3122 - Effect of Intratumoral Necrosis on Tracking Accuracy and Target Coverage in Biology-Guided Radiotherapy

Purpose/Objective(s): Biology-Guided Radiotherapy (BgRT) relies on real-time FDG PET signal for tracked dose delivery. Tumor biology can evolve during treatment, leading to intratumoral necrosis and altering PET uptake distribution while preserving tumor geometry. Such changes in biodistribution may affect delivered dose coverage to a moving target. This study evaluates whether BgRT on a new system under development^† maintains accurate tracking and tumor dose coverage when a previously planned PET-avid target develops a central necrotic core with absent uptake.

Materials/Methods: Two FDG-fillable inserts with identical non-spherical outer geometry (~7 cm maximal dimension) were fabricated. One insert was a uniformly fillable volume. The second incorporated a central embedded solid mass to simulate a treatment-induced necrotic core with absent PET uptake while preserving external tumor geometry. Both inserts were submerged in an anthropomorphic motion phantom comprising a 28.1 L water tank containing ¹8F-FDG background activity (6 kBq/mL). Targets were filled with FDG to achieve an 8:1 target-to-background ratio (TBR).

A BgRT treatment plan (10 Gy/Fx) was prepared with a modeling session using the uniformly fillable insert. The plan achieved a conformity index (CI) of 1.02 and PTV coverage of ~95%. Targets underwent 3D respiratory motion with 16 mm inferior–superior excursion and 8 mm motion in both the anterior–posterior and left–right directions, at a frequency of 15 breaths per minute. Radiochromic films were placed within inserts in the coronal plane.

During delivery, the homogeneous insert demonstrated a normalized target signal (NTS) of 18.82 and an activity concentration (AC) of 26.52 kBq/mL. In comparison, the necrotic-core insert exhibited a decreased NTS of 13.84 and AC of 21.57 kBq/mL. Two experiments were conducted:

1. Baseline delivery: Plan delivered to homogeneous insert, simulating initial treatment fractions without necrosis.
2. Biodistribution change delivery: An identical plan was delivered to necrotic core insert, simulating the evolution of intratumoral PET heterogeneity between treatment fractions.

Results: Film analysis demonstrated strong agreement between planned and delivered dose distributions in both configurations. The delivered dose profiles closely matched the planned profiles, preserving the non-spherical target geometry, indicating accurate dose delivery despite altered PET biodistribution. CTV coverage of 100% was achieved in both the homogeneous and necrotic-core conditions.

Conclusion: BgRT on the system under development maintained accurate dose delivery and 100% CTV coverage despite reduced PET signal and altered uptake distribution from a simulated necrotic core. Delivered dose profiles preserved target geometry under respiratory motion, supporting the robustness of PET-guided delivery to treatment-induced intratumoral heterogeneity on the new system.

† New BgRT system requires regulatory clearance and is not available for sale.