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This paper reports on recent progress made toward the development of a new magnetic resonance imaging (MRI)-compatible robot-assisted surgical system for closed-bore image-guided prostatic interventions: thermal ablation, radioactive seed implants (brachytherapy), and biopsy. Each type of intervention will be performed with a different imageguided, robot-based surgical tool mounted on the same MRIguided robot through a modular trocar. The first stage of this development addresses only laser-based focal ablation. The robot mechanical structure, modular surgical trocar, control architecture, and current stage of performance evaluation in the MRI environment are presented. The robot actuators are ultrasonic motors. A methodology of using such motors in the MRI environment is presented. The robot prototype with surgical ablation tool is undergoing tests on phantoms in the MRI bore. The tests cover MRI compatibility, image visualization, robot accuracy, and thermal mapping. To date, (i) the images are artifact- and noise-free for certain scanning pulse sequences; (ii) the robot tip positioning error is less than 1.2 mm even at positions closer than 0.3 m from the MRI isocenter; (iii) penetration toward the target is imagemonitored in near-real time; and (iv) thermal ablation and temperature mapping are achieved using a laser delivered on an optical fiber and MRI, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Modern PDT for urological tumors is a potentially selective approach in which in situ photosensitization by a nontoxic drug, locally activated by light, generates cytotoxic reactive oxygen species, causing cell death. While urological clinical experience with PDT is largely limited to treatment for superficial bladder cancer, the advent of novel photosensitizers and technologies for treatment planning, light delivery and dosimetry, PDT for prostate and other urological cancers appears increasingly realistic. Materials and Methods: We reviewed the current literature on PDT for urological tumors, in addition to recent emerging data from our laboratory and elsewhere. Results: Remarkable progress has been made in the field of photochemistry and photobiology. Together with improved optical delivery and imaging systems PDT holds promise as an alternative, minimally invasive and potentially curative treatment for localized solid tumors as well as for palliative treatment for isolated, clinically problematic metastases. Conclusions: Current experience with photodynamic therapy using contemporary photosensitizing agents and light sources is mainly restricted to in vivo experimental models and early phase clinical trails. However, ongoing preclinical work and clinical trials indicate that safer and effective PDT treatments in uro-oncology are imminent. [Copyright &y& Elsevier]

Brachytherapy (BT) boost to the whole-gland (i.e., clinical target volume [CTV]) improves oncological outcomes in prostate cancer patients, albeit with higher likelihood of genitourinary (GU) and gastrointestinal (GI) toxicities. Magnetic resonance (MR) imaging can unveil the gross tumour volume (GTV) with high sensitivity and specificity (i.e., 86% (CI 82-89%) and 99% (CI 98-99%), respectively) in patients with localized disease, which also correlates with the most common area of local recurrence after radiation treatment. To improve the therapeutic index of BT boost, one potential approach is circumscribing it to the MR-depicted GTV (i.e., focal BT boost). Another approach is the use of rectal spacers, which significantly decrease the occurrence of radiation-related toxicities. However, their use is limited in ultrasound-guided BT given their echogenic noise limiting visualization of prostate and catheters. An MR-guided BT setting can converge the benefits of improved soft-tissue resolution and rectal spacers in the absence of device-related imaging artifacts. Herein, we present the results of a prospective study using rectal spacers for MR-guided focal BT boost combined with stereotactic body radiotherapy (SBRT) to the prostate. Patients with localized prostate cancer and visible GTV on MR were enrolled in a prospective study (NCT00913939). All patients underwent insertion of rectal spacer under ultrasound guidance. Subsequently, patients received MR-guided HDR BT boost (15Gy in 1 fraction), followed by SBRT to prostate (33Gy to CTV, 30Gy to PTV, in 5 fractions). The present study reports on the first 73 patients enrolled. Seventy-three patients are included in this analysis, with a median follow-up of 42 months (IQR 30-57). Most patients (47/73; 64.4%) had Grade Group 2 disease; while 37 (50.7%) and 27 (37%) were respectively categorised as NCCN favourable and unfavourable intermediate-risk, and 9 (12.3%) high-risk disease. Thirty percent of patients received combinatorial ADT for a medial duration of 6 months (IQR 6-20). Median number of BT catheters were 5 (IQR 4-7). Acute Grade 1 GI and GU toxicities were seen in 22 (30.1%) and 66 (90.4%) of patients, respectively. Only one case reported Grade 2 acute GU toxicity (dysuria). Late (i.e., 3-months after treatment) Grade 1 GI and GU toxicities were observed in 4 (5.5%) and 29 (39.7%) cases, respectively. There was a single case of late Grade 2 GU toxicity (haematuria). No incidence of acute or late Grade 3-4 toxicities was observed. Seven (9.6%) biochemical recurrence events were recorded, with an associated BCR-free survival of 83.7% at 5 years. Among those with BCR, 6 cases had recurrence localization by imaging: two local recurrences alone (both intra-prostatic outside the focal boost volume), while four had regional and/or distant recurrences. MR-guidance allows the incorporation of rectal spacers to the BT treatment paradigm, which together with the use of focal BT boost combined with SBRT renders a favourable therapeutic index for men with localized prostate cancer. [ABSTRACT FROM AUTHOR]

