scholarly journals Tumor irradiation combined with minimally invasive surgery (vascular-targeted photodynamic therapy) enhances anti-tumour effects in preclinical prostate cancer

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Hannah Sjoberg
Keyword(s):  
Prostate Cancer ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Vascular Function ◽  
Locally Advanced ◽  
Tumour Microenvironment ◽  
Proof Of Concept ◽  
Fractionated Radiotherapy ◽  
Tumour Control ◽  
Targeted Photodynamic Therapy

Hanna T Sjoberg, Yiannis Philippou, Anette L Magnussen, Iain DC Tullis, Esther Bridges, Andrea Chatrian, Joel Loefebvre, Ka Ho Tam, Emma A Murphy, Jens Rittscher, Dina Preise, Lilach Agemy, Tamar Yechezkel, Sean C Smart, Paul Kinchesh, Stuart Gilchrist, Danny P Allen, David A Scheiblin, Stephen J Lockett, David A Wink, Alastair D Lamb, Ian G Mills, Adrian Harris, Ruth J Muschel, Boris Vojnovic, Avigdor Scherz, Freddie C Hamdy, Richard J Bryant.   Introduction There is an important clinical need to improve the treatment of high risk localised and locally advanced prostate cancer (PCa), and to reduce the side effects of these treatments. We hypothesised that multi-modality therapy combining radiotherapy and vascular-targeted photodynamic therapy (VTP) could PCa tumour control compared against monotherapy with each of these treatments alone. This could provide proof-of-concept to take to the clinic. VTP is a minimally invasive focal surgical therapy for localised PCa, which rapidly destroys targeted tumours through vascular disruption. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. Fractionated radiotherapy (FRT) alters the tumour microenvironment and promotes transient vascular normalisation. Materials and Methods We investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumour control compared to monotherapy with FRT or VTP alone. Results FRT induced vascular normalisation changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP alone, and improved overall survival. Conclusion Taken together, these results suggest that combining FRT and VTP could become a promising multimodal clinical strategy in PCa therapy. This provides proof-of-concept for this multi-modality therapy approach to take forward to early phase clinical trials.

scholarly journals Tumor irradiation combined with vascular-targeted photodynamic therapy enhances anti-tumor effects in preclinical prostate cancer

2020 ◽  
Author(s):  
Hanna T Sjoberg ◽  
Yiannis Philippou ◽  
Anette L Magnussen ◽  
Iain DC Tullis ◽  
Esther Bridges ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Photodynamic Therapy ◽  
Vascular Function ◽  
Locally Advanced ◽  
Tumor Control ◽  
Proof Of Concept ◽  
Vascular Normalization ◽  
Fractionated Radiotherapy ◽  
Tumour Control ◽  
Targeted Photodynamic Therapy

AbstractRationaleThere is an important clinical need to improve the treatment of high risk localized and locally advanced prostate cancer (PCa), and to reduce the side effects of these treatments. We hypothesized that multi-modality therapy combining radiotherapy and vascular-targeted photodynamic therapy (VTP) could PCa tumour control compared against monotherapy with each of these treatments alone. This could provide proof-of-concept to take to the clinic. VTP is a focal therapy for localized PCa, which rapidly destroys targeted tumors through vascular disruption. Tumor vasculature is characterized by vessel immaturity, increased permeability, aberrant branching and inefficient flow. Fractionated radiotherapy (FRT) alters the tumor microenvironment and promotes transient vascular normalization.ObjectiveWe investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumor control compared to monotherapy with FRT or VTP alone.FindingsFRT induced vascular normalization changes in PCa flank tumor allografts, improving vascular function as demonstrated using dynamic contrast enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumor growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP alone, and improved overall survival.ConclusionTaken together, these results suggest that combining FRT and VTP could become a promising multimodal clinical strategy in PCa therapy. This provides proof-of-concept for this multi-modality therapy approach to take forward to early phase clinical trials.

scholarly journals Tumour irradiation combined with vascular-targeted photodynamic therapy enhances antitumour effects in pre-clinical prostate cancer

2021 ◽  
Author(s):  
Hanna T. Sjoberg ◽  
Yiannis Philippou ◽  
Anette L. Magnussen ◽  
Iain D. C. Tullis ◽  
Esther Bridges ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Photodynamic Therapy ◽  
Vascular Function ◽  
Multimodality Treatment ◽  
Focal Therapy ◽  
Tumour Microenvironment ◽  
Fractionated Radiotherapy ◽  
Tumour Control ◽  
Early Phase Clinical Trials ◽  
Targeted Photodynamic Therapy

