Effects of Advanced Radiotherapy techniques on Normal Tissue Toxicity in Breast Cancer

Whole breast radiotherapy after breast conserving surgery is an effective adjuvant treatment, but is associated with some long-term side effects and breast tissue toxicities including breast shrinkage, breast fibrosis, skin changes and poor overall cosmesis. These breast-specific complications can have a detrimental psychological impact. New radiotherapy techniques including IMRT and IGRT have the potential to reduce late treatment related toxicities. The aim of this thesis was to investigate if the use of IGRT and IMRT can reduce the breast tissue related late complications after whole breast radiotherapy. The project evaluated if the use of clip-based IGRT technique allows the use of smaller safety margins around the tumour bed in breast radiotherapy. It also involved the development of normal tissue complication probability (NTCP) model for breast fibrosis to quantify the clinical benefits of IGRT. The benefits of IMRT were assessed using clinician-based assessment, serial photographs for overall cosmesis and patient-reported outcome measures (PROMs). The project also evaluated if the type of surgical technique used to close the tumour bed has an impact on late breast tissue toxicities. Using set-up errors data from IMPORT HIGH study, this work confirmed that the use of clip-based IGRT technique reduces tumour bed PTV margins as compared to standard portal imaging. The use of clip-based IGRT had a small but significant reduction on the heart dose, especially for left sided breast cancer patients. The NTCP model for breast fibrosis suggests that for moderate-severe fibrosis, the breast tissue behaves as a serial organ and the maximum radiotherapy dose is most predictive of the complication. These results were verified in the independent START trial dataset. This research project confirmed that patients receiving IMRT have superior overall cosmesis and reduced risk of skin telangiectasia as compared to patients receiving standard radiotherapy. However, the benefits of simple IMRT could not be demonstrated using PROMs. The project showed that breast seroma is associated with increased rates of post-operative infection and haematoma. It is also an independent risk factor for tumour bed induration and inferior breast cosmesis at 5 years. The future research in breast cancer radiotherapy would be directed at quantifying patient’s individual risks and benefits and offering risk adapted radiotherapy.

Name dc:type.qualificationname

Doctor of Medicine (MD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2018

Author dc:creator

• Mukesh, Mukesh Bindlish

Advisor dc:contributor.advisor

• Coles, Charlotte

• Breast cancer
• Radiotherapy
• IMRT
• IGRT
• Normal tissue toxicity
• Radiation therapy
• PROMs
• NTCP

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/ceb9089d-7502-4f83-b761-90c68023e57a/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.32473

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/285102