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.

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.

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.

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.

Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases.

PURPOSE: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial. However, it is unknown whether tucatinib with SRS is safe or effective. METHODS: A retrospective analysis of HER2-positive breast cancer treated with SRS and tucatinib for brain metastases management was performed. All patients received tucatinib and SRS for the management of active brain metastases. The primary endpoint was local and distant brain tumor control. Secondary endpoints were intracranial progression free survival (CNS-PFS), systemic PFS, overall survival (OS), and neurotoxicity. RESULTS: A total of 135 lesions treated with SRS over 39 treatment sessions in 22 patients were identified. Median follow-up from tucatinib initiation was 20.8 months. Local brain control was 94% at 12-months and 81% at 24-months. Distant brain control was 39% at 12-months and 26% at 24-months. Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points. Median systemic PFS was not reached, with 12- and 24-month systemic PFS rates of 86% and 57%, respectively. Symptomatic radiation necrosis occurred in 6 (4%) lesions. No additional unexpected toxicities were noted. CONCLUSIONS: SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases. Further prospective evaluation of potential synergistic effects is warranted.

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.

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.

The Role of Augmented Reality in Surgical Training: A Systematic Review.

This review aims to provide an update on the role of augmented reality (AR) in surgical training and investigate whether the use of AR improves performance measures compared to traditional approaches in surgical trainees.PUBMED, EMBASE, Google Scholar, Cochrane Library, British Library and Science Direct were searched following PRIMSA guidelines. All English language original studies pertaining to AR in surgical training were eligible for inclusion. Qualitative analysis was performed and results were categorised according to simulator models, subsequently being evaluated using Messick's framework for validity and McGaghie's translational outcomes for simulation-based learning.Of the 1132 results retrieved, 45 were included in the study. 29 platforms were identified, with the highest 'level of effectiveness' recorded as 3. In terms of validity parameters, 10 AR models received a strong 'content validity' score of 2.15 models had a 'response processes' score ≥ 1. 'Internal structure' and 'consequences' were largely not discussed. 'Relations to other variables' was the best assessed criterion, with 9 platforms achieving a high score of 2. Overall, the Microsoft HoloLens received the highest level of recommendation for both validity and level of effectiveness.Augmented reality in surgical education is feasible and effective as an adjunct to traditional training. The Microsoft HoloLens has shown the most promising results across all parameters and produced improved performance measures in surgical trainees. In terms of the other simulator models, further research is required with stronger study designs, in order to validate the use of AR in surgical training.

Learning Surgical Skills Through Video-Based Education: A Systematic Review.

BACKGROUND: Educational videos are a potent resource for the learning of surgical skills among different study cohorts. However, there is limited evidence on the effectiveness of different educational video interventions and their features.A systematic search of MEDLINE (via PubMed), Embase (via OVID), Cochrane libraries and Clinicaltrials.gov was performed from inception to 28/02/21. Studies included were not limited by date of publication, studies aiming to assess the impact of video-based interventions in the direct acquisition of surgical skill were included. Eligible studies were analysed based on study type, type of video intervention, method of assessment and period of education. The educational impact of the studies was also assessed as per Messick's framework for testing validity of evaluation methods and McGhagie's model for analysing translational outcomes.22 studies were deemed suitable for inclusion, of which 14/22 (63.6%) demonstrated a significant improvement in knowledge/skills following the video-based teaching interventions, 3/22 (13.6%) studies demonstrated an improvement in trainee satisfaction scores. A recurrent limitation of the included studies was the lack of validation of selected assessment methods. None of the included studies scored on all 5 parameters of validity as defined by Messicks validity framework. Furthermore, none of the included trials were conducted for long enough to indicate direct changes to patient outcomes resultant from educational methods. CONCLUSION: Video-based surgical education is effective in learning surgical skills within different levels of surgical training; however, superior study quality and follow-up is required to determine which aspects of video-based interventions are most impactful.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.

Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a particularly high risk of breast cancer brain metastasis (BCBM) and leptomeningeal disease (LMD). Improvements in systemic therapy have translated to improved survival for patients with HER2-positive BCBM and LMD. However, the optimal management of these cases is rapidly evolving and requires a multidisciplinary approach. Herein, a team of radiation oncologists, medical oncologists, neuro-oncologists, and breast surgeon created a review of the evolving management of HER2-positive BCBM and LMD. We assess the epidemiology, diagnosis, and evolving treatment options for patients with HER2-positive BCBM and LMD, as well as the ongoing prospective clinical trials enrolling these patients. The management of HER2-positive BCBM and LMD represents an increasingly common challenge that involves the coordination of local and systemic therapy. Advances in systemic therapy have resulted in an improved prognosis, and promising targeted therapies currently under prospective investigation have the potential to further benefit these patients.

A systematic review of treatment options for post-prostatectomy incontinence.

PURPOSE: Urinary incontinence remains common in men after prostatectomy. Current guidance suggests early corrective surgery to those that are still incontinent after trying Pelvic Floor Muscle Therapy, however, other treatments are now available. This review aims to evaluate all currently available treatment options for men with post-prostatectomy incontinence (PPI). METHODS: A search of MEDLINE and CENTRAL databases on 2/2/2021 produced 879 articles. Any study evaluating incontinence before and after a treatment protocol was eligible for inclusion. After screening, 17 randomized control trials were included, and pre-defined data points were collected. Due to heterogeneity, pooled analysis was not possible, and a descriptive synthesis was produced in accordance with PRISMA guidelines. Cochrane Risk of Bias (RoB) tool was used to evaluate all studies. The search protocol and methods for this study was registered on the PROSPERO database before the search began, ID:(CRD42021229749). RESULTS: 3/17(18%) of studies focussed on pharmacotherapy, 2/17(12%) on vibration therapies, 8/17(47%) on pelvic floor muscle therapy (PFMT), 3/17(18%) on electrical stimulation (ES), and 1/17 (6%) on extracorporeal magnetic innervation (ExMI) as their main intervention. The use of Duloxetine, Solifenacin, PFMT, ES, and ExMI all show effective reduction in incontinence in men suffering from PPI. No study in this review evaluated surgical managements for PPI. CONCLUSION: A large number of treatments are available for PPI using an array of different methods. For this reason, a variety of treatments could be considered before early invasive procedures, to prevent unnecessary surgery and its associated negative complications.

A Systematic Review of Simulation-Based Training in Vascular Surgery.

INTRODUCTION: Recent advancements in surgical technology, reduced working hours, and training opportunities exacerbated by the COVID-19 pandemic have led to an increase in simulation-based training. Furthermore, a rise in endovascular procedures has led to a requirement for high-fidelity simulators that offer comprehensive feedback. This review aims to identify vascular surgery simulation models and assess their validity and levels of effectiveness (LoE) for each model in order to successfully implement them into current training curricula. METHODS: PubMed and EMBASE were searched on January 1, 2021, for full-text English studies on vascular surgery simulators. Eligible articles were given validity ratings based on Messick's modern concept of validity alongside an LoE score according to McGaghie's translational outcomes. RESULTS: Overall 76 eligible articles validated 34 vascular surgery simulators and training courses for open and endovascular procedures. High validity ratings were achieved across studies for: content (35), response processes (12), the internal structure (5), relations to other variables (57), and consequences (2). Only seven studies achieved an LoE greater than 3/5. Overall, ANGIO Mentor was the most highly validated and effective simulator and was the only simulator to achieve an LoE of 5/5. CONCLUSIONS: Simulation-based training in vascular surgery is a continuously developing field with exciting future prospects, demonstrated by the vast number of models and training courses. To effectively integrate simulation models into current vascular surgery curricula and assessments, there is a need for studies to look at trainee skill retention over a longer period of time. A more detailed discussion on cost-effectiveness is also needed.

Fear of cancer recurrence and PSA anxiety in patients with prostate cancer: a systematic review.

