scholarly journals Prognostic Discrimination of Alternative Lymph Node Classification Systems for Patients with Radically Resected Non-Metastatic Colorectal Cancer: A Cohort Study from a Single Tertiary Referral Center

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3898
Author(s):  
Dimitrios Prassas ◽  
Pablo Emilio Verde ◽  
Carlo Pavljak ◽  
Alexander Rehders ◽  
Sarah Krieg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Metastatic Colorectal Cancer ◽  
Regression Models ◽  
Proportional Hazards ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Classification Systems ◽  
Tertiary Referral Center ◽  
Node Classification

Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients with Stage III radically resected CRC.

Influence of dietary insulin scores on survival in patients with metastatic colorectal cancer (mCRC): Findings from CALGB (Alliance) 80405.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3568-3568
Author(s):  
Katherine DiNardo ◽  
Chao Ma ◽  
Fang-Shu Ou ◽  
Chen Yuan ◽  
Brendan John Guercio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Proportional Hazards ◽  
Energy Content ◽  
Insulin Response ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Dietary Recommendations

3568 Background: Diets inducing an elevated insulin response have been associated with increased recurrence and mortality in patients with non-metastatic colorectal cancer, but it remains unknown if postprandial hyperinsulinemia also affects progression and mortality in mCRC patients. The goal of this study was to assess the influence of dietary insulin load (DIL) and dietary insulin index (DII) on survival of mCRC patients. Methods: This was a prospective cohort study of 1,177 patients with previously untreated mCRC enrolled in a phase III trial of systemic chemotherapy plus biologics who reported dietary intake within one month after chemotherapy initiation. DIL was calculated as a function of food insulin index and the energy content of individual foods reported on a food frequency questionnaire. DII was calculated by dividing DIL by total energy intake. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). The primary statistical test was a test for trend, which was performed using the median value for each quintile of dietary insulin score as a continuous variable. Cox proportional hazards regression was used to adjust for potential confounders including assigned treatment arm, known prognostic factors, comorbidities, body mass index, and physical activity. Results: Higher DIL was significantly associated with worse OS (ptrend = 0.04); patients in the highest quintile survived 34.1 months, compared to 27.7 months in the lowest quintile (Cox hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.99 - 1.51). Higher DII was non-significantly associated with worse OS (HR 1.18, 95% CI 0.94 - 1.48, ptrend = 0.09). There was no significant association between dietary insulin scores and PFS. The influence of dietary insulin scores on survival did not differ significantly by various molecular markers involved in the insulin signaling pathway, including C-peptide, adiponectin, IGF-1, IGFBP-3, and IGFBP-7. Higher dietary insulin scores were significantly associated with greater risk of any TRAE. Those with a DIL greater than the median had a 75.4% rate of any TRAE, compared to 70.8% in those with a DIL less than or equal to the median (HR 1.19, 95% CI 1.03 - 1.38, p=0.02); the most significant associations were with neutropenia (HR 1.30, 95% CI 1.05 - 1.61, p=0.01) and diarrhea (HR 1.43, 95% CI 1.00 - 2.06, p=0.05). Conclusions: Higher DIL was significantly associated with worse OS, and both higher DIL and DII were significantly associated with increased TRAEs, in patients with previously untreated mCRC. These findings may inform future dietary recommendations for patients with mCRC. Further investigation into the molecular mechanisms underlying these associations is warranted. Clinical trial information: NCT00265850.

scholarly journals Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Models ◽  
Proportional Hazards ◽  
Treatment Decision ◽  
Tumor Stage ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
Men And Women ◽  
Logistic Regression Models ◽  
Comorbidity Index

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

Il-8 as an underutilized prognostic factor in metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 409-409
Author(s):  
Manasi S Shah ◽  
David R. Fogelman ◽  
Carrie Daniel-MacDougall ◽  
Kanwal Pratap Singh Raghav ◽  
John Heymach ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Principal Component ◽  
Cox Proportional Hazards ◽  
Mortality Data ◽  
Subsequent Work ◽  
Term Survival ◽  
Inflammatory Biomarker ◽  
Kaplan Meier

409 Background: Cancer-associated inflammation has been identified as a key determinant of disease progression and survival in colorectal cancer. We investigated the association between circulating inflammatory cytokines and survival in metastatic colorectal cancer (mCRC) patients. Methods: Plasma levels of 47 cytokines were measured using multiplex-bead assays in a cohort of 168 previously untreated mCRC patients. Demographic, clinical-pathological features, body mass index, and mortality data were abstracted from patient medical records. Overall survival (OS) was evaluated by Kaplan-Meier analysis and Cox proportional hazards regression. Results: Using principal component analysis, we identified a subset of cytokines explaining the maximum variance in OS; and found interleukin (IL)-1b, IL-5, IL-8, IL-12 and VEGF to be significantly associated with OS. However, only IL-8 was significantly and independently associated with OS in multivariable-adjusted models. For each 100 pg/ml increase in the level of circulating IL-8, hazard rate for death increased by 1.6 (95% CI 1.24-1.97). IL-8 measurements ranged from <1 to 413 pg/ml with a median value of 22 pg/ml. Median uncensored survival was 26.5 and 15.5 months among patients with IL-8 levels below and above this value, respectively. ROC analysis of IL-8 demonstrated an AUC of 0.69 (95% CI 0.60-0.76), as compared to 0.52 for CEA (95% CI 0.46-0.59). Conclusions: We identified an association between IL-8 and OS in previously untreated mCRC patients, suggesting its potential role as a prognostic inflammatory biomarker. In this dataset, IL-8 outperformed CEA as a prognostic biomarker, a finding which requires validation in subsequent work. Appropriately identifying, monitoring and managing chronic inflammation and the host inflammatory response during colorectal cancer treatment may be important for improving long-term survival.

