Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION: ClinicaTrials.gov Identifier: NCT03873272.

A Brief Screening Tool for Assessment of Financial Toxicity.

OBJECTIVES: To explore the utility of brief financial screening items to facilitate the implementation of routine financial toxicity screening. SAMPLE & SETTING: 50 women with breast cancer completed a one-time survey that included the Comprehensive Score for Financial Toxicity (COST): A FACIT Measure of Financial Toxicity, a visual analog scale, and a brief sociodemographic questionnaire. METHODS & VARIABLES: Survey responses were examined to assess the psychometric properties of individual COST items and the visual analog scale by calculating Cronbach's alpha and Pearson's correlation coefficients. RESULTS: The mean COST was 21.4, and 27 respondents met criteria for financial toxicity (a COST lower than 22). As expected, all items correlated strongly to the overall COST, but four items (items 3, 6, 8, and 10) performed strongest (r > 0.8). IMPLICATIONS FOR NURSING: This study provides evidence for individual COST items to be used as brief screening items. Future research should test the utility of these items in larger sample sizes with a more diverse representation of patients by age, race, ethnicity, and tumor type and stage.

The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease.

Intestinal lacteals are essential lymphatic channels for absorption and transport of dietary lipids and drive the pathogenesis of debilitating metabolic diseases. However, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover an intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer ASE alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic system-dependent lipid transport. Surprisingly, activation of lymphatic system-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. Our study reveals the molecular mechanism linking gut lymphatic function to the earliest symmetry-breaking Pitx2 and highlights the important relationship between intestinal lymphangiogenesis and the gut-liver axis.