ObjectivesPalliative self-expandable metallic stent (SEMS) insertion is common in patients not suitable for resection of oesophago-gastric (OG) cancer. Factors which may determine survival however are not clear. The present study examined the relationship between tumour and host factors, including the systemic inflammatory response, and survival of patients undergoing palliative SEMS insertion. MethodsPatients with a diagnosis of OG cancer who were considered suitable for palliative SEMS only without systemic therapy were identified. Patient characteristics including Eastern Cooperative Oncology Group performance status, radiological stage and modified Glasgow were associated with shorter survival. The combination of performance status and mGPS stratified three-month survival of patients without metastatic disease from 88% to 20% (P<0.001) and patients with metastases from 43% to 6% (P=0.059). Similar results were 3 observed when analysis was restricted to patients with oesophageal and junctional cancer (M0: 83% to 20%, P=0.008; M1: 33% to 8%, P=0.082). ConclusionPerformance status, metastatic disease and mGPS are independent predictors of survival in patients with OG cancer undergoing palliative SEMS insertion. These routinely available markers provide a rational system on which to base decisions regarding prognosis and treatment.
596 Background: Aspirin use has been reported to reduce the pre-op systemic inflammatory response (SIR) in patients with colorectal cancer (CRC). Moreover, an exaggerated post-op SIR, evidenced by C-reactive protein (CRP) concentrations, is associated with poorer short and long term outcomes, highlighting the importance of CRP as a potential therapeutic target for improving outcomes following surgery for CRC. Drugs such as corticosteroids, aspirin and statins may modulate the post-op SIR, but there is little current evidence supporting this hypothesis. Therefore, the aim of the present study was to determine whether pre-op prescription of aspirin or statins modulated the post-op SIR in patients undergoing surgery for CRC. Methods: Included patients were obtained from a prospectively maintained database of CRC resections from a single institution (2010-2014). The relationship between pre-op aspirin and statin prescription and post-op CRP concentrations was examined. Results: 446 patients were included. The majority of patients were > 65 yrs (64%), male (57%) and underwent elective surgery (91%). 120 patients were prescribed aspirin and 187 prescribed statins with 100 patients prescribed both. Patients prescribed aspirin had a reduced post-op SIR particularly on day 3 (p = 0.009), 4 (p = 0.003) and 5 (p = 0.005). This effect was also observed following elective surgery (n = 402) on day 3 (p = 0.014), day 4 (p = 0.009) and day 5 (p = 0.019). Patients prescribed a statin also had a reduced post-op SIR, particularly on days 3 (p = 0.010), 4 (p = 0.006) and 5 (p = 0.017) and also following elective surgery on day 3 (p = 0.039) and day 4 (p = 0.039). The combination of aspirin and statin, compared with none or each on its own, resulted in the lowest post-op SIR, particularly on day 3 (p = 0.015), day 4 (p = 0.006) and day 5 (p = 0.023). Conclusions: Pre-op prescription of aspirin or statins resulted in a reduced post-op SIR following surgery for CRC. Therefore, pre-op use of these medications may be of benefit in improving outcomes, by reducing the post-op SIR – a reported predictor of both long and short term outcomes, following surgery for CRC.
689 Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation ( p =< 0.001) and high venous invasion ( p =0.003) but not with TNM stage (p= 0.310), perineural invasion ( p= 0.286), tumour budding ( p= 0.568), margin involvement ( p= 0.424), peritoneal involvement ( p= 0.689), tumour necrosis ( p= 0.423) or tumour cell proliferation ( p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3+ p= 0.103, CD8+ p= 0.620) or in the tumour (CD3+ p= 0.540, CD8+ p= 0.713) or with tumour stroma percentage ( p= 0.843). RS location was associated with high mGPS ( p =0.007) and neutrophil:platelet score ( p =0.001) but not NLR ( p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS ( p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.
