ERCC1, Defective Mismatch Repair Status as Predictive Biomarker of Survival for Stage III Colon Cancer Patients Receiving Oxaliplatin Based Adjuvant Chemotherapy

647 Background: Albumin to globulin ratio (AGR) has been reported to predict long term mortality in patients with several cancers. However, prognostic impact of preoperative AGR in colon cancer patients with curative intent has not yet been fully addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in stage I-III colon cancer patients. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA] and AGR) from 251 curative colon cancer patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.32 in current study. Results: Several clinicopathological categories related with tumor progression such as lymph node metastasis, T4 tumor, large tumor size, undifferentiated tumor, venous and lymphatic invasion, and high CEA were significantly associated with low AGR level. The patients with low AGR were significantly poorer OS (P = 0.001) and DFS (P = 0.003) than those with high AGR, respectively. In addition, multivariate analyses demonstrated that low AGR was independently associated with early recurrence (HR = 2.87, P = 0.007) and poor prognosis (HR = 2.56, P = 0.008), respectively. On the other hand, sub analysis of survival curves revealed that stage III colon cancer patients with low AGR were significantly poorer OS (P = 0.007) and DFS (P = 0.02) than those with high AGR, respectively. Furthermore, significantly poorer OS and DFS were also shown in stage I-II colon cancer patients with low AGR, respectively (OS: P = 0.02, DFS: P = 0.01). Conclusions: Preoperative AGR was an independent predictor of early recurrence and poor prognosis in curative colon cancer patients. AGR may represent a simple, potentially useful predictive biomarker for selecting stage I-II colon cancer patients who might need adjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage III colon cancer patients.

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Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence: Results of an accent meta-analysis of seven studies.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3525 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3525-3525 ◽

Cited By ~ 1

Author(s):

Julien Taieb ◽

Levi Pederson ◽

Qian Shi ◽

Steven R Alberts ◽

Norman Wolmark ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Statistical Significance ◽

Multivariable Analysis ◽

Disease Recurrence ◽

Stage Iii ◽

Wild Type ◽

Poor Prognostic Factor ◽

Stage Iii Colon Cancer

3525 Background: Microsatellite instable/deficient mismatch repair (MSI) metastatic colorectal cancers have been reported to be of poor prognosis. The interaction between MSI and BRAFV600E mutation complicates the picture. Methods: Patients with resected stage III CC from 7 studies with disease recurrence and data available for MSI and BRAFV600E status were analyzed. The primary endpoint was survival after recurrence (SAR) to assess the prognostic roles of MSI and BRAFV600E, respectively. Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for clinicopathologic features (data collected 12/1998 to 11/2009). Results: Among 2630 patients with cancer recurrence (1491 men [56.7%], mean age, 58.5 [19-85] years), multivariable analysis revealed that patients with MSI tumors (n = 220) had significantly better SAR (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.69-0.98; P = .029) than patients with microsatellite stable /proficient MMR (MSS) tumors (n = 1766). This was also observed when looking at patients treated by the standard FOLFOX adjuvant regimen only (aHR, 0.76; 0.58-1.00; P = .048). Same trends were observed when looking at MSI/dMMR patients outcome in BRAFV600E wild-type (aHR, 0.84; P = .10) and mutant (aHR, 0.88; P = .43) subgroups separately, without reaching statistical significance. As previously described poor SAR was observed in BRAFV600E mutants vs wild type patients (n = 244; aHR, 2.06; 95% CI, 1.73-2.46; P < .0001) and this was also true in BRAFV600E mutants MSI/dMMR patients (n = 77, aHR, 2.65 ; 95% CI, 1.67-4.21; p < .0001). Other factors associated with a poor SAR were : olderage, male gender, T4/N2, proximal primary tumor location, poorly differentiated adenocarcinoma, and early recurrence (by 1y increase). Conclusions: In stage III colon cancer patients recurring after adjuvant chemotherapy and before the era of immuno-oncologic agents, MSI/dMMR was associated with a better survival compared to MSS. BRAFV600E mutation seems to be a poor prognostic factor for both MSI/dMMR and MSS/pMMR patients.

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Microsatellite instability as a predictor of lower relapse frequency in adjuvant chemotherapy treated stage III colon cancer patients

Pathology - Research and Practice ◽

10.1016/s0344-0338(04)80416-3 ◽

2004 ◽

Vol 200 (4) ◽

pp. 258

Author(s):

W. Dietmaier ◽

M. Woenckhaus ◽

P. Ruemmele ◽

M. Bettstetter ◽

S. Schilling ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Microsatellite Instability ◽

Cancer Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer

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Variation in Delayed Time to Adjuvant Chemotherapy and Disease-Specific Survival in Stage III Colon Cancer Patients

Annals of Surgical Oncology ◽

10.1245/s10434-016-5622-4 ◽

2016 ◽

Vol 24 (6) ◽

pp. 1610-1617 ◽

Cited By ~ 7

Author(s):

Adan Z. Becerra ◽

Christopher T. Aquina ◽

Supriya G. Mohile ◽

Mohamedtaki A. Tejani ◽

Maria J. Schymura ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Stage Iii ◽

Disease Specific Survival ◽

Stage Iii Colon Cancer ◽

Delayed Time ◽

Disease Specific

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The effect of comorbidity on the use of adjuvant chemotherapy and type of regimen for curatively resected stage III colon cancer patients

Cancer Medicine ◽

10.1002/cam4.632 ◽

2016 ◽

Vol 5 (5) ◽

pp. 871-880 ◽

Cited By ~ 14

Author(s):

Mei‐Chin Hsieh ◽

Trevor Thompson ◽

Xiao‐Cheng Wu ◽

Timothy Styles ◽

Mary B. O'Flarity ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Resected Stage

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Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study

10.21203/rs.2.13960/v2 ◽

2019 ◽

Author(s):

Hidetaka Kawamura ◽

Toshitaka Morishima ◽

Akira Sato ◽

Michitaka Honda ◽

Isao Miyashiro

Keyword(s):

Colon Cancer ◽

Cohort Study ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Survival Benefit ◽

Older Patients ◽

Age Groups ◽

Stage Iii ◽

Younger Patients ◽

Stage Iii Colon Cancer

Abstract Background: Adjuvant chemotherapy is relatively underused in older patients with colon cancer in Japan, and its age-specific effects on clinical outcomes remain unclear. This study aimed to assess the effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age in a Japanese real-world setting. Methods: In this multi-center retrospective cohort study, we analyzed patient-level information through a record linkage of population-based cancer registry data and administrative claims data. The study population comprised patients aged ≥18 years who received a pathological diagnosis of stage III colon cancer and underwent curative resection between 2010 and 2014 at 36 cancer care hospitals in Osaka Prefecture, Japan. Patients were divided into two groups based on age at diagnosis (<75 and ≥75 years). The effect of adjuvant chemotherapy was analyzed using Cox proportional hazards regression models for all-cause mortality with inverse probability weighting of propensity scores. Adjusted hazard ratios were estimated for both age groups. Results: A total of 783 patients were analyzed; 476 (60.8%) were aged <75 years and 307 (39.2%) were aged ≥75 years. The proportion of older patients who received adjuvant chemotherapy (36.8%) was substantially lower than that of younger patients (73.3%). In addition, the effect of adjuvant chemotherapy was different between the age groups: the adjusted hazard ratio was 0.56 (95% confidence interval: 0.33-0.94, P=0.027) in younger patients and 1.07 (0.66-1.74, P=0.78) in older patients. Conclusions: The clinical effectiveness of adjuvant chemotherapy in older patients with stage III colon cancer appears limited under current utilization practices.

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