Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.

Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy.

PURPOSE: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS AND MATERIALS: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy). RESULTS: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported. CONCLUSIONS: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended.

Identification of deliberate catheter motion at the left atrial posterior wall during pulmonary vein isolation: Validity of respiratory motion adjustment.

BACKGROUND: During automated radiofrequency (RF) annotation-guided pulmonary vein isolation (PVI), respiratory motion adjustment (RMA) is recommended, yet lacks in vivo validation. METHODS: Following contact force (CF) PVI (continuous RF, 30 W) using general anesthesia and automated RF annotation-guidance (VISITAG™: force-over-time 100% minimum 1 g; 2 mm position stability; ACCURESP™ RMA "off") in 25 patients, we retrospectively examined RMA settings "on" versus "off" at the left atrial posterior wall (LAPW). RESULTS: Respiratory motion detection occurred in eight, permitting offline retrospective comparison of RMA settings. Significant differences in LAPW RF auto-annotation occurred according to RMA setting, with curves displaying catheter position, CF and impedance data indicating "best-fit" for catheter motion detection using RMA "off." Comparing RMA "on" versus "off," respectively: total annotated sites, 82 versus 98; median RF duration per-site, 13.3 versus 10.6 s (p < 0.0001); median force time integral 177 versus 130 gs (p = 0.0002); mean inter-tag distance (ITD), 6.0 versus 4.8 mm (p = 0.002). Considering LAPW annotated site 1-to-2 transitions resulting from deliberate catheter movement, 3 concurrent with inadvertent 0 g CF demonstrated < 0.6 s difference in RF duration. However, 13 deliberate catheter movements during constant tissue contact (ITD range: 2.1-7.0 mm) demonstrated (mean) site-1 RF duration difference 3.7 s (range: -1.3 to 11.3 s): considering multiple measures of catheter position instability, the appropriate indication of deliberate catheter motion occurred with RMA "off" in all. CONCLUSIONS: ACCURESP™ respiratory motion adjustment importantly delayed the identification of deliberate and clinically relevant catheter motion during LAPW RF delivery, rendering auto-annotated RF display invalid. Operators seeking greater accuracy during auto-annotated RF delivery should avoid RMA use.