N3 (> 6 cm) squamous cell carcinoma of the head and neck: outcomes and predictive factors in 104 patients.

OBJECTIVE: To report outcome and predictive factors in patients with N3 (> 6 cm) non-metastatic locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with a conservative approach or with initial surgery. METHODS: 104 patients were included: 69 treated with radiotherapy (RT) ± chemotherapy (CT) and 35 with nodal surgery with or without primary tumour resection, which was completed in 30 patients by adjuvant RT ± CT. Positron-emission tomography-computed tomography (PET-CT) guided surveillance after RT ± CT was standard. RESULTS: Two-year overall survival (OS) and locoregional control (LRC) were 39.4% and 37.5%, respectively. In univariate analysis, body mass index (BMI), performance status (PS), p16 status and haemoglobin value influenced OS and disease-free survival (DFS). In multivariate analysis, p16 positive status and BMI ≥ 25 remained independent prognostic factors for better OS (p = 0.023) and DFS (p = 0.002). Only under/normal weight remained an independent and adverse significant prognostic factor in multivariate analysis for regional control (RC). Patients treated with primary RT ± CT had slightly better 2-year OS (43.5% versus 33.3%, p = 0.31). CONCLUSIONS: Patients with N3 LAHNSCC have poor prognosis, but long term LRC is achievable, especially in overweight patients and those with a good PS.

Inter-observer and segmentation method variability of textural analysis in pre-therapeutic FDG PET/CT in head and neck cancer.

AIM: Characterizing tumor heterogeneity with textural indices extracted from 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) is of growing interest in oncology. Several series showed promising results to predict survival in patients with head and neck squamous cell carcinoma (HNSCC), analyzing various tumor segmentation methods and textural indices. This preliminary study aimed at assessing the inter-observer and inter-segmentation method variability of textural indices in HNSCC pre-therapeutic FDG PET/CT. MATERIALS AND METHODS: Consecutive patients with HNSCC referred in our department for a pre-therapeutic FDG PET/CT from January to March 2016 were retrospectively included. Two nuclear medicine physicians separately segmented all tumors using 3 different segmentation methods: a relative standardized uptake value (SUV) threshold (40%SUVmax), a signal-to-noise adaptive SUV threshold (DAISNE) and an image gradient-based method (PET-EDGE). SUV and metabolic tumor volume were recorded. Thirty-one textural indices were calculated using LIFEx software (www.lifexsoft.org). After correlation analysis, selected indices' inter-segmentation method and inter-observer variability were calculated. RESULTS: Forty-three patients (mean age 63.8±9.3y) were analyzed. Due to a too small segmented tumor volume of interest, textural analysis could not be performed in 6, 11 and 15 cases with respectively DAISNE, 40%SUVmax and PET-EDGE segmentation methods. Five independent textural indices were selected (Homogeneity, Correlation, Entropy, Busyness and LZLGE). There was a high inter-contouring method variability for Homogeneity, Correlation, Entropy and LZLGE (p<0.0001 for each index). The inter-observer reproducibility analysis revealed an excellent agreement for 3 indices (Homogeneity, Correlation and Entropy) with an intraclass correlation coefficient higher than 0.90 for the 3 methods. CONCLUSIONS: This preliminary study showed a high variability of 4 out of 5 textural indices (Homogeneity, Correlation, Entropy and LZLGE) extracted from pre-therapeutic FDG PET/CT in HNSCC using 3 different contouring methods. However, for each method, there was an excellent agreement between observers for 3 of these textural indices (Homogeneity, Correlation and Entropy).

Prognostic value of textural indices extracted from pretherapeutic 18-F FDG-PET/CT in head and neck squamous cell carcinoma.

BACKGROUND: This study aimed at assessing the prognostic value of textural indices extracted from 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/CT in a large cohort of patients with head and neck squamous cell carcinomas (HNSCC) of any anatomic subsite and staging. METHODS: Consecutive patients with HNSCC referred for a pretreatment FDG-PET/CT were retrospectively included and followed up for a minimum of 2 years. Standardized uptake value, metabolic tumor volume (MTV), and textural indices were calculated using LIFEx software. Prognostic significance of parameters was assessed in univariate and multivariate analysis. RESULTS: Textural indices were extracted in 284 patients (mean age = 63.7±9.6 years). In univariate analysis, MTV and 4 textural indices-Correlation, Entropy, Energy, and Coarseness-were significantly correlated with overall survival (OS). In multivariate analysis, MTV (P = .008) and Correlation (P = .028) remained independently correlated to OS. CONCLUSION: This study showed that MTV and 1 textural index extracted from pretherapeutic FDG-PET/CT (Correlation) were independent prognostic factors of OS in patients with HNSCC.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

BACKGROUND: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. OBJECTIVE: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. PATIENTS AND METHODS: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). RESULTS: Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively). CONCLUSIONS: Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.