ESTRO 2022 - Abstract Book

S216

Abstract book

ESTRO 2022

effects of SBRT through the longitudinal assessment of blood circulating cellular biomarkers during and after SBRT. The goal was to generate a hypothesis for the optimal dose and fractionation for combining SBRT with standard immune checkpoint inhibitor (ICI) drugs for NSCLC. Materials and Methods 50 patients with eraly stage NSCLC were prospectively included. Blood samples were obtained just before treatment (RT baseline ), 1 day after the first fraction of SBRT (RT day1 ), at the end of SBRT (RT end ) and at follow-up after 6 weeks (RT FU1 ) and 4.5 months after the start of the treatment (RT FU2 ). Patients received SBRT using the following fractionation/dose regimens: 3 x 18.75 Gy (n=21), 5 x 10 Gy (n=6), 8 x 7.5 Gy (n=21) and 12 x 5.5 Gy (n=1), with a minimum biological effective dose of 100 Gy. Results We found a statistically significant increase in the fraction of expanding (Ki-67 + ) CD8 + and CD4 + T-cells, in both in PD1 + and PD1 – subpopulations, after SBRT (RTend) compared to baseline, and a decrease to baseline levels after 6 weeks (RT FU1 ). These results remained significant in the fractionation/dose subgroup analysis for the patients treated with 8 x 7.5 Gy but not for those treated with 3 x 18.75 Gy. Conclusion Study results indicate that SBRT results in significant systemic increase in activated T cells, which is most prominent at the end of treatment, and that lower doses per fraction might be more effective in inducing this immunomodulatory effect than the higher ones. Based on these data, we suggest that adding ICIs in NSCLC would be more effective applied at the end of SBRT performed with lower doses per fraction. Purpose or Objective Osteoradionecrosis (ORN) of the mandible is an infrequent, yet a severely debilitating toxicity following head and neck cancer (HNC) radiotherapy. The first ORN Normal Tissue Complication Probability (NTCP) models for any grade (ORN I-IV ) and grade IV (ORN IV ) have recently been developed on a cohort of 1259 patients. The aim of this study was to externally validate these recently published multivariable NTCP models in a large HNC patient cohort treated with (chemo-)radiotherapy. Materials and Methods The validation cohort consisted of 1154 HNC patients treated with definitive (chemo)radiotherapy. Patients who underwent a mandibulectomy or had previous radiotherapy in the HN area were excluded. Both cohorts used the ORN grading system published by Tsai et al. who defined grade 4 ORN as ORN requiring major invasive surgery. The original (logistic regression) NTCP models identified D 30% of the mandible and pre-radiotherapy (pre-RT) dental extraction as independent factors for both ORN I-IV and ORN IV . The original NTCP models were externally validated and the performance was described with the AUC and R 2 . Additionally, the closed testing procedure (CTP) was performed to test which model update was appropriate in our cohort: 1) by calibration-in-the-large (re-estimation of model intercept), 2) recalibration (re-estimation of intercept and slope) or 3) model revision (re-estimation of all coefficients). Results The prevalence of ORN I-IV and ORN IV in the validation cohort was 4% (n=44) and 1% (n=9), respectively, whereas the prevalence of ORN I-IV and ORN IV in the development cohort was 13.7% and 5%. Similar as in the published paper, all DVH parameters of the mandible were significantly associated to ORN with univariate analyses. The external validation showed a similarly good and comparable performance for the prediction of ORN I-IV and ORN IV (Table 1). Additionally, the CTP did not detect major differences in the validation cohort but recommended a re-estimation of the model intercept. The intercept decreased from -6.85 to -8.90 for ORN I-IV and from -9.16 to -11.67 for ORN IV , while the coefficients of D 30% and dental extraction remained the same. Please see figure 1 for the NTCP models (validation and previously published NTCP model). OC-0258 External validation of osteoradionecrosis NTCP models in head and neck cancer patients. N. den Haan 1 , S. van Dijk 1 , L. van den Bosch 1 , T. van Zon-Meijer 1 , A. van den Hoek 1 , R. Steenbakkers 1 , H. Verbeek 1 , E. Oldehinkel 1 , A. van der Schaaf 1 , H.P. van der Laan 1 , H. Langendijk 1 1 UMCG, Radiotherapy, Groningen, The Netherlands