The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials.

To report the dosimetric results and impact of volumetric arc therapy (VMAT) on temporary alopecia and hair-loss related quality of life (QOL) in whole brain radiotherapy (WBRT). The potential of VMAT-WBRT to reduce the dose to the hair follicles was assessed. A human cadaver was treated with both VMAT-WBRT and conventional opposed field (OF) WBRT, while the subcutaneously absorbed dose was measured by radiochromic films and calculated by the planning system. The impact of these dose reductions on temporary alopecia was examined in a prospective phase II trial, with the mean score of hair loss at 1 month after VMAT-WBRT (EORTC-QOL BN20) as a primary endpoint and delivering a dose of 20 Gy in 5 fractions. An interim analysis was planned after including 10 patients to rule out futility, defined as a mean score of hair loss exceeding 56.7. A secondary endpoint was the global alopecia areata severity score measured with the "Severity of Alopecia Tool" (SALT) with a scale of 0 (no hair loss) to 100 (complete alopecia). For VMAT-WBRT, the cadaver measurements demonstrated a dose reduction to the hair follicle volume of 20.5% on average and of 41.8% on the frontal-vertex-occipital medial axis as compared to OF-WBRT. In the phase II trial, a total of 10 patients were included before the trial was halted due to futility. The EORTC BN20 hair loss score following WBRT was 95 (SD 12.6). The average median dose to the hair follicle volume was 12.6 Gy (SD 0.9), corresponding to a 37% dose reduction compared to the prescribed dose. This resulted in a mean SALT-score of 75. Compared to OF-WBRT, VMAT-WBRT substantially reduces hair follicle dose. These dose reductions could not be related to an improved QOL or SALT score.

This chapter gives an overview of molecules and mechanisms able to intervene with the biological effects of ionizing radiation (IR), either related to their clinical use in radiotherapy or in the field of radiation protection in case of an accidental exposure to radiation and/or nuclear emergencies. According to the National Cancer Institute, “radiomodifiers” can be classified into (a) radioprotectors (protect molecules and tissues from direct and indirect damage induced by IR) or (b) radiomitigators (reduce and help to repair damage), depending on whether they are administered pre- or post-IR exposure, respectively. Most of them are free radical scavengers and antioxidants (or enhancers of the antioxidant defenses), increase DNA repair mechanisms, have anti-inflammatory properties, and/or prevent cell death. On the other hand, (c) radiosensitizers directly or indirectly enhance DNA damage and ROS production, increasing IR toxicity on tumor cells, thus they are used to increase radiotherapy efficacy in cancer patients. The section “Radionuclides and methods to treat contaminated individuals” describes the medical consequences and treatment modalities of internal contamination by radionuclides. Overall, the chapter discusses the effects of most currently known radiomodifiers, their specific properties, and their mechanisms of action, by emphasizing results obtained in recent preclinical and clinical trials.

This chapter is focused on radiobiological aspects at the molecular, cellular, and tissue level which are relevant for the clinical use of ionizing radiation (IR) in cancer therapy. For radiation oncology, it is critical to find a balance, i.e., the therapeutic window, between the probability of tumor control and the probability of side effects caused by radiation injury to the healthy tissues and organs. An overview is given about modern precision radiotherapy (RT) techniques, which allow optimal sparing of healthy tissues. Biological factors determining the width of the therapeutic window are explained. The role of the six typical radiobiological phenomena determining the response of both malignant and normal tissues in the clinic, the 6R’s, which are Reoxygenation, Redistribution, Repopulation, Repair, Radiosensitivity, and Reactivation of the immune system, is discussed. Information is provided on tumor characteristics, for example, tumor type, growth kinetics, hypoxia, aberrant molecular signaling pathways, cancer stem cells and their impact on the response to RT. The role of the tumor microenvironment and microbiota is described and the effects of radiation on the immune system including the abscopal effect phenomenon are outlined. A summary is given on tumor diagnosis, response prediction via biomarkers, genetics, and radiomics, and ways to selectively enhance the RT response in tumors. Furthermore, we describe acute and late normal tissue reactions following exposure to radiation: cellular aspects, tissue kinetics, latency periods, permanent or transient injury, and histopathology. Details are also given on the differential effect on tumor and late responding healthy tissues following fractionated and low dose rate irradiation as well as the effect of whole-body exposure.

Psychosocial oncology is coming of age

Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. ClinicalTrials.gov Identifier NCT01596933 .