnancy. CONCLUSION: We hypothesize that tongue cancer treatment adhering to standard protocols provides the best guarantee to cure the mother. Based on a growing experience and insight taking fetal safety into consideration, the available data suggest that standard treatment is a realistic option.