Differential radiographic appearance of BRAF V600E mutant metastatic colorectal cancer (mCRC) in patients matched by primary tumor location.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 554-554 ◽  
Author(s):  
Claire Greene ◽  
Chloe Evelyn Atreya ◽  
Ryan McWhirter ◽  
Nabia Ikram ◽  
Katherine Van Loon ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Braf Mutation ◽  
Tumor Location ◽  
Peritoneal Metastases ◽  
Left Colon ◽  
Braf V600e ◽  
Right Colon ◽  
Mutation Status ◽  
Primary Tumor Location ◽  
Braf Mutant

554 Background: BRAF mutation status and location of CRC primary each correlate with pattern of metastatic spread. We sought to determine whether presence of a BRAF V600E (BRAF) mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location. Methods: 40 patients with BRAF mutant mCRC were matched to 80 patients with BRAF wild-type CRC by location of primary tumor (right colon, left colon or rectum), sex, and age ( < 50; 50+). CT scans were reviewed for disease characterization. BRAF mutation status, clinicopathological characteristics, and sites of metastatic disease were associated using proportion tests. Results: Of the 120 matched patients,60% were female. The distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Median age at diagnosis was 57, range 20-88 yrs. Significantly higher frequencies of peritoneal metastases (p = 0.045) and ascites (p = 0.0038) occurred in patients with BRAF mutant tumors. Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. In patients with left colon primaries, BRAF mutations associated with less frequent liver metastases (42% vs. 79%, p = 0.024) and more frequent ascites (58% vs. 12%, p = 0.0038). Disease was not measurable by RECIST version 1.1 criteria in 20% of patients with BRAF mutations, most often with peritoneal metastases and ascites. Conclusions: Presence of a BRAF V600E mutation associated with a greater proportion of peritoneal metastases and ascites, even among patients matched for primary tumor location. Of 20 patients with BRAF mutant mCRC and peritoneal metastases plus ascites, 6 patients (30%) had disease that was not measurable by RECIST version 1.1. Radiographic characterization provides a window on BRAF mutant mCRC biology and also reveals a challenge for response evaluation on clinical trials. [Table: see text]

Prognostic impact of K-RAS mutational status and primary tumor location in patients undergoing resection for colorectal cancer liver metastases: an update

2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Mutation Status

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

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.

scholarly journals Impact of exact segment by segment primary tumor location status on anti-EGFR antibody first-line treatment efficacy in RAS/BRAF wild-type and BRAF mutant metastatic colorectal cancer. A pooled analysis of AIO studies FIRE-1, CIOX, FIRE-3, XELAVIRI, and VOLFI.

2021 ◽  
Author(s):  
Annabel Helga Sophie Alig ◽  
Volker Heinemann ◽  
Michael Geissler ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Tumor Location ◽  
Pooled Analysis ◽  
Trial Registration ◽  
Wild Type ◽  
First Line ◽  
Primary Tumor Location ◽  
Braf Mutant