Magnetic resonance image-guided brachytherapy is essential in the management of locally advanced cervical cancer. This study compares disease and toxicity outcomes in cervical cancer patients treated with 24 Gy/3 fractions (Fr) versus the conventional 28 Gy/4 Fr. This retrospective study included 241 consecutive patients with International Federation of Gynecology and Obstetrics 2018 stage IB to IVA cervical cancer treated with definitive chemoradiation between April 2014 and March 2021. Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cumulative incidence of local failure (LF), distant failure (DF), and G2+ gastrointestinal (GI), urinary and vaginal toxicity were estimated using the cumulative incidence function with death as a competing risk and compared using Gray's test. Of the 241 patients, 42% received 24 Gy/3 Fr and 58% received 28 Gy/4 Fr. With a median follow-up of 3.2 (range, 0.2-9.2) years, there were 14 local, 41 regional nodal, and 51 distant failures in 63 (26%) patients. No significant differences were found between the 24 Gy/3 Fr and 28 Gy/4 Fr groups in 3-year DFS (77% vs 68%, P =.21), the 3-year cumulative incidence of LF (5% vs 7%, P =.57), DF (22% vs 25%, P =.86), G2+ GI toxicity (11% vs 20%, P =.13), or G2+ vaginal toxicity (14% vs 17%, P =.48), respectively. The 3-year cumulative G2+ urinary toxicity rate was lower in the 24 Gy/3 Fr group (9% vs 23%, P =.03). Patients with cervical cancer treated with 24 Gy/3 Fr had similar DFS, LF, DF, GI, and vaginal toxicity rates and a trend toward a lower G2+ urinary toxicity rate compared with those treated with 28 Gy/4 Fr. A less resource-intensive brachytherapy fractionation schedule of 24 Gy/3 Fr is a safe alternative to 28 Gy/4 Fr for definitive treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is the gold standard for delineating cancerous lesions in soft tissue. Catheter‐based interventions require the accurate placement of multiple long, flexible catheters at the target site. The manual segmentation of catheters in MR images is a challenging and time‐consuming task. There is a need for automated catheter segmentation to improve the efficiency of MR‐guided procedures. Purpose: To develop and assess a machine learning algorithm for the detection of multiple catheters in magnetic resonance images used during catheter‐based interventions. Methods: In this work, a 3D U‐Net was trained to retrospectively segment catheters in scans acquired during clinical MR‐guided high dose rate (HDR) prostate brachytherapy cases. To assess confidence in segmentation, multiple AI models were trained. On clinical test cases, average segmentation results were used to plan the brachytherapy delivery. Dosimetric parameters were compared to the original clinical plan. Data was obtained from 35 patients who underwent HDR prostate brachytherapy for focal disease with a total of 214 image volumes. 185 image volumes from 30 patients were used for training using a five‐fold cross validation split to divide the data for training and validation. To generate confidence measures of segmentation accuracy, five trained models were generated. The remaining five patients (29 volumes) were used to test the performance of the trained model by comparison to manual segmentations of three independent observers and assessment of dosimetric impact on the final clinical brachytherapy plans. Results: The network successfully identified 95% of catheters in the test set at a rate of 0.89 s per volume. The multi‐model method identified the small number of cases where AI segmentation of individual catheters was poor, flagging the need for user input. AI‐based segmentation performed as well as segmentations by independent observers. Plan dosimetry using AI‐segmented catheters was comparable to the original plan. Conclusion: The vast majority of catheters were accurately identified by AI segmentation, with minimal impact on plan outcomes. The use of multiple AI models provided confidence in the segmentation accuracy and identified catheter segmentations that required further manual assessment. Real‐time AI catheter segmentation can be used during MR‐guided insertions to assess deflections and for rapid planning of prostate brachytherapy. [ABSTRACT FROM AUTHOR]

High dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) is a widely accepted treatment for patients with clinically localized prostate cancer. A significant impact on sexual health related quality of life (sHRQoL) is reported in published series. The etiology is probably multifactorial, including baseline factors, trauma and dose to the neurovascular bundles (NVB). Magnetic resonance imaging (MRI) enables the visualization and proper localization of the NVB. Herein we aim to analyze the long-term sHRQoL after MRI-guided whole gland HDR-BT boost for prostate cancer and to assess the impact of the dose to the NVB and other factors on sHRQoL. Sixty-one patients were treated with a single 15 Gy MRI-guided HDR-BT followed by EBRT as part of a prospective phase II trial approved by the local Research Ethic Board (09-0026-C). For this analysis, patients who received over 12 months of androgen deprivation therapy (ADT) and / or patients with a baseline erectile dysfunction were excluded. The left and right NVB were delineated in retrospect on T2-weighted images. Sexual HRQoL was prospectively collected using the expanded prostate index composite (EPIC) questionnaire at baseline, 1month, 3 months, 6 months, 12 months and Q12 monthly thereafter until 60 months. A minimally important difference (MID) was defined as a deterioration of sHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. Twenty-eight patients met the criteria to be included in this analysis. A short course of ADT was given to 15 patients. the mean baseline sexual HRQOL score was 48.1 (SD=27.1): 41.9 (SD=28.5) for sexual function and 63.8 (SD=37.9) for sexual bother (37.9). At 12, 24, 36 and 60 months the mean sexual score was 37.5 (SD=26.3), 47(SD=24.3), 45.1 (SD=20.4) and 36.8 (SD=29.1), p>0.05. A MID was reported by 50% of patients at 60 months. The mean sHRQoL score at 60 months of patients who had a short course of ADT was 44.1 (SD=27.1) versus 32.2 (SD=31.1), p >0.05.The mean delineated volume of the NVB was 0.35 cc ± 0.12 on the right and 0.36 cc ± 0.13 on the left. The median number of needles used was 18 [interquartile range(IQR):17-19]. The median dose max to the left NVB is 20.9 Gy (17.4-22.8) and to the right NVB is 21.1 Gy (19.0-24.0). the median dose to the penile bulb was 5.4 Gy (4.2-7.8).There was no association found between any of the baseline or dosimetric parameters with the deterioration sHRQoL. Fifty percent of prostate cancer patients treated with MRI-guided HDR-BT followed by EBRT reported a MID in their sHRQoL at 5 years after. The dose received by the NVB bilaterally was consistently higher than 120% of the prescription dose. A short course of ADT was not associated with a worse sHRQoL score at 5 years. Further studies should focus on using MRI to accurately delineate the NVB and assess the feasibility and impact of limiting the dose to the NVB. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has the potential to simplify and optimize various steps of the brachytherapy workflow, and this literature review aims to provide an overview of the work done in this field. We conducted a literature search in June 2022 on PubMed, Embase, and Cochrane for papers that proposed AI applications in brachytherapy. A total of 80 papers satisfied inclusion/exclusion criteria. These papers were categorized as follows: segmentation (24), registration and image processing (6), preplanning (13), dose prediction and treatment planning (11), applicator/catheter/needle reconstruction (16), and quality assurance (10). AI techniques ranged from classical models such as support vector machines and decision tree-based learning to newer techniques such as U-Net and deep reinforcement learning, and were applied to facilitate small steps of a process (e.g., optimizing applicator selection) or even automate the entire step of the workflow (e.g., end-to-end preplanning). Many of these algorithms demonstrated human-level performance and offer significant improvements in speed. AI has potential to augment, automate, and/or accelerate many steps of the brachytherapy workflow. We recommend that future studies adhere to standard reporting guidelines. We also stress the importance of using larger sample sizes and reporting results using clinically interpretable measures. [ABSTRACT FROM AUTHOR]

