Abstract
Purpose
We aimed to investigate the treatment effect of chemotherapy on ground-glass opacity (GGO)-featured lung adenocarcinoma radiologically and pathologically.
Methods
This retrospective study included patients who met the following criteria: (1) presence of lung GGO lesions before chemotherapy for other concurrent malignancies; (2) underwent surgical resection of GGO-featured primary lung adenocarcinoma. The last computed tomography images before chemotherapy (CT1) and the last images before GGO resection (CT2) were reviewed to assess radiologic response. Specimens of the resected tumors were reviewed to evaluate the histopathologic response. Immunohistochemical staining of ki-67, caspase-3 and β-gal was performed and compared between these tumors and a propensity score-matched (1:1) cohort of GGO-featured lung adenocarcinoma without prior chemotherapy.
Results
Forty-four patients with 55 GGO lesions were included. There were 20 mixed GGOs and 22 invasive adenocarcinomas. These patients all received at least three cycles of chemotherapy for other concurrent malignancies in breast, lung, cervix, ovary or rectum. Thirty-four (77%) patients received chemotherapy regimens that contained platinum, pemetrexed, paclitaxel, docetaxel or gemcitabine. The median interval between CT1 and CT2 was 10 months. Radiologically, all the GGO lesions either remained unchanged or enlarged. There was no chemotherapy-induced histopathologic response (necrosis, fibrosis or inflammation) in any of these tumors. The protein expression of ki-67, caspase-3 and β-gal was comparable between GGO-featured lung adenocarcinoma with or without prior chemotherapy.
Conclusion
GGO-featured lung adenocarcinoma has no response to chemotherapy. For these patients, chemotherapy should not be a treatment option.
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Funding
This work was supported by the National Natural Science Foundation of China (81930073, 81772466, and 81972171), Shanghai Shenkang Hospital Development Center City Hospital Emerging Cutting-edge Technology Joint Research Project (SHDC12017102) and Shanghai Municipal Health Commission Key Discipline Project (2017ZZ02025 and 2017ZZ01019).
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432_2020_3234_MOESM1_ESM.tif
Supplementary figure1 Representative images of protein staining of ki-67, caspase-3 and β-gal in ground glass opacity featured lung adenocarcinoma with or without prior chemotherapy (TIF 2005 kb)
432_2020_3234_MOESM2_ESM.tif
Supplementary figure 2 Batch effects arising from two RNA-seq datasets (Fudan University Shanghai Cancer Center, FUSCC, blue; The Cancer Genome Atlas, TCGA, red) were successfully adjusted using principal components analysis (PCA). The first two principal components of the ComBat-transformed data which capture the most variance are shown. Furthermore, the PCA plot of samples adjusted for batch effects showed a clear separation between tumor (blue) and normal lung tissue samples (red) (TIF 503 kb)
432_2020_3234_MOESM3_ESM.tif
Supplementary figure 3 Ground glass opacity (GGO) featured lung adenocarcinoma had a significantly higher predicted half-maximal inhibitory concentration (IC50) for cisplatin, docetaxel, gemcitabine, vinorelbine and etoposide than solid lung adenocarcinoma. Prediction of chemotherapeutic response for each sample was based on the Genomics of Drug Sensitivity in Cancer (TIF 226 kb)
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Zhang, Y., Deng, C., Ma, X. et al. Ground-glass opacity-featured lung adenocarcinoma has no response to chemotherapy. J Cancer Res Clin Oncol 146, 2411–2417 (2020). https://doi.org/10.1007/s00432-020-03234-6
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DOI: https://doi.org/10.1007/s00432-020-03234-6