3D-Reconstructed Contact Surface Area and Tumour Volume on Magnetic Resonance Imaging Improve the Prediction of Extraprostatic Extension of Prostate Cancer.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p < 0.001). Multivariable logistic regression analysis showed that the radiological tumour stage (p = 0.001), tumour volume (p < 0.001), prostate CSA (p < 0.001), and tumour CSA (p ≤ 0.001) were independent predictors of pathological EPE. A 3D reconstruction of tumour locations in the prostate improves prediction of extraprostatic extension. Tumours with a higher 3D-reconstructed volume, a higher surface area of tumour in contact with the prostate capsule, and higher surface area of prostate capsule in contact with the tumour are at increased risk of side-specific extraprostatic extension.

Development and clinical applicability of MRI-based 3D prostate models in the planning of nerve-sparing robot-assisted radical prostatectomy.

The interpretation of conventional MRI may be limited by the two-dimensional presentation of the images. To develop patient-specific MRI prostate-based virtual and three-dimensional (3D)-printed models. To assess the association between 3D imaging and the pathological outcome of RARP specimen. To assess the clinical applicability of 3D models to guide nerve-sparing robot-assisted radical prostatectomy (RARP). We created virtual 3D and 3D-printed 3D models of 20 prostate cancer patients retrospectively. A comparison was made between conventional MRI and 3D-reconstructed images. The concordance between tumour lesion location in 3D models and pathology reporting of RARP specimens was assessed. Seven urologists assessed the side-specific extent of nerve-sparing based on (1) conventional MR images, (2) virtual 3D models, and (3) 3D-printed models. Clinically relevant changes in nerve-sparing and the absolute agreement between observers was analyzed using the Chi-square test and intra-class correlation coefficient (ICC). The index lesion was correctly visualized in 19/20 (95%) 3D models and the expected location of extraprostatic extension was correctly visualized in all 3D models. Clinically relevant changes in the planned extent of nerve-sparing between MRI and virtual 3D models and MRI and 3D-printed models were found in 25% and 26%. The ICC of the planned extent of nerve-sparing between urologists was 0.40 (95% CI 0.28-0.55) for conventional MRI, 0.52 (95% CI 0.39-0.66) for virtual 3D models and 0.58 (95% CI 0.45-0.71) for 3D-printed models. 3D models of the MRI prostate to guide RARP could aid urologists in the planning of nerve-sparing surgery as shown by a higher inter-observer agreement.

On the Development of a Light Dosimetry Planning Tool for Photodynamic Therapy in Arbitrary Shaped Cavities: Initial Results.

Previous dosimetric studies during photodynamic therapy (PDT) of superficial lesions within a cavity such as the nasopharynx, demonstrated significant intra- and interpatient variations in fluence rate build-up as a result of tissue surface re-emitted and reflected photons, which depends on the optical properties. This scattering effect affects the response to PDT. Recently, a meta-tetra(hydroxyphenyl)chlorin-mediated PDT study of malignancies in the paranasal sinuses after salvage surgery was initiated. These geometries are complex in shape, with spatially varying optical properties. Therefore, preplanning and in vivo dosimetry is required to ensure an effective fluence delivered to the tumor. For this purpose, two 3D light distribution models were developed: first, a simple empirical model that directly calculates the fluence rate at the cavity surface using a simple linear function that includes the scatter contribution as function of the light source to surface distance. And second, an analytical model based on Lambert's cosine law assuming a global diffuse reflectance constant. The models were evaluated by means of three 3D printed optical phantoms and one porcine tissue phantom. Predictive fluence rate distributions of both models are within ± 20% accurate and have the potential to determine the optimal source location and light source output power settings.

Toward assessment of resection margins using hyperspectral diffuse reflection imaging (400-1,700 nm) during tongue cancer surgery.

BACKGROUND AND OBJECTIVES: There is a clinical need to assess the resection margins of tongue cancer specimens, intraoperatively. In the current ex vivo study, we evaluated the feasibility of hyperspectral diffuse reflectance imaging (HSI) for distinguishing tumor from the healthy tongue tissue. STUDY DESIGN/MATERIALS AND METHODS: Fresh surgical specimens (n = 14) of squamous cell carcinoma of the tongue were scanned with two hyperspectral cameras that cover the visible and near-infrared spectrum (400-1,700 nm). Each pixel of the hyperspectral image represents a measure of the diffuse optical reflectance. A neural network was used for tissue-type prediction of the hyperspectral images of the visual and near-infrared data sets separately as well as both data sets combined. RESULTS: HSI was able to distinguish tumor from muscle with a good accuracy. The diagnostic performance of both wavelength ranges (sensitivity/specificity of visual and near-infrared were 84%/80% and 77%/77%, respectively) appears to be comparable and there is no additional benefit of combining the two wavelength ranges (sensitivity and specificity were 83%/76%). CONCLUSIONS: HSI has a strong potential for intra-operative assessment of tumor resection margins of squamous cell carcinoma of the tongue. This may optimize surgery, as the entire resection surface can be scanned in a single run and the results can be readily available. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Adjuvant photodynamic therapy in head and neck cancer after tumor-positive resection margins.

