Outcomes over time (1998-2009) of stage II colon cancer patients (pts) receiving adjuvant FOLFOX: Pooled analysis of 1,122 pts in the ACCENT database.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 728-728
Author(s):  
Mohamed E. Salem ◽  
Jun Yin ◽  
Richard M. Goldberg ◽  
Levi Pederson ◽  
Norman Wolmark ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cox Model ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Pooled Analysis ◽  
Stage Ii ◽  
New Era ◽  
Time To Recurrence ◽  
Stage Ii Colon Cancer ◽  
Over Time

728 Background: Adjuvant FOLFOX therapy for stage II patients remains controversial, and selection criteria are imprecise. We examined the trend of disease-free survival (DFS: time to recurrence or death, whichever occurs first); time to recurrence (TTR: time to recurrence, censored at death without recurrence); survival after recurrence (SAR); and overall survival (OS) of pts treated with FOLFOX over a ten-year period. Methods: Outcomes of pts with stage II colon cancer enrolled in 6 adjuvant trials receiving FOLFOX alone were analyzed. Pt enrollment period was dichotomized as old (1998 – 2003) vs. new era (2004 – 2009) based on the FDA approval date of bevacizumab. 3/5yr event-free rates were estimated using adjusted Kaplan-Meier methods. Outcomes were compared between the two eras by multivariate Cox model. To control for potential confounding effects, all analyses were adjusted for age, gender, performance score, T stage, number of lymph nodes (LNs) examined, tumor side, and histologic grade. Results: In total, 1,122 pts with stage II were identified; 71% and 29% were treated in the old and new era, respectively. Pts enrolled in the new era were significantly younger and more likely to have higher tumor-grade and right-sided tumors compared to old era. More pts in the new era (71%) had ≥12 LNs examined compared to the old era (53%). After adjusting for potential confounding effects, no difference in DFS, TTR, SAR or OS between old and new eras was found (Table). Although median SAR increased from 13.6 to 26 months over time, this was not statistically significant, likely due to lack of power. An increased TTR over time (HRadj. 0.41, padj.= 0.002) was observed in pts with ≥12 LNs examined (3-yr TTR: 92% in old era vs. 96% in new era), but not pts with <12 LNs examined (pinteraction = 0.04). Conclusions: In stage II colon cancer pts who received adjuvant FOLFOX, no significant increase of DFS or OS was observed over time. However TTR was longer only in pts with ≥12 LNs examined. [Table: see text]

Evaluation of outcomes over time (1998-2009) of patients (pts) with stage III colon cancer receiving adjuvant FOLFOX: Analysis of 7,230 patients from MOSAIC, C07, C08, N0147, AVANT, and PETACC8 trials in the ACCENT Database.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 724-724
Author(s):  
Mohamed E. Salem ◽  
Jun Yin ◽  
Richard M. Goldberg ◽  
Levi Pederson ◽  
Norman Wolmark ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Cox Model ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Stage Iii ◽  
New Era ◽  
Stage Iii Colon Cancer ◽  
N2 Disease ◽  
Over Time

724 Background: Adjuvant FOLFOX is the standard of care for pts with stage III colon cancer and a platform to test new agents. Improvements in supportive care and development of newer treatments for metastatic disease impact the overall outcome of pts treated with adjuvant therapy. We examined the trend of disease-free survival (DFS), survival after recurrence (SAR), and overall survival (OS) of pts treated with FOLFOX over a ten-year period. Methods: Outcomes of colon cancer pts enrolled in 6 adjuvant trials receiving FOLFOX alone were analyzed. Pt enrollment period was dichotomized as old (1998 – 2003) vs. new era (2004 – 2009) based on the FDA approval date of bevacizumab. 3/5yr event-free rates were estimated by adjusted Kaplan-Meier methods. Outcomes were compared between the two eras by Cox model. To control for potential confounding effects, all analyses were adjusted for age, gender, performance score, T/N stage, tumor sidedness and histologic grade. Results: In total, 7,230 pts (stage II [n = 1122]; stage III [n = 6,108]) were identified; 32% and 68% were treated in the old and new era, respectively. Stage III pts enrolled in the new era were significantly younger, more likely to have T4/N2 disease, higher tumor grade, and left-sided tumors. After adjusting for pt characteristics, no difference in DFS was seen over time. However prolonged SAR and OS were observed in pts treated in the new era (Table). 5yr OS increased from 76% to 80% over time. Median SAR improved from 14.8 to 26.4 months. Conclusions: Stage III colon cancer pts who received adjuvant FOLFOX experienced significant improvements in SAR and OS—but not DFS—over time. In view of the improvements in OS and nearly doubled SAR, the optimal duration of OS follow-up to evaluate the benefits of adjuvant therapy (currently 5 years) should be reassessed, and ACCENT investigators are planning to conduct these additional analyses using their large pooled-trial database. [Table: see text]

