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• A tool is developed to preselect HNC patients for proton therapy. • The tool uses data from VMAT plan and/or delineation to predict proton indication. • Photon vs. proton plan comparison result was predicted with a 80% accuracy by tool. • Redundant plan comparisons were prevented by 68% using the tool. • This will significantly increase cost-effectiveness of patient selection for proton. In the Netherlands, head and neck cancer (HNC) patients are selected for proton therapy (PT) based on estimated normal tissue complication probability differences (ΔNTCP) between photons and protons, which requires a plan comparison (VMAT vs. IMPT). We aimed to develop tools to improve patient selection for plan comparisons. This prospective study consisted of 141 consecutive patients in which a plan comparison was done. IMPT plans of patients not qualifying for PT were classified as 'redundant'. To prevent redundant IMPT planning, 5 methods that were primarily based on regression models were developed to predict IMPT D mean to OARs, by using data from VMAT plans and volumetric data from delineated targets and OARs. Then, actual and predicted plan comparison outcomes were compared. The endpoint was being selected for proton therapy. Seventy out of 141 patients (49.6%) qualified for PT. Using the developed preselection tools, redundant IMPT planning could have been prevented in 49–68% of the remaining 71 patients not qualifying for PT (=specificity) when the sensitivity of all methods was fixed to 100%, i.e., no false negative cases (positive predictive value range: 57–68%, negative predictive value: 100%). The advanced preselection tools, which uses volume and VMAT dose data, prevented labour intensive creation of IMPT plans in up to 68% of non-qualifying patients for PT. No patients qualifying for PT would have been incorrectly denied a plan comparison. This method contributes significantly to a more cost-effective model-based selection of HNC patients for PT. [ABSTRACT FROM AUTHOR]

• Model-based selection of patients with HNC for proton is clinically feasible. • Around 35% of HNC patients qualify for protons. • Most patients are selected based on ΔNTCP in dysphagia-related models. • Patients with advanced and pharyngeal tumor have higher probability to be selected. In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients. Patients who were subjected to MBS (Jan 2018–Sep 2019) were evaluated. A VMAT plan was created for all patients with optimal sparing of organ at risks (OARs) in normal tissue complication probability (NTCP) models for a number of toxicities. An IMPT plan was created only for those with NTCP difference (ΔNTCP) between VMAT and best-case scenario for proton (assuming 0 Gy dose for all OARs in IMPT plan) that exceeded any ΔNTCP-thresholds defined in Dutch National Indication Protocol. These patients qualified for a robust IMPT-plan creation with similar target doses and subsequent plan comparison. Of 227 patients, 141 (62%) qualified for plan comparison, of which 80 (35%) were eventually selected for proton therapy. Most patients were selected based on the ΔNTCP for dysphagia-related toxicities. The selection rate was higher among patients with advanced disease, pharyngeal tumors, and/or baseline complaints. A significant reduction in all OAR doses and NTCP values was obtained with IMPT compared with VMAT in both selected and non-selected patients, but more pronounced in patients selected for protons. Model-based selection of patients with HNC for proton therapy is clinically feasible. Approximately one third of HNC patients qualify for protons and these patients have the highest probability to benefit from protons in terms of toxicity prevention. [ABSTRACT FROM AUTHOR]

• Sarcopenia is relevant for head and neck cancer patients treated with radiotherapy. • Sarcopenia is an independent adverse prognostic factor for survival outcomes. • For oropharyngeal cancer, survival is more defined by p16 status than by sarcopenia. • Sarcopenia is associated with late radiation-induced toxicities. Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan–Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity. [ABSTRACT FROM AUTHOR]