Mordon S., Cochrane C., Tylcz J. B., Betrouni N., Mortier L., Koncar V.   Light emitting fabric technologies for photodynamic therapy.  Photodiagnosis Photodyn. Ther..  2015 ;12 :1-8

Photodynamic therapy (PDT) is considered to be a promising method for treating various types of cancer. A homogeneous and reproducible illumination during clinical PDT plays a determinant role in preventing under- or over-treatment. The development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of optical fiber into flexible structures could offer an interesting alternative. This paper aims to describe different methods proposed to develop Side Emitting Optical Fibers (SEOF), and how these SEOF can be integrated in a flexible structure to improve light illumination of the skin during PDT. Four main techniques can be described: (i) light blanket integrating side-glowing optical fibers, (ii) light emitting panel composed of SEOF obtained by micro-perforations of the cladding, (iii) embroidery-based light emitting fabric, and (iv) woven-based light emitting fabric. Woven-based light emitting fabrics give the best performances: higher fluence rate, best homogeneity of light delivery, good flexibility.

Moore C. M., Azzouzi A. R., Barret E., Villers A., Muir G. H., Barber N. J., Bott S., Trachtenberg J., Arumainayagam N., Gaillac B., Allen C., Schertz A., Emberton M.   Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy.  BJU Int..  2015 ;116 :888-896

OBJECTIVE: To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. PATIENTS AND METHODS: In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. RESULTS: In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. CONCLUSION: Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).

Montagne R., Berbon M., Doublet L., Debreuck N., Baranzelli A., Drobecq H., Leroy C., Delhem N., Porte H., Copin M. C., Dansin E., Furlan A., Tulasne D.   Necrosis- and apoptosis-related Met cleavages have divergent functional consequences.  Cell Death Dis..  2015 ;6 :e1769

Upon activation by its ligand hepatocyte growth factor/scatter factor, the receptor tyrosine kinase Met promotes survival, proliferation, and migration of epithelial cells during embryogenesis. Deregulated Met signaling can also promote cancer progression and metastasis. Met belongs to the functional family of dependence receptors whose activity switches from pro-survival to pro-apoptotic during apoptosis upon caspase cleavage. Although apoptosis resistance is a hallmark of cancer cells, some remain sensitive to other cell death processes, including necrosis induced by calcium stress. The role and fate of Met during necrotic cell death are unknown. Following treatment with calcium ionophores, cell lines and primary cells undergo necrosis, and the full-length Met receptor is efficiently degraded. This degradation is achieved by double cleavage of Met in its extracellular domain by a metalloprotease of the A disintegrin and metalloproteinase (ADAM) family and in its intracellular domain by calpains (calcium-dependent proteases). These cleavages separate the Met extracellular region from its kinase domain, thus preventing Met activity and its potential pro-survival activity. Although the intracellular fragment is very similar to the fragment generated by caspases, it displays no pro-apoptotic property, likely because of the presence of the last few amino acids of Met, known to inhibit this pro-apoptotic function. The fragments identified here are observed in lung tumors overexpressing the Met receptor, along with fragments previously identified, suggesting that proteolytic cleavages of Met are involved in its degradation in tumor tissues. Thus, Met is a modulator of necrosis, able to protect cells when activated by its ligand but efficiently degraded by proteolysis when this process is engaged.

Metellus P., Tallet A., Dhermain F., Reyns N., Carpentier A., Spano J. P., Azria D., Noel G., Barlesi F., Taillibert S., Le Rhun E.   Global brain metastases management strategy: A multidisciplinary-based approach.  Cancer Radiother..  2015 ;19 :61-65

Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources.