Adjuvant Chemotherapy Use for Medicare Beneficiaries With Stage II Colon Cancer

2002 ◽  
Vol 20 (19) ◽  
pp. 3999-4005 ◽  
Author(s):  
Deborah Schrag ◽  
Sheryl Rifas-Shiman ◽  
Leonard Saltz ◽  
Peter B. Bach ◽  
Colin B. Begg
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Model ◽  
Tumor Grade ◽  
Stage Ii ◽  
Median Income ◽  
Medicare Beneficiaries ◽  
Prognostic Features ◽  
Resected Stage ◽  
Stage Ii Colon Cancer

PURPOSE: Clinical trials have not demonstrated that adjuvant chemotherapy improves survival for patients with resected stage II colon cancer. Nevertheless, patients may receive this treatment despite its uncertain benefit. The objective of this study was to determine the extent to which adjuvant chemotherapy is used for patients with stage II colon cancer. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 3,151 patients aged 65 to 75 with resected stage II colon cancer and no adverse prognostic features. The primary outcome was chemotherapy use within 3 months of surgery ascertained from claims submitted to Medicare. Relationships between patient characteristics and adjuvant chemotherapy use were measured and their significance was assessed using multivariable logistic regression. Survival for treated and untreated patients was compared using a Cox model. RESULTS: Twenty-seven percent of patients received chemotherapy during the 3 postoperative months. Younger age at diagnosis, white race, unfavorable tumor grade, and low comorbidity were each associated with a greater likelihood of receiving treatment. Sex, the number of examined lymph nodes in the tumor specimen, the urgency of the surgical admission, and median income was each unrelated to treatment. Five-year survival was 75% for untreated patients and 78% for treated patients. After adjusting for known between-group differences, the hazard ratio for survival associated with adjuvant treatment was 0.91 (95% confidence interval, 0.77 to 1.09). CONCLUSION: A substantial percentage of Medicare beneficiaries with resected stage II colon cancer receive adjuvant chemotherapy despite its uncertain benefit.

Validation of the 12-gene colon cancer recurrence score (RS) in NSABP C07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5FU/LV (FU) and 5FU/LV+oxaliplatin (FU+Ox).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3512-3512 ◽  
Author(s):  
Michael O'Connell ◽  
Mark Lee ◽  
Margarita Lopatin ◽  
Greg Yothers ◽  
Kim Clark-Langone ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cox Regression ◽  
Cox Model ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Rt Pcr ◽  
Relative Benefit ◽  
Stage Ii Colon Cancer

3512 Background: Standardized clinical tools which accurately quantify recurrence risk are needed for optimal adjuvant treatment of colon cancer. The 12-gene RS has been validated in stage II colon cancer pts from QUASAR and CALGB 9581. We conducted a large prospectively-designed clinical validation study of RS, w/ pre-specified endpoints, methods, and analysis plan, in stage II and III colon cancer pts randomized to FU or FU+Ox in NSABP C-07. Methods: 50% of C-07 pts w/ tissue were randomly selected, stratified on stage (AJCC 6th) and recurrence. Gene expression was quantitated by RT-PCR on 25 µm manually microdissected fixed colon tumor tissue. Data were analyzed by Cox regression controlling for stage and treatment (TRT). Results: RT-PCR was successful in 892/921 pts (97%): 449 FU, 443 FU + Ox; 264 st II, 409 st IIIA/B, 219 st IIIC. The primary endpoint was met: RS predicted recurrence (HR/25 units=1.96, 95% CI 1.50-2.55 p<.001). RS also predicted disease-free survival (p<.001) and overall survival (p<.001). RS predicted recurrence (p=.001) independent of T and N stage, MMR, nodes examined, grade, and TRT. Predefined high RS group (26% of pts) had higher recurrence risk than low RS group (39% of pts): HR=2.11, p<.001. Cox model 5 yr recurrence risk (95%CI) in FU treated pts by RS group (low, int, high): st II 9% (6-13%), 13% (8-17%), 18% (12-25%); st IIIA/B 21% (16-26%), 29% (24-34%), 38% (30-46%); st IIIC 40% (32-48%), 51% (43-59%), 64% (55-74%). RS did not have significant interaction w/ stage (p=0.90) or age (p=0.76). Relative benefit of Ox was similar across range of RS (interaction p=0.48); accordingly, in Cox model and Kaplan-Meier analyses, absolute benefit of Ox increased w/ higher RS. Conclusions: RS predicts recurrence risk in stage II and III colon cancer, capturing underlying biology and providing risk information beyond conventional factors. RS is not predictive of relative benefit of Ox added to adjuvant FU but enables better discrimination of absolute Ox benefit as a function of risk. Incorporating RS into the clinical context may better inform adjuvant therapy decisions for pts w/ stage III as well as stage II colon cancer.

