scholarly journals Adjuvant Chemotherapy for Stage II Colon Cancer With Poor Prognostic Features

2011 ◽  
Vol 29 (25) ◽  
pp. 3381-3388 ◽  
Author(s):  
Erin S. O'Connor ◽  
David Yu Greenblatt ◽  
Noelle K. LoConte ◽  
Ronald E. Gangnon ◽  
Jinn-Ing Liou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Survival Benefit ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Features ◽  
Stage Ii Colon Cancer

Purpose Adjuvant chemotherapy is typically considered for patients with stage II colon cancer characterized by poor prognostic features, including obstruction, perforation, emergent admission, T4 stage, resection of fewer than 12 lymph nodes, and poor histology. Despite frequent use, the survival advantage conferred on patients with stage II disease by chemotherapy is yet unproven. We sought to determine the overall survival benefit of chemotherapy among patients with stage II colon cancer having poor prognostic features. Patients and Methods A total of 43,032 Medicare beneficiaries who underwent colectomy for stage II and III primary colon adenocarcinoma diagnosed from 1992 to 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database. χ2 and two-way analysis of variance were used to assess differences in patient- and disease-related characteristics. Five-year overall survival was examined using Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. Results Of the 24,847 patients with stage II cancer, 75% had one or more poor prognostic features. Adjuvant chemotherapy was received by 20% of patients with stage II disease and 57% of patients with stage III disease. After adjustment, 5-year survival benefit from chemotherapy was observed only for patients with stage III disease (hazard ratio[HR], 0.64; 95% CI, 0.60 to 0.67). No survival benefit was observed for patients with stage II cancer with no poor prognostic features (HR, 1.02; 95% CI, 0.84 to 1.25) or stage II cancer with any poor prognostic features (HR, 1.03; 95% CI, 0.94 to 1.13). Conclusion Among Medicare patients identified with stage II colon cancer, either with or without poor prognostic features, adjuvant chemotherapy did not substantially improve overall survival. This lack of benefit must be considered in treatment decisions for similar older adults with colon cancer.

Impact of adjuvant chemotherapy on recurrence risk in stage II colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 533-533
Author(s):  
Taiwo Adesoye ◽  
Chung-Yuan Hu ◽  
Amanda Cuddy ◽  
Amanda B. Francescatti ◽  
Jessica R. Schumacher ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Recurrence Rate ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
The Impact

533 Background: Although clinical guidelines recommend consideration of adjuvant chemotherapy in high-risk stage II colon cancer, the impact on recurrence risk and cancer related survival is unclear. Furthermore, among Medicare patients, adjuvant chemotherapy was not associated with improved survival. We examine the effect of adjuvant chemotherapy on recurrence risk and overall survival in a diverse cohort. Methods: 6,095 patients who underwent surgery for stage II-III colon cancer (2006-2007) were randomly selected from facilities reporting to the National Cancer Data Base for additional abstraction of tumor information, 5 year recurrence and survival. Death or second cancer within 6 months were excluded. Patients were classified as high or low risk using standard pathologic factors. Multivariate Cox regression with propensity score weighting was performed to compare recurrence risk and overall survival. Results: Of 3,423 patients with stage II colon cancer, 26.9% (n = 883) received chemotherapy compared to 76.2% (n = 1,839) of stage III patients. Among stage II patients, 47.8% (n = 1,636) had at least one high risk feature and 30.8% (n = 481) of these received chemotherapy. Five year recurrence rate in stage II patients was 13% (n = 392), greater in high risk compared to non-high risk patients (13.3% vs 9.3% p < 0.0001) and 24.4% (n = 874) in stage III patients. Chemotherapy did not improve recurrence risk in stage II patients regardless of risk status (High risk: hazard ratio [HR] 1.37; 95% CI 0.96 - 1.97; Non-high risk: HR 1.39; 95% CI 0.91 - 2.11). Chemotherapy was associated with a significant improvement in recurrence risk in stage III patients (HR 0.79; 95% CI 0.63 - 0.96). However, chemotherapy was associated with improved overall survival in both high (HR 0.69; 95% CI 0.51 - 0.92) and non-high risk stage II patients (HR 0.76; 95% CI 0.55 - 1.04), and also in stage III patients (HR 0.47; 95% CI 0.41 - 0.54). Conclusions: Adjuvant chemotherapy was not associated with a lower recurrence rate among stage II colon cancer patients. The observed survival benefit associated with chemotherapy is likely attributable to non-oncologic factors such as patient selection. Decision-making regarding chemotherapy use in this cohort should be carefully approached.

Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4001-4001 ◽  
Author(s):  
S. Tejpar ◽  
F. Bosman ◽  
M. Delorenzi ◽  
R. Fiocca ◽  
P. Yan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Multiple Testing ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Biological Effects ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Stage Iii

4001 Background: Patients with high MSI (MSI H) tumors are increasingly being recognized as a prognostic and predictive subgroup in colon cancer (COC). We investigated the incidence of MSI-H in stage II (n=395) and stage III (n=859) COC, its association with histopathological variables and its prognostic and predictive impact. Methods: The study accrued 3278 patients with Stage II and Stage III COC to receive post-operative 5-FU -LV with or without irinotecan (IRI). Paraffin tissue blocks of 1327/1405 available patients were successfully analyzed for MSI status using the NCI extended panel of 10 markers. MSI-H was defined as instability in ≥3 markers. Relapse Free Survival (RFS) and Overall Survival (OS, median follow up 68 months) were assessed. Results: MSI H was present in 22% (85) of Stage II and 12% (103)of Stage III colon cancer . MSI H status was significantly associated with age <60, higher T stage, higher grade, lower N stage and right sided tumor location. The table presents univariate RFS and OS hazard rates (with 95% confidence intervals) for prognostic and predictive impact per stage and arm, estimated by a survival regression analysis using Cox proportional hazards model and of selected P values by Wald tests. Conclusions: Microsatellite instability is a strong prognostic factor for RFS and OS when considering Stage II and Stage III COC. Subgroup analysis suggests a stronger effect in Stage II than in Stage III, but is limited by sample size and multiple testing. Taken together with differences in incidence between the stages, this may suggest stage specific biological effects of MSI. In contrast to previous reports (a) in Stage II the prognostic effect of MSI remained significant even in pts treated with 5FU (w/o IRI),(b) There is no evidence for an effect of the addition of IRI. [Table: see text] [Table: see text]

Cochrane systematic review and meta-analysis of adjuvant chemotherapy for stage II colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3548-3548
Author(s):  
Brandon Matthew Meyers ◽  
Humaid Obaid Al-Shamsi ◽  
Alvaro Tell Figueredo
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Cochrane Systematic Review ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.

American Society of Clinical Oncology Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer

2004 ◽  
Vol 22 (16) ◽  
pp. 3408-3419 ◽  
Author(s):  
Al B. Benson ◽  
Deborah Schrag ◽  
Mark R. Somerfield ◽  
Alfred M. Cohen ◽  
Alvaro T. Figueredo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Clinical Oncology ◽  
Meta Analysis ◽  
Indirect Evidence ◽  
Stage Ii ◽  
Prognostic Features ◽  
American Society ◽  
Stage Ii Colon Cancer

Purpose To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice. Methods An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003. Results A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology. Conclusion Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.

A retrospective analysis on the impact of preoperative neutrophil to lymphocyte ratio in stage II colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 794-794
Author(s):  
Deepna Jaiswal ◽  
Suparna Mantha ◽  
Lucas Wong ◽  
Luis Seija ◽  
Yolanda Munoz
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Critical Role ◽  
Univariate Analysis ◽  
Neutrophil To Lymphocyte Ratio ◽  
Stage Ii ◽  
Lymphocyte Ratio ◽  
Stage Ii Colon Cancer ◽  
The Impact

