Developing a Raman spectroscopy-based tool to stratify patient response to pre-operative radiotherapy in rectal cancer

• Published in: Analyst (London) Vol. 146; no. 2; pp. 581 - 589
• Main Authors: Kirkby, Chloe J, Gala de Pablo, Julia, Tinkler-Hundal, Emma, Wood, Henry M, Evans, Stephen D, West, Nicholas P
• Format: Journal Article
• Language: English
• Published: England 21.01.2021
• Subjects: Aged; Biopsy; Female; Humans; Male; Middle Aged; Paraffin Embedding; Preoperative Period; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; Spectrum Analysis, Raman - methods; Tissue Fixation; Treatment Outcome
• ISSN: 0003-2654; 1364-5528
• DOI: 10.1039/d0an01803a

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. The use of Raman spectroscopy to stratify rectal cancer patient response to pre-operative radiotherapy, using routine pre-treatment biopsy samples.