Vascular-targeted Photodynamic Therapy Research Articles

MP18-10 ONCOLOGIC OUTCOMES AFTER HEMIABLATION THERAPY FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy1 Apr 2016MP18-10 ONCOLOGIC OUTCOMES AFTER HEMIABLATION THERAPY FOR LOCALIZED PROSTATE CANCER Estefania Linares Espinos, Jose I. Perez-Reggeti, Eric Barret, Arjun Sivaraman, Rafael Sanchez-Salas, Marc Galiano, François Rozet, Dominique Prapotnich, Nathalie Cathala, Annick Mombet, and Xavier Cathelineau Estefania Linares EspinosEstefania Linares Espinos More articles by this author , Jose I. Perez-ReggetiJose I. Perez-Reggeti More articles by this author , Eric BarretEric Barret More articles by this author , Arjun SivaramanArjun Sivaraman More articles by this author , Rafael Sanchez-SalasRafael Sanchez-Salas More articles by this author , Marc GalianoMarc Galiano More articles by this author , François RozetFrançois Rozet More articles by this author , Dominique PrapotnichDominique Prapotnich More articles by this author , Nathalie CathalaNathalie Cathala More articles by this author , Annick MombetAnnick Mombet More articles by this author , and Xavier CathelineauXavier Cathelineau More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Focal therapy was developed in order to limit side effects of conventional prostate cancer (PCa) treatments. We aimed to assess oncologic outcomes after focal thermal ablative primary treatment. METHODS Between January 2009 to August 2015, 277 patients underwent primary thermal hemiablation for localized PCa at our institution. Energy used was either cryotherapy or high intensity focused ultrasound (HIFU) or vascular-targeted photodynamic therapy (VTP). Inclusion criteria for hemiablation treatment were PSA<15ng/dl, Gleason ≤7, unilateral disease and index lesion <10mm and MRI prior to biopsy ≤T2b. We selected patients with post-treatment prostate biopsy and 12 months minimum follow-up. Patients were followed postoperatively with PSA, MRI-imaging and 12-core TRUS protocol biopsy, at 6-12 months. Failure was defined as any positive biopsy in the treated lobe. Cross-tabs applying chi-square were used to assess relationships among categorical variables. A p value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS v21. RESULTS At one year follow-up, 229 patients had post-treatment control biopsy with 48 not available. Among them, 110, 89 and 30 patients underwent a hemiablation of the prostate using cryotherpy, HIFU and VTP respectively. A total of 55 patients had biopsy-proven cancer at follow-up. With a mean age of 65,5 ± 6,7 years, 43 were D'Amico Low risk and 12 Intermediate risk at diagnosis. Initial PSA was 7,44 ± 2,93 ng/dl, 47 Gleason 3+3 and 8 Gleason 3+4. Thirty (27%), 13 (17%) and 12 (40%) had biopsy proven cancer after primary focal cryotherapy, HIFU and VTP, respectively. Residual cancer in the treated side was present in 41 patients (15 bilateral), considered as failure to treatment (18%). De novo contralateral disease was diagnosed in 14 patients. Residual disease had a median core length of 4mm (3-13) and a median number of 2 (1-3) positive cores. No difference were observed in focal treatment failure between primary focal energy modalities (table 1). CONCLUSIONS Short-term data show promising oncologic outcomes in the focal therapy primary setting with 18% failure rate. Focal ablative therapy is an effective treatment option for the primary management of PCa, with no proven differences in failure rates between energy modalities. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e196 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Estefania Linares Espinos More articles by this author Jose I. Perez-Reggeti More articles by this author Eric Barret More articles by this author Arjun Sivaraman More articles by this author Rafael Sanchez-Salas More articles by this author Marc Galiano More articles by this author François Rozet More articles by this author Dominique Prapotnich More articles by this author Nathalie Cathala More articles by this author Annick Mombet More articles by this author Xavier Cathelineau More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy

Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non-tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee-approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material-enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 μm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. (©) RSNA, 2016 Online supplemental material is available for this article.

Palliative treatment of obstructive esophageal cancer by vascular targeted photodynamic therapy (VTP): Preclinical study in orthotopic rat model.

