Elective pelvic nodal irradiation in the setting of ultrahypofractionated versus moderately hypofractionated and conventionally fractionated radiotherapy for prostate cancer: Outcomes from 3 prospective clinical trials.

Background and purpose: Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate. Materials and methods: Between 2011-2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35-40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0). Results: Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6-94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5-19.8 %) for CFRT, 6.5 % (0.8-12.2 %) MHRT, and 1.8 % (0-5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities. Conclusion: ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

Stereotactic Radiation Therapy for Localized Prostate Cancer: 10-Year Outcomes From Three Prospective Trials.

PURPOSE: SABR is growingly accepted for the treatment of localized prostate cancer with recent randomized trials showing noninferiority compared with conventional or moderately hypofractionated radiation therapy. The natural history of prostate cancer necessitates extended surveillance for recurrence; however, there are a few prospective studies reporting long-term outcomes. METHODS AND MATERIALS: This study included patients with low- and intermediate-risk localized prostate cancer from 3 Canadian clinical trials enrolled from 2006 to 2013. All patients received SABR to the prostate consisting of 35 to 40 Gy in 5 fractions over 11 to 29 days. Prostate specific antigen, distant metastasis, and vital status were prospectively recorded. The occurrence of a second malignancy after treatment was assessed by a chart review and classified using modified Cahan's criteria. RESULTS: Two hundred sixty-seven patients were included. Median follow-up was 10.3 years (interquartile range, 7.8-12.7). Ten-year biochemical failure (95% confidence interval) was 7.7% (3.9%-11.5%); 10-year overall survival, prostate cancer-specific survival, and freedom from metastasis were 84.1% (79.3%-89.1%), 99.2% (98.1%-100%), and 98.8% (97.5%-100%), respectively. Twenty-seven of 267 (10.1%) patients experienced a second malignancy (SM), with 6/27 patients (22.2%) classified as having a SM likely (n = 3) or possibly (n = 3) related to prior radiation therapy. Ten-year freedom from SM was 89.2%. CONCLUSIONS: SABR shows excellent long-term disease control for low- and intermediate-risk localized prostate cancer. Patients treated for prostate cancer have a moderate risk of SM, consistent with background rates for the population.

Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The aim of this study was to investigate the cardiovascular safety of romosozumab in postmenopausal women with osteoporosis. Romosozumab, a monoclonal antibody targeting sclerostin, has been shown to increase bone mineral density and reduce the risk of osteoporotic fractures. However, in previous studies, romosozumab therapy was identified as a potential risk factor for cardiovascular events, particularly in patients with predisposing cardiovascular disease. METHODS: A systematic literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science databases to identify randomized controlled trials (RCTs) comparing the safety and efficacy of romosozumab versus alendronate, teriparatide, denosumab, or placebo in postmenopausal women with osteoporosis. Contrast-based network meta-analysis was performed using a random-effects model. The pooled estimates are presented as risk ratios with 95% confidence intervals. RESULTS: Of the 5282 articles retrieved, 25 RCTs were included in this review (n = 24,942), and 18 randomized controlled trials (n = 16,777) were included in the network meta-analysis. The results indicated no significant differences in cardiovascular mortality rate between romosozumab and placebo. Regarding the risk of major cardiovascular events, no significant differences were found in the direct evidence or the network meta-analysis with placebo as the reference. CONCLUSION: Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with this treatment seem less significant than previously suggested, although additional real-world data are required to confirm this conclusion.

Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.

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.