To demonstrate the feasibility of treating cervical cancer patients with MRI-guided brachytherapy (MRgBT) using 24 Gy in 3 fractions (F) versus a standard, more resource-intensive regimen of 28 Gy in 4F, and its ability to meet EMBRACE II planning aims. A retrospective review of 224 patients with FIGO Stage IB–IVA cervical cancer treated with 28 Gy/4F (n = 91) and 24 Gy/3F (n = 133) MRgBT between 2016-2021 was conducted. Multivariable linear regression models were fitted to compare dosimetric parameters between the two groups, adjusting for CTV HR and T stage. Most patients had squamous cell carcinoma, T2b disease, and were treated with intracavitary applicator plus interstitial needles (96%). The 28 Gy/4F group had higher CTV HR (median 28 vs. 26 cm3, p = 0.04), CTV IR D 98% (mean 65.5 vs. 64.5 Gy, p = 0.03), rectum D 2cm3 (mean 61.7 vs. 59.2 Gy, p = 0.04) and bladder D 2cm3 (81.3 vs. 77.9 Gy, p = 0.03). There were no significant differences in the proportion of patients meeting the EMBRACE II OAR dose constraints and planning aims, except fewer patients treated with 28 Gy/4F met rectum D 2cm3 < 65 Gy (73 vs. 85%, p = 0.027) and ICRU rectovaginal point < 65 Gy (65 vs. 84%, p = 0.005). Cervical cancer patients treated with 24 Gy/3F MRgBT had comparable target doses and lower OAR doses compared to those treated with 28 Gy/4F. A less-resource intense fractionation schedule of 24 Gy/3F is an alternative to 28 Gy/4F in cervix MRgBT. [ABSTRACT FROM AUTHOR]

To report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy. Patients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5–46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant. Sixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3–4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p < 0.001) but recovered at 3 months (p > 0.05). Bowel (p < 0.001) and sexual (p < 0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains. MRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT. [ABSTRACT FROM AUTHOR]

Abstract: An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately. [Copyright &y& Elsevier]

Background: Phototherapy is an alternative treatment for patients with localized non-small cell lung cancer who are unable to undergo surgical resection. However, phototherapy is currently limited to treatment of centrally located lung cancer, with the much larger proportion of peripheral lesions remaining inaccessible. There are also concerns over the accuracy of targeted laser treatment because of the need to exchange visualization and irradiation fibers during therapy, preventing the operator from confirming the final location of the irradiation fiber.Methods: A newly developed parallel-type ultrasmall composite optical fiberscope (Laser-eYe Ultrathin fiberscope [LYU]), which enables simultaneous white-light imaging and phototherapy, was evaluated in preclinical lung cancer models. Three models were used: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lungs into which A549 tumor tissue was transplanted. A multifunctional porphyrin-phospholipid nanoparticle (porphysome) was used as a photosensitizer to evaluate fluorescence-guided photothermal therapy.Results: The LYU's 0.97 mm diameter and hydrophilic coating allowed easy passage through the working channel of all types of bronchoscopes and controlled guidance of the LYU tip in any desired direction. The LYU could visualize the peripheral bronchus and porphysome-laden peripheral tumors. The LYU could also perform photothermal therapy with simultaneous imaging.Conclusions: The LYU enables simultaneous imaging and phototherapy that allows accurate irradiation of peripheral lung cancers. This new laser device may enable ultraminimally invasive transbronchial treatment of peripheral lung cancer. [ABSTRACT FROM AUTHOR]

To assess the impact of the dose to the bladder neck (BN) on acute urinary toxicity (AUT) and health-related quality of life (uHRQoL) in patients with prostate cancer treated with MRI-guided high-dose-rate brachytherapy combined to external beam radiotherapy. Sixty-one patients were treated with a single 15-Gy MRI-guided high-dose-rate brachytherapy followed by external beam radiotherapy as part of a prospective Phase II trial. The BN was delineated in retrospect on T2-weighted images. AUT and uHRQoL data were collected prospectively using Common Terminology Criteria for Adverse Events version 4.0 and the expanded prostate index composite. A minimally important difference (MID) was defined as a deterioration of uHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. The median BN volume was 0.6 cc. The median BN and urethral maximum dose (BNDmax and UDmax) were 22 Gy and 20 Gy, respectively. BNDmax was significantly associated with UDmax (p = 0.03). AUT Grade 2 + was observed in 32% of patients. Among those, 4 patients had an acute urinary retention (AUR). No Grade 4 + toxicity was reported. At 3 months, 47% of patients reported an MID in urinary uHRQoL. None of the dosimetric parameters including BNDmax was associated with acute Grade 2 + urinary toxicity or MID. However, 3 of 4 patients with AUR had a BNDmax in the highest quartile; >175% of prescription dose. Although a high BN dose was observed in patients who had an AUR, the predictive value of this parameter is yet to be determined in a larger cohort. [ABSTRACT FROM AUTHOR]

