arXiv subjects

Debabrata Saha

Publications and source records attributed to Debabrata Saha.

5 recordsLinked to original sources

arXiv2026

Exploring Strategies for Personalized Radiation Therapy Part IV: An Interaction-Picture Approach to Quantify the Abscopal Effect

We revisit the controversial "abscopal" effect in the context of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR). By allowing long interval between fractions, PULSAR may enhance systemic immune activation and increase the likelihood of abscopal responses compared with conventional daily fractionation. To quantify treatment-induced effects, we introduce an interaction-picture transformation adapted from quantum mechanics, which separates intrinsic tumor growth from radiation and immune-mediated perturbations. In this preliminary study, we tested this method to two preclinical bilateral tumor models (4T1 and MC38). Our model provides a quantitative measure of the interaction strength between primary and secondary tumors at the individual level, capturing dynamics over time rather than relying solely on cohort averages. This approach frames the abscopal effect as a continuous, stochastic phenomenon rather than a binary response. The framework is flexible for future studies, particularly in concurrent radiation and immunotherapy with PULSAR, where different radiation doses and fractionation schedules can be compared, and immune checkpoint inhibitors (ICIs) can be incorporated to further enhance systemic anti-tumor immunity. The framework can also help us make cross-study comparison of abscopal effects and standardizes the reporting of abscopal magnitude beyond simple statistical significance.

q-bio.QM↗

arXiv2025

Mathematical Modeling of the Synergetic Effect between Radiotherapy and Immunotherapy

Achieving effective synergy between radiotherapy and immunotherapy is critical for optimizing tumor control and treatment outcomes. To explore the underlying mechanisms of this synergy, we have investigated a novel treatment approach known as personalized ultra-fractionated stereotactic adaptive radiation therapy (PULSAR), which emphasizes the impact of radiation timing on treatment efficacy. However, the precise mechanism remains unclear. Building on insights from small animal PULSAR studies, we developed a mathematical framework consisting of multiple ordinary differential equations to elucidate the temporal dynamics of tumor control resulting from radiation and the adaptive immune response. The model accounts for the migration and infiltration of T-cells within the tumor microenvironment. This proposed model establishes a causal and quantitative link between radiation therapy and immunotherapy, providing a valuable in-silico analysis tool for designing future PULSAR trials.

q-bio.QM↗

arXiv2025

A universal bioluminescence tomography system for pre-clinical image-guided radiotherapy research

CBCT-guided small animal irradiators encounter challenges in localizing soft-tissue targets due to low imaging contrast. Bioluminescence tomography (BLT) offers a promising solution, but they have largely remained in laboratorial development, limiting accessibility for researchers. In this work, we develop a universal, commercial-graded BLT-guided system (MuriGlo) designed to seamlessly integrate with commercial irradiators and empower researchers for translational studies. We demonstrate its capabilities in supporting in vitro and in vivo studies. The MuriGlo comprises detachable mouse bed, thermostatic control, mirrors, filters, and CCD, enabling multi-projection and multi-spectral imaging. We evaluate that the thermostatic control effectively sustains animal temperature at 37°C throughout imaging, and quantify that the system can detect as few as 61 GL261-AkaLuc cells in vitro. To illustrate how the MuriGlo can be utilized for in vivo image-guided research, we present 3 strategies, BLT-guided 5-arc, 2-field box, and BLI-guided single-beam, ranging from complicated high-conformal to simplest high-throughput plans. The high conformal BLT-guided 5-arc plan fully covers the gross tumor volume (GTV) at prescribed dose with minimal normal tissue exposure (3.9%), while the simplified, high-throughput BLT-guided 2-field box achieves 100% GTV coverage but results in higher normal tissue exposure (13.1%). Moreover, we demonstrate that the localization accuracy of MuriGlo for both widely-used SARRP and SmART irradiators is within1 mm, and the tumor coverage reaches over 97% with 0.75mm margin. The universal BLT-guided system offers seamless integration with commercial irradiators, achieving comparable localization accuracy, expected to supporting high-precision radiation research.

physics.med-ph↗

arXiv2024

Understanding the PULSAR Effect in Combined Radiotherapy and Immunotherapy through Attention Mechanisms with a Transformer Model

PULSAR (personalized, ultra-fractionated stereotactic adaptive radiotherapy) is the adaptation of stereotactic ablative radiotherapy towards personalized cancer management. For the first time, we applied a transformer-based attention mechanism to investigate the underlying interactions between combined PULSAR and PD-L1 blockade immunotherapy based on a murine cancer model (Lewis Lung Carcinoma, LLC). The proposed approach is able to predict the trend of tumor volume change semi-quantitatively, and excels in identifying the potential causal relationships through both self-attention and cross-attention scores.

physics.med-ph↗

arXiv2024

PULSAR Effect: Revealing Potential Synergies in Combined Radiation Therapy and Immunotherapy via Differential Equations

PULSAR (personalized ultrafractionated stereotactic adaptive radiotherapy) is a form of radiotherapy method where a patient is given a large dose or pulse of radiation a couple of weeks apart rather than daily small doses. The tumor response is then monitored to determine when the subsequent pulse should be given. Pre-clinical trials have shown better tumor response in mice that received immunotherapy along with pulses spaced 10 days apart. However, this was not the case when the pulses were 1 day apart. Therefore, a synergistic effect between immunotherapy and PULSAR is observed when the pulses are spaced out by a certain number of days. In our study, we aimed to develop a mathematical model that can capture the synergistic effect by considering a time-dependent weight function that takes into account the spacing between pulses. By determining feasible parameters, and applying reasonable conditions, we utilize our model to simulate murine trials with varying sequencing of pulses. We successfully demonstrate that our model is simple to implement and can generate tumor volume data that is consistent with the pre-clinical trial data. Our model has the potential to aid in the development of clinical trials of PULSAR therapy.

q-bio.QM↗