Fractionated illumination improves the treatment outcomes of photodynamic therapy for high grade cutaneous leishmaniasis

Abstract Objective: Photodynamic therapy (PDT) using Talaporfin Sodium (TS) is a novel therapeutic strategy to improve local tumor control in high-grade glioma. TS is a photosensitizer that accumulates in tumor cells and produces highly toxic free radicals by intraoperative irradiation of laser with a 664nm wavelength. However, little is known about the treatment outcomes of PDT in recurrent high-grade gliomas (rHGG). In this study, we investigated the treatment outcome of PDT in rHGG and evaluated the correlation between intratumoral TS accumulation and outcomes. Methods: We included 21 patients with rHGG and 22 tumors, who were treated by PDT between June 2016 and March 2021. TS was transvenously administered 22–26 hours before PDT. Intratumoral TS concentrations were measured by liquid chromatography using frozen tissue. Results: The rHGGs included 10 glioblastoma, IDH1/2-wildtype (GBM, IDH1/2-WT: 45.5%), 3 GBM, IDH1/2-mutant (GBM, IDH1/2-Mut: 13.6%), 7 anaplastic oligodendroglioma, IDH1/2-Mut/codel (AO, IDH1/2-Mut/codel: 31.8%), 1 anaplastic astrocytoma, IDH1/2-WT (AA, IDH1/2-WT: 4.5%), 1 high-grade astrocytoma, IDH1/2-WT (4.5%). The median local progression free survival (PFS) time after PDT was 3.6 months and the median survival time from PDT was 19.4 months. The intratumoral TS concentrations of 7 tumors (TS(-): 31.8%) were below the limit of quantification, and the intratumoral TS concentrations of the remaining 15 tumors (TS(+)) were 43.5 ng/mg-protein (14.7–132 ng/mg-protein). The intratumoral TS concentrations were not significantly associated with IDH1/2 mutation status, cellularity, tumor grade, and pattern of enhancement. The median PFS from PDT tended to be longer in TS(+) than in TS(-) (TS(+): 6.3 vs TS(-): 1.4 months, p = 0.054). Conclusions: We found that the intratumoral TS concentrations were heterogeneous and 31.8% were below the limit of quantification. TS(+) tended to have better local tumor control than TS(-), suggesting the intratumoral TS accumulation have an impact of treatment outcomes of PDT.

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A multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira®) as a novel treatment in patients with high grade squamous intraepithelial lesion: APRICITY Phase 3 study protocol

10.1101/2021.12.02.21266991 ◽

2021 ◽

Author(s):

Fei Chen ◽

Zoltán Novák ◽

Christian Dannecker ◽

Long Sui ◽

Youzhong Zhang ◽

...

Keyword(s):

Photodynamic Therapy ◽

Low Grade ◽

High Grade ◽

Efficacy And Safety ◽

Squamous Intraepithelial Lesion ◽

Phase 3 ◽

Link Type ◽

Surgical Methods ◽

Intraepithelial Lesion ◽

Randomised Controlled

AbstractIntroductionHigh-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality.ObjectiveAPRICITY is a multicentre, prospective, double-blind, randomised controlled Phase 3 study further evaluating the efficacy and safety of Cevira®, an integrated drug- and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive therapy for women with HSIL.Methods and analysisPatients with biopsy-confirmed HSIL histology are invited to participate in the study currently being conducted at 47 sites in China and 25 sites in Ukraine, Russia and European Union. The aim is to include at least 384 patients which will be randomised to either Cevira® or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low grade squamous intraepithelial lesion (LSIL). Primary endpoint is the proportion of the responders at 6 months after first treatment. Secondary efficacy endpoints and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints for Cevira® device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira® group will be enrolled in an open, long-term extension study following patients for further 6 months to collect additional efficacy and safety data (study extension endpoints).ConclusionDue to its non-invasiveness and convenient application, Cevira® may be a favourable alternative to surgical methods in treatment of patients with HSIL.Ethics and disseminationThe study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.Trial registration numberclinicaltrials.govNCT04484415

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