Assessment of Cement Leakage in Decompressed Percutaneous Kyphoplasty.

Symptomatic osteoporotic compression fractures are commonly addressed through vertebroplasty and kyphoplasty. However, cement leakage poses a significant risk of neurological damage. We introduced "aspiration percutaneous kyphoplasty", also known as "decompressed kyphoplasty", as a method to mitigate cement leakage and conducted a comparative analysis with high viscosity cement vertebroplasty. We conducted a retrospective study that included 136 patients with single-level osteoporotic compression fractures. Among them, 70 patients underwent high viscosity cement vertebroplasty, while 66 patients received decompressed percutaneous kyphoplasty with low-viscosity cement. Comparison parameters included cement leakage rates, kyphotic angle alterations, and the occurrence of adjacent segment fractures. The overall cement leakage rate favored the decompressed kyphoplasty group (9.1% vs. 18.6%), although statistical significance was not achieved (p = 0.111). Nonetheless, the risk of intradiscal leakage significantly reduced in the decompressed kyphoplasty cohort (p = 0.011), which was particularly evident in cases lacking the preoperative cleft sign on X-rays. Kyphotic angle changes and the risk of adjacent segment collapse exhibited similar outcomes (p = 0.739 and 0.522, respectively). We concluded that decompressed kyphoplasty demonstrates efficacy in reducing intradiscal cement leakage, particularly benefiting patients without the preoperative cleft sign on X-rays by preventing intradiscal leakage.

The Evolution of Spinal Endoscopy: Design and Image Analysis of a Single-Use Digital Endoscope Versus Traditional Optic Endoscope.

Spinal endoscopy has evolved significantly since its inception, offering minimally invasive solutions for various spinal pathologies. This study introduces a promising innovation in spinal endoscopy-a single-use digital endoscope designed to overcome the drawbacks of traditional optic endoscopes. Traditional endoscopes, despite their utility, present challenges such as fragility, complex disinfection processes, weight issues, and susceptibility to mechanical malfunctions. The digital endoscope, with its disposable nature, lighter weight, and improved image quality, aims to enhance surgical procedures and patient safety. The digital endoscope system comprises a 30-degree 1000 × 1000 pixel resolution camera sensor with a 4.3 mm working channel, and LED light sources replacing optical fibers. The all-in-one touch screen tablet serves as the host computer, providing portability and simplified operation. Image comparisons between the digital and optic endoscopes revealed advantages in the form of increased field of view, lesser distortion, greater close-range resolution, and enhanced luminance. The single-use digital endoscope demonstrates great potential for revolutionizing spine endoscopic surgeries, offering convenience, safety, and superior imaging capabilities compared to traditional optic endoscopes.

Randomized Trial of Concomitant Hypofractionated Intensity Modulated Radiation Therapy Boost Versus Conventionally Fractionated Intensity Modulated Radiation Therapy Boost for Localized High-Risk Prostate Cancer (pHART2-RCT).

PURPOSE: The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with elective nodal irradiation. METHODS AND MATERIALS: This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes. RESULTS: One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P = .29). Late grade ≥2 GI (P = .07) and GU (P = .25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P = .01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P = .71) or distant metastasis (P = .31) and overall survival (P = .46). CONCLUSIONS: MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm.

Evaluation of Volumetric Response Assessment From SABR for Renal Cell Carcinoma (RCC).

PURPOSE: SABR is increasingly used to treat renal cell carcinoma (RCC). However, the optimal method to assess treatment response is unclear. We aimed to quantify changes in both volume and maximum linear size of tumors after SABR and evaluate the utility of the 2 approaches in treatment response assessment. METHODS AND MATERIALS: We retrospectively studied patients with RCC treated with SABR at our institution between 2013 and 2020. All available follow-up computed tomography scans were aligned, and tumors were contoured on all scans. Volume and maximum linear size were measured at each follow-up, relative to these measurements at the time of computed tomography simulation. RESULTS: Twenty-four patients with 25 tumors were included. Median follow-up was 32 months (range, 16-67). Nineteen tumors (76%) had 30% volumetric response at a median time of 7 months after SABR, and 12 tumors (48%) had 30% decrease in maximum linear size at a median time of 16 months. Eighteen tumors (72%) decreased in volume on first follow-up scan and continued to shrink, and 5 tumors (20%) displayed transient growth after SABR (average 24% increase in volume). Compared with T1a tumors, T1b or larger tumors were more likely to have transient growth (8% vs 33%; P = .16) and had higher average relative volume 24 months after SABR (0.47 vs 0.8; P = .022). CONCLUSIONS: Volume measurement results in more pronounced and earlier change compared with linear size measurement when assessing response to SABR. These findings may provide guidance when assessing treatment response for patients with RCC treated with SABR.

