ESTRO 2022 - Abstract Book

S222

Abstract book

ESTRO 2022

low tumors, n=1,082) versus radioresistant (RR, RSI-high tumors, n=821). Next, patients were divided into two groups according to immune and stromal scores, immune infiltrated (IF, n= 650) and immune excluded (IE, n=1253) subgroups. Results RS group showed improved prognosis compared to RR group, and IF group had better survival than IE group, however, these tendencies were only significant in ER-negative patients. Radiosensitivity was significantly associated with the activation of antitumor immunity. In contrast, radio-resistance was associated with metastatic properties, such as epithelial- mesenchymal transition and angiogenesis. Differentially expressed gene analysis revealed that ER signaling pathway is correlated with suppression of antitumor immunity. Higher ER was associated with a higher fraction of M2 macrophage and lower PD-1 expression. Integration of immune signature and radiosensitivity index further stratified patients into four subgroups. In ER-negative disease, IF and RS groups were associated with the best prognosis, whereas in ER-positive disease, immune signature and radiation response have no prognostic significance. On multivariable Cox regression, both integrated immune infiltration and radiosensitivity signature was independent predictors of relapse-free survival (HR 1.12, 95% CI 1.06- 1.19, p < 0.001) and overall survival (HR 1.06, 95% CI 1.01-1.11, p = 0.028). Conclusion Taken together, this results suggested that tumor radiosensitivity was associated with activation of antitumor immunity and led to better prognosis particularly in ER negative group. 1 Aarhus University Hospital, Experimental Clinical Oncology-Dept. Oncology, Aarhus N, Denmark; 2 Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus N, Denmark Purpose or Objective Despite the success of immunotherapy, many cancer patients do not respond to this therapy. The aim of this pre-clinical study was to try and convert non-responding tumours into responders using radiation that primarily kills tumour cells directly, but also has an indirect effect through the induction of vascular damage. In addition, we also used OXi4503, a drug that primarily induces vascular damage, but also has a secondary direct cell killing effect. Materials and Methods Experiments were performed using a C3H mammary carcinoma grown in the right rear foot of CDF1 mice and treatments started when tumours reached 200 mm 3 (day 0). Treatments included local tumour irradiation with single proton doses (5- 20 Gy on day 0; given in an 83-107MeV pencil scanning proton beam in the center of a 3 cm spread out Bragg peak), or the vascular disrupting agent, OXi4503 (5-50 mg/kg injected i.p. on days 0, 3, 7 and 10). The radiation and drug treatments were also combined with an antibody to the checkpoint inhibitor CTLA-4 (10 mg/kg; i.p. injected on days 1, 4, 8, and 11). The endpoint was tumour growth time (TGT3; time for tumours to grow to 3 times the treatment volume). A Student’s T- test was used for statistical comparisons (significance level of p<0.05). Results Untreated control tumours had a mean (+ 1 S.E.) TGT3 of 4.3 days (+ 0.5). This was increased in a dose dependent fashion when mice were treated with either protons or OXi4503. Anti-CTLA-4 alone had no significant effect on tumour growth, the TGT3 being 3.9 days (+ 0.1). It also failed to enhance the response to proton irradiation or OXi4503 until the highest doses were reached. With protons, a TGT3 value of 17.7 days (+ 0.7) was obtained with 20 Gy and this was significantly increased to 22.4 days (+ 1.2) when combined with anti-CTLA-4. For OXi4503 the TGT3 at the 50 mg/kg dose was 15.8 days (+ 0.4), which significantly increased to 24.2 days (+ 4.0) with anti-CTLA-4. Interestingly, larger effects were seen when smaller tumours were used. Despite the significant increase in TGT3 when mice bearing 200 mm 3 tumours were treated with OXi4503 and anti-CTLA-4, the number of tumours that were completely controlled was 0/10. However, applying the treatments when tumours were 100 mm 3 in size resulted in 2/9 tumours being controlled, and this level of control further increased to 5/9 tumours when the tumours were at 50 mm 3 when the treatments started. Conclusion Tumours that are unresponsive to checkpoint inhibitors can become responsive after treatment with other therapies. While this effect appears to be independent of how tumor damage is induced, it does seem to depend on the level of damage caused and the size of the tumours at the start of treatment. Supported by grants from the Danish Cancer Society, the Danish Council for Independent Research: Medical Sciences, and The Danish National Board of Health. OC-0265 Using proton radiation or OXi4503 to convert non-immunogenic tumours into immune responders M. Horsman 1 , S. Nygaard 1 , S. Nielsen 1 , M. Sitarz 2 , P. Poulsen 2 , M. Høyer 2 , B. Sørensen 2 , P. Elming 1

OC-0266 Immunotargeting of CD98hc for elimination of radioresistant head and neck squamous cell carcinoma

A.S. Köseer 1

1 National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany. , OncoRay – National Center for Radiation Research in Oncology, Dresden, Germany