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies. [ABSTRACT FROM AUTHOR]

Objective Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. Materials and methods The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. Results FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro . When irradiated with a 671 nm laser at a dose of 10 J/cm 2 , folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. Conclusion Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models. [ABSTRACT FROM AUTHOR]

Background: This Sawbones and cadaver study was performed to assess the accuracy and reproducibility of pelvic bone cuts made with use of a novel navigation system with a navigated osteotome and oscillating saw.Methods: Using a novel navigation system and a three-dimensional planning tool, we navigated pelvic bone cuts that were representative of typical cuts made in pelvic tumor resections. The system includes a prototype mobile C-arm for intraoperative cone-beam computed tomography, real-time optical tracking (Polaris), and three-dimensional visualization software. Three-dimensional virtual radiographs were utilized in addition to triplanar (axial, sagittal, and coronal) navigation. In part one of the study, we navigated twenty-four sacral bone cuts in Sawbones models and validated our results in sixteen similar cuts in cadavers. In part two, we developed three Sawbones models of pelvic tumors based on actual patient scenarios and compared three navigated resections with three non-navigated resections for each tumor model. Part three assessed the accuracy of the system with multiple users.Results: There were ninety navigated cuts in Sawbones that were compared with fifty-four non-navigated cuts. In the navigated Sawbones cuts, the mean entry and exit cuts were 1.4 ± 1 mm and 1.9 ± 1.2 mm from the planned cuts, respectively. In comparison, the entry and exit cuts in Sawbones that were not navigated were 2.8 ± 4.9 mm and 3.5 ± 4.6 mm away from the planned osteotomy site. The navigated cuts were significantly more accurate (p ≤ 0.01). In the cadaver study, navigated entry and exit cuts were 1.5 ± 0.9 mm and 2.1 ± 1.5 mm from the planned cuts. The variation among three different users was 1 mm on both the entry and exit cuts.Conclusions: Navigation to guide pelvic bone cuts is accurate and feasible. Three-dimensional radiographs should be used for improved accuracy. Navigated cuts were significantly more accurate than non-navigated cuts were. A margin of 5 mm between the target tumor volume and the planned cut plane would result in a negative margin resection in more than 95% of the cuts.Clinical Relevance: The accuracy of pelvic bone tumor resections and pelvic osteotomies can be improved with navigation to within 5 mm of the planned cut. [ABSTRACT FROM AUTHOR]

Abstract: Cisplatin (CDDP) has been identified as the primary chemotherapeutic agent for the treatment of cervical cancer, but dose limiting toxicity is a key issue associated with its clinical application. A suite of liposome formulations of CDDP has been developed in efforts to reduce systemic toxicity, but their therapeutic advantage over the free drug has been modest due to insufficient drug release at the tumor site. This report describes the development of a novel heat-activated thermosensitive liposome formulation containing CDDP (HTLC) designed to release approximately 90% of the loaded drug in less than 5min under mild heating conditions (42°C). Physico-chemical characteristics of HTLC were assessed in terms of gel to liquid crystalline phase transition temperature (Tm), drug loading efficiency, particle size, and stability. The pharmacokinetic profile and biodistribution of HTLC in non-tumor-bearing mice were evaluated over a 24h period. A sophisticated spatio-temporal elucidation of HTLC release in tumor-bearing mice was achieved by way of real-time monitoring using a magnetic resonance (MR) imaging protocol, wherein a custom-built laser-based conformal heat source was applied at the tumor volume to trigger the release of HTLC co-encapsulated with the MR contrast agent gadoteridol (Gd-HP-DO3A). MR thermometry (MRT) demonstrated that a relatively uniform temperature distribution was achieved in the tumor volume using the external laser-based heating setup. In mice bearing subcutaneously-implanted ME-180 cervical tumors, the combination of HTLC and heat resulted in a 2-fold increase in tumor drug levels at 1h post-administration compared to HTLC without heating. Furthermore, the overall tumor accumulation levels for the HTLC groups (with and without heat) at 1h post-injection were significantly higher than the corresponding free CDDP group. This translated into a significant improvement in therapeutic efficacy evaluated as tumor growth delay (p<0.05) for the heated HTLC treatment group compared to the unheated HTLC, heated or unheated free CDDP, and saline groups. Overall, findings from this study demonstrate that a heat-activated, triggered release formulation of CDDP results in a significant enhancement in the therapeutic index of this drug. [Copyright &y& Elsevier]

