ONCAlert | 2017 San Antonio Breast Cancer Symposium
Lung Cancer Case Studies

David Berz, MD, PhD, and Philip Bonomi, MD Discuss Liquid Biopsies Versus Tissue Biopsies

Published Online:Mar 12, 2016
This Dialogues in Diagnostics includes David Berz, MD, PhD, clinical oncologist, Beverly Hills Cancer Center, and Philip Bonomi, MD, professor, Rush University Medical Center.

Molecular Diagnostics in NSCLC with David Berz, MD, PhD, and Philip Bonomi, MD



How might mutational results with a liquid biopsy (based on circulating tumor DNA) differ from those obtained through traditional tissue biopsy methods?

 

BERZ: Although somatic mutations are felt to happen on the tissue base, liquid biopsies allow for certain advantages. One of which being our understanding that many tumors, including lung cancers, are highly heterogeneous. Not only can histologies like squamous cell biology and adenocarcinomas coexist within the same tumor volume, there is also a strong degree of molecular heterogeneity identified in those tumors. The liquid biopsy allows for a more comprehensive molecular assessment of the entirety of the tumor burden in any given patient.

 

BONOMI: The other aspect of that is that you may have a fairly sizable mass, but not much tumor cellularity. A tumor could be mostly inflammatory cells and stroma. So in a regular biopsy, putting needles in and getting a lot of cores would not be beneficial for diagnosis. In contrast, a liquid biopsy is likely to show DNA circulating in the blood and you will be able to determine mutations, due to having more information available..

Naoko T. is a 74-year-old retired high school teacher originally from Nagoya, Japan. She currently lives in San Diego, California and enjoys tennis and traveling with her husband.

  • In July of 2013, the patient was diagnosed with NSCLC after presenting to her PCP with dyspnea and intermittent back and chest pain; cardiac workup was negative, and the patient has no history of smoking
  • Initial CT scan showed a large mass in the right lower lobe and 2 small lesions in the T9 and T10 vertebra, suspicious for metastatic disease
  • Biopsy and histology of the primary mass and metastatic lesion showed TTF-1+, p40 -, p60 - consistent with bronchogenic adenocarcinoma NSCLC
  • Mutational analysis on the primary mass showed EGFR exon 19 deletion and no other actionable mutations
  • Biopsy and histology of the primary mass and metastatic lesion showed TTF-1+, p40 -, p60 - consistent with bronchogenic adenocarcinoma NSCLC
  • She is initiated on systemic therapy with erlotinib for metastatic disease
  • After 5 cycles, the patient displays good response, with clinical improvement and radiologic improvement in primary and metastatic lesions

In November 2014, after several months of stable disease, the patient returns for follow-up visit with worsening back pain, and her CT scan is consistent with progression of metastatic lesions.

  • Biopsy and mutational analysis of the thoracic lesion is unsuccessful due to limited DNA content, and the patient is initiated on a second-generation EGFR TKI, with presumed resistance to erlotinib
  • After 2 cycles, the patient developed severe diarrhea and fatigue requiring hospitalization and was not reinitiated on therapy
  • A brief trial of systemic chemotherapy was also unsuccessful due to febrile neutropenia requiring hospitalization

At this point, the patient declined further treatment, and by March 2015, she returned with worsening dyspnea and declining performance status

  • A second biopsy of the thoracic lesion is attempted, and allelotyping shows no actionable mutation; sample is T790M negative
  • Patient is also screened for circulating tumor DNA in urine, which shows T790M-positive disease
  • She is initiated on a third-line TKI and shows clinical and radiologic improvement following 3 cycles
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