scholarly journals Use of a Combination of CEA and Tumor Budding to Identify High-risk Patients with Stage II Colon Cancer

2017 ◽  
Vol 32 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Changzheng Du ◽  
Weicheng Xue ◽  
Fangyuan Dou ◽  
Yifan Peng ◽  
Yunfeng Yao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Disease Progression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Tumor Budding ◽  
High Risk Patients ◽  
Prognostic Accuracy ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

Background High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Methods Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. Results The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. Conclusions The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

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.

Identification of risk factors for stage II colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 375-375
Author(s):  
Sho Sawazaki ◽  
Manabu Shiozawa ◽  
Koji Numata ◽  
Masakatsu Numata ◽  
Teni Godai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Lymphatic Invasion ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

375 Background: The use of adjuvant chemotherapy remains controversial in Stage II colon cancer. However, patients with specific clinicopathological features are thought to have high risk for recurrence. The aim of this study was to identify the subgroup of patients at great risk, by investigating the clinicopathological features associated with poor survived in Stage II. Methods: A total of 282 patients with Stage II colon cancer who underwent curative resection from January 1990 to September 2007 at Kanagawa Cancer Center were enrolled. Then, the clinicopathological data of the patients were retrospectively evaluated. Disease-free survival rates were calculated by the Kaplan-Meier method, and survival curves were compared by the log-rank test. Cox’s regression analysis was used for multivariate analyses. P values <0.05 were considered to be statistically significant. Results: The median follow up was 62.5 months. The 5-year disease-free survival was 92.2% in the study group as a whole. Among the recurrent patients (n=23), the most recurrent site was the liver (n=11, 44%), followed by lung (n=6, 24%), and peritoneum (n=5, 20%). Univariate analysis for 5-year disease-free survival identified two factors; tumor diameter (>5cm vs…5cm, p=0.018), and lymphatic invasion (p=0.009). Multivariate analysis for 5-year disease-free survival identified two independent factors; tumor diameter (hazard ratio [HR], 4.82; 95% CI, 1.55-15.0; p=0.006), and lymphatic invasion (HR, 4.15; 95% CI, 1.68-10.2; p=0.002). The 5-year disease-free survival differed significantly among patients with neither of these prognostic factors (98.6%), those with only 1 factor (93.3%), and those with 2 factors (76.6%, p=0.000). Conclusions: Patients with stage II colon cancer who have both 5cm in diameter and lymphatic invasion are at high risk for recurrence. The use of adjuvant chemotherapy should be considered in this subgroup of patients.

Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

2004 ◽  
Vol 22 (16) ◽  
pp. 3395-3407 ◽  
Author(s):  
Alvaro Figueredo ◽  
Manya L. Charette ◽  
Jean Maroun ◽  
Melissa C. Brouwers ◽  
Lisa Zuraw
Keyword(s):  
Systematic Review ◽  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

scholarly journals High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

2010 ◽  
Vol 28 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Boye Schnack Nielsen ◽  
Stine Jørgensen ◽  
Jacob Ulrik Fog ◽  
Rolf Søkilde ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Colorectal Cancers ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free ◽  
Short Disease Free Survival

Impact of older age on the efficacy of newer adjuvant therapies in >12,500 patients (pts) with stage II/III colon cancer: Findings from the ACCENT Database

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4010-4010 ◽  
Author(s):  
N. A. Jackson McCleary ◽  
J. Meyerhardt ◽  
E. Green ◽  
G. Yothers ◽  
A. de Gramont ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Phase Iii ◽  
Cox Models ◽  
Time To Death ◽  
Time To Recurrence ◽  
Clinically Meaningful Outcomes ◽  
The Impact

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. Methods: We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. Results: Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. Conclusions: Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text]

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