Abstract BackgroundPrimary tumor location (left vs. right) has prognostic and predictive impact on the therapeutic management of metastatic colorectal cancer (mCRC) in particular in the context of anti-epithelial growth factor receptor (anti-EGFR) antibodies. This analysis evaluates the relevance of exact segment-by-segment tumor location in patients with metastatic colorectal cancer on outcome and efficacy of anti-EGFR-antibodies.MethodsThis is a retrospective, pooled analysis of five randomized clinical trials (FIRE-1, CIOX, FIRE-3, XELAVIRI and VOLFI) treating metastatic colorectal cancer patients in a first-line setting, published between 2011-2019. Each trial was a multicentre, phase 2 or phase 3 trial in which patients with untreated metastatic colorectal cancer received chemotherapy regimens with or without monoclonal antibodies (anti-VEGF, anti-EGFR). Eligible were patients with histologically confirmed metastatic colorectal cancer in good performance status who were at least 18 years old. Individual data of 1809 patients with available exact primary tumor location were included into this analysis. Prognostic and predictive effects of primary tumor location were evaluated in uni- and multivariate analyses using the Kaplan Meier method, log rank tests, Cox regressions and logistic regressionsResults Exact primary tumor location is an important determinant of overall survival (OS) in mCRC patients (P<0.001). Multivariate analysis of RAS/BRAF wild-type metastatic colorectal cancer indicate that efficacy of anti-EGFR agents in terms of OS increases continuously from primary tumors located in the caecum (HR 2.63), ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99), left flexure/descending colon (HR 0.91) to the sigmoid (HR 0.71) and rectum (HR 0.58), demonstrating significant benefit in sigmoid and rectal metastatic colorectal cancer, as well as clear detriment in caecum mCRC. Patients with BRAF V600E mutant disease arising from left-sided segments of the colorectum benefitted from EGFR-antibody treatment survival: hazard ratio for death in left-sided tumors: 0.42 (95% CI 0.19-0.92).Conclusions Primary tumor location of metastatic colorectal cancer affects prognosis. Anti-EGFR efficacy increases continuously from proximal to distal segments of the colorectum in metastatic colorectal cancer patients with RAS/BRAF wild-type and BRAF mutant tumors. Therefore, patients with BRAF mutant tumors of the distal segments may benefit from first-line Anti-EGFR-based therapy.Trial registrationFIRE1 trial registration ID n/aCIOX trial registration ID NCT00254137FIRE3 trial registration ID NCT00433927XELAVIRI trial registration ID NCT01249638VOLFI trial registration ID NCT01328171

TRIM29 expression and its survival predictor value in colorectal cancer with different primary tumor location.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15528-e15528
Author(s):  
Jing Han ◽  
Xue Zhang ◽  
Zhisong Fan ◽  
Yudong Wang ◽  
Li Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Protein Expression ◽  
Intestinal Obstruction ◽  
Sample Size ◽  
Primary Tumor ◽  
Tumor Location ◽  
Right Colon ◽  
Primary Tumor Location ◽  
Mrna And Protein Expression

e15528 Background: It is clear that, in colorectal cancer (CRC), patients with different primary tumor location have variant prognosis and distinct clinicopathological features.So, it is very necessary to find specific tumor markers for different tumor sites.Our previous study have found TRIM29 is higher expressed in right colon cancer(RCC) than left colon cancer(LCC) patients in a small sample size reviewed study.So we speculated TRIM29 have different effect on the patients with different tumor side.But in our previous study, we didn’t investigate the TRIM29 expression in rectal cancer patients(RECC) and observed the effect of TRIM29 on the survival by different tumor side patients.So we decide to explore whether TRIM29 plays a different role in patients with three different tumor sites in a larger sample size study. Methods: 227 CRC cases were included in our retrospectively study,the patients were divided into LCC, RCC and RECC three groups. We first tested TRIM29 mRNA and protein expression level in LCC, RCC and RECC respectively to confirm whether TRIM29 expressed differently in patients with different tumor location. Then we explore the relationship between TRIM29 and clinicopathologic features in the patients with three tumor sites respectively.At last, we explore whether TRIM29 has different effect on the survival of the patients with three different tumor location. Results: TRIM29 mRNA and protein expression was significantly higher in RCC than in LCC and RECC ( P< 0.0001, P< 0.001).High TRIM29 expression was only associated with intestinal obstruction before surgery in LCC patients( P = 0.006) and it was associated with higher frequency of stage TNM IIĨIV and younger patients in RECC( P = 0.015 and 0.000), whereas it was associated with higher frequency of male, elder, stage IIĨIV patients, N+ and intestinal obstruction patients in RCC( P = 0.000,0.000,0.000,0.000 and 0.010).Only in the RCC group, patients with high TRIM29 expression both had a significant difference in the risk of recurrence/metastasis and death compared to patients with low TRIM29 expression( P = 0.020,0.000). Conclusions: TRIM29 plays different role in the patients with different tumor sites.TRIM29 has a greater correlation with clinicopathological features and greater effect on the prognosis in right colon cancer.TRIM29 may serve as a new biomarker and a novel therapeutic target in RCC patients.

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.

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