Abstract: Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)–guided focal laser ablation. The tumor was identified on MRI. A laser fiber was delivered via a catheter inserted through a perineal template and guided to the target with MRI. The tissue temperature was monitored during laser ablation by MRI thermometry. Accumulated thermal damage was calculated in real time. Immediate post-treatment contrast-enhanced MRI confirmed devascularization of the target. No adverse events were noted. MRI-guided focal laser therapy of low-risk PCa is feasible and may offer a good balance between cancer control and side effects. [Copyright &y& Elsevier]

Significance: Our work demonstrates in preclinical models that continuous-wave transrectal diffuse optical tomography (TRDOT) can be used to accurately monitor photothermal therapy (PTT) and, in particular, the progression of the photocoagulation boundary toward the rectum. When used in patients, this should prevent rectal damage during PTT, thereby achieving maximum treatment efficacy while ensuring safety, using a technology platform suitable for wide dissemination. Aim: We aim to validate that TRDOT measurements analyzed using a shape-based image-reconstruction algorithm (SBDOT) allow localization of the photocoagulation boundary during PTT within ±1 mm toward the rectum in the transverse plane. Approach: TRDOT measurements were performed in tissue-simulating phantoms, ex vivo tissues, and an in vivo canine prostate model. The accuracy and sensitivity of reconstructing the size and location of the coagulation zone were determined, based on changes in the tissue absorption and reduced scattering coefficients upon photocoagulation. The reconstruction also yields the native and coagulated tissue optical properties. Results: The TRDOT measurements and SBDOT reconstruction algorithm were confirmed to perform sufficiently well for clinical translation in PTT monitoring, recovering the location of the coagulation boundary within ±1 mm compared to the true value as determined by direct visualization postexcision and/or MRI. Conclusions: Implementing previously described TRDOT instrumentation and SBDOT image reconstruction in different tissue models confirms the potential for clinincal translation, including required refinements of the system and reconstruction algorithm. [ABSTRACT FROM AUTHOR]

Significance: Photodynamic therapy (PDT) and photothermal therapy (PTT) show promise as cancer treatments, but challenges in generating large ablative volumes for deep-seated tumours persist. Using simulations, this study investigates combined PDT and PTT to increase treatment volumes, including the impact of a temperature-dependent PDT dose on the treatment volume radius., Approach: A finite-element model, using the open-source SfePy package, was developed to simulate combined interstitial photothermal and photodynamic treatments. Results compared an additive dose model to a temperature-dependent dose model with enhanced PDT dosimetry and examined typical clinical scenarios for possible synergistic effects., Results: Findings revealed that the temperature-dependent dose model could significantly expand the damage radius compared to the additive model, depending on the tissue and drug properties., Conclusions: Characterizing synergistic effects of PDT and PTT could enhance treatment planning. Future work is ongoing to implement additional variables, such as photosensitizer photobleaching, and spatial and temporally varying oxygenation., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

To investigate the effect of using non-uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter-seed and inhomogeneity effects. For standard plaque configurations, uniformly and non-uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2 Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95 Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non-uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye-cancer-busy centers., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT and PTT at the cellular, vascular and tumor microenvironmental levels, as well as translating both modalities in the clinic. Emerging evidence suggests that PDT and PTT may synergize due to their different mechanisms of action, and their nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations have gained momentum in recent years due to the development of multimodal nanoplatforms that simultaneously incorporate photodynamically- and photothermally active agents. In this review, we discuss how combining PDT and PTT can address the limitations of each modality alone and enhance treatment safety and efficacy. We provide an overview of recent literature featuring dual PDT/PTT nanoparticles and analyze the strengths and limitations of various nanoparticle design strategies. We also detail how treatment sequence and dose may affect cellular states, tumor pathophysiology and drug delivery, ultimately shaping the treatment response. Lastly, we analyze common experimental design pitfalls that complicate preclinical assessment of PDT/PTT combinations and propose rational guidelines to elucidate the mechanisms underlying PDT/PTT interactions.

