Focal Therapy Research Articles

Research Progress in Focal Treatment of Prostate Cancer

Prostate cancer is the second most common malignant tumor in men worldwide, and its incidence is increasing in China. Treatment methods of prostate cancer include surgery, radiotherapy, chemotherapy, endocrine therapy, and local therapy. Compared to all treatment options for prostate cancer, local treatment has the advantage of less trauma and fewer complications. With the wide application of PSA screening, improvement and enhancement of transperineal puncture technology under template positioning and the development of multi-parameter MRI, more and more low-grade and localized prostate cancer are detected. Most prostate cancer patients receive total gland therapy after diagnosis, but patients with localized prostate cancer may not benefit from treatment because of the side effects of total gland therapy. With the development of imaging technology and the "main focus" theory, focal therapy techniques have been greatly developed. Focal therapy (FT) is a treatment method for localized prostate cancer (Pca), which mainly targets low and medium-risk localized disease to reduce whole-gland treatment. Such as radical prostatectomy (RP) or the adverse effects of radical external radiotherapy, FT has the advantage of preserving more sexual and bladder function while controlling the tumor. The current focal therapy techniques used in clinic mainly include high-intensity focused ultrasound, focal laser ablation, cryotherapy, irreversible electroporation, and photodynamic therapy. In this study, we reviewed the clinical trials of focal therapy in recent years and found that high-intensity focused ultrasound and focal laser ablation have better failure-free survival and postoperative functional control.

Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer

BackgroundProstate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression.MethodsWe analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan–Meier estimator, log-rank test, and Cox regression.ResultsOur analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR. These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p-value < 0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p-values < 0.05).ConclusionsOur gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application.

Editorial Comment.

No AccessJournal of UrologyAdult Urology21 Jun 2023Editorial CommentThis article comments on the following:Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer Taimur T. Shah Taimur T. ShahTaimur T. Shah Imperial Prostate, Department of Surgery and Cancer, Imperial College London, London, United Kingdom Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003569.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, Publish Ahead of Print, pp. REFERENCES 1. . Biopsy assessment of oncologic control three years following primary partial gland cryoablation: a prospective cohort study of men with intermediate risk prostate cancer. J Urol. 2023; 210(3):000-000. Google Scholar 2. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2023; 388(17):1547-1558. Crossref, Medline, Google Scholar 3. PACE-A: an international phase 3 randomised controlled trial (RCT) comparing stereotactic body radiotherapy (SBRT) to surgery for localised prostate cancer (LPCa)—primary endpoint analysis. J Clin Oncol. 2023; 41(6_suppl):298. Crossref, Google Scholar 4. . MP80-16 Black patients have worse continence outcomes at 12 months following robotic-assisted radical prostatectomy. J Urol. 2023; 209(suppl 4):e1159. Abstract, Google Scholar 5. Early-medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry. Eur Urol. 2019; 76(1):98-105. Crossref, Medline, Google Scholar 6. Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study. Prostate Cancer Prostatic Dis. 2021; 24(2):567-574. Crossref, Medline, Google Scholar © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology7 Jun 2023Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taimur T. Shah Imperial Prostate, Department of Surgery and Cancer, Imperial College London, London, United Kingdom Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom More articles by this author Expand All Advertisement PDF downloadLoading ...

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma.

Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients. In this study, we developed a robust tumoroid-based platform to test chemotherapeutic agents in combination with focal therapy (thermotherapy) - a treatment option widely used in clinical practice - in accordance with clinically relevant trial protocols. The model consists of matrix-embedded tumoroids that retain retinoblastoma features and respond to repeated chemotherapeutic drug exposure similarly to advanced clinical cases. Moreover, the screening platform includes a diode laser (810 nm, 0.3 W) to selectively heat the tumoroids, combined with an on-line system to monitor the intratumoral and surrounding temperatures. This allows the reproduction of the clinical settings of thermotherapy and combined chemothermotherapy treatments. When testing the two main drugs currently used in clinics to treat retinoblastoma in our model, we observed results similar to those clinically obtained, validating the utility of the model. This screening platform is the first system to accurately reproduce clinically relevant treatment methods and should lead to the identification of more efficient drugs to treat retinoblastoma.

Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus Disease 2019 Pneumonia in Lung Cancer Patients: A Single-center Retrospective Study

Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Factors affecting the selection of eligible candidates for focal therapy for prostate cancer.

Focal therapy (FT) is a treatment modality for prostate cancer that aims to reduce side effects. However, it remains difficult to select eligible candidates. We herein examined eligibility factors for hemi-ablative FT for prostate cancer. We identified 412 patients who were diagnosed with unilateral prostate cancer by biopsy and had undergone radical prostatectomy between 2009 and 2018. Among these patients, 111 underwent MRI before biopsy, had 10-20 core biopsies performed, and did not receive other treatments before surgery. Fifty-seven patients with prostate-specific antigen ≥ 15ng/mL and biopsy Gleason score (GS) ≥ 4 + 3 were excluded. The remaining 54 patients were evaluated. Both lobes of the prostate were scored using Prostate Imaging Reporting and Data System version 2 on MRI. Ineligible patients for FT were defined as those with ≥ 0.5mL GS6 or GS ≥ 3 + 4 in the biopsy-negative lobe, ≥ pT3, or lymph node involvement. Selected predictors of eligibility for hemi-ablative FT were analyzed. Among our cohort of 54 patients, 29 (53.7%) were eligible for hemi-ablative FT. A multivariate analysis identified a PI-RADS score < 3 in the biopsy-negative lobe (p = 0.016) as an independent predictor of eligibility for FT. Thirteen out of 25 ineligible patients had GS ≥ 3 + 4 tumors in the biopsy-negative lobe, half of whom (6/13) also had a PI-RADS score < 3 in the biopsy-negative lobe. The PI-RADS score in the biopsy-negative lobe may be important in the selection of eligible candidates for FT. The findings of this study will help reduce missed significant prostate cancers and improve FT outcomes.

MDB-36. SONIDEGIB, GANT61, AND VELIPARIB TREATMENT BOTH ALONE AND IN COMBINATION INCREASES RADIATION SENSITIVITY IN PEDIATRIC SONIC HEDGEHOG MEDULLOBLASTOMA

Abstract Medulloblastoma is the most common malignant brain tumor in children, accounting for 20-25% of all pediatric brain tumors. The current standard of care includes both craniospinal and focal radiation therapy which lead to negative long term consequences in the pediatric population such as bone and tissue hypoplasia, decreased neurocognitive functioning, as well as an increased risk for secondary radiation induced cancers. Thus, there is a need for novel approaches to radiation therapy that can effectively target and kill tumor cells while minimizing radiation toxicity in healthy tissue. Here, we investigate a new approach to radiation therapy relying on two classes of therapeutic agents, Sonic Hedgehog (SHH) inhibitors and Poly (ADP-ribose) Polymerase (PARP) inhibitors. The dysregulation and constitutive activation of the SHH signaling pathway accounts for ~30% of all medulloblastomas. In addition to playing a role in tumorigenesis, the SHH pathway is known to play a role in the radiation sensitivity of various cancer types. PARP1 is known to play a key role in DNA damage repair, and it has previously been shown to affect the radiation sensitivity of pediatric brain cancers including high grade glioma, medulloblastoma, and ependymoma. We hypothesize that both inhibiting the SHH pathway at Smoothened (Smo) or Gli1 and inhibiting PARP1 will enhance medulloblastoma tumor cell killing following radiation therapy. We found that in vitro treatment with Sonidegib, GANT61, and Veliparib alone without radiation was sufficient to decrease tumor cell viability and self-renewal. When followed by radiation, pre-treatment with Sonidegib, GANT61, and Veliparib, both alone and in combination, resulted in further decreased tumor cell viability and self-renewal. These data suggest that inhibition of Smo, Gli1, or PARP1 alone or in combination is a promising therapeutic strategy for increasing the radiation sensitivity of pediatric SHH medulloblastoma.

