Abstract 2423: Image-guided interstitial photodynamic therapy with palliative radiotherapy for ablating extrabronchial malignant central airway obstruction
Authors: Oakley Emily , Chamberlain Sarah , Ivanick Nathaniel , Hutson Alan , Busch Theresa , Shafirstein Gal 
Published: April 2023

Abstract
Background: Patients with extrabronchial tumors that induce malignant central airway obstruction (MCAO) face dire prognoses with significant morbidity and 1-7 months overall survival. These tumors are inoperable. High-dose curative radiotherapy is associated with significant toxicity. Chemotherapy has limited localized benefits and immunotherapy cannot address the immediate need to halt tumor progression. Our preliminary data suggest that image-guided interstitial photodynamic therapy (I-PDT) with porfimer sodium is safe and potentially effective in patients with extrabronchial tumors that induce MCAO and there is a need to further improve the rate of response. Here we present results showing an improved tumor response rate by augmenting I-PDT with palliative radiotherapy (p-XRT).
Methods: We investigated the addition of p-XRT prior to I-PDT to sensitize the target tumor to subsequent photoreaction in mouse models. Eight- to twelve-week-old C3H and C57B/6 mice with locally advanced (400-600 mm3) SCC-VII or LLC tumors, respectively, were treated with I-PDT alone or with p-XRT followed by I-PDT. The p-XRT regimen was 10 Gy x2 over two days. At 24-26 h after the second 10 Gy fraction, the I-PDT was administered with 5 mg/kg porfimer sodium activated with 630-nm laser light at 5.0 mW/cm2 and 45 J/cm2 at tumor margins. Photoacoustic imaging and light dosimetry measurements were used to investigate the impact of p-XRT on the tumor microenvironment as it pertains to the response to I-PDT. Tumor progression was monitored over 60 days. Image-based treatment planning was used to translate the preclinical findings into a treatment in clinical settings (8 Gy x1 followed by I-PDT) for patients with extrabronchial MCAO.
Results: Preceding I-PDT with p-XRT increases tumor oxygenation for 1-2 days after the last radiation fraction and improves light penetration within mouse tumors. Administering p-XRT 24-48 h before I-PDT significantly (p&lt;0.05, log-rank test) increases the rate of complete tumor response and control from 0% in p-XRT alone or 0-6% in I-PDT alone, to 31-64% for p-XRT followed by I-PDT. In patients, administration of I-PDT with porfimer sodium 48 h after 8Gy x1 p-XRT is feasible and can provide control of extrabronchial MCAO accompanied by symptomatic relief.
Conclusions: Augmenting I-PDT with p-XRT improves the rate of tumor response. Murine studies show that p-XRT increases tumor blood oxygenation and light penetration which could contribute to better response to I-PDT. I-PDT with porfimer sodium preceded by p-XRT is feasible with possible benefits in patients with extrabronchial MCAO.
Citation Format: Emily Oakley, Sarah Chamberlain, Nathaniel Ivanick, Alan Hutson, Theresa Busch, Gal Shafirstein. Image-guided interstitial photodynamic therapy with palliative radiotherapy for ablating extrabronchial malignant central airway obstruction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2423.