The prognostic impact of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 47-47
Author(s):  
Jonna Berntsson ◽  
Maria Christina Svensson ◽  
Karin Leandersson ◽  
Bjorn Nodin ◽  
Agnieszka Krzyzanowska ◽  
...  

47 Background: Several studies report dense infiltration of tumour-infiltrating T cells and natural killer cells to be associated with an improved prognosis in colorectal cancer (CRC); but whether these associations differ by tumour location remain unknown. This study investigated the prognostic impact of immune cell infiltration in CRC, with particular reference to the anatomical subsite of the primary tumour. Methods: Immunohistochemical expression of CD3, CD8, FoxP3, and CD56 was analysed in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: In the entire cohort, dense infiltration of all the investigated immune cells correlated significantly with an improved 5-year OS in both univariable and multivariable analysis, adjusted for age, TNM stage, differentiation grade, and vascular invasion. Dense infiltration of CD3+ and CD8+ cells were independent favourable prognostic factors for tumours in the right colon (hazard ratio [HR] = 0.53, 95 % confidence interval [CI] 0.29-0.95 and HR = 0.35, 95% CI 0.19-0.65, respectively), but not in the left colon or rectum. When microsatellite instability status was included in the adjusted model, only CD8+ cells remained an independent favourable prognostic factor in right-sided tumours. Dense infiltration of FoxP3+ cells was an independent favourable prognostic factor for tumours in the rectum (HR = 0.54, 95% CI 0.30-0.99), but not in the right or left colon. Infiltration of CD56+ cells did not carry any independent prognostic impact after stratifying for primary tumour site. Conclusions: The results from this study demonstrate that the prognostic impact of certain T cell subsets in CRC differs by primary tumour site, being most evident in right-sided tumours. These findings indicate that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3528-3528 ◽  
Author(s):  
Stephanie Yasmin Brule ◽  
Derek J. Jonker ◽  
Christos Stelios Karapetis ◽  
Christopher J. O'Callaghan ◽  
Malcolm J. Moore ◽  
...  

3528 Background: RC and LC differ with respect to biology, pathology, and epidemiology. Further, recent SEER data suggests a mortality difference between RC and LC that varies by stage: stage II and III RC having lower and higher mortality, respectively. We examined if the primary tumour site can also predict for outcome in pre-treated, chemotherapy refractory, metastatic colon cancer (MCC). We compared RC vs. LC as a predictor for efficacy of EGFR inhibition with CET. Methods: Using CO.17 (CET vs. BSC), we coded the primary tumour site for 399 pts as RC (cecum to transverse colon) or LC (splenic flexure to rectosigmoid). Fisher’s exact test assessed the association between site of cancer and baseline characteristics. Univariate and multivariate analyses of overall survival (OS) and progression free survival (PFS) by site of cancer were performed using Cox regression models. Results: Pts with RC (150/399) had more poorly differentiated tumours, mutant KRAS status, and peritoneal rather than liver and lung metastases, and they more often entered the study less than two years after initial diagnosis. Among pts receiving BSC, tumour location (RC vs. LC) was not prognostic for PFS (HR 1.07 [0.79, 1.44], p=0.67) or OS (HR 0.96 [0.70, 1.31], p=0.78). Among pts with KRAS wild type tumour status, site of cancer was a predictor of benefit from CET, with much greater PFS observed for LC (interaction p=0.002). Conclusions: In refractory MCC, tumour location within the colon (RC vs. LC) is not a prognostic factor, but is a strong predictor of PFS benefit from CET therapy. Additional research is needed to understand the molecular differences between RC and LC and their interaction with EGFR inhibition. [Table: see text]


Author(s):  
Matthew Devall ◽  
Xiangqing Sun ◽  
Fangcheng Yuan ◽  
Gregory S Cooper ◽  
Joseph Willis ◽  
...  

Abstract There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared to individual-matched left colon (1.51 years; 95% CI = 0.62 to 2.40 years; two-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; two-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.


2021 ◽  
pp. bmjspcare-2021-003321
Author(s):  
Livia Costa De Oliveira ◽  
Emanuelly Varea Maria Wiegert ◽  
Lara Azevedo dos Santos ◽  
Larissa Calixto-Lima

ObjectivesWe aimed (1) to assess the nutritional status (NS) using different methods, according to the primary tumour site and (2) to evaluate the performance of these methods in patients with incurable cancer from a reference centre in Brazil.MethodsCross-sectional analysis of data from patients admitted to the palliative care unit of a reference cancer centre in Brazil, between July 2016 and March 2020. The primary tumour site was the independent variable and the NS using different methods were the dependent variables. Logistic regressions were performed.ResultsA total of 2,144 patients were included in the study. The most common primary tumour site was the upper gastrointestinal (GI) tract (18.0%), followed by gynaecological (17.6%) and head and neck (HN) (13.5%). Our results showed that patients with tumours of the upper GI tract followed by HN presented significantly higher risk of worse NS. In contrast, breast tumours, bone and connective tissues and melanoma presented inverse association. The gynaecological cancer was variably associated with nutritional impairment, according to the assessment method.ConclusionsPatients with incurable cancer present high prevalence of NS impairment, depending on the tumour site, shown to be elevated in patients with tumour in the upper GI tract.


