Maternal cancer may be transmitted to child during vaginal delivery: NEJM

Two boys, 23-months-old and a 6-years-old, whose mothers had undetected cervical cancer at delivery went on to develop lung cancer in early childhood, most likely resulting from mother-to-infant transmission of uterine cervical tumor cells, according to Ayumu Arakawa, MD, of the National Cancer Center in Tokyo, and colleagues. Researchers identified incidentally during an analysis of the results of routine next-generation sequencing testing of paired samples of tumor and normal tissue. This analysis was undertaken in TOP-GEAR (Trial of Onco-Panel for Gene-profiling to Estimate both Adverse Events and Response during Cancer Treatment), a prospective gene-profiling trial involving patients with advanced cancer.

FINDINGS OF PATIENT 1 WERE:

The researchers described a case of 23 months old boy (Patient 1) presented to a local hospital with a 2-week history of a productive cough. Patient's CT revealed multiple masses scattered along the bronchi in both lungs. So, the doctors performed a biopsy which revealed neuroendocrine carcinoma of the lung with focal glandular differentiation. He was delivered vaginally at 39 weeks after his mother previously tested negative for cervical cancer via Pap test 7 months before. However, the mother received a diagnosis for squamous cell carcinoma of the cervix 3 months after giving birth. The child received frequent follow-up but was not treated until he turned age 3 years. He was referred to National Cancer Center for further treatment. The researchers found few lesions were spontaneously regressed, but some masses spread along the bronchi was confirmed using CT.

They administered five cycles of chemotherapy with cisplatin and irinotecan, followed by two cycles of carboplatin and etoposide. They noted some tumors shrank, but others subsequently progressed. After two chemotherapy regimens and further disease progression, physicians enrolled the patient in a clinical trial of nivolumab therapy. He did not inherit HLA class I alleles, a phenomenon that may have led to initial survival of maternal cancer cells. After four cycles of nivolumab at a dose of 3 mg per kg every 2 weeks, researchers observed shrinkage of all lesions. After 14 cycles of nivolumab and lobectomy, researchers noted no evidence of disease recurrence.

FINDINGS OF PATIENT 2 WERE:

A 6-year-old boy (Patient 2) was presented to a local hospital with chest pain. Researchers found a mass on the child's left lung and diagnosed him with mucinous adenocarcinoma. His mother was previously diagnosed with a cervical polypoid tumor during pregnancy. As a cervical cytologic test was negative and the tumor appeared stable, the mother delivered the boy vaginally at 38 weeks.

The tumor in the boy was considered to be inoperable. So they administered him five cycles of paclitaxel and cisplatin followed by three cycles of paclitaxel and carboplatin and two cycles of paclitaxel and irinotecan chemotherapy. By the end of therapy, researchers noted a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels so the treatment was discontinued. Three months later, the disease recurred in the left lung. After several cycles of chemotherapy and disease recurrence, he underwent total left pneumonectomy and, 15 months later, was free from disease.

The authors wrote, "The transmission was demonstrated by the fact that the tumors in both male children lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles (which were not inherited in the children's germline) with tumors from the mothers" and further added, "The peribronchial pattern of tumor growth in both children suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth".

Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors.

The authors concluded, "These cases indicate that mother-to-infant transmission of uterine cervical cancer is possible during vaginal delivery; therefore, a cesarean section should be recommended for mothers with uterine cervical cancer".

They further added, "We report two cases of transmission of uterine cervical tumors in mothers to the lungs of infants. Next-generation sequencing of paired samples of tumor and normal tissue may be a useful tool to diagnose cancer that is transmitted from mothers to infants and to understand the prevalence of this transmission".

For further information:

https://www.nejm.org/doi/full/10.1056/NEJMoa2030391