Metellus P., Reyns N., Voirin J., Menei P., Bauchet L., Faillot T., Loiseau H., Pallud J., Guyotat J., Mandonnet E.   Surgery of brain metastases.  Cancer Radiother..  2015 ;19 :20-24

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

Merlot B., Karbage Y., Bresson L., Meurant J. P., Narducci F., Leblanc E.   MORBIDITY AND MORTALITY IN A CANCER CENTER : A PROSPECTIVE STUDY.  Int. J. Gynecol. Cancer.  2015 ;25 :1581-1581
Manfredi M., Costa Moretti T. B., Emberton M., Villers A., Valerio M.   MRI/TRUS fusion software-based targeted biopsy: the new standard of care?.  Minerva Urol. Nefrol..  2015 ;67 :233-246

The advent of multiparametric MRI has made it possible to change the way in which prostate biopsy is done, allowing to direct biopsies to suspicious lesions rather than randomly. The subject of this review relates to a computer-assisted strategy, the MRI/US fusion software-based targeted biopsy, and to its performance compared to the other sampling methods. Different devices with different methods to register MR images to live TRUS are currently in use to allow software-based targeted biopsy. Main clinical indications of MRI/US fusion software-based targeted biopsy are re-biopsy in men with persistent suspicious of prostate cancer after first negative standard biopsy and the follow-up of patients under active surveillance. Some studies have compared MRI/US fusion software-based targeted versus standard biopsy. In men at risk with MRI-suspicious lesion, targeted biopsy consistently detects more men with clinically significant disease as compared to standard biopsy; some studies have also shown decreased detection of insignificant disease. Only two studies directly compared MRI/US fusion software-based targeted biopsy with MRI/US fusion visual targeted biopsy, and the diagnostic ability seems to be in favor of the software approach. To date, no study comparing software-based targeted biopsy against in-bore MRI biopsy is available. The new software-based targeted approach seems to have the characteristics to be added in the standard pathway for achieving accurate risk stratification. Once reproducibility and cost-effectiveness will be verified, the actual issue will be to determine whether MRI/TRUS fusion software-based targeted biopsy represents anadd-on test or a replacement to standard TRUS biopsy.

Maillard F., Manouvrier S., Biardeau X., Ouzzane A., Villers A.   Lynch syndrome and risk of prostate cancer; review of the literature.  Prog. Urol..  2015 ;25 :225-232

INTRODUCTION: The association between Lynch syndrome and prostate cancer has been studied. Recent studies report an association between these two diseases. MATERIAL AND METHODS: Literature review based on PubMed search was performed using the following keywords: Lynch syndrome and prostate cancer. RESULTS: Eight articles analyzing cohorts of subjects carrying Lynch syndrome were analysed including 6786 patients with 175 cancers. Prostate cancers were more frequent with a standardized incidence ratio (SIR) from 0.93 (95% CI: 0.19-2.7) and 5.9 (95% CI 4.1-17.1) and occurs at a younger age than in the general population mainly for mutations in the MSH2 gene. CONCLUSION: Prostate cancer seem more frequent and occur earlier in individuals harboring a mutation in the MSH2 gene while it does not appear to be any difference compared to the general population for other mutations in Lynch syndrome.

Leroy H. A., Vermandel M., Tetard M. C., Lejeune J. P., Mordon S., Reyns N.   Interstitial photodynamic therapy and glioblastoma: light fractionation study on a preclinical model: preliminary results.  -.  2015 ;9305
Leroy H. A., Vermandel M., Lejeune J. P., Mordon S., Reyns N.   Fluorescence guided resection and glioblastoma in 2015: A review.  Lasers Surg. Med..  2015 ;47 :441-451

High-grade gliomas represent a widely heterogeneous group of tumors, the most frequent of which is glioblastoma multiforme. Its annual incidence has risen over the last decades, particularly amongst elderly people. The actual standards of care allow for a 15-month median survival rate for WHO grade IV gliomas. As recurrence occurs in more than 85% of patients at the surgical margins, the initial resection extent is a cornerstone of disease control. Fluorescence guided resection (FGR) aims at increasing complete resections and, thus, local control. This technique uses 5-aminolevulinic acid (5-ALA), a natural intermediate substance in the heme-porphyrin biosynthesis pathway, and a protoporphyrin IX (PpIX) precursor. PpIX is fluorescent under blue light exposure. Recent studies reported a significant increase in complete resections using FGR, which were associated with prolonged progression free survival, fewer reinterventions, and delayed neurological deterioration. Here, we depict the principles of this surgical technique, its actual outcomes, and future developments.