Purpose: To investigate the impact of treatment-related toxicity on health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma treated with radiotherapy either alone or in combination with chemotherapy or surgery. Patients and Methods: The study sample was composed of 425 disease-free patients. Toxicity was scored according to the European Organisation for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) late radiation-induced morbidity scoring system. HRQoL was assessed using the EORTC Quality of Life Questionnaire C30. These assessments took place at 6, 12, 18, and 24 months after completion of radiotherapy. The analysis was performed using a multivariate analysis of variance. Results: Of the six RTOG scales investigated, two significantly affected self-reported HRQoL, salivary gland (RTOG_xerostomia) and esophagus/pharynx (RTOG_swallowing). Although RTOG_xerostomia was reported most frequently, HRQoL was most affected by RTOG_swallowing, particularly in the first 18 months after completion of radiotherapy. Conclusion: Late radiation-induced toxicity, particularly RTOG_swallowing and RTOG_xerostomia, has a significant impact on the more general dimensions of HRQoL. These findings suggest that the development of new radiation-induced delivery techniques should not only focus on reduction of the dose to the salivary glands, but also on anatomic structures that are involved in swallowing.

The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1mm axial slices. The atlas can also be obtained in DICOM-RT format on request. Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers.

Most new radiation techniques, have been introduced primarily to reduce the dose to normal tissues in order to prevent radiation-induced side effects. Radiotherapy with protons is such a radiation technique that due to its superior beam properties compared to photons enables better sparing of normal tissues. This paper describes a stepwise methodology to select patients for proton therapy when the primary aim is to reduce side effects. This method has been accepted by the Dutch health authorities to select patients for proton therapy. In addition, an alternative method is described in case randomised controlled trials are considered not appropriate.

Purpose: A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods: The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results: The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion: A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.

Purpose The purpose of this meta-analysis was to determine the additional value of neoadjuvant, concurrent, and/or adjuvant chemotherapy to radiation in the treatment of locally advanced nasopharyngeal carcinoma (NPC) with regard to the overall survival (OS) and the incidence of local-regional recurrences (LRR) and distant metastases (DM). Patients and Methods To be eligible, full published studies had to deal with biopsy-proven NPC and have patients randomly assigned to receive conventional radiotherapy (66 to 70 Gy in 7 weeks) or radiotherapy combined with chemotherapy. Results Ten randomized clinical studies were identified, including 2,450 patients. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI, 0.71 to 0.95; P = .01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = .02) was found among these three categories. The largest effect was found for concomitant chemotherapy, with a pooled HR of 0.48 (95% CI, 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of LRR and DM. Conclusion The results of this study indicate that concomitant chemotherapy in addition to radiation is probably the most effective way to improve OS in NPC.