Objective. Laser interstitial thermal therapy (LITT) is an evolving hyperthermia-based technology that may offer a minimally invasive alternative to inoperable lung cancer. LITT of perivascular targets is challenged by higher risk of disease recurrence due to vascular heat sinks, as well as risk of damage to these vascular structures. The objective of this work is to examine the impact of multiple vessel parameters on the efficacy of the treatment and the integrity of the vessel wall in perivascular LITT. Approach. A finite element model is used to examine the role of vessel proximity, flow rate, and wall thickness on the outcome of the treatment . Main result . The simulated work indicates that vessel proximity is the major factor in driving the magnitude of the heat sink effect. Vessels situated near the target volume may act as a protective measure for reducing healthy tissue damage. Vessels with thicker walls are more at risk of damage during treatment. Interventions to reduce the flow rate may reduce the vessel's heat sink effect but may also result in increased risk of vascular wall damage. Lastly, even at reduced blood flow rates, the volume of blood reaching the threshold of irreversible damage (>43 °C) is negligible compared to the volume of blood flow throughout the treatment duration. Significance. This investigative simulation yields results that may help guide clinicians on treatment planning near large vessels., (Creative Commons Attribution license.)

Stereotactic body radiation therapy (SBRT) has shown promising results in the treatment of pancreatic cancer and other solid tumors. However, wide adoption of SBRT remains limited largely due to uncertainty about the treatment's optimal fractionation schedules to elicit maximal tumor response while limiting the dose to adjacent structures. A small animal irradiator in combination with a clinically relevant oncological animal model could address these questions. Accurate delivery of X rays to animal tumors may be hampered by suboptimal image-guided targeting of the X-ray beam in vivo. Integration of bioluminescence imaging (BLI) into small animal irradiators in addition to standard cone-beam computed tomography (CBCT) imaging improves target identification and high-precision therapy delivery to deep tumors with poor soft tissue contrast, such as pancreatic tumors. Using bioluminescent BxPC3 pancreatic adenocarcinoma human cells grown orthotopically in mice, we examined the performance of a small animal irradiator equipped with both CBCT and BLI in delivering targeted, hypo-fractionated, multi-beam SBRT. Its targeting accuracy was compared with magnetic resonance imaging (MRI)-guided targeting based on co-registration between CBCT and corresponding sequential magnetic resonance scans, which offer greater soft tissue contrast compared with CT alone. Evaluation of our platform's BLI-guided targeting accuracy was performed by quantifying in vivo changes in bioluminescence signal after treatment as well as staining of ex vivo tissues with γH2AX, Ki67, TUNEL, CD31 and CD11b to assess SBRT treatment effects. Using our platform, we found that BLI-guided SBRT enabled more accurate delivery of X rays to the tumor resulting in greater cancer cell DNA damage and proliferation inhibition compared with MRI-guided SBRT. Furthermore, BLI-guided SBRT allowed higher animal throughput and was more cost effective to use in the preclinical setting than MRI-guided SBRT. Taken together, our preclinical platform could be employed in translational research of SBRT of pancreatic cancer., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

Percutaneous needle-based interventions such as transperineal prostate brachytherapy require the accurate placement of multiple needles to treat cancerous lesions within the target organ. To guide needle placement, magnetic resonance imaging (MRI) offers excellent visualization of the target lesion without the need for ionizing radiation. To date, multi-needle insertion relies on a grid template, which limits the ability to steer individual needles. This work describes an MR-compatible robot designed for the sequential insertion of multiple non-parallel needles under MR guidance. The 6-DOF system is designed with an articulated arm to extend the reach of the robot. This strategy presents a novel approach enabling the robot to maneuver around existing needles while minimizing the footprint of the robot. Forward kinematics as well as optimization-based inverse kinematics are presented. The impact of the robot on image quality was tested for four sequences (T1w-TSE, T2w-TSE, THRIVE and EPI) on a 3T Philips Achieva system. Quantification of the signal-to-noise ratio showed a 46% signal loss in a gelatin phantom when the system was powered on but no further adverse effects when the robot was moving. Joint level testing showed a maximum error of 2.10 ± 0.72°s for revolute joints and 0.31 ± 0.60 mm for prismatic joints. The theoretical workspace spans the proposed clinical target surface of 10 x 10 cm. Lastly, the feasibility of multi-needle insertion was demonstrated with four needles inserted under real-time MR-guidance with no visible loss in image quality., Competing Interests: AA received support from Mitacs Accelerate Program. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This research was supported by Siemens Healthcare Canada Ltd., and the Natural Sciences and Engineering Research Council., (Copyright © 2022 Aleong, Looi, Luo, Zou, Waspe, Singh, Drake and Weersink.)

