Neo-RT: A Study Investigating Whether Changing the Sequence of Treatments (Starting Radiotherapy Followed by Hormone Therapy Before Surgery) is Feasible

Study Overview
=================
Brief Summary
-----------------
Four in 10 women diagnosed with breast cancer undergo mastectomy with or without breast reconstruction and less than half are satisfied with how they look unclothed. Breast conservation (removing the area with the lump only) can offer less extensive surgery and improved breast appearance, which can therefore increase well-being. Intensity-modulated radiotherapy (IMRT) closely shapes the radiation beam to the cancer and is currently given after breast surgery. A new combination of IMRT followed by hormone treatment given before surgery, may increase the possibility of breast conservation.

Official Title
-----------------
Neo-RT: Pre-operative Breast Intensity Modulated Radiotherapy in Patients Receiving Neo-adjuvant Hormonal Treatment for Breast Cancer - a Feasibility Study.

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Radiation: Intensity modulated radiotherapy (IMRT)
* Drug: Endocrine therapy
* Procedure: Breast conserving surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent to participate Female Aged 18 years and older ECOG performance status 0-2 Histology confirmed invasive breast cancer ER positive (Allred score 6-8) HER2 negative Palpable size ≥20mm Grade I-II (or grade III if considered not suitable for neo-adjuvant chemotherapy) Considered that radiotherapy will make breast conserving surgery easier No evidence of non-breast malignancy if treated with curative intent unless the patient has been disease free ≥5 years Unifocal or multifocal disease, i.e. tumour in the same quadrant and breast conserving surgery still feasible Exclusion Criteria: Contraindications to breast radiotherapy or neo-adjuvant endocrine therapy Bilateral breast cancer Metastatic cancer Multicentric disease Concomitant medical/psychiatric problems preventing completion of study treatment or follow-up Pregnancy Breast feeding

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

Sexes Eligible for Study
-----------------
Female

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

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

Arms and Interventions

| Intervention/Treatment |
| --- |
|Radiation: Intensity modulated radiotherapy (IMRT)|Simultaneous integrated boost technique using IMRT: 48 Gray (Gy) and 40 Gy will treat tumour and breast tissue respectively, in 15 fractions over 3 weeks.|
|Drug: Endocrine therapy|Endocrine therapy will commence following completion of radiotherapy, and will continue for 20 weeks.|
|Procedure: Breast conserving surgery|Surgery carried out using local protocol following completion of endocrine therapy.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients successfully completing neo-adjuvant IMRT and endocrine treatment followed by beast surgery, as per study protocol. | Successful completion of IMRT is defined as: Treatment received was either 48 Gy/15# or 40 Gy/15# with sequential boost Treatment received was 'other', but the reason for different schedule was not due to toxicity related from the radiotherapy Radiotherapy treatment was not delayed by 5 days or more Radiotherapy treatment was delayed by 5 days or more, but the reason was not due to toxicity related from the radiotherapy Successful completion of endocrine treatment is defined as: Patient received at least 80% of endocrine treatment received Patient did not receive 80% of endocrine treatment, but the reason was not due to toxicity or toxicity related from radiotherapy or endocrine Successful surgery is defined as: Planned date of surgery is not delayed Planned date of surgery is delayed, but the reason was not due to toxicity or toxicity related to radiotherapy or endocrine treatment. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03 | Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03 | 3 weeks | 
| Mastectomy rate | Analysis will be descriptive, and in accordance to the statistical analysis plan. | 6 months | 
| Peri/post operative complications | Including: Length of stay Unplanned return to theatre (and reason) Use of antibiotics for wound related issues Number of clinic attendances for wound related problems | 9 months | 
| Volume of residual tumour and response to treatment | There will be a central review (2 readers) of all primary surgery histopathology reports for the secondary endpoint of pathological complete response (pCR). The histopathology slides from the surgical resection will be requested for central assessment of residual disease for all cases where there has not been a pCR. The variables that will be recorded include residual invasive tumour size in two dimensions, residual invasive tumour cellularity, number of lymph node metastases and size of the largest metastasis. A representative tumour tissue block will be selected and requested from the laboratory. Sections from the block will be taken for staining with ER and Ki67 to allow calculation of the histological assessment of residual tumour burden, and cores taken as per the protocol. | 6 months | 
| Late normal tissue toxicity, as assessed by: 1) clinicians | Clinician - post-radiotherapy questionnaire (with permission from IMPORT Trial Management Group and Dr Penny Hopwood) | Annually for 5 years | 
| Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs) | Patient Reported Outcome Measure - Validated Breast-Q questionnaire | Annually for 5 years | 
| Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs) | Patient Reported Outcome Measure - EORTC IL1 Modified BRECON23 PROM questionnaire. | Annually for 5 years |