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Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

ABSTRACT: We recently reported, in a prospective randomized trial, that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use.The current international prospective multicenter cooperative group trial (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon Cancer") evaluates the 12-LN quality measure and nodal ultra-staging impact on DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria included biopsy-proven colon adenocarcinoma; absence of metastatic disease; >12 LNs staged pathologically; pan-cytokeratin immunohistochemistry (IHC) of hematoxylin and eosin (H&E)-negative LNs; and no adjuvant chemotherapy.Of 445 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8 ± 22.1 months (range 0 to 97 months), 94.3% remain disease free. Recurrence was least likely in patients with ?12 LNs, H&E-negative LNs, and IHC-negative LNs (pN0i-): 2.6% vs 16.7% in the pN0i+ group (p < 0.0001).This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (?12 LNs, pN0i-) are unlikely to benefit from adjuvant chemotherapy; 97% remain disease free after primary tumor resection. Both surgical and pathologic quality measures are imperative in planning clinical trials in nonmetastatic colon cancer.

SUBMITTER: Protic M

PROVIDER: S-EPMC4657939 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

Protic Mladjan M Stojadinovic Alexander A Nissan Aviram A Wainberg Zev Z Steele Scott R SR Chen David C DC Avital Itzhak I Bilchik Anton J AJ

Journal of the American College of Surgeons 20150518 3

<h4>Background</h4>We recently reported, in a prospective randomized trial, that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use.<h4>Study design</h4>The current international prospective multicenter cooperative group trial (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon Cancer") evaluate ...[more]

PMID: 26213360

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Project description:BackgroundContemporary treatment of node-positive (N+) colon cancer consists of adjuvant chemotherapy; however, randomized data supporting this practice were derived from lesions T2 or greater. Minimal data exist regarding the use and need for adjuvant chemotherapy in T1N+ disease.ObjectiveThe aim of this study was to determine treatment trends and the effects of adjuvant chemotherapy on T1N+ colon cancers by using the National Cancer Database.DesignThis was a retrospective study. Baseline demographics, tumor, and cancer treatment characteristics were compared. Groups were matched on the propensity to receive chemotherapy. Adjusted long-term survival stratified by chemotherapy use was compared by using the Kaplan-Meier method with the log-rank test. Predictors of not receiving chemotherapy were identified by using a multivariable logistic regression model.SettingsData were collected from the National Cancer Database, which collects cancer data from over 1500 cancer centers.PatientsWe identified patients from 1998 to 2006 with T1N+ disease, excluding those with metastatic disease or previous cancer. Patients were stratified based on whether or not they received chemotherapy.Main outcome measuresThe primary outcome measure of this study was long-term survival.ResultsThree thousand one hundred thirty-seven patients had T1N+ disease; 70.6% (n = 2216) received chemotherapy, and utilization significantly increased from 1998 to 2011 (p < 0.001). Unadjusted analysis revealed that patients treated with chemotherapy were statistically younger and healthier, and had shorter postoperative lengths of stay (all p < 0.001). Unadjusted 5-year survival was higher in patients receiving chemotherapy (87.9% vs 63.0% in patients with no chemotherapy; p < 0.001) and this persisted after propensity matching with (83.4% and 63.0% in patients with or without chemotherapy; p < 0.001). Only age (OR, 0.29; p < 0.001) predicted not receiving chemotherapy.LimitationsLimitations include potential selection bias as well as the inability to compare disease-free survival/recurrence.ConclusionsAdjuvant chemotherapy appears to significantly improve long-term survival in patients receiving chemotherapy in T1N+ disease. Thus, the use of chemotherapy in T1N+ disease is justified and provides a highly significant survival benefit.

Project description:BackgroundSince 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.MethodsWe performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.ResultsAfter 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).ConclusionsAmong patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).

Project description:ImportanceBreast cancer treatment can impact not only short-term health but may also affect longer-term quality of life (QOL).ObjectiveTo describe and evaluate factors associated with diminished QOL following completion of active treatment.Design, setting, and participantsThis was a secondary analysis of a randomized clinical trial included patients with lymph node-positive or high-risk lymph node-negative breast cancer who had undergone definitive surgery and were enrolled in ECOG-ACRIN E5103, a multisite phase 3 trial. A survey was administered 18 months after enrollment to patients enrolled between January and June 2010. Final analysis of the data took place from March to December 2021.InterventionsPatients received adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab or placebo.Main outcomes and measuresQOL and health status assessed with the EuroQol 5-Dimension 3-Levels (EQ-5D-3L), EQ-visual analog scale (EQ-VAS), and the Functional Assessment of Cancer Therapy-Breast Cancer, with arm subscale (FACT-B+4). Groups were compared by Fisher exact test, Wilcoxon rank sum, or Kruskal-Wallis test. Multivariable linear regression was used to assess factors independently associated with FACT-B scores.ResultsData at 18 months were available from 455 of 519 patients (87.7%) enrolled in the trial. Median (range) age at enrollment was 52 (25-76) years. No differences in QOL (median [range] FACT-B scores: group A, 123 [67-146]; group B, 114 [54-148]; group C, 117 [42-148]; P = .23) or health status (median [range] EQ-5D-3L index scores: group A, 0.83 [0.28-1.00]; group B, 0.83 [0.20-1.00]; group C, 0.83 [0.17-1.00], P = .80; median EQ-VAS: group A, 85 [20-100]; group B, 85 [0-100]; group C, 85 [0-100]; P = .79) were observed across treatment groups; results for subsequent analyses were therefore reported irrespective of primary treatment. Overall, half of patients (258 of 444 [58%]) reported at least some pain or discomfort; 170 (38%) reported symptoms of anxiety or depression. In multivariable analyses, mastectomy with radiation (vs breast conserving surgery) and Asian, Black, or American Indian or Alaska Native race (vs White race) were associated with lower QOL (mastectomy with radiation: coefficient: -5.5; 95% CI, -10.1 to -0.9; Asian, Black, or American Indian or Alaska Native race: coefficient: -7.3; 95% CI, -13.2, -1.4).Conclusions and relevanceIn this study, the addition of bevacizumab to chemotherapy was not negatively associated with QOL at 18 months. A substantial proportion of participants reported problems related to pain or discomfort and anxiety or depression, demonstrating persistent consequences for physical and psychosocial well-being in this heavily treated population. Many problems reported are amenable to intervention, underscoring the need for timely referral to supportive resources, especially for women of color and those who have more extensive local therapy.Trial registrationClinicalTrials.gov Identifier: NCT00433511.

Project description:Purpose Bevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2-negative disease. Patients and Methods Patients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease-free survival (IDFS). Results Four thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade ≥ 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation.

Dataset Information

Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

Publications

Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

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