59 Background: Vascular targeted photodynamic therapy (VTP) based on local sensitization of circulating WST11 (Pd-bacteriochlorophyll), enables effective focal ablation of solid tumors. WST11 clears from the circulation with t1/2 ~40 min (in humans) and does not accumulate in tissues which assures high level of safety and minimal adverse effects. Here we evaluate WST11-VTP for the treatment of obstructive esophageal cancer aiming at developing clinically relevant protocol. Methods: Using endoscopy guided procedure rat esophageal cancer cells (JA) were implanted in the mid esophagus. Following intravenous infusion of WST11, established tumors were illuminated by cylindrical fiber using the same endoscope sleeve. Safety and efficacy were evaluated by monitoring animal weight shift and histology of treated esophageal tissues. Treated animals included control (light/no WST11 or WST11/no light), WST11-VTP and WST11-VTP following treatment with bevacizumab at day -3. Results: WST11-VTP on esophageal tissues resulted in coagulative necrosis of the tumor graft and prolonged survival as evident by Kaplan—Meyer curves. The impact was confined to the illuminated site without signs of perforation or death. Following Bevacizumab, WST11-VTP showed similar results while control groups showed no effect. All treated animals started to regain weight at day 7 after VTP. Esophageal tissue and function was completely restored. Conclusions: WST11-VTP could be safely applied for the treatment of esophageal tumors, with only transient and mild adverse effect that are not affected by previous, clinically relevant treatment such as Bevacizumab application. Importantly, VTP effectively eradicated established esophageal tumors and could be translated into a clinical treatment protocol.

Relationship between the blood perfusion values determined by laser speckle imaging and laser Doppler imaging in normal skin and port wine stains

ObjectiveLaser Doppler imaging (LDI) and laser speckle imaging (LSI) are two major optical techniques aiming at non-invasively imaging the skin blood perfusion. However, the relationship between perfusion values determined by LDI and LSI has not been fully explored. Methods8 healthy volunteers and 13 PWS patients were recruited. The perfusions in normal skin on the forearm of 8 healthy volunteers were simultaneously measured by both LDI and LSI during post-occlusive reactive hyperemia (PORH). Furthermore, the perfusions of port wine stains (PWS) lesions and contralateral normal skin of 10 PWS patients were also determined. In addition, the perfusions for PWS lesions from 3 PWS patients were successively monitored at 0, 10 and 20min during vascular-targeted photodynamic therapy (V-PDT). The average perfusion values determined by LSI were compared with those of LDI for each subject. ResultsIn the normal skin during PORH, power function provided better fits of perfusion values than linear function: powers for individual subjects go from 1.312 to 1.942 (R2=0.8967–0.9951). There was a linear relationship between perfusion values determined by LDI and LSI in PWS and contralateral normal skin (R2=0.7308–0.9623), and in PWS during V-PDT (R2=0.8037–0.9968). ConclusionThe perfusion values determined by LDI and LSI correlate closely in normal skin and PWS over a broad range of skin perfusion. However, it still suggests that perfusion range and characteristics of the measured skin should be carefully considered if LDI and LSI measures are compared.

Management of low- and intermediate-risk prostate cancer

the current status of MRI in active surveillance, particularly for predicting tumor stage and site. Here it becomes obvious that the diagnostic accuracy of dedicated centers is not reproduced by non-specialized radiologists. RenardPenna et al. [4] describe promising developments of imaging and molecular pathology in the stratification of patients with early prostate cancer. The second part of the manuscripts is dedicated to focal therapy of prostate cancer. Lebdai et al. [5] carefully describe a ‘standardized operating procedure’ (SOP) for vascular-targeted photodynamic therapy (VTP) followed by a pooled analysis of three phase 2 studies by Azzouzi et al. [6]. The histopathologic results of focal therapy and cryotherapy are summarized by Shah et al. [7], and oncological and functional outcomes of VTP are reviewed by Azzouzi et al. The feasibility of salvage surgery after VTP is described by Lebdai et al. [8]. Karl et al. [9] describe a carefully designed multicenter study on the PSA recurrence rate of men with pT2 prostate cancer and a positive surgical margin without any adjuvant therapy. Opportunistic PSA screening has resulted in increased numbers of patients with low and intermediate risk. This specifically dedicated issue of the World Journal of Urology draws the attention of the reader to the new management options for lowand intermediate-risk prostate cancer in the context of the two ‘new kids on the block,’ multiparametric MRI for diagnosis, and focal therapy for treatment. Van der Poel et al. [1] summarize the recent developments and their implications for the management of prostate cancer. Lellig et al. [2] and Billing et al. [3] examine

