Abstract 2420: Interstitial chemo-phototherapy for treatment of locally advanced hepatocellular carcinoma: A preclinical study
Authors: Oakley Emily , Kim Minhyung , Ghosh Sanjana , Kutscher Hilliard , Lovell Jonathan , Curtin Leslie , Sexton Sandra , Hutson Alan , Shafirstein Gal 
Published: April 2023

Background Patients with hepatocellular carcinoma (HCC) have a poor prognosis with a 5-year survival rate of only 35%. Patients with locally advanced HCC (single or multinodal tumors &gt;3 cm) may not be candidates for curative treatments such as surgical resection, liver transplant or thermal ablation due to tumor size, poor liver function, or other medical co-morbidities. The objective of this study was to investigate the potential use of interstitial chemo-phototherapy (I-CPT) to treat locally advanced HCC with a porphyrin-phospholipid (PoP) liposomal formulation of doxorubicin (Dox) that combines the targeted delivery of doxorubicin with photodynamic therapy to improve local drug delivery. We aimed to identify a safe and effective light dose for the photoactivation of Dox-Pop in the treatment of locally advanced HCC tumors in two pre-clinical models.

Methods Sprague-Dawley rats were inoculated with Morris hepatoma cells directly into the left lateral liver lobe. When the tumors reached 2-2.5 cm along the longest axis, they were treated with Dox-Pop followed by light (i.e. I-CPT). For each rat, we applied our image-based treatment planning to guide the light delivery. Following treatment, tumor response was measured through weekly contrast-enhanced magnetic resonance imaging (CE-MRI). Complete response was defined as no evidence of the tumor via MRI or pathological examination. Our image-based treatment planning was used to translate the findings in the rat study to woodchucks with 1.5-4 cm hepatitis virus induced HCC. Weekly blood samples and bi-weekly CE-MRI were performed to assess tumor response up to 70 days.

Results Five out of the six rats treated with I-CPT had complete response, with three of the five surviving ≥10 weeks post treatment without tumor recurrence or progression. The other two rats with complete response died between 5-7 weeks post treatment. Death was not attributed to the original treatment. Control, untreated rats were euthanized due to tumor progression within 1-2 weeks after tumors reached 2-2.5 cm. From the rat studies, we identified that a light dose rate and dose of respectively, ≥13.4 mW/cm2 and ≥25 J/cm2 can effectively activate the Dox-Pop liposomes. Of the five woodchucks treated with I-CPT using our effective light regimen, two survived ≥ 68 days post treatment without tumor progression. Another woodchuck had a complete response, but was euthanized 55 days post treatment due to the development of a second tumor. One woodchuck had progressive disease following I-CPT. One woodchuck died unexpectedly 5 days post I-CPT. Death was attributed to high tumor necrosis.

Conclusions This study demonstrated the potential use of I-CPT as a treatment option for locally advanced HCC not candidate for standard of care therapies. Ongoing studies are being conducted in woodchucks to optimize the I-CPT light settings and improve tumor response.

Citation Format: Emily Oakley, Minhyung Kim, Sanjana Ghosh, Hilliard Kutscher, Jonathan Lovell, Leslie Curtin, Sandra Sexton, Alan Hutson, Gal Shafirstein. Interstitial chemo-phototherapy for treatment of locally advanced hepatocellular carcinoma: A preclinical study [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 2420.