Adjuvant therapy for high-risk stage II or stage III colon adenocarcinoma: A propensity score-matched, nationwide, population-based cohort study

Purpose: To determine the optimal adjuvant chemotherapy regimen for patients with high-risk stage II or III colon adenocarcinoma, we conducted this propensity score-matched, nationwide, population-based cohort study to estimate the effects of adjuvant treatments in high-risk stage II or III colon adenocarcinoma. Patients and Methods: Using propensity score matching, we minimized the confounding effects of sex, age, pathologic stage, tumor location, total chemotherapy cycles, and Charlson comorbidity index scores on adjuvant treatment outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. We selected the patients from the Taiwan Cancer Registry database and divided them into four groups: Group 1, comprising patients who received surgery alone; group 2, comprising those who received adjuvant fluoropyrimidine alone; group 3, comprising those who received adjuvant oxaliplatin-fluoropyrimidine-leucovorin (FOLFOX); and group 4, comprising those who received adjuvant folinic acid-fluorouracil-irinotecan (FOLFIRI). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs, as well as the 95% confidence intervals (Cis)) for mortality observed for groups 1, 2, and 4 relative to group 3 were 1.55 (1.32 to 1.82), 1.22 (1.05 to 1.43), and 2.97 (2.43 to 3.63), respectively. After a stratified subgroup analysis for high-risk stage II colon adenocarcinoma, we noted that the aHR (95% CI) for mortality for group 2 relative to group 3 was 0.52 (0.30 to 0.89). Conclusions: Adjuvant fluoropyrimidine alone is the most optimal regimen for patients with high-risk stage II colon adenocarcinoma compared with the other adjuvant chemotherapy regimens. Adjuvant FOLFOX can serve as an optimal regimen for patients with pathologic stage III colon adenocarcinoma, regardless of age, sex, or tumor location.

Download Full-text

Adjuvant therapy in the treatment of resected nonmetastatic gallbladder cancer of stage II-IV: A generalized propensity score analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.471 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 471-471

Author(s):

Wenze Wan ◽

Bohao Zheng ◽

Wentao Sun ◽

Jiwen Wang ◽

Sheng Shen ◽

...

Keyword(s):

Propensity Score ◽

Adjuvant Therapy ◽

Gallbladder Cancer ◽

Survival Benefit ◽

Propensity Score Analysis ◽

Stage Ii ◽

Stage Iii ◽

Adjuvant Therapies ◽

Significant Difference ◽

Generalized Propensity Score

471 Background: The benefit of adjuvant therapy for gallbladder cancer (GBC) remains controversial due to the limited evidence. The current study was aimed to explore the efficacy of adjuvant therapy in patients with resected non-metastatic GBC and to establish a prognosis model to predict the survival benefit of GCB patients with different adjuvant therapies. Methods: Patients with resected non-metastatic GBC of stage II-IV were selected from the Surveillance, Epidemiology, and End Results database and divided into non-radiotherapy and chemotherapy (NCRT) group, chemotherapy (CT) group, and chemoradiotherapy (CRT) group. Generalized propensity score (GPS) and inverse probability of treatment weighting (IPTW) was used to reduce the imbalances between groups. Nomogram was constructed based on Cox proportional hazard model, and the model was validated for discrimination and calibration. Results: Among the 2689 enrolled patients, 1193 (44.4%) patients were classified as stage II, 1371 (51.0%) as stage III, and 125 (4.6%) as stage IV according to the 8th American Joint Commotion Cancer staging manual. Patients in NCRT, CT, and CRT groups were 1703, 444, and 542 respectively. After the IPTW, absolute standardized differences of baseline characteristics were less than 0.1 both in patients with stage II tumors and with stage III-IV tumors. In patients with GBC of stage II, no significant difference in OS was observed between the three treatment groups (P > 0.05). In patients with GBC of stage III-IV, CT group has a superior OS compared with the NCRT group (P < 0.001), and CRT group has a superior OS compared with the CT(P < 0.001) and NCRT (P < 0.001) group. Sensitivity analysis showed consistent results. A nomogram was constructed for patients with stage III-IV tumors to predict the survival benefit of adjuvant therapies. The C-index was 0.673 (95% CI: 0.654-0.692) in the validation using the training set (diagnosed at 2004-2012) and was 0.707 (95% CI: 0.677-0·739) in the internal validation using the validation set (diagnosed at 2013-2015). The calibration curves indicated that the predicted probability closely corresponded to the actual observation OS. Conclusions: Patients with GBC of stage II could not benefit from adjuvant therapy. Patients with GBC of stage III-IV could benefit from chemotherapy and chemoradiotherapy while chemoradiotherapy provide a superior OS. A nomogram was built to predict the survival benefit of different adjuvant therapies in patients with GBC of stage III-IV.