PD33-03 TREATMENT OF THE PRIMARY TUMOR WITH VASCULAR-TARGETED PHOTODYNAMIC THERAPY (VTP) OVERCOMES RESISTANCE TO SYSTEMIC PD-1/PD-L1 INHIBITION: EFFECTS ON PRIMARY TUMOR CONTROL AND PREVENTION OF LUNG METASTASIS IN A PRE-CLINICAL RCC MODEL

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2015PD33-03 TREATMENT OF THE PRIMARY TUMOR WITH VASCULAR-TARGETED PHOTODYNAMIC THERAPY (VTP) OVERCOMES RESISTANCE TO SYSTEMIC PD-1/PD-L1 INHIBITION: EFFECTS ON PRIMARY TUMOR CONTROL AND PREVENTION OF LUNG METASTASIS IN A PRE-CLINICAL RCC MODEL Matthew O'Shaughnessy, Katie Murray, Stephen LaRosa, Sebastien Monette, Kwanghee Kim, Renato Beluco Corradi Fonseca, Avigdor Scherz, and Jonathan Coleman Matthew O'ShaughnessyMatthew O'Shaughnessy More articles by this author , Katie MurrayKatie Murray More articles by this author , Stephen LaRosaStephen LaRosa More articles by this author , Sebastien MonetteSebastien Monette More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , Renato Beluco Corradi FonsecaRenato Beluco Corradi Fonseca More articles by this author , Avigdor ScherzAvigdor Scherz More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2101AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Immune checkpoint inhibitors targeting the PD-1 pathway have shown activity against advanced malignancies including renal cell carcinoma in phase 2 clinical trials. The response to PD-1 inhibition is not consistent however and may depend on host factors (ie. PD-L1 expression). Strategies that modulate immune regulation in the tumor microenvironment can impact responses to PD-1 pathway inhibitors. We have previously shown that VTP treatment of primary tumors using the novel photosensitizer WST-11 induces a defined local inflammatory response in the tumor microenvironment. We sought to evaluate whether response to PD-1/PD-L1 inhibition could be enhanced with VTP treatment of primary tumors. METHODS Balb/c mice bearing orthotopically implanted Renca kidney tumors were treated with IgG alone, anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs), VTP alone, or VTP + anti-PD-1/anti-PD-L1 mAbs. VTP treatment of the primary tumor was performed 10 days (d10) after tumor implantation. Primary tumor response, enumeration of lung metastases and histologic analysis was performed on d21. Anti-PD-1 and anti-PD-L1 mAbs were administered by intraperitoneal injection twice weekly. RESULTS Treatment of the primary tumor with VTP and systemic PD-1/PD-L1 inhibition (n=15) resulted in regression of primary tumors whereas PD-1/PD-L1 inhibition alone (n=21) or VTP treatment alone (n=16) did not (no gross tumor vs. median tumor size 96mm2 vs 36 mm2 vs 81 mm2 for combination vs mAbs alone vs VTP alone vs control, p<0.0001). Significant treatment effect was also observed in the combined treatment group by histologic analysis. Furthermore, growth of lung metastases was prevented with the combined treatment regimen compared to either treatment alone (median number lung mets 3 vs 56 vs 53 vs 23 for combination, mAb alone, VTP alone and control, respectively, p=0.0252). CONCLUSIONS Only the combination of systemic PD-1/PD-L1 inhibition and local VTP provided primary tumor control and prevention of distant metastasis in this pre-clinical model of RCC. Modulation of the inflammatory response in the tumor microenvironment with local therapy such as VTP may enhance the effects of systemic PD-1/PD-L1 blockade to provide better local and metastatic tumor control that can be investigated in prospective clinical trials. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e710 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew O'Shaughnessy More articles by this author Katie Murray More articles by this author Stephen LaRosa More articles by this author Sebastien Monette More articles by this author Kwanghee Kim More articles by this author Renato Beluco Corradi Fonseca More articles by this author Avigdor Scherz More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Vascular-targeted photodynamic therapy with TOOKAD® Soluble in localized prostate cancer: standardization of the procedure.

