Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

BACKGROUND: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown. METHODS: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation. Randomization was stratified according to pathological stage, centrally tested programmed death ligand 1 (PD-L1) status, and previous neoadjuvant chemotherapy. The coprimary end points were disease-free survival and overall survival in the intention-to-treat population. We considered the trial to be successful if either disease-free survival or overall survival was significantly longer with pembrolizumab than with observation. RESULTS: A total of 702 patients underwent randomization; 354 were assigned to receive pembrolizumab, and 348 were assigned to observation. As of July 5, 2024, the median duration of follow-up for disease-free survival was 44.8 months. The median disease-free survival was 29.6 months (95% confidence interval [CI], 20.0 to 40.7) with pembrolizumab and 14.2 months (95% CI, 11.0 to 20.2) with observation (hazard ratio for disease progression or death, 0.73; 95% CI, 0.59 to 0.90; two-sided P = 0.003). Grade 3 or higher adverse events (regardless of attribution) occurred in 50.7% of the patients in the pembrolizumab group and in 31.6% of the patients in the observation group. CONCLUSIONS: Among patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, disease-free survival was significantly longer with adjuvant pembrolizumab than with observation. (Funded by the National Cancer Institute of the National Institutes of Health and others; Alliance A031501 AMBASSADOR ClinicalTrials.gov number, NCT03244384.).

A Phase II prospective study of hypofractionated proton therapy of prostate and pelvic lymph nodes: Acute effects on patient-reported quality of life.

BACKGROUND: The objective of this study was to report acute changes in patient-reported quality of life (PRQOL) using the 26-item Expanded Prostate Index Composite (EPIC-26) questionnaire in a prospective study using hypofractionated intensity-modulated proton beam therapy (H-IMPT) targeting the prostate and the pelvic lymph nodes for high-risk or unfavorable intermediate-risk prostate cancer. METHODS: Fifty-five patients were enrolled. H-IMPT consisted of 45 GyE to the pelvic lymph nodes and 67.5 GyE to the prostate and seminal vesicles in 25 fractions. PRQOL was assessed with the urinary incontinence (UI), urinary irritative/obstructive symptoms (UO), and bowel function (BF) domains of EPIC-26 questionnaire. Mean changes in domain scores were analyzed from pretreatment to the end of treatment and 3 months posttreatment. A clinically meaningful change (or minimum important change) was defined as a score change > 50% of the baseline standard deviation. RESULTS: The mean scores of UO, UI, and BF at baseline were 84.6, 91.1, and 95.3, respectively. At the end of treatment, there were statistically significant and clinically meaningful declines in UO and BF scores (-13.5 and -2.3, respectively), while the decline in UI score was statistically significant but not clinically meaningful (-13.7). A clinically meaningful decline in UO, UI, and BF scores occurred in 53.5%, 22.7%, and 73.2% of the patients, respectively. At 3 months posttreatment, all three mean scores showed an improvement, with fewer patients having a clinically meaningful decline in UO, UI, and BF scores (18.4%, 20.5%, and 45.0%, respectively). There was no significant reduction in the mean UO and UI scores compared to baseline, although the mean BF score remained lower than baseline and the difference was clinically meaningful. CONCLUSIONS: UO, UI, and BF scores of PRQOL declined at the end of H-IMPT. UO and UI scores showed improvement at 3 months posttreatment and were similar to the baseline scores. However, BF score remained lower at 3 months posttreatment with a clinically meaningful decline.

Neck strength and force in reaction time task of adolescent athletes with and without concussion history: A pilot study.