579 Background: Colorectal cancer is the second commonest cause of cancer death in Europe and North America with rectal cancer making up a third of this disease burden. Markers of the systemic inflammatory response (SIR) have been shown to be prognostic in cancer. These include ratio of different white blood cells/acute phase proteins such as NLR (neutrophil/lymphocytes), PLR (platelets/lymphocytes), LMR (lymphocytes/monocytes) and CAR (CRP/albumin) and cumulative prognostic scores such as NPS (Neutrophil Platelet Score)/mGPS (modified Glasgow Prognostic Score). The aim of the present study was to compare the prognostic value of SIR markers in patients undergoing surgery for rectal cancer. Methods: A prospectively maintained database of all patients undergoing elective curative rectal resection in our institution was examined. The SIR was measured by the ratios and scores NLR, PLR, LMR, CAR, NPS and mGPS using standard thresholds NLR (>5), PLR (>150), LMR (<2.4), CAR (>0.24), NPS (0, 1, 2) and mGPS (0, 1, 2). Statistical analysis was carried out in SPSS using ROC curve and Cox regression analysis for both cancer specific survival (CSS) and overall survival (OS). Results: Of the 393 patients included in the study, 237 (60%) were male, 91 (25.6%) had neoadjuvant therapy, 341 (87%) had open surgery, 285 (72.5%) had T3/4 disease and 155 (39.4%) and node positive disease. On ROC curve analysis, validated ratios and scores such as NLR (AUC: 0.534 95%CI 0.469-0.600), PLR (AUC: 0.526 95%CI 0.444-0.607), LMR (AUC: 0.574 95%CI 0.472-0.676), CAR (AUC: 0.551 95%CI 0.487-0.615), NPS (AUC: 0.578 95%CI 0.513-0.643) and mGPS (AUC: 0.571 95%CI 0.513-0.629) showed considerable similarities. On multivariate categorical analysis with TNM stage there was a significant relationship between CSS and NPS (HR: 2.09 95%CI 1.14-3.82, p=0.017), CAR > 0.22 (HR: 1.64 95%CI 1.09-2.47, p=0.018) and mGPS (HR: 3.06 95%CI 1.71-5.47, p < 0.001). Conclusions: The SIR as measured by a number of scores/ratios had prognostic value in patients with rectal cancer. Only the NPS and mGPS had prognostic value independent of TNM stage. These scores may be useful in stratifying treatment in patients with rectal cancer.
213 Background: The tumour microenvironment is an important determinant of survival in patients with colon cancer. Although the generalised inflammatory infiltrate as assessed by Klintrup-Mäkinen (KM) grade is a stage-independent prognostic marker, immunohistochemical staining for specific immune cell populations, such as T-cells, may have greater prognostic value. The present study examines the clinical utility of combined assessment of KM grade in addition to cytotoxic (CD8) and regulatory (FoxP3) T-cells. Methods: KM, CD8 and FoxP3 were assessed retrospectively in a cohort of 520 patients with stage I-III colon cancers. The relationship between KM grade, T-cell density and cancer-specific survival was examined. Results: KM was high in 33% of patients, of which: 16% had high FoxP3, 12% high CD8 and 56% both FoxP3 and CD8, while the remaining 15% were high KM alone. Conversely, 67% had low KM and of these: 47% had high CD8 alone or with FoxP3; 27% were high for FoxP3 alone and 25% had no inflammatory infiltrate. KM in the presence of other T-cells resulted in good outcome (Table), whereas CD8 with low KM with or without FoxP3 resulted in intermediate outcome. FoxP3 alone with low KM resulted in poor outcome. Similarly, KM alone without T-cells resulted in poor outcome. When no inflammatory cells were present, outcomes were comparable to KM or FoxP3 alone. Conclusions: A co-ordinated immune response results in good outcome and this can be assessed using a combination of a simple H&E based method (KM) in addition to T-cell markers. Where KM is low, despite the presence of cytotoxic T-cells, survival outcome is worse. Conversely, high KM in the absence of T-cells, or FoxP3 alone, are associated with poor outcome, comparable to no inflammatory response. [Table: see text]
206 Background: The Glasgow Microenvironment Score (GMS), comprised of assessment of the tumour inflammatory cell infiltrate (using Klintrup-Mäkinen (KM) grade) and tumour-associated stroma (TSP), has been reported as a stage-independent prognostic score in patients with colorectal cancer. The present study aims to validate the GMS and examines its prognostic utility in the context of stage and MMR status. Methods: Patients who had undergone resection of stage I-III colon cancer were included ( n= 495). GMS was scored by combining KM and TSP as follows: high KM scores 0; low KM with low TSP scores 1; low KM and high TSP scores 2. Cancer specific (CSS) and overall survival (OS) were primary endpoints. Subgroup analysis was performed to assess the utility of GMS according to TNM, venous invasion and MMR status. Results: There were 30% of patients with GMS 0, 56% with GMS 1 and 14% with GMS 2. Five-year survival for GMS 0, 1 and 2 across the whole cohort were 89%, 74% and 66%, respectively. GMS was associated with age, mode of presentation, TNM, venous invasion and MMR status. On multivariate analysis, GMS was independently associated with CSS (HR 1.35, 95% CI: 1.02-1.79, p= 0.04) and OS (HR 1.23, 95% CI: 1.02-1.48, p= 0.03); this was independent of emergency presentation ( p< 0.01), T-stage ( p= 0.03) and N-stage ( p< 0.001) for CSS. Subgroup analysis found that GMS was able to stratify CSS regardless of node-negative or node-positive disease (both p< 0.01), venous invasion ( p< 0.05), elective presentation ( p< 0.01) and MMR-proficient tumours ( p< 0.001), although it was not able to stratify emergency presentation ( n= 154) or MMR-deficient disease ( n= 102) due to small sample size. Universally, the prognosis for GMS 0 was good, but was poor for GMS 2. The prognosis for GMS 1 varied depending on MMR and nodal status. Conclusions: This study validates the use of the GMS as an independent prognostic pathology-based tool for stratification of colon cancer. It could be readily applied to routine clinical practice and may be used to aid decision making regarding adjuvant treatments in colorectal cancer. It should be further validated in prospective randomised trials.