IntroductionVascular-targeted photodynamic therapy with TOOKAD® Soluble is an innovative focal therapy procedure assessed in localized prostate cancer treatment.Materials and methodsThis mini-invasive technique destroys targeted tissues using a photosensitizer [TOOKAD® Soluble (WST11), STEBA Biotech] activated by laser light in the presence of oxygen. Its application for prostate cancer requires intravenous infusion of TOOKAD® Soluble and the illumination of the targeted area by transperineal optical fibers inserted under trans-rectal ultrasound guidance under general anesthesia.ConclusionBased on the experience gained through hundreds of procedures, we describe here the standardized technique of vascular-targeted photodynamic therapy with TOOKAD® Soluble defined during the phase II and III trials.

Systemic PD-1/PD-L1 inhibition combined with local vascular-targeted photodynamic therapy (VTP): Effects on primary tumor and prevention of lung metastasis in a preclinical RCC model.

477 Background: Immune checkpoint inhibitors targeting the PD-1 pathway have shown activity against advanced renal cell carcinoma in phase 2 clinical trials. The response to PD-1 inhibition is not consistent however and may depend on host factors (ie. PD-L1 expression). Strategies that modulate immune regulation in the tumor microenvironment can impact responses to PD-1 pathway inhibitors. We have previously shown that VTP treatment of primary tumors using the novel photosensitizer WST-11 induces a defined local inflammatory response. We sought to evaluate whether response to PD-1/PD-L1 inhibition could be enhanced with VTP treatment of primary tumors. Methods: Balb/c mice bearing orthotopically implanted Renca kidney tumors were treated with IgG alone, anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs), VTP alone, or VTP + mAbs. VTP treatment of the primary tumor was performed 10 days (d10) after tumor implantation. Primary tumor response, enumeration of lung metastases and histologic analysis was performed on d21. Results: Treatment of the primary tumor with VTP and systemic PD-1/PD-L1 inhibition (n=15) resulted in regression of primary tumors whereas PD-1/PD-L1 inhibition alone (n=21) or VTP treatment alone (n=16) did not (no gross tumor vs. median tumor size 96mm2 vs 36 mm2 vs 81 mm2for combination vs mAbs alone vs VTP alone vs control, p&lt;0.0001). Significant treatment effect was also observed in the combined treatment group by histologic analysis. Furthermore, growth of lung metastases was prevented with the combined treatment regimen compared to either treatment alone (median number lung mets=3 vs 56 vs 53 vs 23 for combination, mAb alone, VTP alone and control, respectively, p=0.0252). Conclusions: Only the combination of systemic PD-1/PD-L1 inhibition and local VTP provided primary tumor control and prevention of distant metastasis. Modulation of the inflammatory response in the tumor microenvironment with local therapy such as VTP may enhance the effects of systemic PD-1/PD-L1 blockade to provide better local and metastatic tumor control that can be investigated in prospective clinical trials.

TOOKAD® Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer.

Purpose To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD® Soluble in patients with localized prostate cancer (LPCa).MethodsWe performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD® Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6.ResultsMonth 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function.ConclusionsFocal VTP treatment with TOOKAD® Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.

Feasibility, safety, and efficacy of salvage radical prostatectomy after Tookad® Soluble focal treatment for localized prostate cancer

To investigate feasibility, safety, and efficacy of salvage radical prostatectomy (RP) for recurrent prostate cancer (PCa) after focal treatment with TOOKAD(®) Soluble vascular-targeted photodynamic therapy (VTP). Nineteen patients underwent RP after biopsy-proven PCa post-focal VTP. We reported: operation time, blood loss, transfusion, complications, urethral catheterization time, functional outcomes, and short-term oncologic outcomes. Median age was 64 years (58-70). Median PSA before VTP was 6.30 ng/ml (3.20-9.80). Median delay between VTP and RP was 17 months (8-48). Median blood loss was 400 ml (100-1,000). Median operation time was 150 min (90-210), median urethral catheterization time was 7 days (5-18), and median hospital stay was 7 days (4-21). There was no perioperative mortality. Three patients had related per-operative complications: one pelvic hematoma (150 cc) (Clavien IIIa), one per-operative transfusion (900 cc hemorrhage) (Clavien II), and one superficial wound infection (Clavien I). After a median follow-up of 10 months (1-46), 13 were completely continent (68 %), five needed ≤1 pad/day, and one needed 3 pads/day (Clavien I). Severe erectile dysfunction was observed before and after RP (respectively 8 and 18). Ten patients regained potency with appropriate treatment. Median postoperative PSA was 0.02 ng/ml (<0.01-0.38) and remained undetectable for 16 patients (84 %). Nine patients had positive margins and six underwent complementary radiotherapy. Positive margins were significantly associated with bilateral VTP [risk ratio = 4.3, 95 % confidence interval (1.6-11.7), p = 0.003]. Salvage RP after VTP treatment was feasible, safe, and efficient to treat most of the locally recurrent PCa. Short-term oncologic and functional outcomes were promising, but further studies are required.

