T101 - Circulating Markers of Systemic Inflammation, Measured After Completion of Neoadjuvant Therapy, Independently Predict Response in Locally Advanced Rectal Cancer

Purpose/Background: The extent of neoadjuvant therapy (NAT) response, prior to surgery, is an important prognosticator in locally advanced rectal cancer (LARC). A spectrum of NAT response exists, with a dearth of reliable response predictors. The host response to treatment remains unexplored. Within operable colorectal cancer, circulating markers of elevated systemic inflammatory response (SIR) associate with poor survival. Studies have suggested that an elevated SIR pre-NAT, including C-reactive protein (CRP), The modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), and Carcino-embryonic antigen (CEA), are associated with poorer response to NAT. This study aimed to comprehensively evaluate haematological markers of SIR pre- and post-NAT.

Methods/Interventions: Consecutive LARC patients from a single cancer centre were included if they underwent curative-intent NAT between; June 2016 – July 2021. Pre-NAT blood tests were defined as the preceding sample taken closest to and within 60 days of starting NAT. Post-NAT blood tests were taken at a time point following completion of NAT, prior to surgery.

Results/Outcomes: 278 patients were included. 67.3% male, median age 65. 27.34% achieved “complete response” (sustained cCR or pCR). 37.05% achieved “good regression” (sustained cCR or Tumour regression grading (TRG) 0-1).
Elevated post-NAT mGPS (p=0.039), pre-NAT CEA (p < 0.001), and post-NAT CEA (p < 0.001) associated with incomplete response. Elevated post-NAT mGPS (p=0.027), pre-NAT CEA (p=0.036), and post-NAT CEA (p=0.005) associated with poor regression.
On logistic regression, CEA was the only pre-NAT marker that associated with incomplete response (p=0.032). No pre-NAT SIR marker associated with regression. Post-NAT mGPS (p=0.012) and CEA (p < 0.001) associated with incomplete response. Post-NAT mGPS (p=0.009) and CEA (p=0.006) associated with poor regression. Multivariate analysis of incomplete response, revealed ymrN+ (OR 3.8, 95%CI 1.46–9.88, p=0.006), elevated post-NAT mGPS (OR 2.8, 95%CI 1.22–6.41, p=0.015), and elevated post-NAT CEA (OR 4.09, 95%CI 1.6–10.44, p=0.003) as independent predictors of response. ymrEMVI+ (OR 5.1, 95%CI 1.88–13.84, p=0.001), ymrCRM+ (OR 2.03, 95%CI 1.11–3.72, p=0.022), and elevated mGPS (OR 2.14, 95%CI 1.08–4.23, p=0.029) were independent predictors of regression.

Conclusion/Discussion: Pre- and post-NAT CEA levels >5μg/L were significantly associated with incomplete response, with post-NAT CEA an independent predictor of incomplete response on multivariate analysis. We report the post treatment mGPS was associated with poorer treatment response, potentially indicating that radiation resistance is associated with development of a pro-tumour inflammatory environment. Further work is required to define the local intra-tumoural processes associated with response and their inter-relationship with systemic parameters. Ultimately, there may be a rationale for testing anti-inflammatory strategies in combination with radiotherapy as an option for optimising treatment response.