PURPOSE: The impact of prostate cancer on the mental wellbeing of patients is increasingly being appreciated. Two important aspects of this include fear of cancer recurrence (FCR) and prostate-specific antigen (PSA) anxiety. However, their prevalence, severity and associating factors remain poorly understood. Therefore, this review aims to evaluate the current evidence for the prevalence, severity and associating features of PSA anxiety and FCR. METHODS: A systematic search of MEDLINE, EMBASE and PsycINFO databases was conducted by two independent reviewers. Observational studies measuring FCR and PSA anxiety in prostate cancer using validated measures were included. Outcome measures were prevalence of significant levels, mean scores and significant correlations of FCR and PSA anxiety scores with patient, disease, treatment or other mental health and quality of life outcomes. RESULTS: One thousand one hundred forty-eight individual records underwent screening with 32 studies included. Median prevalence of significant FCR and PSA anxiety was 16% and 22% respectively across all studies. Longitudinal studies demonstrated severity of both symptoms peaks at diagnosis, with little variability, even several years following this. Evaluating associating factors revealed younger age, generalised quality of life and mental health symptoms to be important factors for both outcomes. Few studies evaluated associations and differences between other patient, disease and treatment characteristics. CONCLUSION: FCR and PSA anxiety are prominent symptoms for prostate cancer patients and importantly when present, are associated with poorer quality of life and mental health symptoms. Screening for these constructs and referral to appropriate services should form part of routine follow-up care.

An exploration of wellbeing in men diagnosed with prostate cancer undergoing active surveillance: a qualitative study.

PURPOSE: There is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing. METHODS: Qualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model. RESULTS: Mental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an 'Emotional Diagnostic Disequilibrium'. Informational awareness and education about prostate cancer helped patients with 'Recognition of the Impact'. Patients experienced an 'Unsettling Monitoring Cycle' due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is 'A Future Problem'. 'Concealment of Diagnosis' left many feeling isolated and highlighted an important coping mechanisms in the 'Importance of a Social Support Network' theme. Finally, physical health mostly changed through alterations in health behaviour, leading to 'A Healthier Lifestyle' with increasing attribution of physical symptoms to age through 'Symptomatic Overshadowing'. CONCLUSION: The greatest disease impact on men's wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life.

The impact of radical prostatectomy on the social well-being of prostate cancer survivors: A qualitative meta-synthesis.

INTRODUCTION: The impact of radical prostatectomy on the social well-being of survivors remains poorly understood. This meta-synthesis therefore aimed to integrate the findings of qualitative research evaluating the impact of surgery on the patient relationships with partners, family and wider societal interactions. METHODS: Medline, CINAHL, PsycINFO and Embase were searched for qualitative studies evaluating social well-being dimensions. A thematic meta-synthesis was conducted to inductively construct descriptive themes and overarching analytical themes. RESULTS: Thirty-one articles were included, with seven descriptive themes under two analytical themes generated to describe the experiences of 469 participants. 'Pathway to Conversion' encompassed three themes on the evolving social behaviour of men with both partners and family to adapt to their new normality postoperatively. 'A Man on My Own' discussed four themes focussing on both intimate and wider social relations, describing the stigma, shame and embarrassment felt by patients due to changes in their perceived body image and physical function. This resulted in men feeling alone, unsupported and seeking isolation. CONCLUSION: Radical prostatectomy's impact on survivors' social well-being extends beyond surgery and causes a shift in their relationship dynamics with partner and family, highlighting the importance of preoperative and postoperative clinician's counselling to both patient and partner.

HoloMentor: A Novel Mixed Reality Surgical Anatomy Curriculum for Robot-Assisted Radical Prostatectomy.