The treatment of esophageal cancer by vascular-targeted photodynamic therapy (VTP) using orthotopic rat model.

91 Background: Vascular targeted photodynamic therapy (VTP) based on local sensitization of circulating WST11, a water-soluble derivative of Pd-bacteriochlorophyll, enables effective focal ablation of solid tumors. Highly toxic oxygen radicals are produced in the vascular lumen upon illumination with near infra-red light (755nm), leading to irreversible occlusion of tumor feeding arteries and veins. WST11 clears rapidly from the circulation and does not accumulate in the body, providing high level of safety and minimizing adverse effects. WST11-VTP completed Phase II clinical trials in USA and Phase III in Europe for the treatment of early localized prostate cancer as a first line monotherapy with above 80% complete response rate. Here we evaluate its’ safety and efficacy for the treatment of esophageal cancer aiming at development of clinically translatable treatment protocol. Methods: We developed an orthotopic model in which esophageal cancer cells are implanted in the mid esophagus using endoscopy guided procedure. Established tumors are illuminated with cylindrical diffuser deployed through the custom built endoscopy guided system following infusion of WST11. For assessment of treatment safety and tissue recovery normal esophagus tissue was subjected to WST11-VTP using the same treatment set up. Selectivity and efficacy were evaluated histologically by examining sections of treated tumors and normal esophageal tissues under various treatment conditions. Results: Safety control VTP procedures on healthy esophageal tissues have shown a confined destruction only at the illuminated zone while collateral damage to neighboring tissues was not observed. The impact runs as deep as the muscularis propria without signs of perforation or death as a result of the procedure. The VTP protocol was able to ablate implanted and established tumors as opposed to the control group with light illumination alone without the sensitizer (WST11). Conclusions: VTP could be safely applied to treat esophageal tumors, with transient and mild adverse effects. Importantly, VTP effectively eradicated established esophageal tumors in tested set up that could be translated into a clinical treatment protocol.

Dynamic contrast enhanced MRI as a predictor of vascular-targeted photodynamic focal ablation therapy outcome in prostate cancer post-failed external beam radiation therapy.

Photodynamic therapy (PDT) can be employed as a focal therapy for prostate cancer. Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can potentially help identify tumour recurrence after failed external-beam radiotherapy (EBRT). The purpose of this study was to determine the ability of DCE-MRI to predict early response to PDT salvage treatment. Patients with post-EBRT prostate cancer recurrence were prospectively enrolled into a Phase I/II trial of PDT using WST09. A 15-patient subgroup of this cohort undergoing 1.5T DCE-MRI at baseline and 1-week post-PDT was retrospectively analyzed. The reference standard was prostate biopsy obtained 6 months post-PDT. Analysis was performed on a patient-by-patient basis, by prostate gland halves, and by prostate sextants. Biopsy 6 months post-PDT identified cancer in 10/15 patients (66.7%), and in 24/90 sextants (26.7%). Residual cancer was identified in 22/37 sextants (59.5%) identified as being involved at baseline. DCE-MRI at 1 week correctly predicted recurrent disease with a sensitivity of 100% (10/10), specificity of 60% (3/5), positive predictive value of 83.3% (10/12), negative predictive value of 100% (3/3), and an overall accuracy of 86.7%, (13/15). When analysis was performed on prostate halves, the sensitivity and negative predictive value remained at 100%, with an improvement in specificity to 88.2% (15/17). The overall accuracy of DCE-MRI was similar regardless of analysis method: 86.7% on a patient-by-patient basis, 86.7% by prostate half and 83.3% by sextant. Changes in prostate-specific antigen (PSA) did not correlate to response. DCE-MRI shows promise as a tool to predict successful outcome when performed 1 week post-PDT and could potentially be used to inform the need for re-treatment at an early time-point.

