ESTRO 2023 - Abstract Book

S202

Saturday 13 May

ESTRO 2023

however, there is a paucity of data on optimal scheduling of IO with respect to (C)RT and how combination therapy impacts on the anti-tumour T-cell response. Materials and Methods The preclinical model of HPV16-positive HNSCC used was subcutaneous mEER (a syngeneic murine cell line harbouring HPV16 E6 and E7) tumours established in the right flank of C57BL/6 mice. Treatment comprised RT 8 Gy × 3 on alternate days, Cisplatin 7 mg/kg intraperitoneally (i.p.) and anti-PD-1 antibody 200 µ g delivered i.p. twice weekly for up to 6 doses. We used the Nr4a3-Tocky model, which allows analysis of transcriptional dynamics induced by T-cell receptor (TCR) stimulation, to demonstrate the temporal changes in effector T-cells following antigen recognition. Tumours were collected from Nr4a3-Tocky mice receiving RT alone versus control and analysed ex vivo , at day 7 or day 10 post-RT, using multi- parameter flow cytometry to characterise the dynamics of TCR signalling following engagement with cognate antigen. Results Our preliminary data show improved tumour control and survival with combination treatment (CRT, aPD-1 and RT or triple combination of Cisplatin, RT and anti-PD-1) compared to controls. Scheduling of aPD-1 is important and adjuvant aPD-1, delivered 7 days after last fraction of (C)RT, provides superior tumour control compared to anti-PD-1 delivered concurrently with (C)RT. Multi-parameter flow cytometry on tumour samples from mEER-bearing Nr4a3-Tocky mice show dynamic changes between day 7 versus day 10 post-RT. Specifically, conventional CD4+ T-cells showed a significant increase in “new” TCR signalling at day 7 but not day 10 following RT. Tumour-infiltrating CD8+ T-cells expressed at high levels the activation markers, CD44 and CD69, and the immune checkpoints, PD-1 and TIGIT, with significantly increased “persistent- arrested” TCR antigen engagement between days 7 and 10 post-RT. Conclusion Our preclinical model supports starting anti-PD-1 therapy in the adjuvant setting with respect to radiotherapy. There may be a therapeutic window to initiate anti-PD-1 treatment, between day 7 and day 10 following RT, at which time there is active CD8+ and conventional CD4+ T-cell antigen engagement. Improved understanding of the fundamental biology underlying the anti-tumour T-cell response may help guide design of future immunoradiotherapy clinical trials. OC-0266 Radiotherapy 3 vs 6 Gy in Gonarthrosis and Coxarthrosis. A non-inferiority Trial. D. Rivas 1 , D. Gonsalves 2 , C. Laria 3 , C. Nuño 4 , R. Hernanz 5 , A. Seral 6 , J.A. González-Ferreira 7 , Á. Acosta 8 , J. Andreescu 9 , Y. Ramírez 10 , E. López 11 1 GenesisCare, Department of Radiation Oncology, Malaga, Spain; 2 GenesisCare, Department Of Radiation Oncology, CyberKnife, Madrid, Spain; 3 GensisCare, Department of Radiation Oncology, Talavera de la Reina, Spain; 4 GenesisCare, Hospital Vithas Benalmádena, Department of Radiation Oncology, Benalmádena, Spain; 5 GenesisCare, Hospital San Francisco de Asís, Department of Radiation Oncology, Madrid, Spain; 6 GenesisCare, Clínica Corachan, Department of Radiation Oncology, Barcelona, Spain; 7 GenesisCare, Department of Radiation Oncology, Sevilla, Spain; 8 GenesisCare, Hospital Inmaculada, Department of Radiation Oncology, Granada, Spain; 9 GenesisCare, Hospital San Juan de Dios, Department of Radiation Oncology, Córdoba, Spain; 10 GenesisCare, Department of Radiation Oncology, Jerez, Spain; 11 GenesiCare, Department of Radiation Oncology (CMO), Madrid, Spain Purpose or Objective Arthrosis is a chronic degenerative disorder of unknow cause characterized by a loss of cartilage in knee and hips. This disease is most prevalent in patients older than 60 years that conforms the 10- 15% of population worldwide. The need for a non-invasive treatment is required as the increased of an aged population. Low dose radiotherapy is recommended in DEGRO Guidelines using a total dose of 3-6 Gy with dose per fraction of 0.5-1 Gy. The objective of this trial is to evaluate the non-inferiority efficacy of low dose radiotherapy 3 or 6 Gy to change in pain with VAS (Visual Analogue Scale).and WOMAC scale (Western Ontario MacMaster Questionnaire). Secondly, we evaluate skin toxicity. Materials and Methods We did a randomize control trial at 13 centers in Spain. Eligible patients were > 50 years old, diagnosed with Gonarthrosis or/and Coxarthrosis with at least 1 year of evolution, non-responsive to drug or surgery treatments and risk of collateral side effects due to the comorbidity with conventional treatments. The exclusion criteria were: previous high dose radiotherapy, Connective tissue disease, inherited Hypersensitivity Syndrome. We randomly allocated patients in a 1:1 single blind ratio to 3 Gy (Arm A) or 6 Gy (Arm B). Randomization was stratified by age, gonarthrosis or coxarthrosis, IMC and pain before treatment. The Arm A group received low dose radiotherapy (0.5 Gy in 6 fractions alternating days) and Arm B group received low dose radiotherapy (1 Gy in 6 fractions alternating days). An evaluation of pain relief and quality of life in 8-12 weeks was done if no effect the patient in Arm B was randomized again to 3 or 6 Gy and in Arm B retreated with 6 Gy. Skin toxicity was rated according to the RTOG scale. This trial is registered with ClinicalTrials.gov number NCT04424628. Results 230 patients were recruited from May 2019 to May 2021, and followed-up at 8 weeks, and 6-12 months after the end of the treatment. 68 were men (29.6%) and 162 women (70.4%), median age 72.7±9.1 years. Allocated groups were well balanced. 1 case of grade 1 skin toxicity was present in both arms. In ARM B, 2 cases of transient increased pain and 1 case of venous thrombosis in right lower limb were recorded. No grade 3-4 toxicity was recorded. 217 patients completed the treatment. 3.9% abandoned the study: 1 for death not related to the trial and 1 for fear of treatment, no patients for side effects. At 6 months, they were statistical differences were comparing improvement in VAS and WOMAC scale p= <0.001, but no statistical differences comparing both arms p=0.58. This result was stabled after a year of follow- up when comparing to basal. VAS scale; IC 95% (4%-23%) and WOMAC scale IC 95% (3%-16%), respectably. VAS and WOMAC evolution are shown in Figures 1 and 2. Proffered Papers: Palliation - Oligometastases