The Role of Adhesion Molecules and Extracellular Vesicles in an In Vitro Model of the Blood-Brain Barrier for Metastatic Disease.

Metastatic brain disease (MBD) has seen major advances in clinical management, focal radiation therapy approaches and knowledge of biological factors leading to improved prognosis. Extracellular vesicles (EVs) have been found to play a role in tumor cross-talk with the target organ, contributing to the formation of a premetastatic niche. Human lung and breast cancer cell lines were characterized for adhesion molecule expression and used to evaluate their migration ability in an in vitro model. Conditioned culture media and isolated EVs, characterized by super resolution and electron microscopy, were tested to evaluate their pro-apoptotic properties on human umbilical vein endothelial cells (HUVECs) and human cerebral microvascular endothelial cells (HCMEC/D3) by annexin V binding assay. Our data showed a direct correlation between expression of ICAM1, ICAM2, β3-integrin and α2-integrin and the ability to firmly adhere to the blood-brain barrier (BBB) model, whereas the same molecules were down-regulated at a later step. Extracellular vesicles released by tumor cell lines were shown to be able to induce apoptosis in HUVEC while brain endothelial cells showed to be more resistant.

Abstract A051: The spatial landscape of clonal somatic copy number alterations in benign and malignant prostate epithelia

Abstract Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. We provide an unsupervised approach (SpatialInferCNV) to study spatial genome integrity, in situ, to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics (Visium, 10x Genomics) to infer spatial copy number variations in &amp;gt;120 000 spatial regions across multiple organs, tissues and tumors, including three whole axial prostates. We used this information to deduce clonal relationships between regions harboring 5-20 cells. We perform an in-depth spatial analysis of prostate cancer that includes an unprecedented interrogation of up to 50,000 tissue domains in a single patient. For these domains we inferred genome-wide information, which facilitated data driven clustering in a tissue wide fashion at high resolution. We observed that genome-wide somatic copy number alterations revealed distinct clonal patterns benign tissue and nearby tumours. In a tissue section from patient 1 (section H2_1), we observed that many CNVs occurred in clone C, most notably in chromosomes 8 and 10 encoding a MYC amplification and a PTEN deletion. This clone constituted a region of exclusively benign acinar cells branching off a duct lined by largely diploid cells in clones A and B. The unobserved ancestor to clone C then gave rise to a further unobserved clone, and then clones E, F and G. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in prostate cancer evolution. Furthermore the spatial information allowed us to identify small clonal units not evident from morphology and hence would be overlooked by pathologists. We present the first comprehensive, large-scale, atlas of genomic evolution at high spatial resolution in prostate cancer. Our study adds an important new approach to the armamentarium of cancer molecular pathology. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for focal therapy in prostate cancer. Citation Format: Andrew Erickson, Mengxiao He, Emelie Berglund, Maja Marklund, Reza Mirzazadeh, Niklas Schultz, Linda Kvastad, Alma Andersson, Ludvig Bergenstråhle, Joseph Bergenstråhle, Ludvig Larsson, Leire Alonso Galicia, Alia Shamikh, Elisa Basmaci, Teresita Díaz De Ståhl, Timothy Rajakumar, Dimitrios Doultsinos, Kim Thrane, Andrew L. Ji, Paul A. Khavari, Firaz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie C. Hamdy, Dan J. Woodcock, Thomas Helleday, Ian G. Mills, Alastair D. Lamb, Joakim Lundeberg. The spatial landscape of clonal somatic copy number alterations in benign and malignant prostate epithelia [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A051.

Magnetic Resonance Imaging Evaluation of Focal Therapy Efficacy for Prostate Cancer

Prostate cancer (PСa) is one of the leading causes of cancer morbidity in men. The incidence of localized PCa is higher in high-income countries. There are different types of treatment for localized PCa: from active surveillance to focal therapy or radical treatment. Both patients and urologists are interested in minimizing side effects of treatment, so focal therapy is an alternative option. Magnetic resonance imaging is one of the leading tools either for primary diagnosis or for following evaluation of treatment efficacy, including focal therapy. Therefore, we summarized literature data published on this topic.

