The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases.

Region Skane

Status: Enrolling

Conditions: Breast Cancer

Treatments: Radiation: De-escalation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05634889

2022-05093-02

Details and patient eligibility

About

T-REX is a randomized multicenter, non-inferiority trial.

Aim: To evaluate whether regional radiotherapy may safely be omitted in clinically node negative breast cancer patients with one or two sentinel node macrometastases and an estrogen receptor positive, HER2-negative tumor. Leading to an improved quality of life and reduced side effects, without worsening recurrence free survival at five years.

Intervention: Patients will be randomized to locoregional radiotherapy towards the breast/chestwall and regional lymph nodes vs. to a de-escalated radiotherapy.

In the intervention arm no lymph node irradiation will be given. Radiotherapy is still given to the remaining breast after breast conserving surgery, but no radiotherapy is given after mastectomy.

Sample size: 1350 patients

Primary end-point: Recurrence free survival at five years.

Gene expression analysis: For all patients gene expression analysis for the gene signatures ARTIC, POLAR and OncotypeDX will be performed and related to risk of recurrence and benefit of adjuvant radiotherapy.

Full description

In this multicenter, prospective randomized trial clinically node-negative breast cancer patients with 1-2 macrometastases in their sentinel lymph node biopsy, and an estrogen receptor positive, HER2-negative tumor, will be randomly assigned to either receive adjuvant locoregional radiotherapy, or no regional radiotherapy.

The main aim is to evaluate whether regional radiotherapy may safely be omitted in patients with limited lymph node metastasis and an estimated low risk of locoregional recurrence. Recurrence free survival after five years is the primary outcome, which for non-inferiority should not worsen more than 4.5 percentage units. Secondary outcomes are locoregional recurrence, regional nodal recurrence, new contralateral BC, distant recurrence free survival, overall survival, non-breast malignancies, cardiac disease, arm morbidity, and health-related quality of life.

Target volumes include:

Standard arm - The remaining breast/chest wall, axillary lymph node levels I-III, the supraclavicular lymph nodes (level IV), the interpectoral lymph nodes and in patients with a medial/central tumor also the internal mammary lymph nodes.

Intervention arm - The remaining breast after breast conserving surgery. No radiotherapy after mastectomy

Enrollment: 1,350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Primary unifocal or multifocal invasive breast cancer T1-T2.
2. Clinically N0.
3. Macrometastasis (>2mm) in 1-2 lymph nodes at sentinel node biopsy.
4. Oral and written consent.
5. Age ≥ 18 years.
6. All resection margins are tumor free (no tumor on ink).
7. Primary tumor ER-positive, HER2-negative.

Exclusion criteria

1. Regional or distant metastases outside the ipsilateral axilla.
2. Previous RT towards the planned target area, i.e. the ipsilateral chest/lymph nodes.
3. Neoadjuvant systemic therapy.
4. Axillary lymph node dissection or other previous axillary surgery on the affected side.
5. Prior history of invasive breast cancer.
6. Pregnancy.
7. Bilateral invasive breast cancer.
8. Contraindication for radiotherapy or systemic treatment.
9. Inability to absorb or understand the contents of the informed consent form; for example, through disability, inadequate language skills or dementia.
10. Other invasive cancer within 5 years prior to breast cancer diagnosis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,350 participants in 2 patient groups

Standard

No Intervention group

Description:

Radiotherapy to the remaining breast after breast conserving surgery or chest wall after mastectomy, and regional axillary lymph node levels I-IV. Internal mammary nodes are included in the target volume if the tumor has a central/medial localization in the breast.

Intervention

Experimental group

Description:

No regional radiotherapy. Radiotherapy is given to the remaining breast after breast conserving surgery. Chest wall radiotherapy after mastectomy only in case of wide spread multifocality.

Treatment:

Radiation: De-escalation