Plasma VEGF-A (pVEGF-A) level in efficacy analysis of metastatic colorectal cancer patients (mCRC) treated with mFOLFOX6/XELOX plus bevacizumab (BV) (WJOG7612GTR).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 699-699
Author(s):  
Wataru Okamoto ◽  
Akitaka Makiyama ◽  
Yoshiyuki Yamamoto ◽  
Kohei Shitara ◽  
Tadamichi Denda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Negative Results

699 Background: Plasma levels of VEGF-A short isoforms (VEGF-A110 and -A121) measured by immunological multiparametric chip technique (IMPACT) were reported to be associated with clinical benefits from bevacizumab (BV) in advanced gastric and pancreatic cancer but not in metastatic colorectal cancer (mCRC). Negative results in mCRC studies might be caused by different sample handling: citrate instead of EDTA and repetition of freeze/thaw. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). A median value of pVEGF-A was used as a cut-off point to categorize patients (pts) into the low and high pVEGF-A groups. Progression free survival (PFS) and overall survival (OS) between the low and high pVEGF-A groups were compared, using Cox proportional hazards model. We hypothesized that BV-containing treatment extend shorter PFS of pts with high pVEGF-A to that with low pVEGF-A, and estimated a threshold hazard ratio (HR) between them as below 1.15. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0] and response rate was 64.6 % [range, 53.3-74.9]. pVEGF-A was measured in 97 pts and the median value was 36.8 pg/ml [range, 6.5- 262.2]. The hazard ratios of PFS and OS between the high and low pVEGF-A groups were 1.23 [95%CI, 0.76-1.97, p = 0.40] and 2.47 [95%CI, 1.14-5.36, p = 0.02], respectively. Conclusions: mCRC pts with high pVEGF-A showed shorter PFS than those with low pVEGF-A beyond the predefined threshold (HR 1.15) in BV-containing chemotherapy, suggesting that pVEGF-A could not be a predictive marker for BV efficacy. Clinical trial information: UMIN000012442.

scholarly journals IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Brendan J Guercio ◽  
Sui Zhang ◽  
Fang-Shu Ou ◽  
Alan P Venook ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Igf Binding Proteins ◽  
C Peptide ◽  
Igf Binding ◽  
Igfbp 3

Abstract Background Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study. Methods Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute–sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided. Results Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; Pnonlinearity &lt; .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; Ptrend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; Ptrend &lt; .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; Ptrend &lt; .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (Pnonlinearity = .03). Conclusions Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

2011 ◽  
Vol 96 (4) ◽  
pp. 291-299 ◽  
Author(s):  
Hideyuki Ishida ◽  
Keiichiro Ishibashi ◽  
Tomonori Ohsawa ◽  
Norimichi Okada ◽  
Kensuke Kumamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Regional Lymph Node ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Synchronous Liver Metastasis ◽  
Hepatic Lymph Node

Abstract The frequency and significance of hepatic lymph node (HLN) metastasis were retrospectively evaluated in 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary tumor and histopathologic evaluation of HLNs between March 1997 and August 2007. HLN metastasis was detected in 12 patients (27.9%). No significant correlations were observed between the presence of HLN metastasis and any of the 12 clinicopathologic factors examined. On multivariate analysis using the Cox proportional hazards model, the presence of HLN metastasis (P  =  0.002), along with a large number (≥4) of regional lymph node metastases (P  =  0.003), and nonuse of oxaliplatin-based chemotherapy (P  =  0.005) were identified as independent risk factors for shorter survival. To establish a new therapeutic strategy for initially unresectable liver metastasis of colorectal cancer, HLNs should be examined histologically in patients undergoing resection of hepatic lesions when they are rendered resectable by effective chemotherapy.