Using machine learning-based boosting algorithm to predict hepatotoxicity after local therapy and association with survival in patients undergoing liver directed therapy.

e16229 Background: Hepatocellular carcinoma typically arises in the setting of chronic liver disease. In carefully selected patients, liver directed therapy has been demonstrated to improve survival; however, this benefit from cancer specific survival may be offset by increased mortality from diminished hepatic functional reserve. Treatment-related hepatotoxicity also may vary between liver directed treatment modalities for a given tumor. Our aim was to determine if a machine learning approach could estimate hepatotoxicity prior to treatment. Methods: We identified all patients with hepatocellular carcinoma who underwent liver directed therapy at a large urban academic health system who also had post-treatment laboratory follow-up at 6 months. Patients were categorized as having worse liver function if they experienced a decline in albumin-bilirubin (ALBI) grade or more than 0.5 absolute decline in ALBI score at post treatment follow-up. A machine learning, extreme-gradient boosting (XGBoost) approach was employed to identify predictive features for hepatotoxicity using fine-tuned hyperparameters. Results: The study cohort consisted of 269 patients. 48 (18%) were categorized as having worsened hepatic function after liver directed therapy, with an average decline of -0.72 in ALBI score. Median survival after liver directed therapy was 5.8 years, with worsening hepatic function associated with a 5 month decline in overall survival. 158 (59%) patients received transarterial chemoembolization, 99 (37%) patients received stereotactic body radiotherapy and 12 (7%) patients received Y-90. A machine learning model was developed resulting in an Area Under the ROC Curve (AUC) of 0.894 in a 10-point decision tree model. On SHAP analysis, the features with the largest impact on hepatotoxicity prior to treatment was pretreatment T-stage followed by Child-Pugh Score. Conclusions: A machine learning model was developed to accurately classify patients who sustained treatment related hepatotoxicity. Significant decline in ALBI score or grade was associated with a worsening of overall survival. Future studies in larger prospective clinical trials utilizing this machine learning-based methodology of assessing liver dysfunction after focal therapy are required to validate these findings.

CAN-2409 plus prodrug with standard of care immune checkpoint inhibitor for patients with stage III/IV NSCLC.

TPS9162 Background: Immune checkpoint inhibitors (ICI) are a standard of care (SOC) treatment that have improved outcomes for patients (pts) with non-small cell lung cancer (NSCLC). However, most pts progress, signaling a need for combination approaches to further improve outcomes. CAN-2409 is a replication-defective adenoviral construct encoding the herpes simplex virus thymidine kinase (HSV-tk) gene that is injected intratumorally followed by 2 weeks of prodrug (valacyclovir or acyclovir). HSV-tk converts the prodrug in the tumor microenvironment into a toxic metabolite, resulting in immunogenic cell death, while the adenoviral proteins provide a strong pro-inflammatory signal. Together, this leads to in situ vaccination against the patient’s own tumor. As a result, CD8+ cytotoxic T cells are educated on how to recognize and kill tumor cells in both the injected tumor and the uninjected metastases. A completed neoadjuvant phase I trial in resectable NSCLC demonstrated safety and immune stimulation (Predina et al 2021), warranting further investigation of CAN-2409 + prodrug as a therapy that can lead to improved long-term outcomes for pts with NSCLC who have a suboptimal response to ICI. Methods: LuTK02 (NCT04495153) is an open-label, multi-arm, phase II clinical trial to evaluate CAN-2409 + prodrug added to SOC ICI (anti-PD-(L)1) therapy in pts with stage III/IV NSCLC presenting with inadequate response (as defined below) to ICI. Cohort 1 includes pts with nonresponding but stable disease ≥18 weeks after starting ICI; cohort 2 includes pts with progressive disease ≥18 weeks after starting ICI. Key eligibility criteria include RECIST-evaluable disease; an injectable lesion (via bronchoscopy or US/IR guidance); ability to continue ICI for the treatment period; no change of ICI or prior interruptions of &gt; 4 weeks within 6 months of enrollment; and no focal therapy at &gt; 3 sites of disease within 12 months prior to enrollment. Key exclusion criteria include a history of ICI immune-related adverse events and known alterations in EGFR, ALK, or ROS1. Eligible patients receive 2 injections of CAN-2409 approximately 6 weeks apart followed by prodrug for 14 days. After treatment of ~40 evaluable pts in cohort 2 with two injections of CAN-2409, the protocol has been amended to include a new cohort (n~20) of pts treated with three injections of CAN-2409 approximately 4 weeks apart, each followed by prodrug for 14 days, to further define the optimal therapeutic regimen. Primary endpoints are overall response and/or disease control rate per RECIST 1.1 criteria and safety of CAN-2409 + prodrug. Secondary endpoints include duration of response, PFS, OS, and biomarker studies. Exploratory endpoints include evaluation of effects in non-injected lesions, changes in non-target (per RECIST) lesions, tumor growth trajectory, and viral shedding. Clinical trial information: NCT04495153 .

