Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Cancer Diagnoses following Abnormal Cell-Free DNA Detected via Non-Invasive Prenatal Testing: A Case Series, Literature Review, and Proposed Management Model (#312)

Eryn Dow 1 , Alison Freimund 1 , Kortnye Smith 1 , Rodney J Hicks 1 , Peter Jurcevic 2 , Mark Shackleton 3 , Paul James 1 , Andrew Fellowes 1 , Mark Pertile 4 , George McGillivray 2 4 , Linda Mileshkin 1
  1. Peter MacCallum Cancer Centre, Parkville, VIC, Australia
  2. The Royal Women's Hospital, Parkville, Victoria, Australia
  3. Alfred Health, Melbourne, Victoria, Australia
  4. Victorian Clinical Genetics Service, Parkville, Victoria, Australia

Background: Non-invasive prenatal testing (NIPT) is a next generation sequencing technology used to screen for foetal chromosomal aneuploidy via cell free DNA (cfDNA) derived from maternal blood1.   As a sensitive screening test that can be performed from 10 weeks gestation, it has been rapidly accepted into obstetric practice1.  NIPT utilises placental cfDNA as surrogate for foetal DNA and can therefore be influenced by several factors including placental mosaicism, maternal mosaicism, and/or co-twin demise.  The NIPT platform detects all cfDNA; it can therefore also be influenced by cell free circulating tumour DNA (ctDNA) from a maternal malignancy.  Prior publications demonstrate that routine NIPT results in the detection of pre-symptomatic malignancy with an incidence of 0.004%2-4. However, evidence supporting the management of these patients remains sparse.

Aims: This study aimed to develop management guidelines for women with NIPT results suspicious for maternal malignancy.

Methods: The Peter MacCallum Cancer Centre’s (PMCC) experience of seven cases where abnormal NIPT results lead to investigation for maternal malignancy were reviewed, along with the published literature.  This information was used to develop guidelines for the management of such cases.

Results: Six of the seven women (86%) referred to PMCC for investigation were diagnosed with advanced malignancies, including colorectal and breast cancer, melanoma and Hodgkin’s lymphoma. Reviewing the diagnostic yield of investigations preformed contributed to the development of the proposed guidelines. This includes low dose 18FDG-PET-CT, which had a 100% sensitivity and specificity in this small series.

Conclusion: Based on our single centre experience of seven cases, as well as a review of the literature, guidelines for the investigation and management of women with NIPT results suspicious of malignancy are proposed.  These guidelines include maternal and foetal investigations as well as consideration of the complex medical, psychological, social and ethical needs of these patients and their families.

  1. Romero R, Mahoney MJ. Noninvasive Prenatal Testing and Detection of Maternal Cancer. JAMA. 2015; 314(2):131-3.
  2. Amant F, Verheecke M, Wlodarska I, Dehaspe L, Brady P, Brison N, et al. Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing. JAMA Oncology. 2015; 1(6):814-9.
  3. Bianchi DW, Chudova D, Sehnert AJ, Bhatt S, Murray K, Prosen TL, et al. Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies. JAMA. 2015; 314(2): 162-9.
  4. Dharajiya NG, Grosu DS, Farkas DH, McCullough RM, Almasri E, Sun Y, et al. Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing. Clinical Chemistry. 2018; 64(2): 329-35.