2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Peng Gao ◽  
Yong-xi Song ◽  
Ying-ying Xu ◽  
Zhe Sun ◽  
Jing-xu Sun ◽  
...  

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
C. S. Kim ◽  
M. B. Hannouf ◽  
S. Sarma ◽  
G. B. Rodrigues ◽  
P. K. Rogan ◽  
...  

IntroductionPatients with cancer of unknown primary (cup) have pathologically confirmed metastatic tumours with unidentifiable primary tumours. Currently, very little is known about the relationship between the treatment of patients with cup and their survival outcomes. Thus, we compared oncologic treatment and survival outcomes for patients in Ontario with cup against those for a cohort of patients with metastatic cancer of known primary site.Methods Using the Ontario Cancer Registry and the Same-Day Surgery and Discharge Abstract databases maintained by the Canadian Institute for Health Information, we identified all Ontario patients diagnosed with metastatic cancer between 1 January 2000 and 31 December 2005. Ontario Health Insurance Plan treatment records were linked to identify codes for surgery, chemotherapy, or therapeutic radiation related to oncology. Multivariable Cox regression models were constructed, adjusting for histology, age, sex, and comorbidities.Results In 45,347 patients (96.3%), the primary tumour site was identifiable, and in 1743 patients (3.7%), cup was diagnosed. Among the main tumour sites, cup ranked as the 6th largest. The mean Charlson score was significantly higher (p < 0.0001) in patients with cup (1.88) than in those with a known primary (1.42). Overall median survival was 1.9 months for patients with cup compared with 11.9 months for all patients with a known-primary cancer. Receipt of treatment was more likely for patients with a known primary site (n = 35,012, 77.2%) than for those with cup (n = 891, 51.1%). Among patients with a known primary site, median survival was significantly higher for treated than for untreated patients (19.0 months vs. 2.2 months, p < 0.0001). Among patients with cup, median survival was also higher for treated than for untreated patients (3.6 months vs. 1.1 months, p < 0.0001).Conclusions In Ontario, patients with cup experience significantly lower survival than do patients with metastatic cancer of a known primary site. Treatment is associated with significantly increased survival both for patients with cup and for those with metastatic cancer of a known primary site.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 628-628 ◽  
Author(s):  
Jonna Berntsson ◽  
Anna Larsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom

628 Background: A plethora of studies report abundant expression of programmed death-ligand 1 (PD-L1) on tumors to be associated with poor outcome in several cancer forms, whereas immune cell-specific expression of PD-L1 has been associated with improved prognosis in colorectal cancer. However, none of these studies have investigated the association with prognosis according to primary tumor location. This study aimed to investigate the clinicopathological correlates and prognostic impact of PD-L1 and its receptor PD-1 in colorectal cancer, with particular reference to the anatomical subsite of the primary tumor. Methods: Immunohistochemical expression of PD-L1 and PD-1 was analysed in tissue microarrays with tumors from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: High PD-L1 expression on tumor-infiltrating immune cells correlated significantly with an improved 5-year OS in univariable and multivariable analysis, adjusted for age, sex, TNM stage, differentiation grade, and vascular invasion, in the full cohort (HR = 0.49; 95 % CI 0.35-0.68), and in primary tumors of the right (HR = 0.43; 95 % CI 0.25-0.74) and the left colon (HR = 0.28; 95 % CI 0.13-0.61), but not in rectal cancer. High tumor-specific PD-L1-expression was not significantly associated with prognosis in neither the full cohort nor according to primary tumor location. High expression of PD-1 on tumor-infiltrating immune cells was significantly associated with an improved 5-year overall survival in the entire cohort (HR = 0.42; 95 % CI 0.21-0.87), but not in subsite analysis according to primary tumor location. Conclusions: This study is, to the best of our knowledge, the first to investigate the prognostic impact of PD-L1 and PD-1 expression according to primary tumor site in colorectal cancer. Dense infiltration of PD-L1+ immune cells was found to be an independent favorable prognostic factor in primary tumors of the right and left colon, but not in the rectum.


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