scholarly journals Impact of relative dose intensity of FOLFOX adjuvant chemotherapy on risk of death among stage III colon cancer patients

2020 ◽  
Author(s):  
Meijiao Zhou ◽  
Trevor D. Thompson ◽  
Hui-Yi Lin ◽  
Vivien W. Chen ◽  
Jordan J. Karlitz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Dose Intensity ◽  
Low Risk ◽  
Stage Iii ◽  
Risk Of Death ◽  
Stage Iii Colon Cancer ◽  
Risk Patients ◽  
Overall Mortality

Abstract Background: Clinical trials have suggested high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) stage III colon cancer patients might need different doses of FOLFOX to reserve a similar survival probability. Observational studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on cancer survival for patients with stage III colon cancer, but nonetheless, the studies focused on very specific populations, and none performed stratified analysis by risk profiles. This study aims to identify the optimal RDI of FOLFOX administered for high-risk and low-risk stage III colon cancer patients. Methods: Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by the eight population-based cancer registries for a CDC National Program of Cancer Registries (NPCR) project focused on Comparative Effectiveness Research. We employed Kaplan-Meier method, cumulative incidence function (CIF), Multivariable Cox model and Fine-Gray competing risks model to explore Optimal RDI defined as the lowest RDI administered without significant differences in either overall or cause-specific death. Results: Among the 168 high-risk patients, the optimal RDI cut-off point was 70% where there was no statistically significant difference in overall mortality (HR=1.59; 95% CI: 0.69-3.66) and cause-specific mortality (HR=1.24; 95% CI: 0.42-3.64) when RDI<70% vs. RDI≥70%, adjusting for sociodemographic and clinical covariates. When the RDI cut-off was lower than the optimal one (<55% vs. ≥55%, <60% vs. ≥60%, or <65% vs. ≥65%), the overall mortality was significantly statistically different between the two groups of each comparison. Among the 239 low-risk patients, none of the evaluated cut-offs were associated with statistically significant differences in overall and cause-specific mortalities between comparison groups. The lowest RDI we assessed was 45%, HR=0.80; 95% CI: 0.24-2.73 for the overall mortality and HR=0.53; 95% CI: 0.06-4.95 for the cause-specific mortality, when RDI<45% vs. RDI≥45%. Conclusions: To best utilize health care resources while maintaining efficacy, RDI can be maintained at a minimum of 70% for high-risk stage III colon cancer patients. For low-risk patients, we found that RDI as low as 45% did not significantly affect the risk of death.

scholarly journals Impact of relative dose intensity of FOLFOX adjuvant chemotherapy on risk of death among stage III colon cancer patients

2020 ◽  
Author(s):  
Meijiao Zhou ◽  
Trevor D. Thompson ◽  
Hui-Yi Lin ◽  
Vivien W. Chen ◽  
Jordan J. Karlitz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Dose Intensity ◽  
Low Risk ◽  
Relative Dose Intensity ◽  
Stage Iii ◽  
Risk Of Death ◽  
Stage Iii Colon Cancer ◽  
Risk Patients

Abstract Background Clinical trials have indicated high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) stage III colon cancer patients might need different doses of FOLFOX to reserve a similar survival probability. Observational studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on cancer survival for patients with stage III colon cancer, but nonetheless, the studies focused on very specific populations, and none performed stratified analysis by risk profiles. This study aims to identify the optimal RDI of FOLFOX administered for high-risk and low-risk stage III colon cancer patients.Methods Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by the eight population-based cancer registries for a CDC National Program of Cancer Registries (NPCR) project focused on Comparative Effectiveness Research. We employed Kaplan-Meier method, cumulative incidence function (CIF), Multivariable Cox model and Fine-Gray competing risks model to explore Optimal Relative Dose Intensity (RDI) defined as the lowest RDI administered without significant differences in either overall or cause-specific death.Results Among the 168 high-risk patients, the optimal RDI cut-off point was 70% where there was no statistically significant difference in overall mortality (HR=1.87; 95% CI: 0.84-4.19) and cause-specific mortality (HR=1.72; 95% CI: 0.61-4.85) when RDI<70% vs. RDI≥70%, adjusting for sociodemographic and clinical covariates. When the RDI cut-off was lower than the optimal one (<55% vs. ≥55%, <60% vs. ≥60%, or <65% vs. ≥65%), the overall and cause-specific mortalities were significantly statistically different between the two groups of each comparison. Among the 239 low-risk patients, none of the evaluated cut-offs were associated with statistically significant differences in overall and cause-specific mortalities between comparison groups. The lowest RDI we assessed was 45%, HR=0.79; 95% CI: 0.23-2.67 for the overall mortality and HR=0.49; 95% CI: 0.05-4.84 for the cause-specific mortality, when RDI<45% vs. RDI≥45%.Conclusions To best utilize health care resources while maintaining efficacy, RDI can be maintained at a minimum of 70% in high-risk stage III colon cancer patients. For low-risk patients, we found that RDI as low as 45% did not impact risk of death.

