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Whether Patients With Stage Ⅱ/Ⅲ Colorectal Cancer Benefit From Adjuvant Chemotherapy: A Modeling Analysis of Literature Aggregate Data.

ABSTRACT: Objective: This study used model analysis to clarify the benefits and risks of postoperative adjuvant chemotherapy compared with surgery alone in patients with stage II/III colorectal cancer. Methods: Clinical trials involving patients with stage II/III colorectal cancer who underwent surgery alone or those who received post-surgical adjuvant chemotherapy were searched in the PubMed and embase databases. By establishing a survival model, the overall survival (OS) and disease-free survival (DFS) of patients who underwent surgery alone or postoperative adjuvant chemotherapy were quantitatively analyzed to compare the differences between the two. In addition, the incidence of grade 3/4 adverse reactions in the adjuvant chemotherapy group was analyzed using the random effects model in the single-arm meta-analysis. Results: A total of 34 studies containing 33,069 patients were included in the analysis. This study found that postoperative adjuvant chemotherapy can effectively improve the OS and DFS of patients with colorectal cancer. The median OS of the adjuvant chemotherapy group and the surgery-only group was 118.8 months (95% CI: 96.6, 146.6) and 74.6 months (95% CI: 57.8, 96.1) respectively; and median DFS was 86.3 months (95% CI: 67.6, 110.6) and 40.8 months (95% CI: 23.7, 69.6) in the adjuvant chemotherapy and surgery-only groups, respectively. Common grade 3/4 adverse reactions in the adjuvant chemotherapy group include diarrhea, stomatitis, leukopenia, and nausea or vomiting, with an incidence of approximately 3%-6%. Conclusion: Patients with mid-stage colorectal cancer can benefit significantly from postoperative adjuvant chemotherapy. This study provides the necessary quantitative information for decision-making regarding the benefits and risks of receiving adjuvant chemotherapy after resection in patients with colorectal cancer.

SUBMITTER: Zha S

PROVIDER: S-EPMC8864068 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Whether Patients With Stage Ⅱ/Ⅲ Colorectal Cancer Benefit From Adjuvant Chemotherapy: A Modeling Analysis of Literature Aggregate Data.

Zha Sijie S Li Ting T Zheng Qingshan Q Li Lujin L

Frontiers in pharmacology 20220209

<b>Objective:</b> This study used model analysis to clarify the benefits and risks of postoperative adjuvant chemotherapy compared with surgery alone in patients with stage II/III colorectal cancer. <b>Methods:</b> Clinical trials involving patients with stage II/III colorectal cancer who underwent surgery alone or those who received post-surgical adjuvant chemotherapy were searched in the PubMed and embase databases. By establishing a survival model, the overall survival (OS) and disease-free s ...[more]

PMID: 35222041

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Project description:BackgroundThe clinical benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) is controversial. This study aimed to explore novel gene signature to predict outcome benefit of postoperative 5-Fu-based therapy in stage II CRC.MethodsGene-expression profiles of stage II CRCs from two datasets with 5-Fu-based adjuvant chemotherapy (training dataset, n = 212; validation dataset, n = 85) were analyzed to identify the indicator. A systemic approach by integrating gene-expression and protein-protein interaction (PPI) network was implemented to develop the predictive signature. Kaplan-Meier curves and Cox proportional hazards model were used to determine the survival benefit of adjuvant chemotherapy. Experiments with shRNA knock-down were carried out to confirm the signature identified in this study.ResultsIn the training dataset, we identified 44 PPI sub-modules, by which we separate patients into two clusters (1 and 2) having different chemotherapeutic benefit. A predictor of 11 PPI sub-modules (11-PPI-Mod) was established to discriminate the two sub-groups, with an overall accuracy of 90.1%. This signature was independently validated in an external validation dataset. Kaplan-Meier curves showed an improved outcome for patients who received adjuvant chemotherapy in Cluster 1 sub-group, but even worse survival for those in Cluster 2 sub-group. Similar results were found in both the training and the validation dataset. Multivariate Cox regression revealed an interaction effect between 11-PPI-Mod signature and adjuvant therapy treatment in the training dataset (RFS, p = 0.007; OS, p = 0.006) and the validation dataset (RFS, p = 0.002). From the signature, we found that PTGES gene was up-regulated in CRC cells which were more resistant to 5-Fu. Knock-down of PTGES indicated a growth inhibition and up-regulation of apoptotic markers induced by 5-Fu in CRC cells.ConclusionsOnly a small proportion of stage II CRC patients could benefit from adjuvant therapy. The 11-PPI-Mod as a potential predictor could be helpful to distinguish this sub-group with favorable outcome.

Project description:BackgroundDespite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy.MethodsWe retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3.FindingsA total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001).InterpretationIASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.

Dataset Information

Whether Patients With Stage Ⅱ/Ⅲ Colorectal Cancer Benefit From Adjuvant Chemotherapy: A Modeling Analysis of Literature Aggregate Data.

Publications

Whether Patients With Stage Ⅱ/Ⅲ Colorectal Cancer Benefit From Adjuvant Chemotherapy: A Modeling Analysis of Literature Aggregate Data.

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