Abstract 1329: Intraoperative light transmission: A translational dosimteric marker for tumor response in interstitial photodynamic therapy

Abstract Background: Interstitial photodynamic therapy (I-PDT) has shown promising outcomes in controlling locally advanced tumors refractory to standard of care therapies. I-PDT utilizes interstitial laser light delivery to activate a light-sensitive drug (photosensitizer) to produce singlet oxygen within the target tumor. The response to I-PDT is controlled by the intratumoral light dosimetry, photosensitizer concentration and tumor oxygenation. We hypothesize that changes in laser light transmission due to changes in tumor vasculature are a dosimetric marker for response to I-PDT. We test this hypothesis in murine models with locally advanced cancer. Methods: The relationship between light transmission and tumor response was studied in eight- to twelve-week-old C3H and C57BL/6 female mice with locally advanced (400-600 mm3) subcutaneous tumors. C3H with squamous cell carcinoma VII (SCCVII) or C57BL/6 with LL/2 (Lewis lung carcinoma) tumors were treated with I-PDT alone or with palliative x-ray radiotherapy (p-XRT) followed by I-PDT at 24 ± 2h after the second fraction of 10 Gy x2 over two days. The I-PDT was conducted with 2 mg/kg verteporfin for injection administered via intravenous tail vein injection 3 h prior to the intratumoral illumination with 689±3 nm laser light planned to generate a minimum of 5 mW/cm2 and 30 or 37.5 J/cm2 in the target tumor. The laser light was delivered through a single 2-cm cylindrical diffuser fiber and measured with a light dosimetry fiber at the tumor margins. Photoacoustic imaging was conducted before and after p-XRT and prior to I-PDT. Tumor progression was monitored over 60 days. Results: In C3H mice with locally advanced SCCVII, the I-PDT produced a 20% (2/10) tumor control rate, while p-XRT followed by the same I-PDT regimen resulted in better (p<0.05, log-rank test) tumor control 88% (8/9). In the C57BL/6 mice with LL2, we observed tumor control at day 60 (0/18) in mice treated with I-PDT and 27% (5/18) complete tumor response at day 60 in mice treated with p-XRT followed by I-PDT. There was a significant improvement in light transmission (p<0.05, t-test for comparing differences of non-linear regression models) in tumors treated with p-XRT prior to I-PDT in comparison to tumors treated with I-PDT only. The photoacoustic imaging shows a significant increase in tumor blood flow (p<0.05, t-test) after the p-XRT and prior to the I-PDT. Conclusions: Increased light transmission due to increases in tumor blood flow results in better tumor response to I-PDT. Changes in light transmission during I-PDT are a potential dosimetric marker to assess tumor response. This measure can be used in clinical settings to adjust laser power to increase light transmission to improve tumor control in I-PDT of refractory cancerous tumors. Citation Format: Cristopher Lawson, Emily Oakley-Gawrys, Sarah Chamberlain, Alan Hutson, Nathaniel Ivanick, Keith Cengel, Theresa Busch, Gal Shafirstein. Intraoperative light transmission: A translational dosimteric marker for tumor response in interstitial photodynamic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1329.