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Objective: Radiotherapy (RT) against head and neck squamous cell carcinomas (HNSCC) may lead to severe toxicity in 30-40% of patients. The normal tissue complication probability (NTCP) models, based on dosimetric data refined the normal tissue dose/volume tolerance guidelines. In parallel, the radiation-induced nucleoshuttling (RIANS) of the Ataxia-Telangiectasia Mutated protein (pATM) is a predictive approach of individual intrinsic radiosensitivity. Here, we combined NTCP with RADIODTECT©, a blood assay derived from the RIANS model, to predict RT toxicity in HNSCC patients., Methods: RADIODTECT© cutoff values (i.e. 57.8 ng/mL for grade⩾2 toxicity and 46 ng/mL for grade⩾3 toxicity) have been previously assessed. Validation was performed on a prospective cohort of 36 HNSCC patients treated with postoperative RT. Toxicity was graded with the Common Terminology Criteria for Adverse Events (CTCAE) scale and two criteria were considered: grade⩾2 oral mucositis (OM2), grade⩾3 mucositis (OM3) and grade⩾2 dysphagia (DY2), grade⩾3 dysphagia (DY3). pATM quantification was assessed in lymphocytes of HNSCC patients. The discrimination power of the pATM assay was evaluated through the Area Under the Receiver Operator Characteristics Curve (AUC-ROC). Two previously described NTCP models were considered, including the dose to the oral cavity and the mean dose to the parotid glands (OM2 and OM3) and the dose to the oral cavity, to the larynx and the volume of pharyngeal constrictor muscles (DY2 and DY3)., Results: Combining NTCP models with RADIODTECT© blood test improved the AUC-ROC. Considering the prediction of mucositis, AUC-ROC NTCP+RADIODTECT© =0.80 was for OM2, and AUC-ROC NTCP+RADIODTECT© =0.78 for OM3. Considering the prediction of acute dysphagia, AUC-ROC NTCP+RADIODTECT© =0.71 for DY2 and for DY3., Conclusions: Combining NTCP models with a radiosensitivity biomarker might significantly improve the prediction of toxicities for HNSCC patients.

Background: To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published., Methods: We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population., Results: Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm 3 were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability., Conclusion: Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population., (© 2019 Wiley Periodicals, Inc.)

Introduction: In head and neck cancer (HNC) patients, fatigue is present throughout the course of treatment and during follow-up. There are limited data about the prevalence and factors associated with fatigue in HNC survivors. The objectives of this study were to assess the prevalence of fatigue and its interference with daily life activities and examine the association between fatigue and gender, age, primary tumour site, Human Papillomavirus (HPV) status, previous oncologic therapy, and time since end of treatment., Methods: Consecutive locally advanced HNC patients having completed curative treatment at least 1 year earlier and free of disease were asked to fill in the Brief Fatigue Inventory (BFI) questionnaire. Fatigue was categorized according to BFI average score as absent (0), mild (>0 to <4), moderate (≥4 to ≤6), and severe (>6 to ≤10)., Results: From February 2015 to July 2016, 129 patients (median age = 60 years old; 67% male) were evaluated. Primary sites of cancer were oropharynx (46%, with 4/5 patients HPV positive), nasopharynx (22%), larynx/hypopharynx (14%), oral cavity (13%), and paranasal sinus or salivary gland (5%). Oncologic treatment was completed 12 to 96 months earlier (median = 34 months). Fatigue was reported as absent in 15% of the patients, mild in 67%, moderate in 11%, and severe in 7%. No association between BFI average score and the analyzed variables was identified., Discussion: Moderate and severe fatigue was reported in 18% of HNC survivors. Further research is needed to assess its causes and improve the management.