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

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

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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