A Multimodal Phantom for Visualization and Assessment of Histotripsy Treatments on Ultrasound and X-Ray Imaging.

Histotripsy is an emerging non-invasive, non-ionizing and non-thermal focal tumor therapy. Although histotripsy targeting is currently based on ultrasound (US), other imaging modalities such as cone-beam computed tomography (CBCT) have recently been proposed to enable the treatment of tumors not visible on ultrasound. The objective of this study was to develop and evaluate a multi-modality phantom to facilitate the assessment of histotripsy treatment zones on both US and CBCT imaging. Fifteen red blood cell phantoms composed of alternating layers with and without barium were manufactured. Spherical 25-mm histotripsy treatments were performed, and treatment zone size and location were measured on CBCT and ultrasound. Sound speed, impedance and attenuation were measured for each layer type. The average ± standard deviation signed difference between measured treatment diameters was 0.29 ± 1.25 mm. The Euclidean distance between measured treatment centers was 1.68 ± 0.63 mm. The sound speed in the different layers ranged from 1491 to 1514 m/s and was within typically reported soft tissue ranges (1480-1560 m/s). In all phantoms, histotripsy resulted in sharply delineated treatment zones, allowing segmentation in both modalities. These phantoms will aid in the development and validation of X-ray-based histotripsy targeting techniques, which promise to expand the scope of treatable lesions beyond only those visible on ultrasound.

The first decade of the DGOU's cartilage register-insights for clinical practice

Registry data provide valuable epidemiological insights that help to further improve process and outcome quality in patient care. The German Cartilage Registry (KnorpelRegister DGOU) was established in 2013 as an instrument for quality assurance after surgical cartilage regenerative procedures on hip, knee and ankle joints. Participation in the German Cartilage Registry is optional for hospitals and practices. Currently, more than 160institutions in Germany, Austria and Switzerland participate in the data collection. The implementation of PROMs ("patient related outcome measurement"), as well as the recording of surgery-related influencing factors, enable adifferentiated scientific analysis and represent akey quality feature of the registry. Initial analyses of the registry data have already provided clinically relevant findings for immediate patient care. For example, patients who underwent focal cartilage therapy prior to ACT show aclinically relevant, significantly worse outcome than patients who underwent primary ACT. First conclusions could also be drawn regarding the relevance of concomitant cartilage therapy. For example, in patients with focal cartilage damage of the medial knee joint compartment, registry data indicate that leg axis correction is indicated even in cases of mild deviation of the mechanical leg axis. The data and findings obtained from the Cartilage Registry represent an important aspect of clinical care research and serve as acomplement to well-designed, clinically prospective cohort studies, RCTs, and meta-analyses.

