Neo-RT: um estudo que investiga se a mudança na sequência de tratamentos (iniciar radioterapia seguida de terapia hormonal antes da cirurgia) é viável (Neo-RT)

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.

Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03

Analysis will be descriptive, and in accordance to the statistical analysis plan.

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

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.

Clinician - post-radiotherapy questionnaire (with permission from IMPORT Trial Management Group and Dr Penny Hopwood)

Patient Reported Outcome Measure - Validated Breast-Q questionnaire

Patient Reported Outcome Measure - EORTC IL1 Modified BRECON23 PROM questionnaire.

Exploratory investigation of potential biomarkers include:

• ctDNA,
• PBMCs,
• Tumour molecular profiles,
• Immunohistochemical/immunofluorescence markers of:

Immune response (TILs) Tumour proliferation (Ki67, Geminin) DNA damage response and cell cycle checkpoint activation (including 53BP1, RAD51, ATM1, BRCA1, p53, p21 and p-chk-1) Tumour microenvironment (hypoxia)

- Multiplexed single cell proteomics of both cellular suspensions (including whole blood) and intact tissues, to investigate the immune response and other novel markers

Since the identification of new biomarkers correlating with disease activity and the efficacy or safety of treatment is rapidly evolving, the definitive list of biomarkers remains to be determined. However they will be detailed in an appropriate analysis plan prior to undertaking any sample analysis.