Dataset Information

Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

ABSTRACT:

Background

Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy.

Methods

A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients' risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models.

Results

A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69-0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23-0.69), whereas it was of no benefit in patients with a MSKCC-CRS ? 2 (HR 0.90; 95% CI 0.57-1.43).

Conclusions

The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

SUBMITTER: Rahbari NN

PROVIDER: S-EPMC4008001 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

Rahbari Nuh N NN Reissfelder Christoph C Schulze-Bergkamen Henning H Jäger Dirk D Büchler Markus W MW Weitz Jürgen J Koch Moritz M

BMC cancer 20140311

<h4>Background</h4>Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy.<h4>Methods</h4>A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoa ...[more]

PMID: 24612620

Similar Datasets

Project description:ImportanceTo date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases.ObjectiveTo assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases.Design, setting, and participantsIn this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates.ExposuresAdjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively.Main outcomes and measuresOverall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity.ResultsOf 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95).Conclusions and relevanceFindings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.

Project description:ImportanceDistant recurrence following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma is common. Adjuvant chemotherapy may improve survival.ObjectiveTo compare adjuvant chemotherapy with postoperative observation following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma.Design, setting, and participantsPropensity score-matched analysis using the National Cancer Database. We included adult patients who received a diagnosis between 2006 and 2013 of clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia who were treated with preoperative chemoradiotherapy and curative-intent resection. Patients receiving adjuvant chemotherapy were matched by propensity score to patients undergoing postoperative observation.ExposuresAdjuvant chemotherapy and postoperative observation.Main outcomes and measuresOverall survival.ResultsWe identified 10?086 patients (8840 [88%] male; mean [SD] age, 61 [9.5] years), 9272 in the postoperative observation group and 814 in the adjuvant chemotherapy group. Patients receiving adjuvant chemotherapy were younger (18-54 years: 252 [31%] vs 1989 [21%]; P?<?.001) and were more likely to have advanced disease (ypT3/4: 458 [62%] vs 3531 [46%]; P?<?.001; ypN+: 572 [72%] vs 3428 [39%]; P?<?.001), as well as shorter postoperative inpatient stays (>2 weeks: 94 [13%] vs 1589 [20%]; P?<?.001). A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group. Adjuvant chemotherapy was associated with improved overall survival compared with postoperative observation (median survival: 40 months; 95% CI, 36-46 months vs 34 months; 95% CI, 32-35 months; stratified log-rank P?<?.001; hazard ratio, 0.79; 95% CI, 0.72-0.88). Overall survival at 1, 3, and 5 years was 88%, 47%, and 34% in the observation group, and 94%, 54%, and 38% in the adjuvant chemotherapy group, respectively. Adjuvant chemotherapy was associated with a survival benefit compared with postoperative observation in most patient subgroups.Conclusions and relevanceFor patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection, adjuvant chemotherapy was associated with improved overall survival. Our findings have important implications for the postoperative treatment of this patient group for which few data are available.

Project description:Rationale: Hepatectomy and adjuvant chemotherapy after resection of colorectal liver metastases (CRLM) may improve survival, however, patients which may benefit cannot currently be identified. Postoperative circulating tumor DNA (ctDNA) analysis can detect minimal residual disease (MRD) and predict the prognosis and efficacy of adjuvant chemotherapy. Our study aims to determine the impact of serial ctDNA analysis to predict the outcome among patients undergoing resection of CRLM. Methods: Between May 2018 and October 2019, 91 CRLM patients were prospectively enrolled. Whole exome sequencing was performed in 50 primary and 48 metastatic liver tissues. Targeted sequencing of 451 cancer relevant genes was performed in 50 baseline plasma to determine plasma-tissue concordance. We prospectively investigated changes in the amount and constitution of ctDNA in 271 serial plasma samples taken at different time points (baseline, pre-operation, post-operation, post-operative adjuvant chemotherapy (post-ACT) and recurrence) during the treatment of CRLM. Results: Detected molecular alterations were highly consistent among baseline ctDNA, primary and liver metastases tissue. Patients with a higher variant allele frequency (VAF) level at baseline ctDNA represent a higher tumor burden, and decreased ctDNA during pre-operative chemotherapy predicted better tumor response. Patients with detectable post-operative and post-ACT ctDNA were associated with significantly shorter recurrence-free survival (RFS). ROC analysis showed that post-ACT ctDNA status was superior to post-operative ctDNA status in predicting RFS with an AUROC of 0.79. A significant difference in overall recurrence rate was observed in patients with detectable vs undetectable levels of ctDNA after resection of CRLM (79.4% vs 41.7%) and after completion of adjuvant chemotherapy (77.3% vs 40.7%). During adjuvant chemotherapy, patients with decreased ctDNA VAF after adjuvant chemotherapy had a recurrence rate of 63.6%, compared to 92.3% in patients with increased ctDNA VAF. Conclusions: We envision that dynamic ctDNA analysis, especially in a post-ACT setting, might be used to not only reflect MRD but also to determine rational personalized adjuvant therapy after the resection of CRLM.

Dataset Information

Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

Background

Methods

Results

Conclusions

Publications

Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets