Integrating Augmented Reality Tools in Breast Cancer Related Lymphedema Prognostication and Diagnosis

Summary

Breast cancer related lymphedema is frequent in breast cancer survivors, but there are not widely employed guidelines for its diagnosis and quantification. Here, we introduce a reliable and cost-effective protocol to define, quantify, and compare upper limb volume in breast cancer patients.

Abstract

Breast cancer related lymphedema (BCRL) is a detrimental condition characterized by fluid accumulation in the upper limb in breast cancer patients subjected to axillary surgery and/or radiations. Its etiology is multifactorial and include also tumor-specific pathological features, such as lymphovascular invasion (LVI) and extranodal extension (ENE). To date, no widely employed guidelines for the early diagnosis of BCRL are available. Here, we illustrate a protocol for a digitally assisted BCRL assessment using a 3D laser scanner (3DLS) and a tablet computer. It has been specifically optimized in a discovery cohort of high-risk breast cancer patients. This study provides a proof-of-principle that augmented reality tools, such as 3DLS, can be incorporated into the clinical workup of BCRL to allow for a precise, reproducible, reliable, and cheap diagnosis.

Introduction

Breast cancer related lymphedema (BCRL) is fluid retention in the upper extremity occurring after axillary surgery and/or radiation therapy in approximately 20-80% of breast cancer patients with lymph node metastases (N>1)^1,2,3. This condition results in swelling of the limb with subsequent reduced functionality, increased risk of comorbidities, frustration, anxiety, and depression^4,5. BCRL is currently considered a long-standing threat for breast cancer survivors given that it can arise up to 9 years after surgery⁶.

BCRL pathogenesis is a subject of lively debate among breast cancer specialists. Hence, several studies have shown that it could be related not only to axillary interventions but also to systemic treatments, such as taxanes-based chemotherapy and anti-HER2 therapy^7,8. Furthermore, there are recent lines of evidence to suggest that tumor-specific pathological characteristics are involved in its pathogenesis^1,6,7. For this reason, the invasion of lymphovascular spaces at the periphery of the tumor by neoplastic cells (lymphovascular invasion, LVI) and of the extension of the metastasis beyond the lymph node capsule (extra-nodal extension, ENE) have been proposed as a complementary analysis for BCRL risk stratification^6,7.

Despite the novel insights of BCRL biology, the arm volume measurement remains a cornerstone phase in the diagnosis and follow-up of these patients⁹. For this task, however, there are not widely-adopted guidelines. The measurement of multiple circumferences across the arm has been traditionally used to estimate its total volume using the truncated cone formula¹⁰. Despite its reliability, however, this circumferential method (CM) lack sensitivity and reproducibility, particularly in the case of arm shape irregularities¹¹. Lately, augmented reality methods, such as three-dimensional laser scanner (3DLS), have emerged as promising tools for the measurement of the upper limb volume¹². This technology is cheap, user-friendly, reproducible, and extremely precise also in the presence of gibbousness and swelling^12,13.

The aim of this study was to assess the reliability of 3DLS in comparison to the circumferential method for BCRL diagnosis and quantification. Here, a protocol is detailed for real-time measurements of the upper limb volume by means of 3DLS in breast cancer patients at increased risk for BCRL.

Protocol

This study was approved by the Institutional Review Boards from the Authors' Institutions. This protocol applies to node-positive (i.e., N>1 according to the TNM staging system)¹⁴ breast cancers showing LVI and/or ENE.

1. Real time arm measurements

1. Install the free downloadable application (e.g., Captevia) on a tablet computer.
2. Take a marker of the highest-contrast color compared to the skin of the patient (e.g., white, black).
   1. Mark the skin of the upper limb to be analyzed using point-landmarks at 5 cm starting from wrist to the elbow, and from elbow to proximal portion of the arm. Draw the circumferences on the skin of the upper limb to be analyzed at the level of each landmark.
3. Position the patient in an upright position in a room with sufficient space to move around her/him. Raise the patient's upper limb anteriorly by 90°. Ask the patient to remain still in this position for all the scan duration.
   NOTE: In case of difficulty of the patient to maintain this position, a support at hand level (e.g., a stick) can be used.
4. Hook and link the 3DLS device to the tablet.
5. Open the application from the tablet and enter the credentials of the subject to be examined within the patient database.
   1. Click Connection and then + to enter a new patient. Enter the patient's Name and Surname together with other preset anamnestic variables (such as date of birth, height, weight, etc.) and others as desired in the dedicated space.
6. Click the 3D icon. Select the area to be examined by modulating the distance and size of the cube that appears on the screen using 2 fingers on the touch screen
7. Click Scan and start the three-dimensional scan framing the upper limb of the patient on all the planes of the space. Rotate around the limb from all the views many times in order to optimize the quality of the acquired image.
   NOTE: A good acquisition takes on average time of 30 seconds. Do not stray more than one meter from the limb to be examined. Do not move the tablet too quickly.
8. Once the acquisition is completed, press Done. If needed, revise the form to assess any acquisition defects or missing part.
9. Select the acquisition and press the icon at the bottom right of the screen to send the file. Enter an email to send the file to and click Send.
10. Start the PC and download the data file sent by e-mail. Then insert the USB key with the software license, double click the software icon, confirm selected license type, and open the data file.
11. View the scan and press Create New Patient. Name the patient's file, select the destination to save the file, and press Save.
12. Select File in the upper left corner. Select the patient's file previously named.
13. Select the scan and press Extract to extract the scan. Select the extracted scan and press Cleaning.
14. Select the image. Clean the shape by orienting it in the space (x, y and z axis). Cut off any segments included in the scan on the various axes (x, y and z). It will also be possible to view any skin marks included in the scan to more precisely cut the scan. Validate the cut figure.
15. Name the shape obtained from the scan. Press Create a new shape.
16. Orient the shape axis on the 3 planes of the space and press End.
17. Select the processed form and press Open: the software will provide the total volume of the processed form.
18. Calculate the volume of different sections, press Volume. Move and select the upper and lower margin of the section from which to extract the volume.

Results

This was a pilot single-blind, randomized controlled study involving adult individuals. Inclusion criteria were the following: 1) young adults aged >18 and <45 years; 2) normal weight (body mass index, BMI, >18 and <25 kg/m²); 3) absence of any kind of skin lesion at upper limb level; 4) absence of trauma and/or any kind of condition able to modify arm structure and volume. The exclusion criteria: 1) cardiovascular comorbidities; 2) vascular diseases involving the u...

Discussion

The use of an accurate and reliable tool for limb volume measurement is mandatory in breast cancer survivors, given that an early diagnosis of BCRL is related to improved outcomes. In addition, the identification of high-risk individuals should consider not only clinical and surgical data but also tumor-specific pathological features. This study demonstrates the reproducibility and reliability of a new portable 3DLS device in upper limb volume measurement both in healthy subjects and in a BCRL women with high-risk featur...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Structure sensor + Captevia V3.1	Rodin4D, Rodin SAS		Three dimensional laser scanner