Health Services Needs Assessment for Retinoblastoma in Ethiopia.

The aim of this study was to document the available resources and needs for the detection, diagnosis, and treatment of retinoblastoma (RB) in Ethiopia. A health services needs assessment focused on RB care in Ethiopia was conducted. Information was obtained through a web-based survey and field visits. Facilities offering RB service delivery were categorized into three tiers, on the basis of the ability to detect (tier 1) and manage simple (tier 2) or complex (tier 3) patients with RB. Descriptive statistics were performed to quantify human and material resources available at each facility. The web survey received 29 responses from ophthalmologists at 19 health care facilities. Of the 19 units surveyed, seven (36.8%) had an ophthalmologist dedicated to RB treatment, classifying them as either a tier 2 or 3 facility. All tier 3 facilities had an affiliated health facility offering access to off-site pediatric oncology and pathology services. Of the focal therapies offered at tier 3 facilities, none included local chemotherapy or brachytherapy. Enucleation was offered at all tier 2 facilities, but availability of orbital implants and ocular prostheses was variable. None of the health facilities offered genetics services. This study demonstrated that the human and material resources needed for RB care in Ethiopia are constrained. Tier 3 RB facilities are rare and concentrated in urban areas, which could make it difficult for many patients to access. With focused capacity-building efforts, it is possible to increase the efficiency of RB therapy.

AI-Based Isotherm Prediction for Focal Cryoablation of Prostate Cancer

Focal therapies have emerged as minimally invasive alternatives for patients with localized low-risk prostate cancer (PCa) and those with postradiation recurrence. Among the available focal treatment methods for PCa, cryoablation offers several technical advantages, including the visibility of the boundaries of frozen tissue on the intraprocedural images, access to anterior lesions, and the proven ability to treat postradiation recurrence. However, predicting the final volume of the frozen tissue is challenging as it depends on several patient-specific factors, such as proximity to heat sources and thermal properties of the prostatic tissue. This paper presents a convolutional neural network model based on 3D-Unet to predict the frozen isotherm boundaries (iceball) resultant from a given a cryo-needle placement. Intraprocedural magnetic resonance images acquired during 38 cases of focal cryoablation of PCa were retrospectively used to train and validate the model. The model accuracy was assessed and compared against a vendor-provided geometrical model, which is used as a guideline in routine procedures. The mean Dice Similarity Coefficient using the proposed model was 0.79±0.08 (mean+SD) vs 0.72±0.06 using the geometrical model (P<.001). The model provided an accurate iceball boundary prediction in less than 0.4second and has proven its feasibility to be implemented in an intraprocedural planning algorithm.

Prostate Imaging after Focal Ablation (PI-FAB): A Proposal for a Scoring System for Multiparametric MRI of the Prostate After Focal Therapy

At present there is no standardised system for scoring the appearance of the prostate on multiparametric magnetic resonance imaging (MRI) after focal ablation for localised prostate cancer. We propose a novel scoring system, the Prostate Imaging after Focal Ablation (PI-FAB) score, to fill this gap. PI-FAB involves a 3-point scale for rating MRI sequences in sequential order: (1) dynamic contrast-enhanced sequences; (2) diffusion-weighted imaging, split into assessment of the high-b-value sequence first and then the apparent diffusion coefficient map; and (3) T2-weighted imaging. It is essential that the pretreatment scan is also available to help with this assessment. We designed PI-FAB using our experience of reading postablation scans over the past 15 years and include details for four representative patients initially treated with high-intensity focus ultrasound at our institution to demonstrate the scoring system. We propose PI-FAB as a standardised method for evaluating prostate MRI scans after treatment with focal ablation. The next step is to evaluate its performance across multiple experienced readers of MRI after focal therapy in a clinical data set. Patient summaryWe propose a scoring system called PI-FAB for assessing the appearance of magnetic resonance imaging scans of the prostate after focal treatment for localised prostate cancer. This will help clinicians in deciding on further follow-up.

