Development of a Bladder Injury Classification System for Endoscopic Procedures: A Mixed-methods Study Involving Expert Consensus and Validation.

BACKGROUND AND OBJECTIVE: The widespread adoption and rapid integration of new technologies and techniques in endoscopic and laser bladder interventions, particularly endoscopic enucleation, have led to new types of bladder injuries. This underscores the need for an intraoperative injury classification system. This study aims to develop and validate the Bladder Injury Classification System for Endoscopic Procedures (BICEP), which standardizes the classification of complications and intervention requirements. METHODS: This mixed-methods study involved experts from the European Association of Urology Section of Urotechnology to standardize and validate the BICEP classification system. An iterative process involving focus groups, expert surveys, and revisions assessed clarity, relevance, comprehensiveness, and practicality. Validity was confirmed through expert surveys conducted in two rounds for face and content validity, using a 5-point Likert scale to correlate ratings with expected outcomes. KEY FINDINGS AND LIMITATIONS: The novel BICEP classification system categorizes bladder injuries into ten subcategories with scores ranging from 0 to 4, reflecting injury severity and management requirements. Face validity was demonstrated by a 95% consensus on the system's clarity, relevance, and comprehensiveness. Content validity was supported by high acceptance rates in expert surveys, with average scores of 4.53 and 4.58 in the first and second rounds, respectively. This demonstrates strong support for its applicability in clinical practice. However, the primary limitation is the lack of external validation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study demonstrates that the BICEP system is a robust and comprehensive classification system, with strong support for its face and content validity. The BICEP system is a proposal based on expert opinion, and additional studies are necessary to ensure its widespread adoption and efficacy. PATIENT SUMMARY: Our study addressed the critical need for standardized classification in the increasingly widespread context of urology endoscopic technologies by focusing on intraoperative evaluation, reporting, and standardization of bladder injuries. This study provides a globally standardized basis for the classification and treatment of bladder injuries in urology endoscopic procedures.

Impact of complete versus culprit-only revascularization on major adverse cardiovascular event in diverse subpopulations.

Background: Myocardial infarction management relies on pharmaceuticals and interventions like percutaneous coronary intervention (PCI). While complete PCI has shown noninferiority to culprit-only PCI, its impact on major adverse cardiovascular events (MACE) outcomes in multiple subpopulations has been unknown.Methods: A systematic literature search (from January 2000 to May 2024) identified four relevant randomized controlled trials involving ST-segment elevation myocardial infarction patients. Data analysis employed a random-effects model with inverse variance weighting.Results: MACE risk was significantly lower in males than females undergoing complete PCI compared with culprit-only PCI (hazard ratio: 0.52; 95% CI: 0.39-0.68; p < 0.01; I2 = 53%). Furthermore, complete PCI significantly lowered the risk of MACE outcomes in patients without diabetes and in patients under the 65-year age limit in comparison to culprit-only PCI.Conclusion: Complete PCI reduces MACE risk in male, nondiabetic ST-segment elevation myocardial infarction patients under 65 with multivessel coronary artery disease, necessitating further investigation into outcome differences among different subpopulations.

[Box: see text].

Controversies in neuro-oncology: Focal proton versus photon radiation therapy for adult brain tumors.

Radiation therapy (RT) plays a fundamental role in the treatment of malignant and benign brain tumors. Current state-of-the-art photon- and proton-based RT combines more conformal dose distribution of target volumes and accurate dose delivery while limiting the adverse radiation effects. PubMed was systematically searched from from 2000 to October 2023 to identify studies reporting outcomes related to treatment of central nervous system (CNS)/skull base tumors with PT in adults. Several studies have demonstrated that proton therapy (PT) provides a reduced dose to healthy brain parenchyma compared with photon-based (xRT) radiation techniques. However, whether dosimetric advantages translate into superior clinical outcomes for different adult brain tumors remains an open question. This review aims at critically reviewing the recent studies on PT in adult patients with brain tumors, including glioma, meningiomas, and chordomas, to explore its potential benefits compared with xRT.

Prediction of radiologic outcome-optimized dose plans and post-treatment magnetic resonance images: A proof-of-concept study in breast cancer brain metastases treated with stereotactic radiosurgery.

