Targeted treatments after chemoradiotherapy failure in a patient with relapsed, advanced non‑small cell lung cancer with on‑therapy circulating tumor biomarker monitoring: A case report

Abstract

Ongoing investigations of targeted therapeutic agents and their increased clinical applications, together with research in genomics and proteomics, have explored a variety of novel approaches for treatment of lung cancer, and 'molecular subtypes' have been defined based on specific actionable genetic aberrations. Liquid biopsies, including circulating tumor DNA (ctDNA) testing, are of value for cancer diagnosis and comprehensive genomic profiling, such as the identification of cancer subtypes and major genetic alterations in cancer cells. The case of a 66-year-old male patient with newly-diagnosed driver mutation-negative advanced non-small cell lung cancer (NSCLC) who underwent conventional therapy is described in the present report. The patient underwent regular monitoring, including continuous ctDNA analysis, imaging and assessment of tumor marker levels such as carcinoembryonic antigen (CEA). The patient initially presented with deep vein thrombosis which affected both lower extremities and without any symptoms in the lung, with a positron emission tomography scan identifying irregular pulmonary nodules in the right lower lobe and enlarged right supraclavicular lymph nodes. Subsequent ultrasound-guided fine-needle aspiration with nodule biopsy indicated advanced unresectable disease at stage IIIB based on the Tumor-Node-Metastasis staging system by the American Joint Committee on Cancer. Next-generation sequencing of tumor tissue and peripheral blood confirmed driver mutation-negative genes, including epidermal growth factor receptor, rat sarcoma, ALK receptor tyrosine kinase, ROS1 proto-oncogene receptor tyrosine kinase and rearrangement during transfection (RET). After 5 years of chemoradiotherapy and surveillance of ctDNA and CEA levels, detectable kinesin family member 5B (KIF5B)-RET fusion in ctDNA and rising CEA levels prompted early scans, which identified disease progression. The patient subsequently received the oral RET inhibitor pralsetinib, with treatment being currently ongoing for ≥17 months without detectable KIF5B-RET ctDNA or elevated CEA levels, with an ongoing minor response and stable disease based on Response Evaluation Criteria in Solid Tumors v1.1 on imaging. The present case illustrates the potential role of on-therapy circulating tumor biomarker monitoring as a non-traumatic method to evaluate therapy response and detect early disease progression in patients with advanced NSCLC. Integration of circulating tumor biomarker testing into the management of patients with advanced NSCLC requires additional prospective studies to actively assess and elucidate optimal treatment strategies.

Keywords: NSCLC; RET fusion; case report; ctDNA; pralsetinib.

Figure 1.

Histopathology showing cancer cells in the lymphoid tissue from the right supraclavicular fossa since the first visit in April 2016. Epithelioid cells are present in scattered nests and micropapillary structures, and focal calcifications, cytological atypia and mitotic figures occur in the lymphoid tissue from the right supraclavicular fossa.

Figure 2.

Imaging assessments of abdominal lymph node metastasis during treatment. The numeric value adjacent to the image number represents the time interval in days from the first visit. (A and B) No significant changes from earlier images of biopsy-confirmed RET-fusion-positive stage IV NSCLC prior to pralsetinib treatment. (C and D) Stable disease with pralsetinib during treatment. (E and F) Stable disease with pralsetinib on-treatment. Red arrows indicate changes in the size of abdominal lymph node metastasis. (A) and (B) demonstrated no significant changes from earlier images of biopsy-confirmed RET-fusion-positive stage IV NSCLC prior to pralsetinib treatment. (C-H) demonstrate stable disease with pralsetinib on-treatment. Size in (A-H) show changes in size of the left adrenal metastasis. CT, computed tomography; NSCLC, non-small cell lung cancer.

Figure 3.

Changes in carcinoembryonic antigens, neutrophil, and hemoglobin during pralsetinib treatment. (A) Changes in CEA since November 2021. Elevated levels of CEA pretreatment and decreased levels posttreatment were demonstrated during post-line treatment since November 2020. (B and C) The neutrophil count (×10⁹/l) and hemoglobin level (g/l) were measured before and after treatment with pralsetinib, starting from 1,994 days after the initial visit. CEA, carcinoembryonic antigen.