Salvage Radical Prostatectomy after Primary Focal Ablative Therapy: A Systematic Review and Meta-Analysis.

Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.

Clinical impact of carbon-ion radiotherapy on hepatocellular carcinoma with Child-Pugh B cirrhosis.

Hepatocellular carcinoma (HCC) patients with Child-Pugh (CP)-B not eligible for surgery nor other focal therapy options due to impaired liver function, have very limited treatment options. This study aims to retrospectively investigate the toxicity and efficacy of Carbon-ion radiotherapy (C-ion RT) on HCC with CP-B patients. Patients with CP-B, no extrahepatic metastasis, and treated with C-ion RT between May 2000 and March 2020 were retrospectively extracted and included in this study. Sixty-nine lesions of 58 patients were included. The median follow-up duration was 20.5 (2.7-108) months. During follow-up, recurrence was observed in 43 patients, including 2 local recurrences and 39 intrahepatic recurrences beyond the irradiation field. A grade 3 acute hepatotoxicity was observed in one patient during the observation period. No acute or late adverse event of grade ≥4 was observed. Overall survival was 80.4% and 46.0% at 1 and 2 years, respectively, and the median survival time was 22.6 months. Local control rate was 96.4% at both 1 and 2 years, and progression-free survival was 38.6% and 6.9% at 1 and 2 years, respectively, with a median of 9.7 months. The C-ion RT showed low toxicity and good local effect in patients with HCC and CP-B. Therefore, C-ion RT could be an appropriate treatment for patients with HCC with poor liver function.

A Novel Nomogram to Identify Candidates for Focal Therapy Among Patients with Localized Prostate Cancer Diagnosed via Magnetic Resonance Imaging–Targeted and Systematic Biopsies: A European Multicenter Study

BackgroundSuitable selection criteria for focal therapy (FT) are crucial to achieve success in localized prostate cancer (PCa). ObjectiveTo develop a multivariable model that better delineates eligibility for FT and reduces undertreatment by predicting unfavorable disease at radical prostatectomy (RP). Design, setting, and participantsData were retrospectively collected from a prospective European multicenter cohort of 767 patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies followed by RP in eight referral centers between 2016 and 2021. The Imperial College of London eligibility criteria for FT were applied: (1) unifocal MRI lesion with Prostate Imaging-Reporting and Data System score of 3–5; (2) prostate-specific antigen (PSA) ≤20 ng/ml; (3) cT2–3a stage on MRI; and (4) International Society of Urological Pathology grade group (GG) 1 and ≥6 mm or GG 2–3. A total of 334 patients were included in the final analysis. Outcome measurements and statistical analysisThe primary outcome was unfavorable disease at RP, defined as GG ≥4, and/or lymph node invasion, and/or seminal vesicle invasion, and/or contralateral clinically significant PCa. Logistic regression was used to assess predictors of unfavorable disease. The performance of the models including clinical, MRI, and biopsy information was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A coefficient-based nomogram was developed and internally validated. Results and limitationsOverall, 43 patients (13%) had unfavorable disease on RP pathology. The model including PSA, clinical stage on digital rectal examination, and maximum lesion diameter on MRI had an AUC of 73% on internal validation and formed the basis of the nomogram. Addition of other MRI or biopsy information did not significantly improve the model performance. Using a cutoff of 25%, the proportion of patients eligible for FT was 89% at the cost of missing 30 patients (10%) with unfavorable disease. External validation is required before the nomogram can be used in clinical practice. ConclusionsWe report the first nomogram that improves selection criteria for FT and limits the risk of undertreatment. Patient summaryWe conducted a study to develop a better way of selecting patients for focal therapy for localized prostate cancer. A novel predictive tool was developed using the prostate-specific antigen (PSA) level measured before biopsy, tumor stage assessed via digital rectal examination, and lesion size on magnetic resonance imaging (MRI) scans. This tool improves the prediction of unfavorable disease and may reduce the risk of undertreatment of localized prostate cancer when using focal therapy.