Application of machine learning and its effects on the development of a nursing guidance mobile app for sarcopenia.

BACKGROUND: Aging leads to changes in the body system, such as sarcopenia. This can result in several health issues, particularly physical and mobility dysfunction. Asian people typically have little awareness of sarcopenia. Thus, this study incorporated nursing instruction into the mobile application design to allow users to easily learn about sarcopenia. OBJECTIVE: This study evaluated a model for predicting high-risk populations for sarcopenia in home settings. We further developed a sarcopenia nursing guidance mobile application and assessed the effectiveness of this application in influencing sarcopenia-related knowledge and self-care awareness among participants. METHODS: Using a one-group pretest-posttest design, data were collected from 120 participants at a teaching hospital in northern Taiwan. This study used an artificial intelligence algorithm to evaluate a model for predicting high-risk populations for sarcopenia. We developed and assessed the sarcopenia nursing guidance mobile application using a questionnaire based on the Mobile Application Rating Scale. RESULTS: The application developed in this study enhanced participants' sarcopenia-related knowledge and awareness regarding self-care. After the three-month intervention, the knowledge and awareness was effectively increase, total score was from 4.15 ± 2.35 to 6.65 ± 0.85 and were significant for all questionnaire items (p values < 0.05). On average, 96.1% of the participants were satisfied with the mobile app. The artificial intelligence algorithm positively evaluated the home-use model for predicting high-risk sarcopenia groups. CONCLUSIONS: The mobile application of the sarcopenia nursing guidance for public use in home settings may help alleviate sarcopenia symptoms and reduce complications by enhancing individuals' self-care awareness and ability. TRIAL REGISTRATION: NCT05363033, registered on 02/05/2022.

Dosimetric correlates of toxicities and quality of life following two-fraction stereotactic ablative radiotherapy (SABR) for prostate cancer.

PURPOSE: There is no evidence-based data to guide dose constraints in two-fraction prostate stereotactic ablative radiotherapy (SABR). Using individual patient-data from two prospective trials, we aimed to correlate dosimetric parameters with toxicities and quality of life (QoL) outcomes. MATERIALS AND METHODS: We included 60 patients who had two-fraction prostate SABR in the 2STAR (NCT02031328) and 2SMART (NCT03588819) trials. The prescribed dose was 26 Gy to the prostate+/-32 Gy boost to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC-26 questionnaire. The outcomes evaluated were acute and late grade ≥ 2 toxicities, and late minimal clinical important changes (MCIC) in QoL domains. Dosimetric parameters for bladder, urethra, rectum, and penile bulb were evaluated. RESULTS: The median follow-up was 56 months (range: 39-78 months). The cumulative incidence of grade ≥ 2 genitourinary (GU), gastrointestinal (GI), and sexual toxicities were 62%, 3%, and 17% respectively in the acute setting (<3 months), and 57%, 15%, and 52% respectively in late setting (>6 months). There were 36%, 28%, and 29% patients who had late MCIC in urinary, bowel and sexual QoL outcomes respectively. Bladder 0.5 cc was significant predictor for late grade ≥ 2 GU toxicities, with optimal cut-off of 25.5 Gy. Penile bulb D5cc was associated of late grade ≥ 2 sexual toxicities (no optimal cut-off was identified). No dosimetric parameters were identified to be associated with other outcomes. CONCLUSION: Using real-life patient data from prospective trials with medium-term follow-up, we identified additional dose constraints that may mitigate the risk of late treatment-related toxicities for two-fraction prostate SABR.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases.

PURPOSE: Stereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. METHODS: Patients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. RESULTS: A total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. CONCLUSION: SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

Risk-adjusted chemoradiation according to human papilloma viral status for anal cancer: a pilot study.

Background and purpose: HPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV-) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status. Materials and methods: HPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV- received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category. Results: In the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV- patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients. Conclusion: De-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.

Impact of Aspiration Percutaneous Vertebroplasty in Reducing Bone Cement Leakage and Enhancing Distribution-An Ex Vivo Study in Goat Vertebrae.

Osteoporosis-induced vertebral compression fracture (OVCF) occurs commonly in people over the age of 50, especially among menopausal women. Besides conservative therapy, minimally invasive percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used in clinical treatment and achieved good efficacy. However, the leakage of bone cement (CL) during vertebroplasty (PV) is a major risk that can cause (serious) complications such as compression of the spinal cord, pulmonary embolism, or even paraplegia. In this study, we introduced a new aspiration technique with standard PV procedures (APV) to ameliorate the risk of leakage with quantitative verifications of its effectiveness. APV intends to create a differential pressure to guide the direction of cement flow within the vertebrae. To test this technique, Nubian goats' ex vivo vertebral bodies (VBs) were used to simulate the PV surgical process in humans. Results show that the proposed APV has a lower leakage rate of 13% compared to the 53% of conventional PV. Additionally, the APV approach achieves more uniform cement distribution via the 9-score method with a value of 7 ± 1.30 in contrast to 4 ± 1.78 by conventional PV.

