ESTRO 2023 - Abstract Book

S198

Saturday 13 May

ESTRO 2023

OC-0260 Delayed tumor draining lymph node irradiation to maximize radioimmunotherapy combinations M. Pruschy 1 , C.S. Yong 1 , I. Telarovic 1 1 University Hospital Zurich, Dept. of Radiation Oncology, Zurich, Switzerland Purpose or Objective Tumor draining lymph nodes (TDLNs) are a common site of early metastatic spread and therefore often irradiated as part of curative treatment. However, TDLNs are the primary site of anti-tumor immune response generation. Therefore, therapeutic sterilization of the TDLNs at the time of RT might abrogate the immunostimulatory effects of RT, especially in combination with immunotherapy. Here we investigate whether temporal distancing between RT of the tumor and RT of the TDLN maximizes the positive effects of RT on the anti-tumor immune response, while preserving the beneficial effect of metastatic tumor cell killing by delayed RT of the TDLN. Materials and Methods We use mice bearing subcutaneous tumors (B16F10-Luc melanoma cell line) with an early disease spread into the TDLNs. Using a small animal image-guided RT treatment platform, we precisely irradiate the axillary and inguinal TDLNs either concomitantly (CON) or at variable times after primary tumor irradiation (adjuvant treatment, ADJ) and investigate the effect of delayed TDLNs irradiation either with RT alone or in combination with immunotherapy. Results Irradiation in absence of immune checkpoint inhibition (ICI) did not reveal any differential treatment response in between concomitant and adjuvant TDLN irradiation. On combining irradiation with anti-CTLA-4 inhibition the concomitant TDLN irradiation regimen did not enhance the primary tumor response, indicating the relevance of an intact TDLN to support CTLA-4-oriented ICI. In contrast and surprisingly, a strongly improved primary tumor response was observed upon adjuvant TDLN irradiation, performed as early as 48 hours and up to 7 days after primary tumor irradiation when combining RT with anti-CTLA-4 inhibition (50% versus 0% complete responses in “ADJ” versus “CON” treatment groups). Upon tumor rechallenge in the mice with complete responses, all mice rejected the tumor (versus a 100% take rate in the control group), thereby demonstrating formation of immunological memory. Mechanistic-oriented immunophenotyping with the aim of identifying optimal timing and the immune cells that play key roles in the observed effect of delayed TDLN irradiation suggest the induction of an immunosuppressive environment on concomitant irradiation of the primary tumor and TDLN. Conclusion The benefit of TDLNs irradiation is being widely revisited, especially in the setting of radioimmunotherapy, with TDLNs as the primary site of anti-tumor immune response generation upon RT. However, with an extensive metastatic spread, it is unlikely that complete avoidance of TDLNs irradiation can be achieved without a negative effect on the survival. Delayed irradiation of the TDLNs will preserve the beneficial function of the TDLNs at the time of the primary tumor irradiation, while still eradicating the metastatic tumor cells. Here we demonstrate a strong, positive effect of a delayed TDLNs irradiation on the treatment response to RT combined with immunotherapy, but not to RT alone. OC-0261 Impact of radiation to host immune system in patients treated for locally advanced NSCLC C. Pasquier 1 , L. Chaltiel 2 , C. Massabeau 1 , A. Rabeau 3 , L. Lebas 4 , J. Texier 5 , N. Caunes-Hilary 6 , E. Cohen-Jonathan Moyal 1 , J. Mazières 3 , J. Khalifa 1 1 Institut Universitaire du Cancer Toulouse - Oncopole, Department of Radiotherapy, Toulouse, France; 2 Institut Universitaire du Cancer Toulouse - Oncopole, Department of Biostatistics, Toulouse, France; 3 Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Thoracic Oncology Department, Toulouse, France; 4 Centre Hospitalier Intercommunal des Vallées de l'Ariège (CHIVA), Department of Pneumology, St-Jean de Verges, France; 5 Institut Universitaire du Cancer Toulouse - Oncopole, Department of Nuclear Medicine, Toulouse, France; 6 Institut Universitaire du Cancer Toulouse - Oncopole, Department of medical oncology, Toulouse, France Purpose or Objective The optimal modalities of radiotherapy when combining concurrent chemoradiation (CCRT) and immunotherapy (IO) for unresectable locally advanced non-small cell lung cancer (NSCLC) remain to be determined. The aim of this study was to investigate the impact of radiation to different immune structures and immune cells upon clinical outcomes in patients treated by CCRT followed by durvalumab. Materials and Methods Patients with locally advanced NSCLC treated with CCRT and consolidation IO were analysed. Dosimetric data such as dose to non-involved tumor draining lymph nodes (NITDLN), vertebrae (T1-T12), spleen or estimated radiation dose to immune cells (EDRIC) were collected. Patients were divided into two groups according to the inclusion (NILN-R+) or not (NILN-R-) of at least one NITDLN in the clinical target volume (CTV). Complete blood counts were assessed before CCRT, at the end of CCRT and at the initiation of consolidative IO. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method with 95% confidence intervals (CI). Univariable and multivariable analysis were performed using the Logrank test and the Cox proportional hazards model. Results Fifty patients were included with a median follow-up of 23.2 months (95% CI 18.3-35.2). Median PFS was 31.4 months (95% CI 14.0 – not reached). 2-year overall survival (OS) was 66.2% (95% CI 46,5 – 80,1). In univariable analysis, NILN-R+ (HR: 2.60, 95%CI 1.08-6.27; p=0.028), EDRIC > 6.3 Gy (HR: 3.19, 95%CI 0.94-10.82; p=0.049) and lymphopenia ≤ 500/mm3 at IO initiation (HR: 2.69, 95%CI 1.12-6.46; p=0.021) were correlated with PFS and lymphopenia ≤ 500/mm3 at IO initiation was also associated with poor OS (HR: 3.46, 95%CI 1.10-10.87;p=0.024). In multivariable analysis, NILN-R+ was the strongest factor associated with PFS (HR: 3.15, 95%CI 1.23-8.10; p=0.017).