The Safety Management of Cardiac Toxicity in Breast Cancer Patients Under Multidiscipline Therapy.

Study Overview
=================
Brief Summary
-----------------
This trial is to explore the optimal strategies for guaranteeing the cardiac safety of breast cancer patients following adjuvant radiotherapy in the modern era of multidisciplinary treatment.

Detailed Description
-----------------
With the development of modern radiotherapy techniques, the dose-volume of heart irradiated could be kept in much low level. However, until now, the optimal dose-volume parameters for limiting heart irradiation, the optimal follow-up interval for cardiac safety after adjuvant radiotherapy, the optimal screening examinations and treatments for irradiation-induced cardiac toxicity are unclear. We designed this trial to find answer for above questions to establish rationalization proposal for prevention, treatment and follow-up for cardiac toxicity associated with adjuvant radiotherapy for breast cancer.

Official Title
-----------------
A Randomized Multi-center Phase III Study About the Safety Management of Cardiac Toxicity in Breast Cancer Patients Under Multidiscipline Therapy.

Conditions
-----------------
Breast Neoplasms, Cardiotoxicity

Intervention / Treatment
-----------------
* Other: limit heart dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients willing to participate the research and sign the informed consent file; Patients aged 18-80 years; KPS≥70; Pathological diagnosis for invasive breast cancer; Patients received anthracycline/paclitaxel based chemotherapy, or herceptin based targeted therapy; No functional heart disease; LVEF≥50%; Patients received breast conserving surgery; Patients received modified radical mastectomy: T1-2 with N1-3 or T3-4 with any N; Tumor margin negative; No metastases; No other malignant tumor history. Exclusion Criteria: Patients with metastases; Tumor margin positive; Patients received modified radical mastectomy with T1-2 and N0; Patients have other malignant tumor; Patients have a history of heart disease; Patients received chest radiotherapy previously; Patients with severe organic and functional disease; Unqualified patients with sufficient reasons; Cannot or no willing to sign the informed consent file; Patients with autoimmune disease; Women with pregnancy, planned pregnancy or lactating.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart safety management<br>limit heart dose more frequent follow up of cardiac function professional management of cardiac toxicity | Other: limit heart dose<br>* limit heart dose: Dmean≤6Gy,V30≤20%,V10≤50%<br>* Other names: management of cardiotoxicity;|
| No Intervention: Control group<br>without any restrict heart dose limitation for RT Follow up of cardiac function Observation and without any special management of cardiac toxicity | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac toxicity event free survival | The time from the date of randomization to any recurrence of clinical or subclinical cardiac toxicity | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac toxicity event free survival | The time from the date of randomization to any recurrence of clinical or subclinical cardiac toxicity | 5 years | 
| cardiac toxicity event free survival | The time from the date of randomization to any recurrence of clinical or subclinical cardiac toxicity | 10 years | 
| overall survival | The time from the date of randomization to the date of death from any cause | 5 years | 
| overall survival | The time from the date of randomization to the date of death from any cause | 10 years | 
| relative change of value of serum cardiac biomarkers of creatine kinase (CK)-MB | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 1 year | 
| relative change of value of serum cardiac biomarkers of Cardiac troponin (cTn)-I | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 1 year | 
| relative change of value of serum cardiac biomarkers of N-terminal pro brain natriuretic peptide (NT-proBNP) | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 1 year | 
| relative change of value of serum cardiac biomarkers of CK-MB | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 5 years | 
| relative change of value of serum cardiac biomarkers of cTn-I | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 5 years | 
| relative change of value of serum cardiac biomarkers of NT-proBNP | The change of value of serum cardiac biomarkers during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 5 years | 
| relative change of left ventricular ejection fraction (LVEF) | The change of value of LVEF during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 1 year | 
| relative change of LVEF | The change of value of LVEF during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapyThe change of value of LVEF during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 5 year | 
| relative change of LVEF | The change of value of LVEF during and after adjuvant radiotherapy compared with baseline before initiation of adjuvant radiotherapy | 10 year | 
| Quality of Life-EORTC QLQ-C30 | Quality of life will be assessed using self-administered questionnaire EORTC QLQ-C30 | 1 year | 
| Quality of Life-EORTC QLQ-BR23 | Quality of life will be assessed using self-administered questionnaire EORTC QLQ-BR23 | 1 year | 
| Quality of Life-EORTC QLQ-C30 | Quality of life will be assessed using self-administered questionnaire EORTC QLQ-C30 | 5 years | 
| Quality of Life-EORTC QLQ-BR23 | Quality of life will be assessed using self-administered questionnaire EORTC QLQ-BR23 | 5 years |