Prospective Surveillance for Breast Cancer-Related Lymphedema (PROTECT)

Prospective Surveillance for Breast Cancer-Related Lymphedema: A Randomized Trial

This randomized trial will test the effect of a prospective surveillance program for early detection and subclinical management of breast cancer-related lymphedema on the prevalence of chronic lymphedema.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Prospective surveillance

Detailed Description

Design and setting: This trial is a multi-center single-blind trial involving five hospitals in Denmark.

Procedure: All women booked for surgery for breast cancer at one of the study sites will be invited to participate. Women, who provide written informed consent, will have BIS measurements, and perform self-measurements of arm circumference. Further, participants will complete a sociodemographic questionnaire which will be used to ensure recruitment of a representable sample. This data will be collected at the hospital of surgery at pre-treatment. After surgery, women who had >6 lymph nodes removed and have planned radiation therapy will be randomized 1:1 into intervention or control.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bolette S Rafn, PhD; Phone Number: +45 22913873; Email: bolette.skjoedt.rafn@regionh.dk
• Study Contact Backup: Name: Christoffer Johansen, Professor; Phone Number: +45 26169014; Email: christoffer.johansen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Copenhagen University Hospital Rigshospitalet
    • Contact: Bolette Rafn
  • Herlev, Denmark
    • Recruiting
    • Herlev Hospital
    • Contact: Bolette Rafn
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
    • Contact: Bolette Rafn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• female;
• ≥18 years;
• surgery for breast cancer (unilateral and bilateral) including ALDN with >6 lymph nodes removed;
• can effectively communicate verbally in Danish;

Exclusion Criteria:

• surgery for breast cancer with SLNB or < 6 nodes removed;
• pre-existing lymphedema (primary or secondary);
• previous treatment for breast cancer;
• pace maker;
• conditions known to cause swelling (pregnancy, congestive heart failure, chronic/acute renal disease, cor pulmonale, nephrotic syndrome, nephrosis, liver failure or cirrhosis, pulmonary edema, and thrombophlebitis or deep vein thrombosis in the arms).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (INT); INT participants will be asked to perform self-measurements of arm circumference at five points along the arm at home every three months. Additional measurements can be performed if the participants experience signs of BCRL. Participants will report the self-measurements in cm and mm in an online questionnaire, or over the phone to a physiotherapist navigator, along with reporting sign and symptoms of BCRL.	Other: Prospective surveillance; A participant with an increase from pre-surgery in total arm volume of ≥6% by self-measurement, or symptoms of BCRL ≥2 NRS will receive an assessment by a lymphedema therapist. At this appointment, participants will receive a physical examination of the arm along with a BIS measurement. A participant is considered having subclinical BCRL if an increase in lymphedema index (L-DEX) ≥7 from pre-surgery measured by BIS is identified. A fitted compression garment and gauntlet is then provided, free of charge, for daily wear 10 hours/day for four weeks along with a recommendation to use the arm for daily activities and maintain regular physical activity. Following the four-week compression period, participants will be re-measured using BIS to evaluate response. Participants who do not respond to compression will receive CDT delivered by the lymphedema therapist.
No Intervention: Control (CON); The CON group will follow the usual post-operative care. CON participants will be prompted every 6 months by an online questionnaire to report if they have been diagnosed with BCRL and if so, month of initiation of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of chronic lymphedema	A binary outcome (y/n) defined as BIS ≥10 from pre-surgery or outside normal range ±10	At 24 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-treatment	INT group: The time (weeks) from surgery to first elevated L-DEX score which triggers immediate treatment along with time (weeks) to resolution of BCRL from diagnosis. For CON: time from surgery to BCRL diagnosis, time from diagnosis to BCRL treatment, and time from initiation to termination of treatment	INT group: will be collected throughtout the study period. CON group: at 6, 12, 18 and 24 months post-surgery
Health-related quality of life	This will be measured by the EQ-5D questionnaire	pre-treatment, 6, 12, 18 and 24 months post-surgery
Arm function	This will be measured by the QuickDASH questionnaire	pre-treatment, 6, 12, 18 and 24 months post-surgery

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Odense University Hospital; Zealand University Hospital; Aarhus University Hospital; Herlev Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: lymphedema; Prospective surveillance
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Postoperative Complications; Breast Diseases; Breast Neoplasms; Lymphedema; Breast Cancer Lymphedema
• Other Study ID Numbers: PROTEcT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No