Normal Tissue Complication Probability (NTCP) modeling and validation of quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline using quality of life questionnaire for parotid gland during head and neck radiotherapy

Introduction:
Radiation therapy is the main treatment method for head and neck cancers, which comprise 3–5% of all cancers. A major side effect of this treatment is complication of the parotid glands, i.e. xerostomia, which occurs at relatively low doses. This complication leads to mouth dryness which is the most common problem for head and neck cancer survivors. There are different grades of xerostomia and severe xerostomia is defined as a long-term reduction in the function of salivary gland to less than 25% relative to the pre-radiotherapy baseline value. The grading of xerostomia is usually assessed by patient self-reports carried out by the quality of life questionnaire (QoL), designed based on indigenous criteria and internationally recognized protocols. In recent years several studies have focused on normal tissue complication probability (NTCP) modeling of xerostomia using quality of life questionnaires with or without functional analysis based on various standard model parameters. Lyman (LKB) model is commonly used to predict the normal tissue complication probability (NTCP). This model uses the patient’s calculated dose volume histogram of (DVH) of an organ at risk (OAR) and the dose response curve parameters. The quantitative analysis of normal tissue effects in the clinic (QUANTEC) effort is to refine the guidelines based on 3D dose/volume and outcome data. According to QUANTEC guideline to limit the severity of xerostomia, maximum dose received by one or both of parotid glands should be 20 Gy and 25 Gy (20/25 Gy), respectively. The aim of this study was to evaluate the NTCP model parameters for all grades of acute parotid complications using the LKB model during head and neck conformal radiotherapy treatment and using a QoL questionnaire. Materials and Methods:
 50 patients with head and neck cancer who have been referred for radiotherapy to Milad Hospital in Isfahan, Iran, were selected. QoL questionnaire datasets of patients with squamous cell carcinoma and lymph node cancers beside the parotids were within the radiation field were analyzed. The European organization for research and treatment of cancer (EORTC) QLQ HN35 was used in three stages (before, during and at the end of treatment). Prescribed dose per fraction was modified to 2 Gy/fraction equivalent dose for each patients. The LKB model with DVH reduction to form the equivalent uniform dose (EUD), known as LEUD was used.  The model parameters of TD₅₀ (Tolerance Dose 50%) and m was assessed by fitting the patient reported complication data to the normal tissue complication probability (NTCP) curve. Results:
 One patient (2%) at stage 2 and 5 patients (10%) at stage 3 experienced grade 3 xerostomia. The dose-response curves (LKB model) for occurrence of xerostomia was fitted to the QoL data which were collected at stages 2 and 3. These parameters were TD₅₀ =23.3Gy, m =1 and TD₅₀ =21.6 Gy, m =1 at stage 2 and stage 3, respectively.
Conclusion:
 The agreement between the NTCP modeling based on QoL questionnaire data and the QUANTEC guidelines, confirms the cutoff values of 20/25 Gy to spare the parotid gland.