OBJECTIVES: Assess the impact of concussion by comparing reaction time, peak force recruitment, and rate of force development of adolescent athletes returning from concussion against age- and sex-matched controls in visual-elicited neck movement. DESIGN: Athletes sat secured in a custom-built isometric device with their heads secured in a helmet and attached to a 6-axis load cell. They performed neck flexion, extension, and lateral flexion in response to a visual cue. Three trials in each direction were used for statistical analyses; peak force and rate of force development were normalized against athlete mass. SETTING: Laboratory. PARTICIPANTS: 26 adolescent/young adult athletes (8F/18M), either recently concussed (and cleared for return to sport) or an age- and sex-matched healthy control. MAIN OUTCOME MEASURES: Reaction time, angle, standard deviation of angle, deviation from target angle, peak force, and RFD over 50, 100, 150,and 200 ms of movement were measured for each trial. RESULTS: Concussed athletes had decreased normalized peak force (P = 0.008) and rate of force development (P < 0.001-0.007). In neck extension, concussed athletes also had decreased movement precision (P = 0.012). CONCLUSIONS: Concussion is associated with alterations of neck biomechanics that decrease overall neck strength.

Surgical treatment of snapping proximal hamstring tendon syndrome: the resolution of snapping and excellent patient satisfaction.

Snapping proximal hamstring is an uncommon phenomenon, with few case reports documenting surgical treatment. The purpose of this study is to report snapping resolution, minimum 2-year post-operative patient-reported outcome (PRO), satisfaction scores and complications from patients who underwent surgical release of the conjoint tendon from the sacrotuberous ligament with reattachment to the ischial tuberosity. Prospectively collected data from two institutional databases were retrospectively reviewed for patients who underwent hamstring repair for partial- or full-thickness tears. Patients were included if they demonstrated 'snapping proximal hamstrings' on preoperative physical examination, including ultrasound confirmation, and repair subsequently performed. Patients were excluded if they had reconstruction of the proximal hamstring tendon or claimed worker's compensation. With a total of 20 patients (15 females and 5 males), successful resolution of snapping was reported in 100% of the cohort. For patients with pre- and post-surgical lower-extremity functional scores (LEFS), post-surgical LEFS were significantly higher than pre-surgical LEFS (pre-surgical: 17.0 ± 4.0, post-surgical: 73.6 ± 3.3, P < 0.001). Average post-operative PROs were as follows: International Hip Outcome Tool-12, 92.3 ± 8.3; modified Harris Hip Score, 93.2 ± 7.8; Non-arthritic Hip Score, 92.5 ± 6.8; Hip Outcome Score-Sports Specific Subscale, 94.4 ± 6.7; LEFS, 73.9 ± 3.4; and median visual analog scale of 0 with an interquartile range of 0-1. Patient satisfaction was 'very satisfied' in 19 (95%) patients and 'satisfied' in 1 (5%) patient. At a minimum 2-year follow-up, patients who underwent surgical treatment for chronic snapping of the proximal hamstrings demonstrated complete resolution of painful posterior snapping, reported high PROs and satisfaction, and had no reported post-operative complications.

Late Toxicity of Moderately Hypofractionated Intensity-Modulated Proton Therapy Treating the Prostate and Pelvic Lymph Nodes for High-Risk Prostate Cancer.

PURPOSE: To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes. METHODS AND MATERIALS: A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: NCT02874014) of moderately hypofractionated IMPT. IMPT with pencil beam scanning was used to deliver 6750 and 4500 cGy relative biological effectiveness in 25 daily fractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using Common Terminology Criteria for Adverse Events version 4.0, at baseline, weekly during radiation therapy, 3-month postradiation therapy, and then every 6 months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method. RESULTS: Median age was 75.5 years. Fifty-four patients were available for late toxicity evaluation. Median follow-up was 43.9 months (range, 16-66). The actuarial rate of late grade ≥2 GI toxicity at both 2 and 3 years was 7.4% (95% confidence interval [CI], 0.2%-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI, 0%-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥2 GU toxicity was 20.5% (95% CI, 8.9%-30.6%) at 2 years, and 29.2 % (95% CI, 15.5%-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity. CONCLUSIONS: A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase 3 study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiation therapy.