scholarly journals Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS790-TPS790
Author(s):  
Eric P van der Stok ◽  
Cornelis Verhoef ◽  
Dirk J. Grunhagen ◽  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Risk Profile ◽  
Colorectal Metastases ◽  
High Risk Patients ◽  
Risk Patients ◽  
Neo Adjuvant Chemotherapy

TPS790 Background: Colorectal carcinoma is a leading cause of cancer death worldwide, mostly as a consequence of metastatic disease. If metastases are confined to the liver, surgical resection is the only therapy providing potential for cure. Efforts to improve the outcome of hepatectomy for colorectal liver metastases (CRLM) by combining surgery with chemotherapy have failed to demonstrate overall survival (OS) benefit. This may partly be explained by the fact that previous trials on this subject involved strict inclusion criteria. Consequently, patients with a high oncological risk profile - who might benefit the most from chemotherapy – might have been underrepresented in previous trials. Several Clinical Risk Scores (CRS) have been developed predicting patients’ prognosis after resection of CRLM. The most widely used and validated CRS was described by Fong et al., which characterizes 2 risk groups (high versus low) based on 5 independent clinicopathologic prognostic variables. Each variable is assigned 1 point. Multiple retrospective observations showed that neo-/adjuvant chemotherapy induced significant OS benefit in patients with a high-risk profile (CRS of 3 to 5 points). The CHARISMA trial evaluates the impact of neo-adjuvant chemotherapy in patients with high-risk, primarily resectable liver-only colorectal metastases. We hypothesize that adding neo-adjuvant chemotherapy to surgery improves OS in this high-risk patient group. Methods: The CHARISMA trial is a randomized (1:1) phase III trial. Patients receive either surgery only for CRLM (arm A) or 6 cycles of neo-adjuvant Oxaliplatin + Capecitabine, followed by surgery (arm B). The primary endpoint is OS. On basis of retrospective data, the expected hazard ratio for arm B is 0.60. With an expected 5-year OS of 25% in arm A, a two-sided significance level α = 0.05 and power 1 - β = 0.8, 224 patients have to be recruited. Major eligibility criteria are: liver-only metastases, primarily resectable CRLM, high-risk patients (CRS 3-5). The trial is currently accruing in 10 Dutch liver centers and is registered in the “Dutch Trial Register”: NTR4893 ( www.trialregister.nl ). Clinical trial information: NTR4893.

Outcome of patients with early ovarian cancer undergoing three courses of adjuvant chemotherapy following complete surgical staging

2005 ◽  
Vol 15 (4) ◽  
pp. 601-605 ◽  
Author(s):  
M. Shimada ◽  
J. Kigawa ◽  
Y. Kanamori ◽  
H. Itamochi ◽  
T. Oishi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Surgical Staging ◽  
High Risk Patients ◽  
Platinum Based Chemotherapy ◽  
Early Ovarian Cancer ◽  
Risk Patients ◽  
Stage Ia

We conducted the present study to determine the outcome of patients with early ovarian cancer who underwent three courses of adjuvant chemotherapy after complete surgical staging. One hundred consecutive patients with stage I–II epithelial ovarian cancer who had undergone complete surgical staging and received three courses of platinum-based chemotherapy were entered in this study. Twenty-one patients were low risk, defined as stage IA–B, grade 1 and histologic types except for clear cell adenocarcinoma, and remaining 79 were high risk. All patients with stage IA or IB, whatever histologic type and histopathologic grade, were alive without disease. The 5-year survival rate was 89.4% for patients with stage IC and 76.2% for those with stage II. The 5-year survival rate for low- and high-risk patients was 100% and 89.4%, respectively. The survival rate for grade 1 was significantly better than that for grade 2 or 3. Multivariate analysis revealed that histologic grade was an independent prognostic factor in stage IC–II ovarian cancer. The outcome of patients with early ovarian cancer undergoing three courses of chemotherapy after complete surgical staging was favorable even in high-risk patients

Genomic classifiers (ColoPrint/MSI-Print) predict outcome and chemotherapy benefit in stage II and III colon cancer patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 378-378 ◽  
Author(s):  
Scott Kopetz ◽  
Zhi-Qin Jiang ◽  
Michael J. Overman ◽  
Christa Dreezen ◽  
Sun Tian ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Additional Treatment ◽  
Low Risk ◽  
Stage Ii ◽  
High Risk Patients ◽  
Risk Patients

378 Background: Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment. ColoPrint is a gene expression classifier that distinguish patients with low or high risk of disease relapse. It was developed using whole genome expression data and has been validated in public datasets, independent European patient cohorts and technical studies (Salazar 2011 JCO, Maak 2012 Ann Surg). Methods: In this study, the commercial ColoPrint test was validated in stage II (n=96) and III patients (n=95) treated at the MD Anderson Cancer Center from 2003 to 2009. Frozen tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 64 months) were available. The 64-gene MSI-signature developed to identify patients with deficient mismatch repair system (Tian 2012 J Path) was evaluated for its accuracy to identify MSI patients and also for prognosis. Results: In this cohort, ColoPrint classified 56% of stage II and III patients as being at low risk. The 3-year Relapse-Free-Survival (RFS) was 90.6% for Low Risk and 78.4% for High Risk patients with a HR of 2.33 (p=0.025). In uni-and multivariate analysis ColoPrint and stage were the only significant factors to predict outcome. The MSI-signature classified 47 patients (24.6%) as MSI-H and most MSI-H patients were ColoPrint low risk (81%). Patients who were ColoPrint low risk and MSI-H by signature had the best outcome with a 3-year RFS of 95% while patients with ColoPrint high risk had a worse outcome independently of the MSI-status. Low risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment (90.1% 3-year RFS for treated patients, 91.4% for untreated patients) while ColoPrint high risk patients treated with adjuvant chemotherapy had 3-year RFS of 84%, compared to 70.1% 3-year RFS in untreated patients (p=0.026). Conclusions: The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help the identification of patients at higher risk who are more likely to benefit from additional treatment

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