Molecular Testing for Gastric Carcinoma

Bassel El-Rayes, MD: Molecular testing has become a key part of treating patients with gastric carcinoma, especially now that we understand not all gastric cancers are the same, and there are subgroups that require different treatment approaches. In my practice, I usually perform NGS [next-generation sequencing] on all patients with newly diagnosed stage IV gastric cancer.

In management, especially in the frontline setting, one of the biomarkers of importance is HER2/neu. Patients who have HER2/neu expression would benefit from chemotherapy plus trastuzumab, as is our case.

Another important marker is MSI [microsatellite instability]. Patients who have microsatellite instability would benefit from immune therapy in the upfront setting. Similarly, PD-L1 expression is measured by using the CPS [combined positive score], an important predictor for immune therapy response. This is especially important since immune therapy is becoming a more commonly used treatment in the upfront setting in stage IV gastric cancer.

Given the number of biomarkers that are key in making a clinical decision, I have found that NGS sequencing allows me to get the input on all these biomarkers plus additional biomarkers that may come into play in treatment selection.

Furthermore, liquid biopsies are available and have certain advantages over tumor biopsies. They are available when tissue is scanned or the biopsies are not of good quality for analysis, and they can be used serially to monitor changes in the molecular profile of patients as they progress from frontline, to second-line, to third-line therapy, making it more feasible than tumor biopsies. In my practice I tend to use both because I feel they complement each other.

In addition to the challenges of managing gastric cancer in 2020, we have to add the challenge of COVID-19 [coronavirus disease 2019]. In patients with gastric cancer, chemotherapy affects immunity, and that increases the risk of complications from infectious diseases, especially COVID-19. Therefore, as we plan the care of these patients it is key to make sure that we educate them about preventive measures for COVID-19, and encourage patients to receive vaccinations for the flu and other illnesses that can exacerbate COVID-19. Lastly, we want to ensure that our workplace is kept safe for patients who are accessing our work environment.

These are 3 steps that I have implemented to try to mitigate some of the risks of treating with chemotherapy and immune-suppressive agents during this pandemic.

Transcript edited for clarity.

Case: A 66-Year Old Male With HER2+ Gastric Cancer

Initial presentation

  • A 66-year-old man complains of a 4-month history of decreased appetite and diffuse abdominal pain
  • PMH: DM, medically controlled; colonoscopy at age 55 was unremarkable; no personal or family history of cancer
  • PE: bloating; abdominal pain on deep palpation; otherwise unremarkable

Clinical Workup

  • Labs: Hb 9.5 g/dL, plt 104 x 109/L; other lab values WNL
  • Endoscopy with biopsy: showed well differentiated papillary adenocarcinoma with invasion into the lamina propria
  • EUS: irregular borders on extraluminal surfaces with hyperechogenic spots
  • Abdominal/pelvic CT confirmed a 5.1 cm lesion with indistinct margins in the antrum of the stomach
  • Stage IV gastric adenocarcinoma; ECOG 1
  • IHC score for HER2 expression 3+
  • Biomarker testing: PD-L1 0%, NTRK -
  • MSI by PCR/MMR by IHC: stable


  • He was started on FOLFOX + trastuzumab
    • Well tolerated for 5 cycles
    • Imaging showed 3 new small pulmonary lesions
  • Treatment changed to docetaxel + ramucirumab
    • Treatment was well tolerated for 4 cycles when he developed neutropenia
  • Patient was started on trastuzumab deruxtecan; repeat HER2 expression score was not indicated
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