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Published on: September 25, 2018
[Histological Transformation from Non-small Cell Lung Cancer to Small Cell Lung Cancer Induced by Immune Checkpoint
Xiting Chen1, Wenyuan He2, Ning Yang3
1Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Abstract:
Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Insights
Immune checkpoint inhibitors can cause non-small cell lung cancer to transform into small cell lung cancer, a rare event indicating resistance and poor prognosis. Monitoring NSE and repeat biopsies are crucial for managing this transformation.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biology
Background:
- Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype.
- Immune checkpoint inhibitors (ICIs) have improved outcomes for driver gene-negative NSCLC.
- Histological transformation to small cell lung cancer (SCLC) after ICI treatment is an emerging concern.
Purpose of the Study:
- To investigate the phenomenon of histological transformation from NSCLC to SCLC following ICI therapy.
- To analyze clinical characteristics, molecular basis, and treatment strategies for this transformation.
- To highlight the significance of this transformation as a mechanism of immunotherapy resistance.
Main Methods:
- Case report of SCLC transformation in a KRAS-mutated lung adenocarcinoma patient after 16 months of ICI combination therapy.
- Systematic review of 22 similar published cases.
- Analysis of clinical data, molecular profiles, and treatment responses.
Main Results:
- Small cell transformation is identified as a critical mechanism of immunotherapy resistance.
- Patients with transformed SCLC demonstrate a poor prognosis.
- The study identified 23 cases of NSCLC transforming to SCLC post-ICI therapy.
Conclusions:
- Histological transformation to SCLC is a significant challenge in NSCLC treatment with ICIs.
- Dynamic monitoring of neuron-specific enolase (NSE) and repeat biopsies are essential for early detection.
- Improved recognition and management strategies are needed to enhance outcomes for patients experiencing this transformation.