To Boost or Not to Boost: Pooled Analyses From 2-Fraction SABR Trials for Localized Prostate Cancer.

PURPOSE: Focal boost to dominant intraprostatic lesion (DIL) is an approach for dose escalation in prostate radiation therapy. In this study, we aimed to report the outcomes of 2-fraction SABR ± DIL boost. METHODS AND MATERIALS: We included 60 patients with low- to intermediate-risk prostate cancer enrolled in 2 phase 2 trials (30 patients in each trial). In the 2STAR trial (NCT02031328), 26 Gy (equivalent dose in 2-Gy fractions = 105.4 Gy) was delivered to the prostate. In the 2SMART trial (NCT03588819), 26 Gy was delivered to the prostate, with up to 32 Gy boost to magnetic resonance imaging-defined DIL (equivalent dose in 2-Gy fractions = 156.4 Gy). The reported outcomes included prostate-specific antigen (PSA) response (ie, <0.4 ng/mL) at 4 years (4yrPSARR), biochemical failure (BF), acute and late toxicities, and quality of life (QOL). RESULTS: In 2SMART, median DIL D99% of 32.3 Gy was delivered. Median follow-up was 72.7 months (range, 69.1-75.) in 2STAR and 43.6 months (range, 38.7-49.5) in 2SMART. The 4yrPSARR was 57% (17/30) in 2STAR and 63% (15/24) in 2SMART (P = 0.7). The 4-year cumulative BF was 0% in 2STAR and 8.3% in 2SMART (P = 0.1). The 6-year BF in 2STAR was 3.5%. For genitourinary toxicities, there were differences in grade ≥1 urinary urgency in the acute (0% vs 47%; P < .001) and late settings (10% vs 67%; P < .001) favoring 2STAR. For urinary QOL, no difference was observed in the acute setting, but lower proportion in 2STAR had minimal clinically important changes in urinary QOL score in the late setting (21% vs 50%; P = .03). There were no significant differences in gastrointestinal and sexual toxicities and QOL in both acute and late settings between the 2 trials. CONCLUSIONS: This study presents the first prospective data comparing 2-fraction prostate SABR ± DIL boost. The addition of DIL boost resulted in similar medium-term efficacy (in 4yrPSARR and BF), with impact on late urinary QOL outcomes.

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

Designing an eSports intervention for middle-aged and older adults in Hong Kong: Social marketing approach.

This study examined the perceptions and experiences of middle-aged and older adult participants in electronic sports (eSports) in Hong Kong (HK), China, by using the social marketing (SM) approach. This qualitative study applied SM approach to the design of a center-based eSports intervention for middle-aged and older adults in HK. Interviews were conducted with 39 adults stratified in terms of age (i.e., 45-64 vs. ≥65 years) and experience with eSports. Ten administrators working in community elderly centers were invited for semistructured interviews. Thematic analysis was performed on the data by incorporating SM. Main findings are presented in terms of five P's. The product component of an eSports intervention includes the foundation of eSports (e.g., safety, eSports training), suitable games for older adults, and professional equipment (e.g., large-screen devices and motion-controlled Nintendo Switches). The price component comprises affordability and the frequency and duration of each eSport session, and the place component includes accessibility and spaces to play eSports. The promotion component should be educational in nature and can incorporate free trials and gaming days, short films about older adults playing eSports, promotional channels, physical evidence and annual eSports competitions. The people component consists of support from administrators and the center in charge, the availability of skilled program instructors and staff, and appropriate partnering, team sizes and instructor-to-participant ratios. The 5P's enhance the design of future center-based eSports interventions and can help researchers and practitioners determine which aspects encourage middle-aged and older adults to participate in eSports.

Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion - Results from the 2SMART phase 2 trial.

PURPOSE: This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. MATERIALS AND METHODS: Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). RESULTS: Thirty men were enrolled in the study - 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39-49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. CONCLUSION: This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. METHODS: PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. FINDINGS: We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. INTERPRETATION: In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. FUNDING: Accuray.

An Analysis of Waiting Time for Emergency Treatment and Optimal Allocation of Nursing Manpower.

OBJECTIVE: Emergency care is the frontline of the healthcare system. Taiwanese typically seek emergency care when suffering from an acute or unknown illness, which leads to a large number of emergency patients and the related misallocation of nursing manpower, and the excessive workloads of emergency service providers have become serious issues for Taiwan's medical institutions. PARTICIPANTS: This study conducted purposive sampling and recruited patients and nursing staffs from the emergency room of a medical center in New Taipei City as the research participants. METHODS: This study applied the queueing theory and the derived optimal model to solve the problems of excessive workloads for emergency service providers and misallocation of nursing manpower, in an attempt to provide decision makers with more flexible resource allocation and process improvement suggestions. RESULTS: This study analyzed the causes of emergency service overload and identified solutions for improving nursing manpower utilization. CONCLUSIONS: A wait-time model and the queueing theory were used to determine resource parameters for the optimal allocation of patient waiting times and to develop the best model for estimating nursing manpower.