Traitement des cancers localisés de la prostate par photothérapie dynamique

Focal therapies are new options for the treatment of localized prostate cancer. Vascular-targeted photodynamic therapy (VTP) with WST11 is one of these options. The aim of this treatment is to destroy a targeted area of the prostate by the associated action of the WST11 drug, light exposure and oxygen. The procedure is performed under general anesthesia. Fibers are introduced trans-perineally in the prostate by ultrasound guidance. The injection of WST11 is then performed with light illumination of the specific targeted area. Current data report 83% negative biopsies 6 months after treatment with good tolerance of the treatment. However, VTP still needs to be evaluated.

The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy

Blood flow and pO2 changes after vascular-targeted photodynamic therapy (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F2BMet) as photosensitizer were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F2BMet generates both singlet oxygen and hydroxyl radicals under near-infrared radiation, which consume oxygen. Partial oxygen pressure was lowered in PDT-treated tumors and this was ascribed both to oxygen consumption during PDT and to fluctuations in oxygen transport after PDT. Similarly, microcirculatory blood flow changed as a result of the disruption of blood vessels by the treatment. A novel noninvasive approach combining electron paramagnetic resonance oximetry and laser Doppler blood perfusion measurements allowed longitudinal monitoring of hypoxia and vascular function changes in the same animals, after PDT. C-PDT induced parallel changes in tumor pO2 and blood flow, i.e., an initial decrease immediately after treatment, followed by a slow increase. In contrast, V-PDT led to a strong and persistent depletion of pO2, although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase in VEGF level 24h after treatment. C-PDT caused a ca. 5-day delay in tumor growth, whereas V-PDT was much more efficient and led to tumor growth inhibition in 90% of animals. The tumors of 44% of mice treated with V-PDT regressed completely and did not reappear for over 1 year. In conclusion, mild and transient hypoxia after C-PDT led to intense pO2 compensatory effects and modest tumor inhibition, but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition.

MP12-14 VASCULAR TARGETED PHOTODYNAMIC THERAPY IN THE SWINE URETER: TRANSMURAL ABLATION DOES NOT PRODUCE OBSTRUCTION IN THE SUBACUTE SETTING

You have accessJournal of UrologyImaging/Radiology III1 Apr 2014MP12-14 VASCULAR TARGETED PHOTODYNAMIC THERAPY IN THE SWINE URETER: TRANSMURAL ABLATION DOES NOT PRODUCE OBSTRUCTION IN THE SUBACUTE SETTING Ashley Winter, Simon Kimm, Haruyuki Takaki, Sebastien Monette, Avigdor Scherz, and Jonathan Coleman Ashley WinterAshley Winter More articles by this author , Simon KimmSimon Kimm More articles by this author , Haruyuki TakakiHaruyuki Takaki More articles by this author , Sebastien MonetteSebastien Monette More articles by this author , Avigdor ScherzAvigdor Scherz More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.449AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES An ideal technology for endoscopic management of upper tract urothelial tumors can penetrate the ureteral wall without resulting in perforation or obstruction. We created transmural ureteral ablations using percutaneously deployed vascular-targeted photodynamic therapy (VTP) in normal swine and monitored them for development of hydronephrosis and renal function deterioration. METHODS 5 female Yorkshire pigs were utilized. The photosensitizing agent, WST-11, was infused at a dose of 4mg/kg. Percutaneous access to the renal pelvis and ureter was established with ultrasound guidance. Light was delivered through a 2.0cm cylindrical diffusing fiber for 10 minutes at laser fluence of 200mW/cm. Animals underwent CT-urography at 24hrs, 1wk, and 2wks post-procedure. Blood-urea nitrogen (BUN) and creatinine levels were drawn at quarantine and prior to each CT. Animals were euthanized at 24hrs, 1 or 2 weeks. Kidneys, ureters, and bladder were harvested and submitted for review. RESULTS There was no change in BUN/Cr in any animal relative to baseline. No hydronephrosis or urine extravasation was noted weeks (Fig 1). Trichrome staining demonstrated preservation of ureteral collagen at 24hrs and restructuring of ablated areas at 2 weeks (Fig 2). CONCLUSIONS Vascular targeted photodynamic therapy produced transmural ureteral ablations with minimal morbidity in this pre-clinical trial. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e110-e111 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Ashley Winter More articles by this author Simon Kimm More articles by this author Haruyuki Takaki More articles by this author Sebastien Monette More articles by this author Avigdor Scherz More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Monitoring blood volume fraction and oxygen saturation in port-wine stains during vascular targeted photodynamic therapy with diffuse reflectance spectroscopy: Results of a preliminary case study

