Dataset Information

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

ABSTRACT:

Background

For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers.

Methods

Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses.

Results

We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs.

Conclusions

These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.

SUBMITTER: Liao L

PROVIDER: S-EPMC10835817 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

Liao Leen L Tang Jinghua J Hong Zhigang Z Jiang Wu W Li Yuan Y Kong Lingheng L Han Kai K Hou Zhenlin Z Zhang Chenzhi C Zhou Chi C Zhang Linjie L Sui Qiaoqi Q Xiao Binyi B Mei Weijian W Yu Jiehai J Yang Wanjun W Pan Zhizhong Z Ding Pei-Rong PR

BMC cancer 20240202 1

<h4>Background</h4>For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers.<h4>Methods</h4>Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, a ...[more]

PMID: 38302968

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Project description:BackgroundThe addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.Subjects and methodsPatients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided.ResultsThe survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity.ConclusionThe addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.

Project description:ImportanceThe prognostic impact of DNA mismatch repair (MMR) status in stage III colon cancer patients receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) adjuvant chemotherapy remains controversial.ObjectiveTo determine the association of MMR status with disease-free survival (DFS) in patients with stage III colon cancer treated with FOLFOX.Design, setting, and participantsThe evaluated biomarkers for MMR status were determined from prospectively collected tumor blocks from patients treated with FOLFOX in 2 open-label, phase 3 randomized clinical trials: NCCTG N0147 and PETACC8. The studies were conducted in general community practices, private practices, and institutional practices in the United States and Europe. All participants had stage III colon adenocarcinoma. They were enrolled in NCCTG N0147 from February 2004 to November 2009 and in PETACC8 from December 2005 to November 2009.InterventionsPatients in the clinical trials were randomly assigned to receive 6 months of chemotherapy with FOLFOX or FOLFOX plus cetuximab. Only those patients treated with FOLFOX alone were included in the present study.Main outcomes and measuresAssociation of MMR status with DFS was analyzed using a stratified Cox proportional hazards model. Multivariable models were adjusted for age, sex, tumor grade, pT/pN stage, tumor location, ECOG (Eastern Cooperative Oncology Group) performance status, and BRAF V600E mutational status.ResultsAmong 2636 patients with stage III colon cancer treated with FOLFOX, MMR status was available for 2501. Of these, 252 (10.1%) showed deficient MMR status (dMMR; 134 women, 118 men; median age, 59 years), while 2249 (89.9%) showed proficient MMR status (pMMR; 1020 women, 1229 men; median age, 59 years). The 3-year DFS rates in the dMMR and pMMR groups were 75.6% and 74.4%, respectively. By multivariate analysis, patients with dMMR phenotype had significantly longer DFS than those with pMMR (adjusted hazard ratio, 0.73; 95% CI, 0.54-0.97; P = .03).Conclusions and relevanceThe deficient MMR phenotype remains a favorable prognostic factor in patients with stage III colon cancer receiving FOLFOX adjuvant chemotherapy.Trial registrationclinicaltrials.gov Identifier: NCT00079274 for the NCCTG N0147 trial and EudraCT identifier: 2005-003463-23 for the PETACC8 trial.

Project description:BackgroundDeficient mismatch repair (dMMR) is associated with a good prognosis in patients with stage II colon cancer and observation is recommended after surgery in these patients. In contrast, patients with high-risk factors and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is associated with a poor prognosis in colon cancer. However, the prognosis and treatment of patients with dMMR colon cancer combined with high-risk factors or KRAS mutation remains unclear. This study aimed to evaluate whether patients with dMMR colon cancer combined with high-risk factors or KRAS mutation require further treatment.MethodsThis single-center retrospective study included patients who received radical surgical resection and mismatch repair (MMR) immunohistochemical detection at The Sixth Affiliated Hospital of Sun Yat-sen University between May 2011 and March 2021. The high-risk factors and KRAS mutation were assessed by clinicopathological data and targeted sequencing. Associations with disease-free survival (DFS) were evaluated using multivariable Cox models.ResultsAmong the 1,357 patients with stage II colorectal cancer included, 226 of these patients had dMMR. Patients in the dMMR group were more likely to be younger [<50 years: odds ratio (OR) =0.401, 95% CI: 0.288-0.558, P<0.001], with poor differentiation (OR =5.800, 95% CI: 3.437-9.787, P<0.001), no perineural invasion (OR =0.132, 95% CI: 0.047-0.368, P<0.001), and more than 12 excised lymph nodes (OR =0.427, 95% CI: 0.188-0.968, P=0.042). The disease-free survival (DFS) of patients with stage II dMMR colon cancer with high-risk factors was similar to that of patients without high-risk factors (hazard ratio (HR) =1.285, 95% CI: 0.273-6.051, P=0.607). A total of 836 patients had complete data regarding KRAS status. Compared with KRAS wild-type patients, patients with KRAS gene mutation had a trend of poor prognosis in patients with stage II colon cancer (HR=1.483, 95% CI: 0.983-2.239, P=0.061). In addition, dMMR appeared to be a protective factor in patients with KRAS mutation (HR =0.138, 95% CI: 0.019-1.002, P=0.0501).ConclusionsThe survival of patients with stage II dMMR colon cancer with high-risk factors was similar to that of patients without high-risk factors, regardless of the presence of KRAS mutation.

Dataset Information

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

Background

Methods

Results

Conclusions

Publications

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

Similar Datasets

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