Abstract
BackgroundA novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. Considering the anti-tumor immune response homeostatic fluctuation, which is cyclically suppressed and incited (“switched off and on”), we synchronized SBRT-PATHY with its most excitable phase, in order to overcome tumor tolerance locally and systemically. The aim of this study, therefore, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY.Materials and methodsIn order to serially map the homeostatic anti-tumor immune response-fluctuations, High Sensitive C-Reactive Protein (HS-CRP), Lactate Dehydrogenase (LDH) and Lymphocyte/Monocyte Ratio (LMR) were analyzed using high-order polynomial trend analysis as surrogate of immune system response. After the biomarker data analysis detected the immune fluctuations and related idiosyncratic immune cycle periodicity, we determined the “most favourable” and “least favourable” treatment time-positions in the immune cycle. In order to evaluate the impact of an idiosyncratic immune cycle on treatment outcomes, our first consecutive four patients were treated on the “most favourable” while the remaining four on the “least favourable” day.ResultsThe median follow-up was 11.8 months. The biomarker data analysis showed periodic immune response fluctuations of regular frequency. The “right” synchronization of SBRT-PATHY with the “most favorable day” of anti-tumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate.ConclusionWe believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE.Present study has been retrospectively registered on 18th of October 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 37/19.
Highlights
Clinical exploitation of the bystander (BE) and abscopal effects (AE) was an objective of our long-standing translational oncology research aimed to overcome the outcome-limiting factors related to the unresectable bulky tumors
The “right” synchronization of SBRT-PATHY with the “most favorable day” of antitumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate
We believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE
Summary
Clinical exploitation of the bystander (BE) and abscopal effects (AE) was an objective of our long-standing translational oncology research aimed to overcome the outcome-limiting factors related to the unresectable bulky tumors. The subsequent translation of these findings to a clinic led to the introduction of a novel SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) showing promising BE/AE-response rates [2, 4]. Considering the immune-mediated nature of BE/AE and in order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints [4, 6]. A novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. The aim of this study, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY
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