Download Full-text

Adjuvant Therapy in Resected Nonmetastatic Stage II–IV Gallbladder Cancer: A Generalized Propensity Score Analysis

Oncology Research and Treatment ◽

10.1159/000517113 ◽

2021 ◽

pp. 1-9

Author(s):

Wenze Wan ◽

Bohao Zheng ◽

Wentao Sun ◽

Jiwen Wang ◽

Sheng Shen ◽

...

Keyword(s):

Propensity Score ◽

Adjuvant Therapy ◽

Gallbladder Cancer ◽

Propensity Score Analysis ◽

Stage Iv ◽

Stage Ii ◽

Stage Iii ◽

Adjuvant Therapies ◽

Generalized Propensity Score ◽

Clinical Benefits

Background: The clinical benefits and efficacies of adjuvant therapies for gallbladder cancer (GBC) have not been verified due to insufficient clinical evidence. Methods: Patients with resected nonmetastatic stage II–IV GBC were selected from the Surveillance, Epidemiology, and End Results database and distributed into nonchemotherapy and chemoradiotherapy (NCRT), chemotherapy (CT), and chemoradiotherapy (CRT) groups. Generalized propensity score and inverse probability of treatment weighting (IPTW) were used to reduce the imbalances between groups. Results: A total of 2,689 patients were enrolled, among whom 1,193 (44.4%) were classified as stage II, 1,371 (51.0%) as stage III, and 125 (4.6%) as stage IV GBC. A total of 1,703, 444, and 542 patients were placed in the NCRT, CT, and CRT groups, respectively. After the IPTW, there were no significant differences in overall survival (OS) between the 3 treatment groups (p > 0.05) in stage II GBC patients. In patients with stage III–IV GBC, the CT group exhibited a superior OS compared to the NCRT group (p < 0.001). In addition, the CRT group exhibited a superior OS compared to the CT (p < 0.001) and NCRT (p < 0.001) groups. For patients with stage III–IV tumors, a nomogram was constructed to predict the survival benefits of adjuvant therapies. Conclusion: Patients with stage II GBC may not benefit from adjuvant therapy, while patients with stage III–IV GBC were shown to benefit from chemotherapy and chemoradiotherapy. Furthermore, chemoradiotherapy exhibited a superior OS. Nevertheless, the results need to be explained in the context of retrospective studies.

Download Full-text

Utilization and effectiveness of adjuvant chemotherapy (ACT) for colon cancer (CC) in the general population.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.702 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 702-702

Author(s):

James Joseph Biagi ◽

William J. Mackillop ◽

Sulaiman Nanji ◽

Xuejiao Wei ◽

Yingwei Peng ◽

...

Keyword(s):

High Risk ◽

General Population ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards Model ◽