A new look at the IDEA classification: Defining novel predictive and prognostic markers in stage III colon cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 845-845
Author(s):  
Ofer Margalit ◽  
Ronac Mamtani ◽  
Yu-Xiao Yang ◽  
Kim Anna Reiss ◽  
Talia Golan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Risk Patients ◽  
Doublet Chemotherapy

845 Background: The IDEA pooled analysis compared 3 to 6 months of adjuvant chemotherapy for newly defined low- and high-risk stage III colon cancer patients, suggesting low-risk patients may be offered only 3 months of treatment. We aimed to evaluate the benefit of monotherapy vs doublet chemotherapy in low and high IDEA risk groups. Methods: Using the NCDB (2004-2014) we identified 56,728 and 47,557 individuals as low and high IDEA risk groups, respectively. We used multivariate COX regression to evaluate the magnitude of survival differences between IDEA risk groups, according to treatment intensity (doublet vs monotherapy). In a secondary analysis, we examined the predictive value of subgroups of age. Results: Low and high IDEA risk groups derived similar benefit from doublet chemotherapy compared to monotherapy, with hazard ratios of 0.83 (95%CI 0.79-0.86) and 0.80 (95%CI 0.78-0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients above the age of 72 (HR = 0.95, 95%CI 0.90-1.01) and high-risk patients above the age of 85 (HR = 0.90, 95%CI 0.77-1.05). Conclusions: IDEA risk classification does not predict benefit from doublet chemotherapy in stage III colon cancer. However, omission of oxaliplatin can be considered in IDEA low-risk patients above the age of 72.

Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with mFOLFOX6 (three versus six months) in the prospective IDEA France cohort study (PRODIGE-GERCOR).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 10-10
Author(s):  
Franck Pages ◽  
Thierry Andre ◽  
Julien Taieb ◽  
Dewi Vernerey ◽  
Julie Henriques ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cohort Study ◽  
High Risk ◽  
Cancer Patients ◽  
Predictive Value ◽  
External Validation ◽  
Disease Free Survival ◽  
Low Risk ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

10 Background: In stage III colon cancer patients treated with CAPOX, 3 months of therapy was as effective as 6 months. It was not the case for those receiving mFOLFOX6. We assessed the prognostic and predictive value of the Immunoscore (IS) in the mFOLFOX6 subgroup (90% of patients enrolled) of the IDEA France cohort study. Methods: 1200 patients randomly assigned to 3 months (n = 593) or 6 months (n = 607) of mFOLFOX6, with available tumor sample, were included. Densities of CD3+ and cytotoxic CD8+ T-cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS using the pre-defined cut-off. The IS performance to predict disease-free survival (DFS) was assessed in each arm and adjusted in multivariate Cox models. Results: In a two-category IS analysis, Low and (Int+High) IS were observed in 423 (43.5%) and 550 (56.5%) patients, respectively. Low IS identified patients with higher-risk of relapse or death (HR = 1.60; 95% CI 1.27-2.01, P < 0.0001). The 3-year DFS was 66.34% (95% CI 61.54-70.69) and 77.66% (95% CI 73.86-80.97) for Low and (Int+High) IS, respectively. In multivariate analysis, IS remained independently associated with DFS (P = 0.0007) when combined with T/N stage. A statistically significant interaction was observed for the IS predictive value for treatment duration (3 vs 6 months) in term of DFS in the whole population (P = 0.0566) and TN subgroups (Low-risk T1-3, N1 vs High-risk T4 and/or N2; P = 0.0015). The 3-year DFS of patients with (Int+High) IS in the 3-month arm was 71.5% (95% CI 65.7-76.6) versus 83.8% (95% CI, 78.8-87.8) in the 6-month arm (HR = 0.528; 95% CI 0.372-0.750; log-rank P = 0.0004); the benefit retained in low-risk and high-risk patients (all P≤0.010). 6-month mFOLFOX6 showed no significant benefit for patients with Low IS (HR = 0.836, log-rank P = 0.269). Conclusions: The IS prognostic value in patients treated with mFOLFOX6 was confirmed. Its predictive value for benefit of longer duration treatment, despite a strong statistical signal, needs to be confirmed in an external validation cohort. Clinical trial information: NCT03422601.

