A 49-year-old woman with no smoking history presented to the clinic with patchy shadows in her lung, but she had no respiratory symptoms. On examination, laboratory tests showed a modestly elevated level of carcinoembryonic antigen (CEA) at 6.98 ng/ml, and no signs of active infection were found. A computed tomography (CT) scan showed pneumonia-like opacities and high-density lesions with aerated bronchus in the right middle and lower lobes (Fig. 1a), as well as a few pneumonia-like opacities in the left lower lobe (Fig. 1b). The percutaneous biopsy of the right middle lobe revealed lepidic adenocarcinoma. The patient then underwent a right middle and lower lobectomy, a right upper lobe wedge resection, and lymph node dissection. Pathological examination of the specimens from the right middle and lower lobes revealed a moderately to poorly differentiated adenocarcinoma with predominant lepidic growth and a small area of micropapillary pattern (Fig. 1c). The specimen from the right upper lobe showed adenocarcinoma in situ (Fig. 1d). The surgical margins were negative, and no lymph node involvement was observed (0/14). The diagnosis was primary lung adenocarcinoma (P-ADC), pT4(m)N0. Next-generation sequencing (NGS) identified KRAS G12V and PTCH1 E340V mutations, and immunohistochemical (IHC) staining indicated negative PD-L1 expression (tumor proportion score, TPS < 1%).

CT scan of lung-mediastinal window and pathology test. A, B Axial CT images of the chest showing pneumonia-like opacities and high-density lesions with aerated bronchus. H&E of the surgical specimens of right middle and lower lobes (C) and right upper lobe (D) confirm an adenocarcinoma

Following surgery, the patient received four cycles of adjuvant chemotherapy with pemetrexed plus cisplatin. However, after treatment, her CEA levels increased from 1.9 to 6.3 ng/ml, and CT scan revealed increased ground glass opacities (GGO) in the left lower lobe (Fig. 2a). Percutaneous biopsy of the left lung confirmed the presence of well-differentiated adenocarcinoma with predominant papillary morphology. NGS also revealed the presence of KRAS G12V and PTCH1 E340V mutations, and PD-L1 expression was positive (TPS 2%). Despite receiving multiple lines of treatment with chemotherapy, immunotherapy, and antiangiogenic therapy (Fig. 3), the disease continued to progress, as evidenced by markedly elevated serum CEA levels (Fig. 3) and increasing diffuse GGO, patches of high density, and nodular shadows on CT scan (Fig. 2b).

Finally, the therapeutic schedule with Afatinib, Bevacizumab plus Vinorelbine was prescribed. This new regimen resulted in shrinkage of the lesion area (improved stable disease) (Fig. 2c) and simultaneous decrease in serum CEA levels (Fig. 3). At the time of the manuscript preparation, the patient was still taking Afatinib and had achieved a progression-free survival over 14 months, with no apparent adverse effects observed.

CT scan of lung-mediastinal window after four-cycles of adjuvant chemotherapy (A), at disease progression (B), and achieving lesion aera shrinkage (C)

Treatment course and dynamic monitoring of CEA with time line