Background and purpose: Information in multiparametric Magnetic Resonance (mpMR) images is relatable to voxel-level tumor response to Radiation Treatment (RT). We have investigated a deep learning framework to predict (i) post-treatment mpMR images from pre-treatment mpMR images and the dose map ("forward models"), and, (ii) the RT dose map that will produce prescribed changes within the Gross Tumor Volume (GTV) on post-treatment mpMR images ("inverse model"), in Breast Cancer Metastases to the Brain (BCMB) treated with Stereotactic Radiosurgery (SRS). Materials and methods: Local outcomes, planning computed tomography (CT) images, dose maps, and pre-treatment and post-treatment Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced (T1w) and contrast-enhanced (T1wCE), T2-weighted (T2w) and Fluid-Attenuated Inversion Recovery (FLAIR) mpMR images were curated from 39 BCMB patients. mpMR images were co-registered to the planning CT and intensity-calibrated. A 2D pix2pix architecture was used to train 5 forward models (ADC, T2w, FLAIR, T1w, T1wCE) and 1 inverse model on 1940 slices from 18 BCMB patients, and tested on 437 slices from another 9 BCMB patients. Results: Root Mean Square Percent Error (RMSPE) within the GTV between predicted and ground-truth post-RT images for the 5 forward models, in 136 test slices containing GTV, were (mean ± SD) 0.12 ± 0.044 (ADC), 0.14 ± 0.066 (T2w), 0.08 ± 0.038 (T1w), 0.13 ± 0.058 (T1wCE), and 0.09 ± 0.056 (FLAIR). RMSPE within the GTV on the same 136 test slices, between the predicted and ground-truth dose maps, was 0.37 ± 0.20 for the inverse model. Conclusions: A deep learning-based approach for radiologic outcome-optimized dose planning in SRS of BCMB has been demonstrated.

Radiation Therapy Followed by Intrathecal Trastuzumab-Pertuzumab for ERBB2-Positive Breast Leptomeningeal Disease: A Phase 1 Nonrandomized Controlled Trial.

This nonrandomized controlled trial examines the safety of radiation therapy (RT) followed by intrathecal trastuzumab and pertuzumab for patients with ERBB2-positive breast leptomeningeal disease (LMD).

Clinical Outcomes of Patients with Non-Small Cell Lung Cancer Leptomeningeal Disease Following Receipt of EGFR-Targeted Therapy, Immune-Checkpoint Blockade, Intrathecal Chemotherapy, or Radiation Therapy Alone.

BACKGROUND: EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD). PATIENTS AND METHODS: This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC). RESULTS: EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (n = 20; 77%), stereotactic radiation (n = 3; 12%), and palliative spine radiation (n = 2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank P = .026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank P = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, P = .006) and CS-PFS (HR 0.39, P = .013). CONCLUSIONS: The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

The Role of Artificial Intelligence in Medical Education: A Systematic Review.

BACKGROUND: To examine the artificial intelligence (AI) tools currently being studied in modern medical education, and critically evaluate the level of validation and the quality of evidence presented in each individual study. METHODS: This review (PROSPERO ID: CRD42023410752) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A database search was conducted using PubMed, Embase, and Cochrane Library. Articles written in the English language between 2000 and March 2023 were reviewed retrospectively using the MeSH Terms "AI" and "medical education" A total of 4642 potentially relevant studies were found. RESULTS: After a thorough screening process, 36 studies were included in the final analysis. These studies consisted of 26 quantitative studies and 10 studies investigated the development and validation of AI tools. When examining the results of studies in which Support vector machines (SVMs) were employed, it has demonstrated high accuracy in assessing students' experiences, diagnosing acute abdominal pain, classifying skilled and novice participants, and evaluating surgical training levels. Particularly in the comparison of surgical skill levels, it has achieved an accuracy rate of over 92%. CONCLUSION: AI tools demonstrated effectiveness in improving practical skills, diagnosing diseases, and evaluating student performance. However, further research with rigorous validation is required to identify the most effective AI tools for medical education.

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

PURPOSE: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. METHODS: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. RESULTS: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). CONCLUSION: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

Multicentric evaluation of high and low power lasers on RIRS success using propensity score analysis.