794 Background: Inflammation has a critical role in tumor genesis and progression of cancer. The neutrophil to lymphocyte ratio (NLR) is an indication of balance between the immune systems pro and defense mechanism against cancer. Elevated NLR is of interest in many cancers, including colon cancer. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant chemotherapy for stage II colon cancer has remained debatable. We proposed to study the impact of the NLR in patients with stage II colon cancer and to identify high risk patients who would benefit from adjuvant chemotherapy. Methods: Three hundred and eighty patients diagnosed with Stage II colon cancer at our institution were included in this retrospective study. Kaplan-Meir curves and multivariate Cox-regression analyses were calculated for overall survival. Results: Univariate analysis showed NLR was not statistically significant as predictor of mortality (p-value=0.0857). However, after adjusting for recurrence, chemotherapy, age, white blood cell count, the NLR was predictive for survival, with a hazard ratio of 1.05 and 95% confidence interval of (1.006 - 1.1). Recurrence and age were also significant predictors of survival (p-values of <0.0001 for both), and HR of 3.1 (2.0 – 4.6) and 1.4 (1.2 – 1.5), respectively. Conclusions: The neutrophil to lymphocyte ratio might be an independent prognostic marker for overall survival in stage II colon cancer patients. Given the retrospective nature of our study, further studies are indicated to confirm our findings.

Adjuvant therapy for stage II and III colon cancer in elderly patients: NCDB analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 863-863
Author(s):  
Samip R. Master ◽  
Lawrence Shi ◽  
Chintan Shah ◽  
Runhua Shi
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Survival Difference ◽  
Multi Agent ◽  
Comorbidity Index

863 Background: Data on safety and efficacy of adjuvant chemotherapy for stage II and III colon cancer in elderly patients is area of controversy as these patients are underrepresented in clinical trials. We did a retrospective analysis of Medicare patients aged 70 or older with stage II and stage III colon cancer to investigate the adjuvant chemotherapy effect on colon cancer patients’ survival. Methods: Data was analyzed from 110, 993 men and women (≥ 70 years of age) registered in the National Cancer Database (NCDB) who were diagnosed with AJCC Stage II and Stage III colon cancer between 2004 and 2012 and had follow-ups to end of 2013. The primary predictor variable was adjuvant chemotherapy received, and overall survival was the outcome variable. Only patients with Medicare insurance were investigate for ease of analysis. Additional variables addressed and adjusted included gender, age, race, Charlson Comorbidity Index, the level of education, income, grade of tumor, distance traveled, facility type and diagnosing/treating facility. Results: The mean age was 79.5 years and SD was 5.9 years. In multivariate analysis, after adjusting for secondary predictor variables, receipt of adjuvant chemotherapy was a statistically significant predictor of overall survival of the stage II and stage III colon cancer. Relative to patients who did not receive adjuvant chemotherapy, the patients who got single agent adjuvant chemotherapy had 47.7% and those who were treated with multi agent chemotherapy had 49.8% decreased risk of mortality. There was no significant survival difference between single agent and multi agent adjuvant chemotherapy. Among the factors analyzed, age, gender, race, comorbidity index, diagnosing /treating facility and grade of tumor were found to be significant predictors of survival. Conclusions: Among the patients aged 70 years or older with stage II and stage III colon cancer, adjuvant chemotherapy lead to improved survival outcomes. However, survival difference between single agent vs multi agent adjuvant chemotherapy was not statistically significant.

Evaluating the prognostic significance of lymphovascular invasion in stage II and III colon cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
Dorotea Mutabdzic ◽  
Shalana BL O'Brien ◽  
Elizabeth A. Handorf ◽  
Karthik Devarajan ◽  
Sanjay S. Reddy ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Lymphovascular Invasion ◽  
Lymph Node Involvement ◽  
Stage Ii ◽  
Stage Iii ◽  
Node Involvement

