Development and validation of a prognostic index for efficacy evaluation and prognosis of first-line chemotherapy in stage III-IV lung squamous cell carcinoma.

objectivesTo establish a pre-therapy prognostic index model (PIM) of the first-line chemotherapy aiming to achieve accurate prediction of time to progression (TTP) and overall survival among the patients diagnosed with locally advanced (stage III) or distant metastasis (stage IV) lung squamous cell carcinoma (LSCC).

methodsNinety-six LSCC patients treated with first-line chemotherapy were retrospectively enrolled to build the model. Fourteen epidermal growth factor receptor (EGFR)-mutant LSCC patients treated with first-line EGFR-tyrosine kinase inhibitor (TKI) therapy were enrolled for validation dataset. From CT images, 56,000 phenotype features were initially computed. PIM was constructed by integrating a CT phenotype signature selected by the least absolute shrinkage and selection operator and the significant blood-based biomarkers selected by multivariate Cox regression. PIM was then compared with other four prognostic models constructed by the CT phenotype signature, clinical factors, post-therapy tumor response, and Glasgow Prognostic Score.

resultsThe signature includes eight optimal features extracted from co-occurrence, run length, and Gabor features. By using PIM, chemotherapy efficacy of patients categorized in the low-risk, intermediate-risk, and high-risk progression subgroups (median TTP = 7.2 months, 3.4 months, and 1.8 months, respectively) was significantly different (p < 0.0001, log-rank test). Chemotherapy efficacy of the low-risk progression subgroup was comparable with EGFR-TKI therapy (p = 0.835, log-rank test). Prognostic prediction of chemotherapy efficacy by PIM was significantly higher than other models (p < 0.05, z test).

conclusionThe study demonstrated that the PIM yielded significantly higher performance to identify individual stage III-IV LSCC patients who can potentially benefit most from first-line chemotherapy, and predict the risk of failure from chemotherapy for individual patients. KEY POINTS: • TTP and OS of first-line chemotherapy in individual stage III-IV LSCC patients could be predicted by pre-therapy blood-based biomarkers and image-based signatures. • Risk status of pre-therapy indicators affected the efficacy of first-line chemotherapy in stage III-IV LSCC patients. • Those stage III-IV LSCC patients who were able to achieve similar efficacy to EGFR-TKI therapy through chemotherapy were identified.