664 Background: The tumor microenvironment is increasingly recognized as an important determinant of disease progression and outcome in colorectal cancer (CRC). The aim of the present study was to examine the clinical utility of a novel histopathological prognostic score based on both the tumor inflammatory cell infiltrate and the tumor stroma percentage, termed the Glasgow Microenvironment Score (GMS), in patients with primary operable CRC. Methods: Using routine H&E pathological sections, Klintrup-Mäkinen (KM) grade was graded as strong or weak, and tumor stroma percentage (TSP) was assessed as high (>50%) or low (≤50%) retrospectively in 319 patients undergoing resection of stage II-III CRC. The relationship between a cumulative score based on these factors and cancer-specific survival (CSS) was examined. Results: Median survival of survivors was 122 months with 106 cancer deaths. 63% of patients had stage II CRC. 5-year CSS of patients with stage II and stage III CRC was 82% and 58% respectively (p<0.001). 33% of patients were GMS=0 (strong KM/high or low TSP), 47% were GMS=1 (weak KM/low TSP), and 20% GMS=2 (weak KM/high TSP), with 5-year CSS of 86%, 74%, and 48% (p<0.001) respectively. On multivariate analysis, GMS was associated with CSS (HR 1.77, p<0.001), independent of age, emergency presentation, TNM stage and venous invasion (all p<0.01), and peritoneal involvement (p<0.05). The combination of TNM and GMS stratified 5-year CSS from 92% (stage II, GMS=0) to 35% (stage III, GMS=2) (Table). Conclusions: The present study shows the clinical utility of a novel, routinely available assessment of the tumor microenvironment in patients undergoing curative resection of CRC. [Table: see text]
589 Background: There is increasing evidence that red blood cell distribution width (RDW) has prognostic value in cardiovascular and autoimmune disease. It may reflect, in part, the systemic inflammatory response (SIR), a recently recognised prognostic factor in cancer. However, no studies have examined this hypothesis and prognostic value in cancer. The aim was to examine the relationship between pre-op RDW, markers of the SIR and survival in patients undergoing curative surgery for colorectal cancer (CRC). Methods: Data from consecutive patients (n=408) from a single institution (March 2008 to May 2013) were studied. The relationship between RDW (>14.5%) and markers of the SIR (modified Glasgow Prognostic Score (mGPS) and neutrophil-lymphocyte ratio (NLR)) and survival (cancer specific, CSS and overall, OS) were analysed using Spearman’s rank correlation and Cox regression analysis respectively. Results: The majority of patients were male (54%), had node negative disease (65%) and did not receive adjuvant therapy (70%). RDW was correlated with mGPS (rs =0.228, p <0.001) but not NLR (rs=0.069, p = 0.331). Median follow up was 31 months with 48 cancer and 29 non-cancer deaths. On univariate survival analysis pre-op mGPS and RDW but not NLR were associated with CSS (mGPS, HR 1.66, CI 1.22-2.27, p = 0.001; RDW, HR 2.24, CI 1.25-4.03, p = 0.007; NLR, HR 1.21, CI 0.57-2.56, p = 0.621) and OS (mGPS, HR 1.50, CI 1.16-1.93, p = 0.002; RDW, HR 2.78, CI 1.73-4.48, p <0.001; NLR, HR 0.96, CI 0.52-1.75, p = 0.890). On multivariate analysis, including TNM stage and other tumour factors, RDW was independently associated with OS (HR 2.19, CI 1.34-3.58, p = 0.002). Conclusions: RDW was significantly associated with markers of the SIR and was, independent of tumour factors, associated with survival in patients with CRC. These results point to the importance of the SIR on red blood cell formation and on outcome.
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