Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.

BackgroundTyrosine kinase inhibitors (TKIs) and checkpoint inhibitors have been established as effective treatment for metastatic renal cell carcinoma (mRCC), but only a minority of patients achieve complete response. Additional strategies are necessary to improve these agents’ efficacy.MethodsPatients with stable disease for at least 4 months on TKI or checkpoint inhibitors were included. Stereotactic body radiotherapy (SBRT) was delivered to an organ with comparable lesions, where one lesion was in the treatment target and the other one was intentionally left untreated (control lesion). Response in both lesions was scored using the Response Evaluation Criteria in Solid Tumors V.1.1 criteria 2 months after completion of SBRT. The primary endpoint was the rate of SBRT adverse events, and the secondary endpoints included the rate of reduction in target lesion size.Results17 patients were enrolled (14 men and 3 women, median age: 54.5 years old). SBRT was delivered to the lungs (n=5), bones (n=4), lymph nodes (n=4), liver (n=1), primary renal cell carcinoma (RCC) (n=1) and locally recurrent RCC (n=2). The equivalent dose in 2 Gy with an alpha to beta ratio of 2.6 was 114 Gy. With a median follow-up of 8 months, the cumulative rate of SBRT-related toxicity (grade 1) was 12% (n=2), consisting of oesophagitis and skin erythema. No grade 2 or higher toxicity was detected. Radiographic response in the target lesion was seen in 13 patients (76%), with complete response in 5 (29%) patients and partial response in 8 (47%), including abscopal effect in 1 patient. Control lesions remained stable in 16 patients. The difference between response in the target and control lesions as judged by the mean sizes of these lesions before and at 2 months after SBRT was statistically significant (p<0.01). Fraction size of 10 Gy or greater was associated with complete response (p<0.01).ConclusionExtracranial SBRT in patients with mRCC treated with TKI or checkpoint inhibitors is well tolerated and could be effective.Trial registration number NCT02864615

Photodynamic therapy (PDT) has been successfully used in clinical practice for decades; however, clinical outcome data are not always consistent resulting in a great necessity for real-time monitoring to predict the therapy outcome.In a retrospective clinical study, 402 patients with non-melanoma skin malignancies were enrolled who underwent PDT treatment and fluorescence real-time imaging. The photosensitizer used was a chlorine e6 derivative (FotoditazinBaseline

Microvascular networks of human basal cell carcinomas (Bcc) and surrounding skin were assessed with optical coherence angiography (ocA) in conjunction with photodynamic therapy (pDt). ocA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months posttreatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success. Basal cell carcinoma (BCC) is the most common slow-growing locally invasive malignant epidermal skin tumor, with majority of the lesions localized on the head and neck 1. There are many different classification schemes for the BCC types and subtypes including nodular, superficial, infundibulocystic, fibroepithelial and the aggressive growth variants such as infiltrative, micronodular and morpheaform (sclerosing) plus some combinations 2,3. BCC treatment management starts with accurate diagnosis, including histopathology 4,5 and the development of reliable and non-invasive techniques for its diagnosis is crucial. Currently such non-invasive technologies have limited reliability and more development and validation work is needed 6. Dermatoscopy is a useful tool in the preoperative prediction of the BCC subtype 7. However, the evidence of its clinical diagnostic efficacy is somewhat limited and in ambiguous lesions, the BCC subtype has to be assessed histopathologically 8. Modern optical imaging modalities such as wide-field fluorescence imaging 9 , confocal microscopy 10 , optical coherence tomography (OCT) 11-13 , polarization-sensitive OCT 14,15 , OCT-based angiography (OCA) 16,17 and photoacoustic imaging 18 and their combinations 19,20 offer new possibilities for detection and visualization of human skin tumor structure and microvascular network in real time. OCT is particularly promising as it offers non-invasive structural and functional 3D imaging of biological tissues with high spatial resolution 11 , in particular for BCC 9,13,21. For the first time in this study, we used spectral domain OCT/OCA system to assess the after-treatment effects following photodynamic therapy (PDT) in patients with different BCC subtypes. PDT involves administration of photosensitizes which preferentially accumulate in malignant tissues, followed by local light activation at appropriate wavelength, producing oxygen free radicals and singlet oxygen 22. The generation of these reactive oxygen species subsequently causes tumor cell death by apoptosis, necrosis

Soft biological tissues, breast cancer tissues in particular, often manifest pronounced nonlinear elasticity, i.e., strong dependence of their Young’s modulus on the applied stress. We showed that compression optical coherence elastography (C-OCE) is a promising tool enabling the evaluation of nonlinear properties in addition to the conventionally discussed Young’s modulus in order to improve diagnostic accuracy of elastographic examination of tumorous tissues. The aim of this study was to reveal and quantify variations in stiffness for various breast tissue components depending on the applied pressure. We discussed nonlinear elastic properties of different breast cancer samples excised from 50 patients during breast-conserving surgery. Significant differences were found among various subtypes of tumorous and nontumorous breast tissues in terms of the initial Young’s modulus (estimated for stress < 1 kPa) and the nonlinearity parameter determining the rate of stiffness increase with increasing stress. However, Young’s modulus alone or the nonlinearity parameter alone may be insufficient to differentiate some malignant breast tissue subtypes from benign. For instance, benign fibrous stroma and fibrous stroma with isolated individual cancer cells or small agglomerates of cancer cells do not yet exhibit significant difference in the Young’s modulus. Nevertheless, they can be clearly singled out by their nonlinearity parameter, which is the main novelty of the proposed OCE-based discrimination of various breast tissue subtypes. This ability of OCE is very important for finding a clean resection boundary. Overall, morphological segmentation of OCE images accounting for both linear and nonlinear elastic parameters strongly enhances the correspondence with the histological slices and radically improves the diagnostic possibilities of C-OCE for a reliable clinical outcome.