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- Lung and Thoracic cancer
- Histological Assessment and Interobserver Agreement in Major Pathologic Response for Non–Small Cell Lung Cancer with Neoadjuvant Therapy
- Sungjin Kim, Jeonghyo Lee, Jin-Haeng Chung
- Cancer Res Treat. 2025;57(2):401-411. Published online September 9, 2024
- DOI: https://doi.org/10.4143/crt.2024.670
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Abstract
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Supplementary Material
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ePub - Purpose
Major pathologic response (MPR), defined as ≤ 10% of residual viable tumor (VT), is a prognostic factor in non–small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction.
Materials and Methods
This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images.
Results
Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; intersection-over-union score, 0.92). Excellent agreement was achieved for VT (%) (intraclass correlation coefficient=0.959) and MPR using 10% cutoff (Fleiss’ kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p < 0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012).
Conclusion
While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.
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- Genomic Landscape of Pulmonary Sarcomatoid Carcinoma
- Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung
- Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023
- DOI: https://doi.org/10.4143/crt.2023.764
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Abstract
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- Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC. -
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- Pulmonary pleomorphic carcinoma associated with cystic airspace and recurrent spontaneous pneumothorax: A case report
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- 217 Download
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