685 Background: Presence of lymphovascular invasion (LVI) is known to be a predictor of lymph node involvement in colon adenocarcinoma (CA). Lymph node involvement is associated with poorer prognosis necessitating adjuvant therapy. While some studies have suggested that LVI is a predictor of worse overall survival in early stage colon cancer, the significance of LVI on prognosis has not been tested in a comprehensive North American data set. Methods: Patients with stage II and III CA with LVI data available and those who received predefined standard of care treatment were identified from the National Cancer Data Base (NCDB) from 2011 to 2015. The relationship between LVI and overall survival was tested using Kaplan-Meier survival curves and Cox proportional hazards regression analysis after adjusting for relevant clinical and demographic variables. Hazard ratios and 95% confidence intervals are reported along with median overall survival (OS) where available. Results: The dataset included 93,070 patients with stage II and 66,701 patients with stage III CA. The proportion of patients with LVI was 13% in stage II and 47% in stage III CA. After adjusting for age, sex, gender, race, comorbidities, socioeconomic status, T, and N stage, LVI was associated with worse OS in stage II, HR 1.2 (1.15-1.25, p < 0.001), and in stage III, HR 1.25 (1.21-1.30, p < 0.001), CA. Median OS was 6.51 years with LVI versus. 6.85 years without LVI in stage II compared with 6.57 years with LVI versus not reached without LVI in stage III CA. Of the stage II patients with LVI, 20% received adjuvant chemotherapy (CT) and median OS was 6.91 years for those who did versus 6.07 years for those who did not receive CT. Conclusions: Our data suggest that LVI is an important predictor of OS in stage II and III CA. There is evidence that adjuvant chemotherapy improves OS in advanced CA but there remains uncertainty as to the benefit in stage II. Despite this uncertainty, guidelines suggest consideration of adjuvant CT in patients with high-risk stage II disease. Our data support the recommendation that LVI be considered a high-risk feature in stage II disease. Further studies are necessary to examine whether the type or duration of CT should differ for patients with CA and LVI.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: A multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 248-248
Author(s):  
Suganija Lakkunarajah ◽  
Daniel Adam Breadner ◽  
Hanbo Zhang ◽  
Jennifer L. Spratlin ◽  
Karen E. Mulder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Survival Data ◽  
Dose Intensity ◽  
Developed Countries ◽  
Stage Ii ◽  
Stage Iii ◽  
N2 Disease

248 Background: Colorectal cancer remains the second leading cause of cancer death in developed countries. The benefit of using fluorouracil-based chemotherapy with oxaliplatin, such as FOLFOX (fluorouracil (5-FU), leucovorin, oxaliplatin) and CAPOX (capecitabine and oxaliplatin) is well established. The optimal dose intensity (DI) under which overall survival (OS) is inferior is not established. Methods: Patients (pts) treated with adjuvant chemotherapy between 2006 and 2011 for resected stage III colon cancer (CC) from four academic cancer centres in Canada were retrospectively analysed. Patients that received CAPOX and FOLFOX were examined for the relationship between DI and OS. Results: A total of 625 pts with resected high risk stage II or stage III CC that received adjuvant chemotherapy were analysed. The median age was 63. Pts with T4 and N2 disease comprised 35.4% and 29.9% of pts, respectively. Median follow-up was 3.2 years. There was available survival data for 319 pts. The median oxaliplatin DI was 70%. The frequency of pts reaching an oxaliplatin DI of > 80% was 43%, while 76.6% of pts had a dose intensity of > 80% for their FU component. An oxaliplatin DI of > 80% was associated with a significant improvement in survival, HR = 0.42 (95%CI 0.21 – 0.81, p < 0.01). Achieving a DI of > 80% for capecitabine or 5-FU did not improve OS. Other factors associated with inferior OS included T4 (HR = 3.5, p = 0.03) and N2 (HR = 5.27, p = 0.0005) subgroups. The improvement in OS was not significant when restricting the analysis to pts with non-T4 and non-N2 disease (n = 144), HR = 0.16 (0.02 – 1.26; p = 0.08). Conclusions: Oxaliplatin DI of > 80% is associated with improved OS in patients receiving chemotherapy for high risk stage II and stage III CC.

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