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

scholarly journals Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study

2020 ◽  
Author(s):  
Jolanta Żok ◽  
Michał Bieńkowski ◽  
Barbara Radecka ◽  
Jan Korniluk ◽  
Krzysztof Adamowicz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Therapy ◽  
Risk Group ◽  
Dose Intensity ◽  
Early Recurrence ◽  
Low Risk ◽  
Relative Dose Intensity ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

Abstract Background: Oxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients. Methods: The study included 365 patients treated at five oncology centers in Poland between 2000 and 2014.Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the αlevel of 0.05 was employed. Results: The median follow-up was 51.8 months (range 8.2-115.1). Early recurrence <36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt <60% of RDI-O was associated with early recurrence within 18 months after surgery (OR=2.05; 95%CI: 1.18-3.51; p=0.010),especially in low-risk group (HR=1.56 (95%CI: 0.96-2.53), p=0.07). In the multivariate analysis early recurrence was correlated with grade (OR=2.47; 95% CI: 1.25-4.8; p=0.008), pN (OR=2.63; 95% CI: 1.55-4.54; p<0.001), the number of lymph nodes harvested (OR=0.51; 95% CI: 0.29-0.86; p=0.013) and RDI-O (OR=1.91; 95%CI: 1.06-3.39; p=0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR=22.9 (95%CI: 13.9-37.6; p<0.001). Conclusions: RDI-O <60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.

Venous Thromboembolism (VTE) and Survival in a Cancer Chemotherapy Outpatient Clinic: A Retrospective Chart Review Validation of a VTE Predictive Model.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2503-2503 ◽  
Author(s):  
Julia C. Kearney ◽  
Suzanne Rossi ◽  
Keren Glinert ◽  
David H. Henry
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Mortality Rate ◽  
Predictive Model ◽  
Cancer Patients ◽  
Low Risk ◽  
Intermediate Risk ◽  
Clinical Model ◽  
Risk Patients ◽  
Overall Mortality

Abstract Abstract 2503 Poster Board II-480 Because venous thromboembolism (VTE) often occurs as a complication of cancer and chemotherapy, cancer patients have a 47-fold elevation of risk of VTE compared to the general population (Khorana et al., Journal of Thrombosis and Haemostasis 2007). However, until recently there was not a model to accurately predict which cancer patients would experience a VTE during their treatment. Khorana et al. have developed such a model (Khorana et al., Blood 2008). We conducted a retrospective study to test the effectiveness of Khorana and colleagues' clinical model at predicting risk of VTE in patients with metastatic cancer. We collected data from an outpatient oncology clinic for 112 patients with solid tumors or malignant lymphoma who had undergone active chemotherapy in the last two years. The data included the five predictive variables outlined in Khorana et al.'s model: site of cancer (2 points for a very high-risk site, 1 point for a high-risk site); a platelet count of 350 × 109/L or more; hemoglobin less than 100g/L and or/use of erythropoiesis-stimulating agents; leukocyte count more than 11 × 109/L; and body mass index of 35kg/m2 or more (1 point each) (Khorana et al., Blood 2008). All data was collected on the first day of chemotherapy or the most recent labs before the start of chemotherapy. A score of 0 points represented a low risk of VTE, 1-2 points represented an intermediate risk and 3-4 points represented a high risk. There were 20 low risk patients, 63 intermediate risk and 29 high risk. We found that the clinical model accurately predicted which patients would experience a VTE (Table 1). Of the total 112 patients, 23 experienced a VTE. We determined that patients considered high risk were 8-fold more likely to experience a VTE as compared to low risk patients (see Table 1). Kuderer et al. demonstrated that this risk model also predicts overall mortality for patients receiving chemotherapy (Kuderer et al., ASH 2009). The results of our study also showed a strong correlation between overall mortality and a higher risk score. The mortality rate of high risk patients during the trial period was 69.0% compared to 30.0% of low risk patients and 42.9% of intermediate risk patients. Our retrospective review validates Khorana and colleagues' clinical model to predict VTE and survival rates in cancer patients. Our results, combined with data from previous studies, indicate that patients who are at risk for VTE also have a higher mortality rate. With an accurate predictive model, primary prophylaxis treatment for VTE could be considered for high risk patients. Disclosures: No relevant conflicts of interest to declare.

Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for stage III colon cancer patients who underwent curative resection (KSCC1303).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 739-739
Author(s):  
Nobutomo Miyanari ◽  
Yasunori Emi ◽  
Akihito Tsuji ◽  
Kenji Sakai ◽  
Hideaki Anai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

739 Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.

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