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

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