ESTRO 2022 - Abstract Book

S223

Abstract book

ESTRO 2022

Purpose or Objective Most patients with head and neck squamous cell carcinomas (HNSCC) are diagnosed at the locally advanced stage and show heterogeneous tumor response, including therapy resistance. Previously, we showed that low SLC3A2 mRNA and low expression levels of its protein product CD98hc are associated with better locoregional control in patients with HNSCC treated with primary radiochemotherapy or postoperative radiochemotherapy (1,2). This suggests that CD98hc could be a target for HNSCC radiosensitization. One of the strategies for tumor radiosensitization is targeted immunotherapy. However, Chimeric Antigen Receptor (CAR)-equipped T-cell therapy cannot be fully controlled. Therefore, the switchable Universal CAR (UniCAR) system was developed (3, 4) that is currently in phase I clinical trial (NCT04230265) (5). UniCAR T cell activity and specificity are controlled by the presence of target modules (TM). Our previous proof-of-concept study showed that eradicating CD98hc positive cells by retargeted UniCAR T cells significantly inhibited tumor growth in mice xenograft models (6). We aim to define the clinical value of new treatment approaches by combining radio(chemo)therapy with CD98hc-targeted immunotherapy. Materials and Methods We have used previously described radioresistant Cal33 HNSCC cells for spheroid formation (2). These spheroids were co- cultured with UniCAR T cells in the presence or absence of a novel CD98 TM as a monotherapy or combined with radio(chemo)therapy. Specific cell lysis and viable cell percentage after UniCAR treatment as well as CD3 + T cell infiltration and T cell activation were assessed as described previously (6,7). Results Our data show that CD98hc-redirected UniCAR T cells can induce significant cell lysis of radioresistant Cal33 spheroid in vitro . Combination therapies of immunotherapy and radio(chemo)therapy increased the efficacy of the treatment resulted in the disintegration of the spheroids. We demonstrated enhanced infiltration of CD3 + UniCAR T cells in the presence of CD98TM. The validation of these results for other HNSCC cell lines is ongoing. Conclusion Overall, we showed that radioresistant Cal33 spheroids can be significantly eliminated via the UniCAR system and combination therapies including radiotherapy and radiochemotherapy. This system can be used to approach the combination of the UniCAR system with radio(chemo)therapy for synergistic improvement of treatment efficacy of patients with metastatic radioresistant tumors. The most promising combination of the therapeutic approach will be further tested in xenograft tumor models to evaluate the best performing combination of immunotherapy and radio(chemo)therapy. References: 1. Linge A, et al., Clin Cancer Res . 2016. 2. Digomann D, et al., Clin Cancer Res . 2019. 3. Koristka S, et al., Blood . 2014. 4. Bachmann M, et al., Immunol Lett . 2019. 5. Wermke M. et al., Blood . 2021. 6. Arndt C, et al., Oncoimmunology . 2020. 7. Zboralski D, et al., Cancer Immunol Res . 2017. F. Piqeur 1 , B. Hupkens 2 , P. Meijnen 3 , H. Ceha 4 , M. Berbee 5 , M. Dieters 6 , J. Burger 7 , H. Rutten 7 , J. Nederend 8 , C. Marijnen 9,10 , H. Peulen 2 , M. Witte 11 1 Catharina Hospital , Radiation Oncology, Eindhoven, The Netherlands; 2 Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands; 3 Amsterdam University Medical Centre, Radiation Oncology, Amsterdam, The Netherlands; 4 Haaglanden Medical Centre, Radiation Oncology, Leidschendam, The Netherlands; 5 Maastro Clinic, Radiation Oncology, Maastricht, The Netherlands; 6 University Medical Centre Groningen, Radiation Oncology, Groningen, The Netherlands; 7 Catharina Hospital, Surgery, Eindhoven, The Netherlands; 8 Catharina Hospital, Radiology, Eindhoven, The Netherlands; 9 Antoni van Leeuwenhoek Hospital, Radiation Oncology, Amsterdam, The Netherlands; 10 Leiden University Medical Centre, Radiation Oncology, Leiden, The Netherlands; 11 The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands Purpose or Objective Locally recurrent rectal cancer (LRRC) requires multidisciplinary management. The PelvEx-II trial evaluates the benefit of induction chemotherapy (IC) preceding chemoradiotherapy (CRT) for LRRC. CRT is used to downstage the tumour volume and facilitate a radical resection. However, delineation in LRRC is hampered by factors such as previous surgery, multifocality and presence of fibrosis. Additionally, radiation oncologists (ROs) often have limited experience with LRRC and evidence-based resources to aid in delineation are lacking. Therefore, target volumes may vary, potentially causing tumour miss or unnecessary re-irradiation of OAR. Through 2 workshops we developed a delineation guideline to optimize consistency within the trial. Materials and Methods 7 ROs from 7 Dutch centres treating > 10 yearly cases of LRRC participated in 2 meetings. ROs delineated 3 cases per meeting. During meeting 1, 3 surgeons and a radiologist identified regions at risk for re-recurrence or involved resection margins, leading to guidelines for RT naive patients and patients undergoing re-irradiation. These were validated and adjusted during meeting 2. Case 1.2 was repeated in case 2.1 to test guideline adherence. A median delineation was calculated per case. Dice similarity coefficient (DSC) was calculated for each GTV and CTV, in reference to the median delineation. Proffered Papers: Lower GI OC-0267 Comprising a consensus-based delineation guideline for locally recurrent rectal cancer