In this study, we aimed to evaluate the effect of HPL on different parameters by different centers and urologists. While doing this, we evaluated different parameters by comparing HPL(High Power laser) and LPL(Low-power laser). This is an observational, retrospective, comparative, multicentric study of prospectively organised database. A total of 217 patients who underwent RIRS for kidney stones smaller than 2 cm in three different centers were included in the study. The patients were divided into two groups; LPL used (Group1, n:121 patients) and HPL used (Group2, n:96). Propensity score matching was done in the data analysis part. After matching, a total of 192 patients, 96 patients in both groups, were evaluated. There was no difference between the groups regarding age, gender, stone side, and stone location. The stone-free rate on the first day was 80.3% in Group 1, it was 78.1% in Group 2 (p = 0.9). In the third month, it was 90.7% in Group 1 and 87.5% in Group 2 (p:0.7).Hospitalization duration was significantly higher in Group 1. (2.35 ± 2.27 days vs. 1.42 ± 1.10 days; p < 0.001).The operation duration was 88.70 ± 29.72 min in Group1 and 66.17 ± 41.02 min in Group2 (p < 0.001). The fluoroscopy time (FT) was 90.73 ± 4.79 s in Group 1 and 50.78 ± 5.64 s in Group 2 (p < 0.001). Complications according to Clavien Classification, were similar between the groups(p > 0.05). According to our study similar SFR and complication rates were found with HPL and LPL. In addition, patients who used HPL had lower operation time, hospital stay, and fluoroscopy time than the LPL group. Although high-power lasers are expensive in terms of cost, they affect many parameters and strengthen the hand of urologists thanks to the wide energy and frequency range they offer.

Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care.

Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.

Evaluation of a Patient Decision Aid for Refractive Eye Surgery.

BACKGROUND: We developed a prototype patient decision aid, EyeChoose, to assist college-aged students in selecting a refractive surgery. EyeChoose can educate patients on refractive errors and surgeries, generate evidence-based recommendations based on a user's medical history and personal preferences, and refer patients to local refractive surgeons. OBJECTIVES: We conducted an evaluative study on EyeChoose to assess the alignment of surgical modality recommendations with a user's medical history and personal preferences, and to examine the tool's usefulness and usability. METHODS: We designed a mixed methods study on EyeChoose through simulations of test cases to provide a quantitative measure of the customized recommendations, an online survey to evaluate the usefulness and usability, and a focus group interview to obtain an in-depth understanding of user experience and feedback. RESULTS: We used stratified random sampling to generate 245 test cases. Simulated execution indicated EyeChoose's recommendations aligned with the reference standard in 243 (99%). A survey of 55 participants with 16 questions on usefulness, usability, and general impression showed that 14 questions recorded more than 80% positive responses. A follow-up focus group with 10 participants confirmed EyeChoose's useful features of patient education, decision assistance, surgeon referral, as well as good usability with multimedia resources, visual comparison among the surgical modalities, and the overall aesthetically pleasing design. Potential areas for improvement included offering nuances in soliciting user preferences, providing additional details on pricing, effectiveness, and reversibility of surgeries, expanding the function of surgeon referral, and fixing specific usability issues. CONCLUSION: The initial evaluation of EyeChoose suggests that it could provide effective patient education, generate appropriate recommendations, connect to local refractive surgeons, and demonstrate good system usability in a test environment. Future research is required to enhance the system functions, fully implement and evaluate the tool in naturalistic settings, and examine the findings' generalizability to other populations.

Virtual reality vs. physical models in surgical skills training. An update of the evidence.

PURPOSE OF REVIEW: Simulation is a key component of surgical training, enabling trainees to develop their skills in a safe environment. With simulators broadly grouped into physical models and virtual-reality (VR) simulators, it is important to evaluate the comparative effectiveness of the simulator types in terms of validity as well as cost. The review aims to compare the benefits and drawbacks of novel VR and physical simulators within the broader themes of endourology, laparoscopic and robotic operations, and other urological procedures. RECENT FINDINGS: Key benefits of bench models include their comparatively lower cost, easy access and provision of haptic feedback, whereas VR simulators are generally self-sufficient, reusable and enable skills of haemostasis to be practised. The advent of perfused 3D printed simulators across a range of urological procedures may replace cadavers as the traditional gold-standard simulation modality. SUMMARY: Although possessing differing strengths and downsides, VR and physical simulators when used together can have an additive effect due to skill transferability across the platforms. Further comparative studies are required to directly quantify the differences between physical models and VR simulators in terms of performance metrics and cost-effectiveness. There is lack of validated VR simulators for open and reconstructive procedures.

Orbital cellulitis with panophthalmitis and scleral necrosis - a case report.