OBJECTIVES: The disruption to surgical training and medical education caused by the global COVID-19 pandemic highlighted the need for realistic, reliable, and engaging educational opportunities available outside of the operating theatre and accessible for trainees of all levels. This article presents the design and development of a virtual reality curriculum which simulates the surgical mentorship experience outside of the operating theatre, with a focus on surgical anatomy and surgical decision-making. METHOD: This was a multi-institutional study between London's King's College and Imperial College. The index procedure selected for the module was robotic radical prostatectomy. For each stage of the surgical procedure, subject-matter experts (N = 3) at King's College London, identified (1) the critical surgical-decision making points, (2) critical anatomical landmarks, and (3) tips and techniques for overcoming intraoperative challenges. Content validity was determined by an independent panel of subject-matter experts (N = 8) at Imperial College, London, using Fleiss' kappa statistic. The experts' teaching points were combined with operative footage and illustrative animations, and projected onto a virtual reality headset. The module was piloted to surgical science students (N = 15). Quantitative analysis compared participants' confidence regarding their anatomical knowledge before and after taking the module. Qualitative data were gathered from students regarding their views on using the virtual reality model. RESULTS: Multi-rater agreement between experts was above the 70.0% threshold for all steps of the procedure. Seventy-three percentage of pilot study participants "agreed" or "strongly agreed" that they achieved a better understanding of surgical anatomy and the rationale behind each procedural step. This was reflected in an increase in the median knowledge score after trialing the curriculum (p < 0.001). 100% of subject-matter experts and 93.3% of participants "agreed" or "strongly agreed" that virtual mentorship would be useful for future surgical training. CONCLUSIONS: This study demonstrated that virtual surgical mentorship could be a feasible and cost-effective alternative to traditional training methods with the potential to improve technical skills, such as operative proficiency and nontechnical skills such as decision-making and situational judgement.

Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis.

BACKGROUND: Despite advances in cancer genomics, radiotherapy is still prescribed on the basis of an empirical one-size-fits-all paradigm. Previously, we proposed a novel algorithm using the genomic-adjusted radiation dose (GARD) model to personalise prescription of radiation dose on the basis of the biological effect of a given physical dose of radiation, calculated using individual tumour genomics. We hypothesise that GARD will reveal interpatient heterogeneity associated with opportunities to improve outcomes compared with physical dose of radiotherapy alone. We aimed to test this hypothesis and investigate the GARD-based radiotherapy dosing paradigm. METHODS: We did a pooled, pan-cancer analysis of 11 previously published clinical cohorts of unique patients with seven different types of cancer, which are all available cohorts with the data required to calculate GARD, together with clinical outcome. The included cancers were breast cancer, head and neck cancer, non-small-cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. Our dataset comprised 1615 unique patients, of whom 1298 (982 with radiotherapy, 316 without radiotherapy) were assessed for time to first recurrence and 677 patients (424 with radiotherapy and 253 without radiotherapy) were assessed for overall survival. We analysed two clinical outcomes of interest: time to first recurrence and overall survival. We used Cox regression, stratified by cohort, to test the association between GARD and outcome with separate models using dose of radiation and sham-GARD (ie, patients treated without radiotherapy, but modelled as having a standard-of-care dose of radiotherapy) for comparison. We did interaction tests between GARD and treatment (with or without radiotherapy) using the Wald statistic. FINDINGS: Pooled analysis of all available data showed that GARD as a continuous variable is associated with time to first recurrence (hazard ratio [HR] 0·98 [95% CI 0·97-0·99]; p=0·0017) and overall survival (0·97 [0·95-0·99]; p=0·0007). The interaction test showed the effect of GARD on overall survival depends on whether or not that patient received radiotherapy (Wald statistic p=0·011). The interaction test for GARD and radiotherapy was not significant for time to first recurrence (Wald statistic p=0·22). The HR for physical dose of radiation was 0·99 (95% CI 0·97-1·01; p=0·53) for time to first recurrence and 1·00 (0·96-1·04; p=0·95) for overall survival. The HR for sham-GARD was 1·00 (0·97-1·03; p=1·00) for time to first recurrence and 1·00 (0·98-1·02; p=0·87) for overall survival. INTERPRETATION: The biological effect of radiotherapy, as quantified by GARD, is significantly associated with time to first recurrence and overall survival for patients with cancer treated with radiation. It is predictive of radiotherapy benefit, and physical dose of radiation is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalising radiotherapy prescription dose. FUNDING: None. VIDEO ABSTRACT.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases.

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.