Advanced stage nasopharyngeal cancer (NPC) shows highly variable treatment outcomes, suggesting the need for independent prognostic factors. This study aims at developing a magnetic resonance imaging (MRI)-based radiomic signature as a prognostic marker for different clinical endpoints in NPC patients from non-endemic areas. A total 136 patients with advanced NPC and available MRI imaging (T1-weighted and T2-weighted) were selected. For each patient, 2144 radiomic features were extracted from the main tumor and largest lymph node. A multivariate Cox regression model was trained on a subset of features to obtain a radiomic signature for overall survival (OS), which was also applied for the prognosis of other clinical endpoints. Validation was performed using 10-fold cross-validation. The added prognostic value of the radiomic features to clinical features and volume was also evaluated. The radiomics-based signature had good prognostic power for OS and loco-regional recurrence-free survival (LRFS), with C-index of 0.68 and 0.72, respectively. In all the cases, the addition of radiomics to clinical features improved the prognostic performance. Radiomic features can provide independent prognostic information in NPC patients from non-endemic areas.

In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools.

Acute dermatitis is the most common radio-induced side effect during treatment for head and neck cancer. The use of a wide variety of agents is reported to handle skin toxicity. Our aim was to review the literature and synthesize current available evidence. A comprehensive search was performed on multiple electronic databases until February 2017 and a systematic approach was carried out according to PRISMA guidelines. A total of 17 papers (950 patients on the whole) met the inclusion/exclusion criteria, with 12 randomized controlled trials and five nonrandomized observational and prospective studies. Generally speaking, there was no strong evidence to support the superiority of any specific intervention neither in prevention nor in therapeutic settings. Well-designed randomized studies including quality of life measurements are needed.

Background: This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT). Methods: Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients' quality of life (QoL) through Skindex-16 questionnaire.

Background: Occupational exposure to carcinogens contributes greatly to the etiology of sinonasal cancer (SNC), but the role of different risk factors in determining different histological subtypes is disputed. Methodology: All consecutive surgical epithelial SNC cases (case-series study) underwent a systematic occupational medicine examination to determine previous exposure to a wide range of work-related chemical hazards. Results: We investigated 65 SNC cases including intestinal-type adenocarcinoma [ITAC] squamous-cell carcinoma [SCC], and others. Occupational exposure was recognized for 39 cases. Occupational exposures were sensibly more frequent among ITAC than among SCC or other histotypes. Occupational exposure in ITAC cases was to leather or wood dust only, while among non-ITAC cases, we recognised exposure to formaldehyde, solvents and metal fumes. A high proportion of SNC with occupational exposure originated in the ethmoidal epithelium. Conclusion: In our case-series of SNC, a very high frequency of previous occupational exposure to carcinogens was detected, suggesting that occupational hazards may be associated to the aetiopathogenesis, primarily for ITAC, but also for other histotypes. Besides leather or wood, other chemical agents must be recognized as occupational risk factors.

No abstract

6066 Background: Sinonasal epithelial tumors are rare diseases with several histotypes and poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment - IC, surgery and RT - modulated by histology, molecular profile and response to IC. Methods: Pts with untreated, operable squamous cell carcinoma (SCC), p53 wild type intestinal type adenocarcinoma (ITAC), sinonasal undifferentiated and neuroendocrine carcinoma (SNUC, SNEC) were enrolled in a single-arm, phase II, multicenter clinical trial from 2014 to 2018. Pts was treated with up to 5 IC cycles, whose regimen was selected according to histotype, followed either by curative radio-chemotherapy (CRT) (pts with ≥80% reduction of initial tumor volume (TV)) or surgery and adjuvant (C)RT. Photon and/or proton/carbon ion-based RT was employed according to disease site and stage. Primary endpoint was 5 years PFS, secondary endpoints were OS, IC ORR per RECIST 1.1 and safety. Results: Out of 39 enrolled pts, 35 pts were evaluable for primary endpoint. Two pts were only considered for safety analyses because definitive diagnosis on surgical specimen did not meet the study entry criteria; other two pts were screening failure due to inoperable disease. Five-year PFS was 38% (95% CI, 21 – 69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28 – 75), with a median OS of 36 months. Responses to IC are reported in table. Globally, 15 pts avoided surgery. Overall treatment safety was in line with multimodality intensive head and neck cancer treatments (5% of pts with G3-4 adverse event during IC). One sudden cardiac death was recorded. At a median follow up of 27 months, 5 G3-4 RT related late adverse events have been recorded (1 G3 neurotoxicity, 2 G3 hearing impairment, 2 G3 xerostomia). Three-year PFS - OS for pts achieving PR/CR vs SD/PD to IC were 49.8% - 56.7% vs 43.2% - 53%, respectively. Conclusions: Treatment of advanced SNC with histology-driven IC followed by locoregional therapy tailored to response to IC was safe and showed survival rate similar to surgery containing case series. In the first prospective study, a surgery sparing multimodal approach proved feasible and effective in IC responsive pts. Clinical trial information: NCT02099175. [Table: see text]

Background: Radiation-induced xerostomia is one of the most prevalent adverse effects of head and neck cancer treatment, and it could seriously affect patients’ qualities of life. It results primarily from damage to the salivary glands, but its onset and severity may also be influenced by other patient-, tumour-, and treatment-related factors. We aimed to build and validate a predictive model for acute salivary dysfunction (aSD) for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. Methods: A cohort of consecutive NPC patients treated curatively with IMRT and chemotherapy at 70 Gy (2–2.12 Gy/fraction) were utilised. Parotid glands (cPG, considered as a single organ) and the oral cavity (OC) were selected as organs-at-risk. The aSD was assessed at baseline and weekly during RT, grade ≥ 2 aSD chosen as the endpoint. Dose-volume histograms were reduced to the Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Model validation was performed on two cohorts of patients with prospective aSD, and scored using the same schedule/scale: a cohort (NPC_V) of NPC patients (as in model training), and a cohort of mixed non-NPC head and neck cancer patients (HNC_V). Results: The model training cohort included 132 patients. Grade ≥ 2 aSD was reported in 90 patients (68.2%). Analyses resulted in a 4-variables model, including doses of up to 98% of cPG (cPG_D98%, OR = 1.04), EUD to OC with n = 0.05 (OR = 1.11), age (OR = 1.08, 5-year interval) and smoking history (OR = 1.37, yes vs. no). Calibration was good. The NPC_V cohort included 38 patients, with aSD scored in 34 patients (89.5%); the HNC_V cohort included 93 patients, 77 with aSD (92.8%). As a general observation, the incidence of aSD was significantly different in the training and validation populations (p = 0.01), thus impairing calibration-in-the-large. At the same time, the effect size for the two dosimetric factors was confirmed. Discrimination was also satisfactory in both cohorts: AUC was 0.73, and 0.68 in NPC_V and HNC_V cohorts, respectively. Conclusion: cPG D98% and the high doses received by small OC volumes were found to have the most impact on grade ≥ 2 acute xerostomia, with age and smoking history acting as a dose-modifying factor. Findings on the development population were confirmed in two prospectively collected validation populations.