BACKGROUND: Orbital cellulitis is common in young children and is often secondary to coexisting sinus disease. Coexisting orbital cellulitis and panophthalmitis is a rare clinical event and usually occurs secondary to trauma or from an endogenous source. CASE PRESENTATION: A febrile 2-year-old male presented with periorbital inflammation and exudative retinal detachment. Imaging showed acute sinusitis and extensive orbital cellulitis. Because of progressive scleral thinning, the patient underwent enucleation. CONCLUSION: We present a case of concurrent orbital cellulitis, panophthalmitis, and scleral necrosis in an immunocompetent pediatric patient. Timely intervention is important to prevent life threatening complications with the rare occurrence of coexistent orbital cellulitis and panophthalmitis.

What is the effect of laser anatomical endoscopic enucleation of the prostate on the ejaculatory functions? A systematic review.

INTRODUCTION: Laser anatomical endoscopic enucleation of the prostate (LAEEP) has emerged as a promising new approach in endoscopic surgery for BPH. LAEEP could still result in ejaculatory dysfunction. AIM: This systematic review aimed to examine the impact of LAEEP on male ejaculatory functions. METHODS: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and 15 records were included. Outcomes of interest included ejaculatory dysfunction (retrograde ejaculation, painful ejaculation, etc.) and validated questionnaire scores. The quality of studies included in the systematic review was determined using QUADAS scoring. RESULTS: We retrieved data for 1877 men in 15 clinical studies investigating LAEEP surgery and reporting EjD rates. While only three of the obtained studies were on thulium fiber (ThuLEP), the rest were on holmium (HoLEP). The definition of "Ejaculatory Dysfunction" was not standardized, but in most works, it is referred to as retrograde ejaculation (RE). There were no data on the relationship between other LAEEP techniques and ejaculation functions. The authors compared the outcomes of used standard laser enucleation techniques with the modified techniques. The RE rate in LAEEP was 62.1 ± 25.1%, 71.3 ± 16.1% in standard techniques, and 27.2 ± 18.1% in ejaculation-preserving modified techniques (p < 0.001). CONCLUSION: This review demonstrated that ejaculation-preserving techniques, i.e., modified techniques are superior to standard techniques. Studies have also shown that ejaculatory dysfunction rates gradually decrease with long-term follow-ups. Future well-designed studies could further investigate the ejaculation-preserving modification of LAEEP techniques and how they impact EjD rates and other sexual function outcomes.

Prognostic factors for mental wellbeing in prostate cancer: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients. METHODS: We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible. RESULTS: A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes. CONCLUSION: We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.

Graduate and postgraduate educational challenges during the COVID-19 pandemic period: its impact and innovations-a scoping review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has transformed the global view of education, including graduate and postgraduate education making the development of an alternative approach in times of social isolation an academic imperative. The present review aims to investigate the challenges experienced among undergraduate and postgraduate education and the strategies adopted to address these challenges during the pandemic. METHOD: The preferred reporting items for the systematic review and meta-analyses extension for Scoping Reviews (PRISMA-ScR) were followed. The aim was to include journal articles published in the English language that discussed the influence of the pandemic on educational processes and applied innovative approaches as a solution to educational challenges. From January to August 2020, PubMed, EMBASE, and Google Scholar were searched for articles, yielding 10,019 articles. Two groups of authors examined the retrieved articles separately to avoid any risk of bias. The title and abstract of the articles were used for scrutiny, followed by full-text screening based on the established inclusion and exclusion criteria. The facts and findings of the studies were also discussed based on per capita income, literacy rate, and Internet accessibility. RESULTS: Thirty of the obtained articles were included in the study. The selected articles were from North and South/Latin America, Asia & Pacific, South Africa, and Europe regions. Nineteen of the selected articles dealt with undergraduate education, ten with postgraduate, and one with both groups. The affordability of digital devices and the availability of Internet services were the major challenges for low- and middle-income economies. The ZOOM platform has been adopted by more than 90% of the education systems. CONCLUSION: Means of communication, including visual media, digitized content, and other web-based platforms, have been recognized as efficient learning and training tools, but have not been fully accessible for mass application and use due to the lack of availability of resources, their cost, and insufficient training among the users. In light of this review, it is suggested that harmonized and collaborative efforts should be made to develop cost-effective and user-friendly tools to overcome the current challenges and prevent future educational crises. SYSTEMIC REVIEW REGISTRATION: The review was not registered.

Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases.

BACKGROUND: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. METHODS: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. RESULTS: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). CONCLUSIONS: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.