Photothermal therapy (PTT) is enhanced by the use of nanoparticles with a large optical absorption at the treatment wavelength. However, this comes at the cost of higher light attenuation that results in reduced depth of heating as well as larger thermal gradients, leading to potential over- and under-treatment in the target tissue. These limitations can be overcome by using photothermal enhancing auto-regulating liposomes (PEARLs), based on thermochromic J-aggregate forming dye-lipid conjugates that reversibly alter their absorption above a predefined lipid phase-transition temperature. Under irradiation by near-infrared light, deeper layers of the target tissue revert to the intrinsic optical absorption, halting the temperature rise and enabling greater light penetration and heat generation at depth. This effect is demonstrated in both nanoparticle solutions and in gel phantoms containing the nanoparticles., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Focal therapy using lasers is emerging as an alternative strategy for prostate cancer treatment. However, to our knowledge no anatomically correct models are available to test imaging and ablation techniques. Animal models present ethical, anatomical and cost challenges. We designed and validated an inexpensive but anatomically correct prostate phantom incorporating tumor, rectum and urethra that can be used for simulated and experimental magnetic resonance guided focal intervention. Our secondary aim was to asses the phantom using other imaging modalities., Materials and Methods: The phantom, which was constructed of ballistic gel, includes an 80 gm prostate with urethra, tumor, perineum and rectum. Gadolinium was added to make the gel visible to magnetic resonance imaging. To recreate a tumor an irregularly shaped 5 cc volume of coagulable gel was inserted into the prostate phantom. The phantom was evaluated using magnetic resonance, computerized tomography and transrectal ultrasound. Thermal ablation was delivered via interstitial placement of laser fibers. Magnetic resonance thermometry was done to record real-time tissue temperatures during thermal ablation., Results: With all modalities tested the phantom emulated human prostate anatomy. The coagulable gel tumor allowed us to generate focal thermal lesions. The phantom had magnetic resonance imaging properties comparable to in vivo properties, allowing ablative zones to be accurately assessed and magnetic resonance thermometry to be done., Conclusions: The phantom is a useful tool to test different aspects of thermal focal ablation for prostate cancer using multiple imaging modalities, particularly magnetic resonance. It is inexpensive and easily constructed, and may be considered a valuable model to train on and teach focal therapy., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: We report a case study of the application of contrast-enhanced ultrasonography (CEUS) for intraoperative monitoring of thermal ablation of a single focus of prostate cancer., Methods: A patient presented with biopsy-proven, solitary-focus, low-risk prostate cancer and was recruited into a clinical trial of interstitial laser thermal focal therapy. Multiparametric magnetic resonance imaging (MRI) was used to locate the single dominant focus, and photothermal ablation was performed at the tumour site under the guidance of transrectal ultrasonography. Transrectal CEUS using systemic bolus injections of the intravascular contrast agent Definity was performed immediately before, several times during and on completion of therapy. Lesions observed on CEUS were compared with treatment effect as measured by tissue devascularization on 1-week gadolinium (Gd)-enhanced MRI., Results: Baseline images showed CEUS contrast-agent signal throughout the prostate. During and after treatment, large hypocontrast regions were observed surrounding the treatment fibres, indicating the presence of an avascular lesion resulting from photothermal therapy. Lesion size was found to increase during the delivery of thermal energy. Lesion size measured using CEUS (16 x 11 mm) was similar to the 7-day lesion measured using Gd-enhanced T(1)-weighted MRI., Conclusion: Focal therapy for prostate cancer requires both complete treatment of the dominant tumour focus and minimal morbidity. The application of CEUS during therapy appears to provide an excellent measure of the actual treatment effect. Hence, it can be used to ensure that the therapy encompasses the whole target but does not extend to surrounding critical structures. Future clinical studies are planned with comparisons of intraoperative CEUS to Gd-enhanced MRI at 7 days and whole-mount pathology samples.