Photodynamic therapy of brain tumors—A work in progress

Müller, Paul J.; Wilson, Brian C.

doi:10.1002/lsm.20338

Cited by 128 publications

(85 citation statements)

References 18 publications

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“…Preclinical interstitial (IS) PDT studies have also been performed in parallel and include brain tumors (7), vertebral metastases (8), and prostate cancer (9).…”

Section: Introductionmentioning

confidence: 99%

Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: AnIn vivoStudy

Standish¹,

Lee

Jin

et al. 2008

Cancer Research

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We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n = 28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm À2 for 25 minutes.High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R 2 = 0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle + light, no drug, n = 3) showed minimal microvascular changes or necrosis (4% F 1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients. [Cancer Res 2008;68(23):9987-95]

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“…Preclinical interstitial (IS) PDT studies have also been performed in parallel and include brain tumors (7), vertebral metastases (8), and prostate cancer (9).…”

Section: Introductionmentioning

confidence: 99%

Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: AnIn vivoStudy

Standish¹,

Lee

Jin

et al. 2008

Cancer Research

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“…Most clinical reports provide an insu±cient discussion of neurological de¯cits post-PDT or the appropriate progression-free survival time points. The Muller group, 26 showed for Photofrin-mediated PDT a reduction in the Karnofsky score for a radiant exposure dose of 80 J cm À2 compared to the 40 J cm À2 group with a statistical signi¯cant reduction evident up to three months post-PDT. This is of concern if prolonged longer survival is to be achieved by means of higher radiant exposure alone.…”

Section: Clinical Evaluations Of Pdt's Added Value In Treating Gliomasmentioning

confidence: 95%

“…This enables the ability of repeat PDT based therapies as proposed 22,23 for metronomic PDT (mPDT) and already employed in a modi¯ed version in vivo by Eljamel and colleagues. 24 Photosensitizers can be administered in their photoactivable form, such as Hematoporphyrin derivative (HpD), 25 Photofrin, 26 chlorine in the form of metatetrahydroxyphenylchlorin (mTHPC), 27 Talapor¯n sodium 28 or conversely as a pro-drug as in aminolevulinic acid induced protoporphyrin IX (PpIX) as photochemical active drug. 29 Various groups have used PDT treatment as a primary and adjuvant therapy following surgery with some initial success.…”

Section: Introductionmentioning

confidence: 99%

“…29 Various groups have used PDT treatment as a primary and adjuvant therapy following surgery with some initial success. 25,26,28,30 Selectivity of PDT is provided by physical connement of the minimum required light°uence È [J cm À2 ] to the boundary of the clinical target volume (CTV). This can be achieved by an appropriate photon source distribution within the limits governed by the optical properties of the tissue.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that personalized cancer medicine concepts are equally applying to PDT for GBM. The pharmacokinetic-based selectivity of the various photosensitizers translate at least partially into a clinical impact and prolong the survival times in early clinical trials, but not to the extent anticipated based on the large di®erences in photosensitizer uptake initially observed in preclinical studies for ALA induced PpIX 36,37 and also in some clinical studies for Photofrin, 26 HpD 25 and ALA induced PpIX 30 reporting speci¯c uptake ratio (SUR) of less than 10. In part, this is due to the intrinsic high sensitivity or low resilience of the normal tissue structures, particular astrocytes and neurons within the PDT treatment¯eld as shown by Lilge and Wilson.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

Fisher

Lilge

2015

J. Innov. Opt. Health Sci.

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Invasive grade III and IV malignant gliomas remain di±cult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade, whereas some improvements have been obtained towards¯ve-year survival rates for which completeness of resection is a prerequisite. Optical techniques such as°uorescence guided resection (FGR) and photodynamic therapy (PDT) are promising adjuvant techniques to increase the tumor volume reduction fraction. PDT has been used in combination with surgical resection or alternatively as standalone treatment strategy with some success in extending the median survival time of patients compared to surgery alone and the current standard of care. This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches. It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment e±cacy through exploiting both physical and biological-based approaches to maximize PDT selectivity and therapeutic index, particularly in brain adjacent to tumor (BAT). Potential reasons for failing to demonstrate a signi¯cant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.

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Chemophototherapy: An Emerging Treatment Option for Solid Tumors

et al. 2016

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Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted.

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Photodynamic therapy of brain tumors—A work in progress

Abstract: Photofrin-PDT was safe. However, higher light doses than were used in these patients may be required for improved responses.

Cited by 128 publications

References 18 publications

Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: AnIn vivoStudy

Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: AnIn vivoStudy

Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

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