Patterns of care and survival trends in elderly metastatic colorectal cancer patients: A SEER-Medicare analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 520-520
Author(s):  
V. Shankaran ◽  
S. J. Beck ◽  
D. K. Blough ◽  
Y. Yim ◽  
E. Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Resection ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
New Drugs ◽  
Hazards Model ◽  
Colorectal Cancer Patients

520 Background: Over the last decade, the treatment of metastatic colorectal cancer (mCRC) has changed dramatically as new drugs and hepatic resection have been incorporated into practice. The goal of this study is to examine treatment patterns and survival trends for older patients (pts) with mCRC. Methods: Pts ≥ age 65 with mCRC diagnosed (dx) 2001-2005 were identified from the SEER-Medicare database. Pts were excluded for lack of Medicare parts A and B in the year prior to dx, second malignancy, or non- adenocarcinoma histology. First-line (1L) chemotherapy (CTx) use was identified by claims within 3 months of dx. Metastatectomy was identified by various claims for liver resection. Comorbidity was assessed by Klabunde index. A Cox proportional hazards regression model was used to assess the effect of demographic and treatment factors on survival. Results: A total of 5,725 pts (median age 77) met inclusion criteria. 274 pts (5%) underwent hepatic resection and 2,647 (46%) received CTx. From 2001-2003, 43% of pts received 1L CTx (34% and 1% with regimens containing irinotecan (Iri) and oxaliplatin (Ox) and 49% with 5-FU/cap alone). From 2004-2005, 51% of pts received 1L CTx (25%, 14%, and 37% with regimens containing bevacizumab (Bv), Iri, and Ox and 40% with 5-FU/cap alone). In the multivariate analysis using the Cox proportional hazards model, survival was significantly improved in pts receiving CTx or hepatic resection and in pts dx 2004-2005 (Table). Conclusions: In an older mCRC population, hepatic resection, CTx use, and mCRC dx in 2004-2005 are associated with improved survival. Improved survival of pts dx in 2004-2005 coincides with the 2004 approval dates and uptake of Bv and Ox, and may be associated with the use of these therapies. Further analysis will examine the associations between specific Ctx regimens, Bv, and survival and will include pts dx through 2007. [Table: see text] [Table: see text]

Real-world study of cetuximab used every other week versus weekly in US patients with metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15087-e15087 ◽  
Author(s):  
Francois-Xavier Lamy ◽  
Michael Batech ◽  
Shaista Salim ◽  
Emmanuelle Boutmy ◽  
Chris Pescott ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Cox Proportional Hazards ◽  
Patient Death ◽  
Claims Database ◽  
Proportional Hazards Regression ◽  
The Mean

e15087 Background: After an initial dose of 400 mg/m², cetuximab (CET) at a dose of 250 mg/m² in combination with chemotherapy (CT) is approved for once-weekly (q1w) use in the treatment of RAS wild-type metastatic colorectal cancer (mCRC). However, off-label use of CET 500 mg/m2 administered every other week (q2w) has been observed in clinical practice. This study aimed to test the noninferiority of q2w vs q1w administration on overall survival (OS) using US claims data. Methods: Using IBM MarketScan, a large US insurance claims database, a cohort of patients with mCRC treated with CET + CT between 2010 and 2016 was identified and classified as q1w or q2w based on observed infusion patterns. The initial CET prescription was defined as the index date, and patient death was determined using a previously published algorithm. Confounding was accounted for using high-dimensional propensity scoring (hdPS) methodology with inverse probability of treatment weighting (IPTW). OS for both groups was compared using Cox proportional hazards regression. Confounders that remained imbalanced after hdPS with IPTW were added to the Cox model. The noninferiority of the q2w regimen was tested with a margin hazard ratio (HR) of 1.25 for q2w vs q1w. Results: 2,869 patients with mCRC exposed to CET were identified of which 1,865 (65.0%) and 1,004 (35.0%) were classified in the q1w and q2w groups, respectively. The mean age of patients was 60.1±11.7 years for q1w and 58.1±11.1 years for q2w. Most patients were male: 57.5% and 60.8% in q1w and q2w, respectively. Approximately 70% of patients in both groups had received prior treatment for mCRC. The most frequently used CT with CET was irinotecan based (64.5% in q1w and 76.5% in q2w). There were 1,628 deaths observed during follow-up (56.7%). After hdPS with IPTW adjustment, differences remained in associated CT (standardized difference <0.25). Crude HR for OS was 1.05 (95% CI, 0.94-1.18), and adjusted HR for OS was 1.04 (95% CI, 0.93-1.17). The inferiority hypothesis was rejected at p<0.001. Conclusions: In this large US claims database, when assessing OS, the q2w administration schedule was found to be noninferior to the q1w schedule in patients with mCRC.

scholarly journals Association of Age With Survival in Patients With Metastatic Colorectal Cancer: Analysis From the ARCAD Clinical Trials Program

2014 ◽  
Vol 32 (27) ◽  
pp. 2975-2982 ◽  
Author(s):  
Christopher H. Lieu ◽  
Lindsay A. Renfro ◽  
Aimery de Gramont ◽  
Jeffrey P. Meyers ◽  
Timothy S. Maughan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Mutational Status ◽  
Increased Risk ◽  
Risk Of Progression

Purpose This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). Patients and Methods A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study. Results Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P < .001) and PFS (P < .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status. Conclusion Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.

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