Prognostic Indicators for Radiation-induced Breast Fibrosis

Identifying Prognostic Indicators for the Development of Radiation-induced Breast Fibrosis

To study the inflammatory response during and after radiotherapy, especially by measuring the concentration of an enzyme called autotaxin and its product LPA in the blood plasma.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Breast Cancer Radiotherapy

Detailed Description

To study the inflammatory response during and after radiotherapy, especially by measuring the concentration of an enzyme called autotaxin and its product LPA in the blood plasma. Autotaxin and LPA cause fibrosis in other situation, but they have not been tested in radiation-induced fibrosis. We will determine if the duration and magnitude of the autotaxin and LPA responses are prognostic for the 15-28% of patients who will develop fibrosis. This fibrosis will be detected by ultrasound and a novel application of elastography, which should provide much earlier and quantifiable fibrotic changes compared to conventional physical examination.

• Study Type: Observational
• Enrollment (Estimated): 27

Contacts and Locations

• Study Contact: Name: Zsolt Gabos, MD; Phone Number: 780-432-8783; Email: Zsolt.Gabos@ahs.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

We will study a low risk group of 27 post-menopausal patients with luminal A breast cancer after they have received breast conserving surgery (lumpectomy). Women who have smoked or received chemotherapy will be excluded to minimize variables.

Description

Inclusion Criteria:

1. Female participants capable of giving informed consent, or if appropriate, participants having an acceptable individual capable of giving consent on the participant's behalf
2. Post-menopausal.
3. Treatment with breast conserving surgery.
4. Intended adjuvant whole breast radiotherapy dose to a dose of 40-42.5 Gy in 15-16 fractions.
5. Luminal A subtype as determined by clinipathologic factors (ER/PR positive, Her-2 negative, low Ki-67 or low OncotypeDx recurrence score

Exclusion Criteria:

1. Women who have smoked within the last 5 years
2. Patients requiring adjuvant chemotherapy.
3. Requirement for regional nodal radiotherapy.
4. Requirement for tumour bed boost.
5. Breast implants
6. Patients to be treated with partial breast irradiation.
7. Uncontrolled intercurrent illness or active infection.
8. Patients who have previously received chemotherapy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women undergoing radiation treatment after lumpectomy for breast cancer.; There is no specific study intervention being used. Samples will be collected from participants undergoing standard of care radiotherapy at pre-specified timepoints.	Radiation: Breast Cancer Radiotherapy; 4000-4250 cGy in 15-16 daily fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the ATX-LPA (ATX) inflammatory response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis.	Measurement of longitudinal changes in plasma ATX in the irradiated breast.	Samples will be collected four times during RT treatment (3-4 weeks) and once every 3 months for an year.
Measurement of the ATX-LPA-inflammatory (LPA) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis.	Measurement of longitudinal changes in plasma LPA in the irradiated breast.	Samples will be collected four times during RT treatment (3-4 weeks) and once every 3 months for an year.
Measurement of the ATX-LPA-inflammatory (cytokines) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis.	Measurement of longitudinal changes in plasma cytokines in the irradiated breast.	Samples will be collected four times during RT treatment (3-4 weeks) and once every 3 months for an year.
Measurement of the ATX-LPA-inflammatory (chemokines) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis.	Measurement of longitudinal changes in plasma chemokines in the irradiated breast.	Samples will be collected four times during RT treatment (3-4 weeks) and once every 3 months for an year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Radiotherapy Toxicity	Radiotherapy associated toxicities will be assessed per CTCAE v5.0 by the study investigators.	Throughout the duration of the study, a total of 4 years .
Structural changes in the irradiated breast and the non-irradiated breast	The ultrasound procedure will provide a 3D analysis of the breast structure as well as a measurement of breast elasticity. Fibrotic changes in the breast will be measured by combining the 3D analysis and breast elasticity indices (median (kPa), IQR (kPA) and IQR/median (%))	3, 6, 12, 24 and 48 months after RT

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Investigators: Principal Investigator: Zsolt Gabos, MD, AHS-CCI

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: IIT-0026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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