Stage Ii ◽

Stage Iii ◽

High Risk Disease ◽

Study Population ◽

Geographic Regions

702 Background: International guidelines recommend ACT for patients (pts) with stage III CC based on level I evidence showing improved survival. For stage II CC ACT is not routinely recommended but may be considered for pts with high-risk features. Here we describe practice patterns and outcomes associated with ACT in a routine population-based setting. Methods: All CC cases treated with surgery in Ontario 2002-2008 were identified using the population-based Cancer Registry. Electronic treatment records were linked to the registry to identify surgical procedures and utilization of ACT. Pathology reports were obtained for a 25% random sample of all cases to obtain details of extent of disease; pts with stage II or III were included in the study population. High-risk stage II was defined as: T4, <12 lymph nodes, poorly differentiated histology and/or lymphovascular invasion. Logistic regression was used to evaluate factors associated with ACT utilization. Cox proportional hazards model was used to evaluate cancer-specific (CSS) and overall (OS) survival. Results: The study population included 2,801 stage III and 2,488 stage II pts (47% of which were high-risk). In the stage III subgroup 66% received ACT, but was 90% among ages 20-49 vs 68% for ages 70-79 (p<0.001). ACT was associated with increased CSS (HR 0.63, 95% CI 0.54-0.73) and OS (HR 0.63, 95% CI 0.55-0.71). Among all stage II pts 18% received ACT but 24% in the high-risk disease subset. ACT utilization was higher in younger patients (51% for ages 20-49 vs. 16% ages 70-79, p<0.001) and varied across geographic regions (range 10-39%, p<0.001). Among all stage II pts ACT was not associated with improved CSS (HR 1.41, 95%CI 1.09-1.82) or OS (HR 1.16, 95%CI 0.94-1.42). Stratified analysis for high-risk stage II disease also did not show benefit to ACT (CSS HR 1.14, 95%CI 0.84-1.55; OS HR 1.02, 95%CI 0.79-1.31). Conclusions: One third of pts with stage III CC in the general population do not receive ACT, with age the strongest predictor of treatment. For stage II pts, ACT utilization varies substantially across age groups and geographic regions. ACT is associated with improved CSS and OS in stage III pts but not stage II pts, including those with high-risk disease.

Download Full-text

Evaluation of Postoperative Chemotherapy Duration of Capecitabine-Alone Regimen for Surgery Treated Elderly Colon Cancer Patients : A Cohort Study

10.21203/rs.3.rs-410084/v1 ◽

2021 ◽

Author(s):

Weiwei Chen ◽

Hongmin Dong ◽

Gang Wang ◽

Juan Chen ◽

Wenling Wang

Keyword(s):

Colon Cancer ◽

Cohort Study ◽

High Risk ◽

Cancer Patients ◽

Threshold Effect ◽

Postoperative Chemotherapy ◽

Stage Ii ◽

Stage Iii ◽

Proportional Hazard ◽

Cox Proportional Hazard

Abstract Background: Only 50-70% elderly colon cancer patients could complete a six-month postoperative chemotherapy. It is unknown whether a shorter duration of postoperative capecitabine-alone chemotherapy would not compromise the survival. We thus conducted this study to analyze the association between postoperative chemotherapy duration of capecitabine-alone regimen and cancer specific survival (CSS) in the surgery treated elderly colon cancer patients.Methods: We performed a retrospective cohort study in surgery treated stage III and high-risk stage II colon cancer patients aged >= 70 from two medical centers. Cox proportional hazard regression models were utilized to calculate crude and adjusted hazard ratios (HRs). The non-linear relationship between postoperative chemotherapy duration and CSS was analyzed through the restricted cubic spline regression analysis, and the threshold effect was calculated by the two-piece-wise Cox proportional hazard model.Results: A total of 1,217 surgery treated colon cancer patients between August 1, 2013 and September 1, 2019 were reviewed and 257 stage III and high-risk stage II patients aged >= 70 were finally enrolled. Postoperative chemotherapy with capecitabine was delivered in 114 patients and 143 cases only received surgery. The capecitabine duration was generally associated with a 11% risk decrease in death (HR=0.89, 95% confidence interval (CI) 0.82 - 0.96). Non-linearity exploration suggested a threshold effect of capecitabine duration on CSS in stage III disease. The HR for death was 0.79 (95% CI: 0.68 - 0.92) with duration <= 16 (week) while 1.34 (95% CI: 0.91 – 1.97) with duration > 16 (week).Conclusions: The postoperative capecitabine duration was significantly associated with CSS in elderly colon cancer. However, a threshold effect of capecitabine duration on survival may suggest a short-term chemotherapy could be an alternative for the conventional six-month regimen in the elderly stage III colon cancer.

Download Full-text

Duration of FOLFOX Adjuvant Chemotherapy in High-Risk Stage II and Stage III Colon Cancer With Deficient Mismatch Repair

Frontiers in Oncology ◽

10.3389/fonc.2020.579478 ◽

2020 ◽

Vol 10 ◽

Author(s):

Huabin Hu ◽

Zehua Wu ◽

Chao Wang ◽

Yan Huang ◽

Jianwei Zhang ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Propensity Score ◽

