PMC6010587_01
Panel A shows the series of treatments the patient received for metastatic non-small cell lung cancer as well as the duration of each treatment. Panel B shows computed tomographic images of the primary left upper lung tumor before gefitinib administration, when the disease subsequently relapsed at 20 months, and during the response to combination chemotherapy of cisplatin and etoposide. After treatment with several chemotherapy agents and immunotherapy sequentially, the primary lesion enlarged and a metastatic lesion appeared in right lower lung after CPT-11 therapy (marked with arrows). A radiologic response to osimertinib was noted after 4 weeks of treatment. Panel C shows serial monitoring of CEA levels and pro-GRP levels before and after retreatment with osimertinib, which was initiated at a dose of 80 mg per day on day 1. The CEA level decreased with tumor shrinkage. Panel D shows the results of histology. (1) A tissue section from pleural dissemination (hematoxylin and eosin stained, magnification x400) at first diagnosis shows metastatic adenocarcinoma. (2) Tissue section of re-biopsy from the left upper lung after resistance to gefitinib (hematoxylin and eosin stained, magnification x400) shows small cell carcinoma. (3) Tissue section of second re-biopsy from the same lesion at resistance to sequential chemotherapy for SCLC (hematoxylin and eosin stained, magnification x400) shows adenocarcinoma.
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Then, because re-progression was observed during the second-line treatment, chemotherapy and immunotherapy were initiated with two cycles of amrubicin, two cycles of nivolumab, and two cycles of CPT-11 administered over a 6-month period (Fig. 1A). A follow-up CT showed worsening of the primary lesion (Fig. 1B) accompanied by an increase in plasma carcinoembryonic antigen (CEA), which is a known tumor marker of adenocarcinoma. T790M mutations. Thus, osimertinib was started at a dose of 80 mg per day, which resulted in rapid and dramatic clinical improvement with a decrease in serum CEA levels (Fig. 1C). Serial CT after initiation of osimertinib showed a partial response that lasted almost 3 months (Fig. 1B).