Photodynamic therapy is a safe and feasible adjunct to percutaneous drainage of deep tissue abscesses: Results of a first in humans Phase 1 clinical trial

Baran, Timothy M.; Bass, David A.; Christensen, Laurie; Longbine, Erica; Favella, Maria D.; Foster, Thomas H.; Sharma, Ashwani K.

doi:10.1101/2023.10.16.23297086

Cited by 6 publications

(22 citation statements)

References 35 publications

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“…Based on encouraging pre- clinical results showing that PDT with methylene blue (MB) is efficacious against multiple bacteria typically found in abscesses 6,11,12 , we initiated a Phase 1 clinical trial investigating the safety and feasibility of MB-PDT at the time of abscess drainage (ClinicalTrials.gov identifier: NCT02240498). We found that MB-PDT was safe, with no study-related adverse events observed 8 . Additionally, preliminary analysis suggests that symptom resolution was faster and drainage catheter discharge was reduced in subjects receiving higher fluence.…”

Section: Introductionmentioning

confidence: 60%

“…In all cases, the goal was to determine the delivered optical power (threshold optical power) and lipid emulsion concentration necessary to achieve a desired fluence rate of 4 mW/cm 2 or 20 mW/cm 2 in 95% of the abscess wall, while limiting the portion of the wall that receives a fluence rate of 400 mW/cm 2 to less than 5%. The 4 mw/cm 2 target is based upon an efficacious pre- clinical condition 6,12 , while the 20 mW/cm 2 target is the target fluence rate used clinically 8 to account for the more demanding in vivo scenario. The final treatment plan was determined by the lipid emulsion concentration that minimized the threshold optical power.…”

Section: Methodsmentioning

confidence: 99%

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Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

Li,

Hannan,

Sharma

et al. 2023

Preprint

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Background: Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a recently completed Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect the expected light dose to the abscess wall and eventual PDT response. Purpose: The objective of this study was to simulate PDT treatment planning for the 13 subjects that received optical spectroscopy prior to clinical abscess PDT. Our goal was to determine the impact of these measured optical properties on our ability to achieve fluence rate targets in 95% of the abscess wall. Methods: During a Phase 1 clinical trial, 13 subjects received diffuse reflectance spectroscopy prior to PDT in order to determine the optical properties of their abscess wall. Retrospective treatment plans seeking to achieve fluence rate targets in 95% of the abscess wall were generated for all subjects for 3 conditions: (1) at the laser power delivered clinically with assumed optical properties, (2) at the laser power delivered clinically with measured optical properties, and (3) with patient-specific treatment planning using these measured optical properties. Factors modified in treatment planning included delivered laser power and intra-cavity Intralipid (scatterer) concentration. The effects of laser fiber type were also simulated. Results: Using a flat-cleaved laser fiber, the proportion of subjects that achieved 95% abscess wall coverage decreased significantly when incorporating measured optical properties for both the 4 mW/cm^2 (92% vs. 38%, p=0.01) and 20 mW/cm^2 (62% vs. 15%, p=0.04) fluence rate thresholds. However, when measured optical properties were incorporated into treatment planning, a fluence rate of 4 mW/cm^2 was achieved in 95% of the abscess wall for all cases. In treatment planning, the optimal Intralipid concentration across subjects was found to be 0.14 +/- 0.09% and the optimal laser power varied from that delivered clinically but with no clear trend (p=0.4). The required laser power to achieve 4 mW/cm^2 in 95% of the abscess wall was significantly correlated with measured absorption at the abscess wall (rho=0.7, p=0.008), but not abscess surface area (rho=0.2, p=0.53). When using spherical diffuser fibers as the illumination source, the optimal intralipid concentration decreased to 0.028 +/- 0.026% (p=0.0003), and the required laser power decreased also (p=0.021), compared to flat cleaved fibers. If the intra-cavity lipid emulsion (Intralipid) was replaced with a non-scattering fluid, all subjects could achieve the 4 mW/cm^2 fluence rate threshold in 95% of the abscess wall using a spherical diffuser, while only 69% of subjects could reach the same criterion using a flat cleaved fiber. Conclusions: The range of optical properties measured in human abscesses reduced coverage of the abscess wall at desirable fluence rates. Patient-specific treatment planning including these measured optical properties could bring the coverage back to desirable levels by altering the Intralipid concentration and delivered optical power. These results motivate a future Phase 2 clinical trial to directly compare the efficacy of patient-specific-treatment planning with fixed doses of Intralipid and light.

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Section: Introductionmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

Li,

Hannan,

Sharma

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Spectroscopy data were collected from subjects enrolled in a Phase 1 clinical trial examining the safety and feasibility of methylene blue photodynamic therapy performed at the time of percutaneous abscess drainage (ClinicalTrials.gov Identifier: NCT02240498). The primary results of this clinical trial are reported separately 8 . Of the 18 subjects treated in this trial, optical spectroscopy data were collected from the final 13 subjects as described below.…”

Section: Participants and Regulatory Approvalmentioning

confidence: 99%

“…All subjects first had their abscess drained using standard of care image-guided percutaneous drainage, as described in the main trial report 8 . This procedure utilized CT guidance for 16 subjects and ultrasound guidance for 2 subjects.…”

Section: Clinical Data Collectionmentioning

confidence: 99%

“…After the completion of optical spectroscopy measurements, the optical probe was removed and photodynamic therapy was performed as described in the main clinical trial report 8 . This consisted of infusion of a lipid emulsion to scatter treatment light through the irregular abscess cavity, insertion of a sterile optical fiber, and delivery of laser light at 665 nm.…”

Section: Clinical Data Collectionmentioning

confidence: 99%

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First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy byin vivodiffuse reflectance spectroscopy

Hannan,

Sharma,

Baran

2023

Preprint

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SignificanceEfficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects.AimThe objective was to extract optical properties and photosensitizer concentration from spatially-resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a Phase 1 clinical trial.ApproachDiffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties.ResultsPre-MB abscess wall absorption coefficients at 665 nm were 0.15±0.1 cm−1(0.03-0.36 cm−1) and 10.74±15.81 cm−1(0.08-49.3 cm−1) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm−1(4.8-13.2 cm−1) and 5.6±2.26 cm−1(1.6-9.9 cm−1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83±35.78% (5.6-100%) pre-MB and 36.29±25.1% (0.0001-76.4%) post-MB. Determined MB concentrations were 71.83±108.22 µM (0-311 µM).ConclusionsWe observed substantial inter-subject variation in both native wall optical properties and methylene blue uptake. This underscores the importance of making these measurements for patient-specific treatment planning.

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Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

Li,

Hannan,

Sharma

et al. 2024

Phys. Med. Biol.

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Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW/cm2 (92% vs. 38%, p=0.01) and 20 mW/cm2 (62% vs. 15%, p=0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW/cm2 target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW/cm2 target was significantly correlated with measured abscess wall absorption (ρ=0.7, p=0.008), but not abscess surface area (ρ=0.2, p=0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p=0.0005) and required laser power (p=0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW/cm2 target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy.

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Photodynamic therapy is a safe and feasible adjunct to percutaneous drainage of deep tissue abscesses: Results of a first in humans Phase 1 clinical trial

Cited by 6 publications

References 35 publications

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy byin vivodiffuse reflectance spectroscopy

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

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