Abstract Background There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. FRT alters the tumour microenvironment and promotes transient ‘vascular normalisation’. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP. Methods We investigated whether sequential delivery of FRT followed by VTP 7 days later improves flank TRAMP-C1 PCa tumour allograft control compared to monotherapy with FRT or VTP. Results FRT induced ‘vascular normalisation’ changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast-enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP, and improved overall survival. Conclusion Combining FRT and VTP may be a promising multimodal approach in PCa therapy. This provides proof-of-concept for this multimodality treatment to inform early phase clinical trials.

scholarly journals Decision Regret and Quality of Life after Focal Therapy with Vascular-Targeted Photodynamic Therapy (TOOKAD®) for Localized Prostate Cancer

2021 ◽  
pp. 1-6
Author(s):  
Luka Flegar ◽  
Martin Baunacke ◽  
Bjoern Thorben Buerk ◽  
Rick Proschmann ◽  
Aristeidis Zacharis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Decision Making ◽  
Photodynamic Therapy ◽  
Local Recurrence ◽  
Post Treatment ◽  
Decision Regret ◽  
Targeted Photodynamic Therapy ◽  
Decisional Regret

<b><i>Purpose:</i></b> The aim of the study was to assess quality of life (QoL), decision involvement, and decisional regret after treatment with vascular-targeted photodynamic therapy (VTP) (TOOKAD®) for unilateral low-risk prostate cancer. <b><i>Methods:</i></b> Validated questionnaires (EORTC QLQ-C30 and QLQ-PR25) capturing QoL post-treatment, involvement in decision-making (Control Preferences Scale) and decision regret (Decisional Regret Scale), were given to patients at the 12-month visit after undergoing VTP at our institution between May 2018 and February 2021. <b><i>Results:</i></b> Out of 44 patients, 36 patients were included in this study and 31 (86.1%) responded to the questionnaires. Mean overall health score capturing QoL at 12 months was 79.3 (standard deviation: ±18.1). 70.9% of the patients (<i>n</i> = 22) had no decision regret, and 67.8% of men (<i>n</i> = 21) had an active role in decision-making. In control biopsy at 12 months post-treatment, 19.4% of patients (<i>n</i> = 7) presented with local recurrence and progression to higher Gleason score (GS) was found in 13.8% of patients (<i>n</i> = 5). Patients (<i>n</i> = 3) presenting with tumor recurrence or progression to higher GS in control biopsy showed a significantly higher level of decision regret (<i>p</i> &#x3c; 0.009). <b><i>Conclusion:</i></b> Only 9.7% of men (<i>n</i> = 3) felt a strong emotion of regret at 12 months after VTP. Level of decision regret was significantly higher in patients with local recurrence or tumor progression detected in control biopsy. QoL was stable after VTP.

scholarly journals Focal Treatment of Prostate Cancer with Vascular-Targeted Photodynamic Therapy

2008 ◽  
Vol 8 ◽  
pp. 963-973 ◽  
Author(s):  
Scott E. Eggener ◽  
Jonathan A. Coleman
Keyword(s):  
Prostate Cancer ◽  
Photodynamic Therapy ◽  
Focal Therapy ◽  
Attractive Alternative ◽  
Screening Programs ◽  
Sexual Side Effects ◽  
Pathologic Features ◽  
Focal Treatment ◽  
Risk Of Progression ◽  
Targeted Photodynamic Therapy

Epidemiologic and pathologic features of prostate cancer have given rise to an interest in focal treatment for carefully selected patients. Prostate cancer remains highly prevalent, particularly in the U.S. and Europe. As screening programs have become more aggressive and widespread, a substantial proportion of men diagnosed with localized prostate cancer have disease characteristics associated with a low risk of progression. Treatments such as radical prostatectomy and radiation therapy can lead to durable recurrence-free survival in most patients, but carry variable risks of bowel, urinary, and sexual side effects. Few men and few urologists are comfortable leaving a potentially curable prostate cancer untreated. Focal therapy offers an attractive alternative for the patient faced with a choice between aggressive local intervention (radiation or surgery) and watchful waiting. Contemporary diagnostic biopsy strategies and imaging tools, and the development of predictive statistical models (nomograms), have led to improvements in tumor characterization and risk stratification, making focal therapy a viable treatment option for specific men. This article reviews the rationale and indications for focal therapy and highlights vascular-targeted photodynamic therapy (PDT) as one of many promising focal therapy techniques.

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