Abstract Book

S345

ESTRO 37

blind, sham-controlled RCT of HBO versus best standard care in patients with radiation proctitis failed to confirm these benefits, reporting comparable improvements in patient-reported rectal bleeding in both HBO and sham- treated groups(6). HBO is a cumbersome intervention but high quality hyperbaric medicine facilities exist in many countries. The risks of HBO are small provided standard precautions are taken and well-established procedures are followed. The moderate economic costs would makes HBO a very cost-effective intervention, but only if the research community succeeds in generating a more substantial body of high quality evidence. References 1. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc. 1985;111(1):49-54. 2. Marx RE. Hyperbaric Medicine Practice: Chapter 23, Radiation Injury to Tissue. Hyperbaric Medicine Practice. Second ed: Best Publishing Company; 1994. p. 448-501. 3. Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2016;4:CD005005. 4. Annane D, Depondt J, Aubert P, Villart M, Gehanno P, Gajdos P, et al. Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo- Controlled, Double-Blind Trial From the ORN96 Study Group. J Clin Oncol. 2004. 5. Clarke RE, Tenorio LM, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008;72(1):134- 43. 6. Glover M, Smerdon GR, Andreyev HJ, Benton BE, Bothma P, Firth O, et al. Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. Lancet Oncol. 2015. SP-0650 Advances in clinical radiobiology: modelling of normal tissue complication probability R. Pacelli 1 1 Università "Federico II" di Napoli, Scienze Biomediche Avanzate, Napoli, Italy Abstract text Clinical radiobiology may be defined as the study of the action of ionizing radiations on human being considering clinical relevant endpoints. Tumor control and normal tissue complications are the clinical endpoints considered by a radiation oncologist. In a judgement of a treatment plan designed for a given patient, the trade-off between tumor control probability (TCP) and normal tissue complication probability (NTCP) is the kingmaker of the decisional process. Modern clinical radiobiology started with the use of 3D treatment planning implying a different geometry of the beam entry in the body compared to the conventional parallel opposed technique. Emami et al. charted in the seminal paper of 1991 normal tissue tolerance in the case of partial volume and/or inhomogeneous organ irradiation. The few available toxicity records reported in the scientific literature were very heterogeneous and qualitatively poor. However, with all these limitations, the information gathered in that article enriched by the personal experience of expert radiation oncologists, resulted in proposed dose/volume effect for 1/3, 2/3 and whole volume of 28 critical sites. The data were fundamental for the birth of the Lyman-Kutcher-Burman (LKB) and the relative seriality models, mathematical radiobiological tools largely used by the radiation

oncology community for plan evaluation. These predictive models centered on the relation between dosimetric information, represented by the graphical simplification of dose-volume histograms (DVH), and clinical endpoints considered (i.e. NTCP). The weak points of these useful tools consisted in a large approximation of the prediction due to the low quality of the toxicity information, and the fact that the relation was made just with a single virtual uniform dose created by an algorithm to translate heterogeneous distribution of a DVH to uniform dose to a part or a whole of an organ at risk (OAR). In 2010 the quantitative analysis of normal tissue effects in the clinic (QUANTEC), updated the Emami’s information with almost twenty years more of clinical experience with 3D-conformal and intensity modulated radiation therapy. Moreover, the report gave some practical guidance in classifying toxicity risk and suggested studies design to improve the knowledge about the issue. Meanwhile several researchers involved in the radiation oncology discipline proposed predictive models taking into account more than one dosimetric parameter, and patient specific, treatment, topographic, or imaging information in the determinism of a given toxicity. An important contribution to these more complex prediction models came from the work of El Naqa et al. in 2006 that elegantly described alternative methods for building multivariable dose–response models. Behind the tools for data collection and analysis (i.e. CERR, Computational Environment for Radiotherapy Research) and the sophisticated statistical methodology, their work represents a very good source of information on the modalities to report and collect data about toxicity to build NTCP models. In this framework, our group studied homogeneously treated Hodgkin’s lymphoma patient populations testing for relation among a single clinical endpoint and multiple clinical and dosimetric factors. For hypothyroidism, we showed that the absolute volume of thyroid gland exceeding 30 Gy in combination with thyroid gland volume and gender obtained the best prediction power. For hearth valve defects, we found a consistent association with lung volume. Interestingly, a model for lung fibrosis prediction included mass of hearth receiving dose > 30 Gy. The technology progress and the advanced computational systems generated the “omics” science, with the possibility to relate clinical endpoints even with genomic, proteomic and radiomic factors. We topographically identified by a voxel-based approach (2017) the cervical portion of the esophagus and the cricopharyngeus muscle as regions with significant differences in dose distribution between head and neck cancer patients that developed or not radiation induced acute disphagia. van Dijk et al. (2017) found that 18 FDG- PET image biomarkers (intensity and textural) improved the prediction of xerostomia at 12 months over the reference model (contralateral parotid mean dose and baseline xerostomy). Genomics and proteomics are mostly used for TCP prediction improvement, but can even be used for refinement of NTCP prediction. Identification of distinctive and significant factors in patients population allows more and more accurate risk stratification towards individualized TCP and NTCP calculation and customized radiation treatment plans. Biotechnological and computational tools represent an intellectual challenge for radiation oncologists that historically are the physicians more prone to face physical and mathematical problems. The necessarily tight cooperation with our physicist companions is today requested more than ever.