Prognostic impact of PD-L1 and PD-1 expression by primary tumor location in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 628-628 ◽  
Author(s):  
Jonna Berntsson ◽  
Anna Larsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Primary Tumor ◽  
Tumor Location ◽  
Left Colon ◽  
Prognostic Impact ◽  
Full Cohort ◽  
Primary Tumors ◽  
Primary Tumor Location ◽  
Entire Cohort

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.

The prognostic impact of RAS and TP53 mutation according to primary tumor location in colorectal liver metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3582-3582
Author(s):  
Yongjun Cha ◽  
Bun Kim ◽  
Seung Jae Roh ◽  
Moon Ki Choi ◽  
Dong Woon Lee ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Tp53 Mutation ◽  
Gene Mutations ◽  
Tumor Location ◽  
Left Colon ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Ras Mutation ◽  
Primary Tumor Location ◽  
Somatic Gene

3582 Background: Somatic gene mutations have been suggested to impact survival following resection of colorectal liver metastases (CRLM). However, most studies included a selected population with known mutation data and did not employ homogeneous methods. This study aimed to determine the prognostic impact of somatic gene mutations and microsatellite instability (MSI) in CRLM using a standardized protocol and assess their survival effects according to primary tumor location. Methods: A total of 568 patients who underwent resection of CRLM during 2001-2014 were identified from a prospectively maintained registry of the National Cancer Center. MassARRAY based mutation profiling of cancer-related genes ( KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, PTEN, APC, TP53)/MSI analysis was made in primary tumors from 538 (94.7%)/526 (92.6%) patients. Results: Primary tumor locations were: right colon for 51 (9.0%); transverse colon for 42 (7.4%); left colon for 238 (34.5%); rectum for 279 (49.1%) patients. Right sided tumors were associated shorter overall survival (OS) after liver resection compared to left colon primary tumors (5-year OS, 31.4% vs. 54.0% [ P = 0.011]). Mutation frequencies were: 45.9% for RAS ; 2.4% for BRAF ; 8.4% for PIK3CA ; 0.2% for PTEN ; 0.4% for MET ; 12.1% for APC ; 24.3% for TP53. RAS (5-year OS, 40.8% vs. 55.7% [ P = 0.001], PIK3CA (5-year OS, 31.1% vs. 50.5% [ P = 0.027]), and TP53 mutation (5-year OS, 42.7% vs. 50.8% [ P = 0.035]) were associated with worse OS after liver resection. On multivariable analyses, RAS (hazard rato [HR] 1.27; P = 0.033) and TP53 mutation (HR 1.35; P = 0.014) were significantly associated with poor OS after adjustment for covariates. Co-mutation in RAS/ TP53 (12.4%) was associated with the worst oncologic outcome (HR 1.81; P <.001). Notably, while the negative prognostic impact of RAS mutation did not differ significantly according to primary tumor location, the adverse effect of TP53 mutation was limited to rectal cancer (interaction P = 0.002). In this study, MSI-high (2.3%) was not associated with survival. Conclusions: Both RAS and TP53 mutation are associated with worse survival following CRLM resection. In contrast to RAS mutation, the negative prognostic impact of TP53 mutation appears to be limited to CRLM from the rectal origin.

scholarly journals Prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). A 5 year retrospective analysis of our treated population.

2017 ◽  
Vol 28 ◽  
pp. iii118-iii119
Author(s):  
Gonçalo Atalaia ◽  
Marta Vaz Baptista ◽  
Tiago Tomás ◽  
Susana Almeida ◽  
Inês Eiriz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Analysis ◽  
Primary Tumor ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Primary Tumor Location

Primary tumor location and expression of mir-664 as a combined biomarker for bevacizumab effectiveness in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3572-3572 ◽  
Author(s):  
Mogens Karsboel Boisen ◽  
Christian Dehlendorff ◽  
Dorte Linnemann ◽  
Jim S. Larsen ◽  
Kell Oesterlind ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Sigmoid Colon ◽  
Primary Tumor ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
First Line ◽  
Significant Positive Association ◽  
Primary Tumors ◽  
Primary Tumor Location

