ESTRO 2024 - Abstract Book

S1562

Clinical - Lower GI

ESTRO 2024

278 patients were included. 67.3% patients were 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. Percentage change in SIR pre- to post-NAT did not associate with response for any SIR marker. 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, with SIR and imaging variables, 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:

We demonstrated an association between an elevated mGPS as well as elevated levels of CEA, measured at post NAT timepoints, and degree of response or regression.

The behaviour of the tumour in its local and peri-tumoural environment has influence over the systemic immune system and is highly complex. Elevated CRP in cancer patient blood samples likely represent an inflammatory pro tumour microenvironment and has been reported as an independent predictor of recurrence and poor prognosis in rectal cancer (11, 12). The mGPS combines scores of acute phase proteins CRP and albumin and has independent prognostic value in patients with cancer (6, 13). To our knowledge no study has analysed the significance of post-NAT CRP measurements or mGPS.

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.

NLR appears to be the most extensively studied SIR marker as a predictor of response in LARC, however in our study there was no statistical significance in NLR (9, 14, 15).

This study is unique as it analyses the prognostic ability of a variety of SIR markers at both pre- and post-NAT timepoints and analyses the significance of percentage changes in systemic inflammation that occur as a result. Our multivariate analysis model is a robust test of the mGPS as an independent predictor as it is tested against validated, prognostic, re-staging MRI features and not other SIR markers alone (16). The attraction of readily available biomarkers of response is that they can be used not only to predict but monitor response. We hypothesise that an elevated SIR is reflective of a pro-tumour inflammatory tumour microenvironment (TME) that has a degree of resistance to radiotherapy. The presence of an elevated SIR should be correlated to the presence of local inflammation within TME in future projects. Patients with elevated SIR post NAT may benefit from additional neoadjuvant therapies, such as anti-inflammatory and immunomodulating medication, prior to progressing to resection.

Keywords: Inflammation, rectal, response