Radiomic biomarkers for platinum-refractory head and neck cancer in the era of immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

Preoperative prediction model to evaluate salvage surgery in patients with recurrent or second primary oral cavity squamous cell carcinoma.

OBJECTIVE: In approximately 50% of patients with oral cavity squamous cell carcinoma (OCSCC), the disease progresses after curative surgery. However, the role of salvage surgery (SS) is controversial, and life expectancy after SS is unknown. METHODS: In this study, 262 patients with OCSCC with locoregional recurrence and second primary OCSCC were retrospectively enrolled and divided into a resectable (55.0%, 144/262) and unresectable (45.0%, 118/262) groups. After excluding neck recurrence only, SS had been performed 195 times in the resectable group. The corresponding preoperative clinicopathologic factors and postsurgery survival (PSS) of each SS were pooled for analysis. RESULTS: Median survival after disease progression was 64.2 and 10.4 months for the resectable and unresectable groups, respectively. In the resectable group, one-fifth (19.5%, 37/190) of the patients died within 1 year of SS (PSS < 1 year), and one-third (32.8%, 64/195) of the patients had undergone SS two or more times. The interval from the last surgery ≤ 12 months, depth of invasion of the last surgery > 1 cm, and clinical evidence of nodal disease at the preoperative evaluation were independent predictors of poor PSS. A scoring prediction model was established with 1 point for each factor. The results revealed 1-year postsurgery death rates of 10.3% in the low-risk group (score: 0-1) and 48.6% in the high-risk group (score: 2 or 3) (P < 0.001). CONCLUSIONS: In conclusion, an effective scoring model predicting life expectancy after SS for patients with OCSCC was established.

Prediction Model of Distant Metastasis in Oral Cavity Squamous Cell Carcinoma With or Without Regional Lymphatic Metastasis.

Patients with oral cavity squamous cell carcinoma (OCSCC) who develop distant metastasis (DM) face poor outcomes, and effective prediction models of DM are rare. A total of 595 patients with OCSCC were retrospectively enrolled in this study. Because pathological N staging significantly influences the development and mechanisms of DM, the patients were divided into nodal-negative (pN-) and -positive (pN+) groups. Clinical outcomes, prognoses, and prediction models were analyzed separately for both groups. Overall, 8.9% (53/595) of these patients developed DM. Among the DM cases, 84.9% (45/53) of them developed DM within the first 3 years. The median overall survival, locoregional recurrence-free survival, time until DM development, and postmetastatic survival were 19.8, 12.7, 14.6, and 4.1 months, respectively. Distinguishing patients who only developed locoregional recurrence from those with DM according to locoregional conditions was difficult. Age, surgical margin, and early locoregional recurrence were predictors of DM that were independent of time until DM in the pN- group; the lymphocyte-to-monocyte ratio, presence of lymphovascular invasion, and early locoregional recurrence in the pN+ group were determined. If one point was scored for each factor, then two scoring systems were used to classify the patients into low- (score = 0), intermittent- (score = 1), or high- (score = 2 or 3) risk for the pN- and pN+ groups. According to this scoring system, the 3-year DM rates for the low, intermittent, and high risk subgroups were 0.0%, 5.9%, and 17.8% for the pN- group and 7.1%, 44.9%, and 82.5% for the pN+ group, respectively. These systems also effectively predicted DM, and the areas under the curve predicted DM occurring within the first 3 years were 0.744 and 0.820 for the pN- and pN+ groups, respectively. In conclusion, effective scoring models were established for predicting DM.

Predictors of early progression after curative resection followed by platinum-based adjuvant chemoradiotherapy in oral cavity squamous cell carcinoma.

OBJECTIVES: Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown. METHODS: In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical-pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for DFIs. Survival was estimated using the Kaplan-Meier method and log-rank tests, and a scoring system for predicting early progression was established. RESULTS: One-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or <2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively. CONCLUSIONS: The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.