OBJECTIVE: In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the clinical benefit of PDT as adjuvant therapy next to surgery with positive resection margins. The role of the time interval between surgery and PDT on survival outcomes also was investigated. STUDY DESIGN: Retrospective cohort analysis. METHODS: Adjuvant PDT was performed in patients with a malignancy in the head and neck region with close or positive resection margins who were not eligible for conventional treatment options. The primary endpoint was progression-free survival. Secondary endpoints were disease-free survival, overall survival, and optimal time interval between surgery and PDT. RESULTS: Fifty-four patients were treated with surgery followed by meta-tetrahydroxyphenylchlorin-mediated PDT. There was a large diversity in tumor location and histopathology, as well as in time interval between surgery and PDT. The 2-year progression-free survival rate was 30%; 2-year disease-free survival rate was 28%; and 2-year overall survival was 51%. Disease-free survival was significantly better when the time interval between surgery and PDT was ≥ 6 weeks (P = 0.02). CONCLUSION: PDT can be applied as adjuvant therapy after surgery in cases of a malignancy with close or positive tumor resection margins. However, the clinical benefits are yet to be determined. There is a significantly better disease-free survival with a time interval between surgery and PDT of minimal 6 weeks. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:657-663, 2018.

MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: description of the method.

BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep-seated recurrent head and neck cancers. STUDY DESIGN/METHODS: The described treatment algorithm in this manuscript consists of the treatment simulation, implantation of light sources, verification, modification of the treatment plan if necessary, and illumination. The tumor is delineated on imaging sections (CT, MRI, and/or PET/CT) and the treatment is simulated by virtually introducing light sources to the tumor volume on specially modified brachytherapy software. This enables us to determine if the treatment is technically feasible, and information about approximate number and location of light sources necessary. Following implantation of catheters in which the light sources will be introduced, CT or MR scan is performed to verify the actual location of the implanted catheters. The verification-CT is imported to the software and co-registered with pre-treatment images to observe the deviations from the simulation. The simulation is run again with the actual position of the light sources to determine if any additional light sources are necessary and adaptation of the source length in order to cover the tumor volume (modification). Thereafter the tumor is illuminated. RESULTS: This method has the potential to help with identifying iPDT feasible patients by simulating before the actual treatment. The suboptimal placement of light sources can be identified and corrected. The simulations were documented and saved for subsequent evaluation of the technique. CONCLUSION: The proposed technique can help standardize and document iPDT.

Optical biopsy of breast tissue using differential path-length spectroscopy.

Differential path-length spectroscopy (DPS) was used to determine the local optical properties of breast tissue in vivo. DPS measurements were made on healthy and malignant breast tissue using a fibre-optic needle probe, and were correlated to the histological outcome of core-needle biopsies taken from the same location as the measurements. DPS yields information on the local tissue blood content, the local blood oxygenation, the average micro-vessel diameter, the beta-carotene concentration and the scatter slope. Our data show that malignant breast tissue is characterized by a significant decrease in tissue oxygenation and a higher blood content compared to normal breast tissue.

Performance assessment of photon migration instruments: the MEDPHOT protocol.

We propose a comprehensive protocol for the performance assessment of photon migration instruments. The protocol has been developed within the European Thematic Network MEDPHOT (optical methods for medical diagnosis and monitoring of diseases) and is based on five criteria: accuracy, linearity, noise, stability, and reproducibility. This protocol was applied to a total of 8 instruments with a set of 32 phantoms, covering a wide range of optical properties.

In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVES: Previous studies with PhotoDynamic Therapy (PDT) in bladder and bronchi have shown that due to scattering and reflection, the actually delivered fluence rate on the surface in a hollow organ can be significantly higher than expected. In this pilot study, we investigated the differences between the primary calculated and the actual measured fluence rate during PDT of Barrett's Esophagus (BE) using 23 independent clinical measurements in 15 patients. STUDY DESIGN/MATERIALS AND METHODS: A KTP-dye module laser at 630 nm was used as light source. Light delivery was performed using a cylindrical light diffuser inserted in the center of an inflatable transparent balloon with a length corresponding to the length of the Barrett's epithelium. The total light output power of the cylindrical diffuser was calibrated using an integrating sphere to deliver a primary fluence rate of 100 mW cm(-2). Two fiber-optic pseudo sphere isotropic detectors were placed on the balloon and were used to measure fluence rate at the surface of the esophageal wall during PDT. RESULTS AND CONCLUSIONS: The actual fluence rate measured was 1.5-3.9 times higher than the primary fluence rate for 630 nm. In general, the fluence rate amplification factor decreased with increasing redness of the tissue and was less for shorter diffusers. Fluence rate variations in time were observed which coincided with patients coughing, movement, and esophageal spasms. These factors combined with inter patient variability of the fluence rate measured appears to justify the routine application of this technique in PDT of BE.