Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit

Simple Summary Oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The aim of this study is to test whether radiomic and blood-derived biomarkers are good candidates for refining the prognostic stratification in OPSCC. The results show that the integration of clinical, immunological, and computed tomography-derived features generally yields an improvement, regardless of the HPV status, in the prognostic stratification of OPSCC patients who are candidates for curative-intent radiotherapy. Specifically, we documented a significant role of the Lymphocyte-to-Monocyte Ratio (LMR) in this population, which has been scarcely investigated in OPSCC, as well as the detrimental effects of lymphopenia and anemia. Results are promising, and model performances compare favorably with available radiomic scores in the same setting. Further investigations on our findings are warranted to validate the results and include a more in-depth study of the prognostic role of the LMR in OPSCC. Future analyses of this dataset are planned to provide a more complete overview of the tumor-immune system interplay. Abstract Aims: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Methods: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models’ performance was compared by the C-index. Results: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52–66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5–7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80–0.84] for OS and 0.77 [CI: 0.75–0.79] for LRPFS. Conclusions: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.