ESTRO 2020 Abstract Book

S101 ESTRO 2020

Purpose or Objective A brief chemotherapy (CT) followed by radiation therapy (RT) is routinely used in the treatment of Hodgkin Lymphoma (HL), and is the standard of care for early stages. Given the high success rate of these treatments, with 80-90% of patients surviving many decades after getting cured, reduction of late complication - second cancer and cardiovascular diseases (CAD) - is of pivotal relevance. Historically, the cardiovascular risk of patients receiving mediastinal RT is roughly 5-fold increased. To reduce such a relevant risk, high dose gradient techniques like intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) are increasingly used in the daily routine. Moreover, the application of Involved Site RT (ISRT) and Involved Node RT (INRT) contouring principles allows to irradiate progressively smaller volumes. These strategies reduce the radiation doses received by the organs at risk (OARs) located in the close proximity of the target, which may translate in a decrease of long term treatment complications. In our study, we evaluated the risk of CAD in a large cohort of HL patients that received a course of mediastinal radiotherapy planned with the application of modern contouring and We enrolled 213 consecutive patients (age 31, range 15- 77) affected with HL and treated at our institution between 2010 and 2018. Overall, 179 patients (84%) received mediastinal RT according to the disease extension. Many patients had a huge mediastinal involvement with 51.2% of them with a bulky lesion at the time of diagnosis (109/213). All patients received a combined-modality treatment, with CT followed by RT. Median prescription dose to the PTV was 30 Gy (range 20- 40). The treatment target was delineated according to ISRT and INRT principles. Structures as lungs, breasts, heart and cardiac substructures (chambers, valves and coronary arteries) were all contoured as OARs. For each of them, mean (Dmean) and maximum doses (Dmax) were calculated (Table 1). A predictive model for CAD was estimated, according to previously published reports ( van Nimwegen et al., JCO, 2016) . Results The clinical outcome of our cohort was extremely good and comparable to literature data. The PTV coverage was in respect of ICRU criteria with a median V95% = 95.1% (Table 1). The adoption of an IMRT/VMAT planning kept low doses (Dmean and Dmax reported) to all organs at risk, as detailed on the attached table. In particular, mean heart dose was only 5.1 Gy in our population. The median relative risk of CAD of our patients, compared to healthy people, was only 1.79 (CI 95%: 1.00-6.48), which is significantly lower to the 5-fold risk reported in historical reports (Figure 1). delivery techniques. Material and Methods

Conclusion Our study shows that the application of modern RT planning and delivery techniques, combined with a detailed contouring of the heart and of the cardiac substructures favors a reduction of the risk of RT-related CAD in patients affected with HL.

Proffered Papers: Proffered papers 9: Radiation effects on stem cells and the microenvironment

OC-0202 Combining hyperthermia or a VDA with checkpoint inhibitors to increase tumour immunogenicity P.B. Elming 1 , T.R. Wittenborn 1 , M.R. Horsman 1 1 Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus, Denmark Purpose or Objective Although checkpoint inhibitors (CIs) have improved outcome for some cancer patients, many patients do not respond. Our pre-clinical studies were designed to test whether treatments like hyperthermia or vascular disrupting agents (VDAs) that kill tumour cells both directly due to cytotoxicity and indirectly via the induction of vascular damage could improve tumor response to CIs. Material and Methods Male or female CDF1 mice were inoculated on the right rear foot with a C3H mammary carcinoma and treated when tumours reached a volume of 200mm 3 . These treatments included local water bath heating (42.5°C for 1 hour) applied on day 0; intra peritoneal (i.p.) injection with the VDA OXi4503 (25 mg/kg) on days 0, 3, 7 and 10; and anti-CTLA-4 (10 mg/kg; i.p.) on days 1, 4, 8 and 11. Tumour size was measured daily, with the endpoint being the time to reach five times treatment volume (TGT5). Tumours were also excised upto 10 days after treatment with heat or OXi4503 and histologically assessed for CD4, and CD8 expression, and HSP70 expression assessed using ELISA. Statistical comparisons were performed using an unpaired t-test (significance level of P<0.05).