Abstract
Rectal cancer patients frequently receive pre-operative radiotherapy (RT), prior to surgical resection. However, colorectal cancer is heterogeneous and the degree of tumour response to pre-operative RT is highly variable. There are currently no clinically approved methods of predicting response to RT, and a significant proportion of patients will show no clinical benefit, despite enduring the side-effects. We evaluated the use of Raman spectroscopy (RS), a non-destructive technique able to provide the unique chemical fingerprint of tissues, as a potential tool to stratify patient response to pre-operative RT. Raman measurements were obtained from the formalin-fixed, paraffin-embedded (FFPE) pre-treatment biopsy specimens of 20 rectal cancer patients who received pre-operative RT. A principal component analysis and linear discriminant analysis algorithm was able to classify patient response to pre-operative RT as good or poor, with an accuracy of 86.04 ± 0.14% (standard error). Patients with a good response to RT showed greater contributions from protein-associated peaks, whereas patients who responded poorly showed greater lipid contributions. These results demonstrate that RS is able to reliably classify tumour response to pre-operative RT from FFPE biopsies and highlights its potential to guide personalised cancer patient treatment.
Highlights
Colorectal cancer (CRC) is common, it affects approximately 42000 people in the UK annually, and is the second most common cause of cancer related death.[1]
Treatment varies across the National Health Service (NHS), as current guidelines from the National Institute for Health and Care Excellence (NICE) state that in the UK, pre-operative short course RT (SCRT) or long course chemoradiotherapy (LCCRT) can be offered to rectal cancer patients with operable tumours and a predicted moderate or high risk of local recurrence.[2,3]
From the 20 cases analysed, those showing a poor response to pre-operative RT had a median percentage reduction in tumour cell density (TCD) of −2.5% (IQR −29.4–7.9%), and those that showed a good response had a median percentage reduction in TCD of 94.7% (IQR 90.6–97.9%)
Summary
Colorectal cancer (CRC) is common, it affects approximately 42000 people in the UK annually, and is the second most common cause of cancer related death.[1]. Treatment varies across the National Health Service (NHS), as current guidelines from the National Institute for Health and Care Excellence (NICE) state that in the UK, pre-operative SCRT or LCCRT can be offered to rectal cancer patients with operable tumours and a predicted moderate or high risk of local recurrence.[2,3] Pre-operative RT aims to reduce the risk of pre-operative RT has been shown to reduce the risk of local recurrence, it is associated with significant adverse effects, and can increase the risk of longterm morbidity following surgical resection.[4,5,6] Adverse effects from pre-operative RT vary depending on the individual patient and the treatments received, but they range from mild to severe and in some cases fatal.
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