3572 Background: We aimed to identify tissue microRNAs (miRs) that could predict outcome for patients with metastatic colorectal cancer (mCRC) treated with first line bevacizumab (BEV) and chemotherapy (CT) but not for patients treated with CT alone. Methods: Patients with mCRC treated with first line capecitabine and oxaliplatin (CT) with or without BEV at ten hospitals were identified and data was extracted retrospectively. Formalin-fixed paraffin-embedded tissue samples from primary tumors were collected and RNA was purified from 3 x 10 µm sections, without micro-dissection. miR expression was measured using Applied Biosystems TaqMan Custom LDA cards profiling 22 selected miRs in duplicate. The 22 miRs were selected from a previous discovery study profiling 754 miRs. miR expression was related to time to disease progression (TTP) and overall survival (OS) in multivariate analyses using Cox proportional hazards models with adjustment for age, prior adjuvant treatment, and no. of metastatic sites. We have previously found that patients with primary tumors originating in the sigmoid colon and rectum (S+R) experienced a better outcome than patients with other primary tumor locations (caecum to descending colon) when treated with BEV, so our analyses were stratified by primary tumor location. Results: miR expression was measured in samples from 399 patients: 155 samples from the original CT+BEV discovery study, 119 samples from a new CT+BEV cohort, and 125 samples from a CT alone cohort. Expression of miR-664 showed a significant positive association with increasing TTP, OS, and response rate (RR), but only in the cohort of patients with sigmoid colon- and rectal primary tumors treated with CT+BEV (n=183). Conclusions: We have identified a subgroup of patients with mCRC that are likely to benefit from BEV addition to first line CT using the combined information of location of the primary tumor and expression level of miR-664. [Table: see text]

scholarly journals Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: A propensity score matching analysis

2020 ◽  
Author(s):  
Yuanping Zhang ◽  
Yongjin Wang ◽  
Yichuan Yuan ◽  
Jiliang Qiu ◽  
Yuxiong Qiu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Colorectal Liver Metastases ◽  
Tumor Location ◽  
Recurrence Free Survival ◽  
Primary Tumors ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Before And After

Abstract Background: Whether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy. Methods: From 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from cecum to transverse colon were defined as right-sided group (n = 141); tumors located from splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score matching (PSM) analysis. Results: Before PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM (P = 0.575; P = 0.453). However, significant different recurrence-free survival (RFS) rate was found before and after PSM between right-sided and left-sided group (P = 0.028, P = 0.003). Conclusions: Compared to patients with left-sided primary tumors, patients with right-sided primary tumors had a worse RFS but similar OS. Careful preoperative evaluation, intensive preoperative chemotherapy and frequent follow-up to detect early recurrence might be justified for CRLM patients with right-sided primary tumors.

scholarly journals Impact of biomarkers and primary tumor location on the metastatic colorectal cancer first-line treatment landscape in five European countries

2021 ◽  
Author(s):  
George Kafatos ◽  
Victoria Banks ◽  
Peter Burdon ◽  
David Neasham ◽  
Kimberly A Lowe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Treatment Strategies ◽  
Treatment Decisions ◽  
Tumor Location ◽  
First Line ◽  
Primary Tumor Location ◽  
The Uk ◽  
Prognostic And Predictive Factors

Background: Advances in therapies for patients with metastatic colorectal cancer (mCRC) and improved understanding of prognostic and predictive factors have impacted treatment decisions. Materials & methods: This study used a large oncology database to investigate patterns of monoclonal antibody (mAb) plus chemotherapy treatment in France, Germany, Italy, Spain and the UK in mCRC patients treated in first line in 2018. Results: Anti-EGFR mAbs were most often administered to patients with RAS wild-type mCRC and those with left-sided tumors, while anti-VEGF mAbs were preferred in RAS mutant and right-sided tumors. Adopted treatment strategies differed between countries, largely due to reimbursement. Conclusion: Biomarker status and primary tumor location steered treatment decisions in first line. Adopted treatment strategies differed between participating countries.

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