AbstractObjective:Monitoring dynamic changes during vascular targeted photodynamic therapy (V-PDT) for port-wine stains (PWS) is crucial for achieving an optimal therapeutic outcome. The present investigation is a preliminary research study designed to quantify and monitor the vascular parameters, e.g., blood volume fraction (Material and methods:A portable DRS detection system was developed with an appropriate source-detector distance of 520 μm for fiber-optic probe. The diffuse reflectance spectra from 450 to 800 nm in specific regions of interest (ROIs) within a PWS lesion were recorded before and 3, 5, 10, 15, and 20 min during V-PDT. In order to extract the optical properties and vascular parameters of the PWS lesion, a modified well-known diffusion theory model with a correction factor for the vessel package effect was employed to analyze the steady state-diffuse reflectance spectra.Results:The corrected reflectance spectra of the PWS lesion can be fitted very well with the modified diffusion theory model. Differences in pretreatment values ofConclusion:The ability of using DRS for quantifying and monitoring the

TOOKAD®Soluble vascular‐targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer

To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer. Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size <60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected. In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P < 0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of <1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of <1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study. Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in >80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

Assessment of tissue perfusion changes in port wine stains after vascular targeted photodynamic therapy: a short-term follow-up study

The occlusion effect of vascular targeted photodynamic therapy (V-PDT) for malformed vessels in port wine stains (PWS) often last for some time after the treatment. A relatively longer period after V-PDT is needed to accurately assess the final response of PWS microcirculation to the treatment. In this study, we intended to use laser speckle imaging (LSI) to assess the tissue perfusion changes of PWS at follow-up after V-PDT and preliminarily analyze the relationship between perfusion change and color bleaching. Seventeen patients with 40 PWS lesions were scanned by LSI before and 3-6months after they received V-PDT. The speckle flow indices of PWS lesions and normal skin before and at follow-up after V-PDT were recorded. We also performed analyses on the correlation between perfusion changes and color bleaching. Before V-PDT, the 40 PWS lesions showed higher perfusion than the normal skin (1,421 ± 463 and 1,115 ± 386 perfusion unit (PU), respectively, P < 0.01). The PWS lesions scanned at follow-up showed decreased perfusion level compared to the preoperative values (1,282 ± 460 and 1,421 ± 463 PU, respectively, P < 0.01). After V-PDT, the perfusion change rates coincide well with the color bleaching rates (correlation coefficient, 0.73). In conclusion, the LSI system is capable of imaging PWS perfusion precisely, and it has shown promising results in assessing the changes of tissue perfusion of V-PDT for PWS, with objective and quantitative data, real-time images, and a shorter detection time. It may also provide an effectiveness assessment method for the treatment of PWS.

Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer

Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy (such as external radiotherapy or radical prostatectomy), but both have significant side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach for localized, low-volume, and low-Gleason score (≤6) carcinomas. We report histological modifications observed in prostate biopsies of 56 patients, performed 6months after VTP using the photosensitizer TOOKAD® Soluble (WST11) and low-energy laser administered in the tumor area transperineally by optic fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars, with or without rare atrophic glands, sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages. Mild chronic inflammation, hemosiderin, and coagulative necrosis were also observed. When residual cancer was present in a treated lobe (17 patients), it was always located outside the scar, most often close to the prostate capsule, and it showed no therapy-related modification. Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward, in contrast with that of prostate biopsies after radio or hormonal therapy, which introduces lesions difficult to interpret. VTP resulted in complete ablation of cancer in the targeted area.

Endoscopic Vascular Targeted Photodynamic Therapy with the Photosensitizer WST11 for Benign Prostatic Hyperplasia in the Preclinical Dog Model

Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.