A 37-year-old non-smoker Hispanic woman without relevant medical background sought medical attention due to a 6-week history of cough, dyspnea, general weakness, and intermittent fever in March 2018. A computed tomography (CT) scan revealed a left lung solid lesion and ipsilateral pleural effusion. Histopathological analysis of the performed biopsy reported a poorly differentiated adenocarcinoma with a predominant micropapillary pattern, positive for cytokeratin 7, thyroid transcription factor-1, and napsin A. Pleural fluid cytological examination was positive for malignant cells. EGFR mutation (exon 19 deletion) was confirmed by polymerase chain reaction (PCR).
Positron emission tomography/computed tomography (PET-CT) showed nodular thickening of the left parietal pleura associated with pleural effusion and a dominant pulmonary lesion in the left upper lobe associated with an increased 18-FDG uptake (SUVmax 12.09). A secondary lesion was identified in the apicoposterior segment, also associated with an increased uptake (SUVmax 5.2) ( Figure 1A ). Brain magnetic resonance imaging (MRI) was negative for metastatic disease.
She started therapy with afatinib (40 mg per day) in April 2018. The first radiological evaluation at week 8 showed stable disease; however, the disease-related symptoms significantly improved. A second imaging evaluation in December 2018 exhibited a partial response, with residual disease in the apicoposterior segment, receiving stereotactic body radiation therapy (SBRT) as consolidative therapy. In July 2019, the patient experienced an oligoprogression within the radiation field, visualizing an enlargement and increased uptake in the follow-up PET/CT ( Figure 1B ). The patient underwent a left upper lobectomy and mediastinal lymphadenectomy achieving a complete response (CR) as the best outcome ( Figure 1C ). From August 2019 to January 2021, the patient continued afatinib until the 34th cycle maintaining CR. In January 2021, the patient became pregnant confirmed by hCG determination and transvaginal ultrasound showing the viability of the fetus. Once the pregnancy was documented, afatinib was discontinued. The fetus was exposed to afatinib for less than 6 weeks according to her last menstrual cycle. The mother decided to keep with the ongoing pregnancy after a discussion with the multidisciplinary tumor board (MTB) and institutional ethics committee.
After counseling with the MTB, involving neonatologists, perinatologists, and medical oncologists, the chosen tyrosine kinase inhibitor (TKI) to proceed was osimertinib (80 mg per day) initiated at week 12, corresponding to the second trimester. Osimertinib was the preferred option based on the increased selectivity to EGFR binding pocket and was administered with acceptable tolerance during the second trimester (May 2021 to July 2021). The initial evaluation with a pelvic ultrasound reported no morphological alterations in the baby ( Figures 2A-C ). Nevertheless, at 28 weeks of gestation (WOG), severe oligohydramnios and intrauterine growth restriction (IUGR) (low fetal weight of 835 +- 107 g) were demonstrated in the ultrasound. As a result, osimertinib treatment was delayed and resumed 2 weeks later until the amniotic fluid was normalized and the fetal weight improved. At 32.4 WOG, the follow-up ultrasound revealed for the second time signs of oligohydramnios and reduced fetal weight (1,476 +- 145 g). At this time, the MTB decided to discontinue osimertinib until delivery.
At 37.3 WOG, an elective C-section was performed. The patient delivered a female baby weighing 2,466 g and measuring 48 cm. Apgar scores were 8 and 9 at 1 and 10 min, respectively. No congenital malformations or organic alterations were identified at childbirth. Screening for genetic and metabolic disorders ruled out any deficiency. The baby was discharged after 2 days in stable condition. No evidence of metastasis in the placenta or amniotic fluid was found. After delivery, the patient resumed osimertinib at the same dose. In her most recent PET/CT scan (February 2023), the patient continues without disease progression. At 16 months of age, the baby is healthy with no developmental alterations.
The clinical events described in this case are represented in a timeline in  Figure 3 .