New Triazolyl N

Cisplatin and other metallodrugs have realised great success in clinical chemotherapeutic applications as anticancer drugs. However, severe toxicity to healthy cells and non-selectivity to cancer cells remains a challenge, warranting the further search for alternative agents. Herein, we report the anticancer potential of a series of complexes of the general formula [MCl(p-cym)(k2-N^N-L)]+ X− and [MCl(Cp*)(k2-N^N-L)]+ X−, where M is the metal centre (Ru(II), Os(II), Rh(III) or Ir(III)), L = 1-benzyl-4-pyridinyl-1-H-1,2,3-triazole for L1 and 1-picolyl-4-pyridinyl-1-H-1,2,3-triazole for L2 and X− = Cl−, BF4−, BPh4−. When evaluated for activity against some cancerous and non-cancerous cell lines (namely, HeLa, HEK293, A549 and MT4 cancer cells and the normal healthy kidney cells (BHK21)), most of the compounds displayed poor cytotoxicities against cancer cells except for complexes C2 ([RuCl(p-cym)(k2-N^N-L1)]+ BPh4−, EC50 = 9−16 µM and SI = 14), C7 ([RuCl(p-cym)(k2-N^N-L2)]+ BPh4−, EC50 = 17−53 µM and SI = 4) and C11 ([IrCl(Cp*)(k2-N^N-L2)]+ BF4−, EC50 < 5 µM and SI > 10). Selected complexes C1 ([RuCl(p-cym)(k2-N^N-L1)]+ BF4−), C5 ([IrCl(Cp*)(k2-N^N-L1)]+ BF4−) and C11 showed significant interactions with model biomolecules such as guanosine-5'-monophosphate (5'-GMP), bovine serum albumin (BSA) and amino acids under physiological conditions, possibly through carbenylation and N-coordination with 5'-GMP, N-coordination with L-Histidine and L-proline. While the compounds showed good activities in reducing pyruvate to lactate, there was no direct correlation between catalytic transfer hydrogenation of pyruvate and the observed cytotoxic activities. As observed in this work, the marked influence of single atom replacement in ligand may provide a pivotal approach to improving the cytotoxicity and fine-tuning the selectivity to cancer cells.

Cost Effectiveness Analysis of Radiofrequency Ablation (RFA) Versus Stereotactic Body Radiotherapy (SBRT) for Early Stage Renal Cell Carcinoma (RCC).

OBJECTIVES: To conduct a cost-effectiveness analysis of stereotactic body radiotherapy (SBRT) versus radiofrequency ablation (RFA) in the non-surgical management of early stage renal cell carcinoma (RCC) according to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria in the Canadian healthcare system. METHODS: A Markov state transition model was constructed for initial local treatment with RFA or SBRT for early stage, kidney confined, medically inoperable RCC in a hypothetical cohort. Incremental cost effectiveness ratios (ICER) were then calculated to compare the two treatments. The analysis was conducted over 5-year time horizon from the perspective of a publicly funded health system in Canada. Secondary analyses were conducted to assess the effect of small versus large size (< 4 cm vs. > 4 cm) RCC on ICERs. Multiple one-way deterministic sensitivity analysis were conducted. Discounting of 1.5% per year was applied. RESULTS: Over 5 years, SBRT economically dominated RFA with a gain of 4.103 quality-adjusted life years (QALYs) and a cost of $16,097, compared with 3.607 QALYs at a cost of $18,324 for RFA. The ICER was $4490 CAD less per QALY for SBRT in the base case analysis (BCE). In patients with small tumors (T1a), SBRT compared with RFA was more effective and marginally more costly, resulting in an ICER of $2207 CAD per QALY gained, while for larger tumors (T1b), SBRT was less costly and more effective than RFA, resulting in an ICER of -$22904. Sensitivity analysis demonstrated significant variability in the cost-effectiveness of SBRT versus RFA when parameters were varied, with rates of distant metastasis following RFA or SBRT having the greatest implications on ICERs. CONCLUSION: Overall, SBRT used as a primary treatment for RCC shows promising effectiveness at an overall reduction in cost compared with RFA in the Canadian healthcare system. The use of SBRT appears to be cost-effective for larger tumors as well as smaller tumors. The validity of these conclusions are highly sensitive to the accuracy of local and distant progression rates reported in previous studies, and may be adjusted as the available data on SBRT and RFA continues to evolve and mature.