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Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.
Objective: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy.
Materials and methods: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival.
Results: In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p = 0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p < 0.01) but not with distant metastases.
Conclusions: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.
Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG).
Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed.
Results: For the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55–0.75]) on the validation cohort along with significant patient stratification (p = 0.005) and good calibration.
Conclusion: We identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.