Mismatch Repair ◽

Therapy Group ◽

Stage Ii ◽

Stage Iii ◽

Deficient Mismatch Repair ◽

The Impact

BackgroundWe evaluated the impact of 3 months of mFOLFOX6 adjuvant chemotherapy or surgery alone in comparison with 6 months of mFOLFOX6 on disease-free survival (DFS) in deficient mismatch repair (dMMR) colon cancer (CC) patients.MethodsThis retrospective study identified a cohort of patients with high-risk stage II and III dMMR CC who underwent curative surgery between May 2011 and July 2019. DFS was compared using the Kaplan-Meier survival methods and Cox proportional hazards models. Propensity-score matching was performed to reduce imbalance in baseline characteristics.ResultsA total of 242 dMMR CC patients were identified; 66 patients received 6 months of mFOLFOX6, 87 patients received 3 months of mFOLFOX6, and 89 patients were treated with surgery alone. The 3-year DFS rate was 72.8% in 3-month therapy group and 86.1% in 6-month therapy group, with a hazard ratio (HR) of 2.78 (95CI%, 1.18 to 6.47; P= 0.019). The difference in DFS between surgery alone group and 6-month therapy group was also observed but was nonsignificant (HR= 2.30, 95%CI, 0.99 to 5.38; P=0.054). The benefit of 6-month therapy in DFS compared with 3-month therapy group was pronounced for patients with stage III (HR=2.81, 95%CI, 1.03 to 7.67; P=0.044) but not for high-risk stage II patients. Propensity score matched analysis confirmed a DFS benefit in the 6-month therapy group.ConclusionThis study suggested that a 6-month duration of mFOLFOX6 adjuvant chemotherapy in dMMR CC patients may be associated with improved DFS compared with 3-month therapy, particularly in patients with stage III. The observational nature of the study implies caution should be taken in the interpretation of these results.

Download Full-text

Pilot study of the combination of capecitabine + oxaliplatin as adjuvant therapy for patients with stage III and high risk stage II colon cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.15093 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 15093-15093

Author(s):

C. Olier ◽

C. Reyna ◽

J. M. Aramendia ◽

J. Rodriguez ◽

A. Viudez ◽

...

Keyword(s):

Colon Cancer ◽

Pilot Study ◽

High Risk ◽

Adjuvant Therapy ◽

Stage Ii ◽

Stage Iii ◽

Stage Ii Colon Cancer

Download Full-text

Association of NCCN guideline adherence with improved survival in high-risk stage II and stage III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.543 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 543-543 ◽

Cited By ~ 1

Author(s):

Genevieve Marie Boland ◽

Yj Chiang ◽

Ryaz Chagpar ◽

Yan Xing ◽

Chung-Yuan Hu ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Treatment Guidelines ◽

Colon Adenocarcinoma ◽

Relative Survival ◽

Stage Ii ◽

Stage Iii ◽

Adherence To Guidelines ◽

Nccn Guidelines ◽

Stage Iii Colon Cancer

543 Background: Evidence-based treatment guidelines have been proposed as a quality metric for cancer care. There is significant variability in the treatment of high-risk stage II (defined by tumor depth, histologic grade, margin status, and # of nodes retrieved) and stage III colon cancer patients in the National Cancer Database (NCDB). This study examines whether adherence to guidelines is associated with improved outcomes. Methods: Patients with colon adenocarcinoma (1998-2002) were identified from the NCDB. The stage-specific NCCN guidelines were used to classify patients into two groups based on adherence to guidelines (adherent or non-adherent). Overall survival (OS) and relative survival (RS) were calculated for both groups. Relative survival was used as a surrogate for disease-specific survival and calculated using the methods of Dickman et al. Results: A total of 77,350 patients were included in the analytic cohort. Stage-specific outcomes were compared and stage is an independent predictor of survival. As reported in our previous analyses, nonadherence as a result of omission of chemotherapy, was noted in 64.3% and 26.4% of high-risk stage II and stage III patients, respectively. Nonadherence was associated with decreased OS and RS with a hazard ratio for death of 1.43 (95% CI: 1.33, 1.54) for high-risk stage II and 1.89 (95% CI: 1.82, 1.95) for stage III (p < 0.001, Table) RS. Additionally, regression analysis demonstrated that gender, age, race, insurance, income, and type of facility were associated with differences in RS. Conclusions: Guideline-based practice, particularly for high-risk stage II and stage III colon cancer, is associated with improved survival outcomes. Therefore, these guidelines may be appropriate as a metric of performance comparable across various institutions. Additionally, factors associated with deviations from guidelines can be used to focus improvements in the access to and delivery of cancer treatment. [Table: see text]

Download Full-text