The prognostic value of serum CA 19-9 in patients with metastatic colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15131-e15131 ◽  
Author(s):  
Camilla Stedstrup Mosgaard ◽  
Mathias Holsey Gramkow ◽  
Christian Dehlendorff ◽  
Dorte Nielsen ◽  
Per Pfeiffer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Continuous Variables ◽  
Female Ratio ◽  
Cox Regression Analysis ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

e15131 Background: CEA is regarded as the marker of choice for monitoring patients with colorectal cancer (CRC), but the value of using CA19-9 is insufficient. The prognostic value of serum CA19-9 in combination with CEA was evaluated in patients with metastatic CRC (mCRC) before first (1) and third line therapy (3LT). Methods: From April 2004 to May 2015, pretreatment serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 [range 33-87] and male/female ratio 243(59%)/172(41%). Serum CA19-9 was determined by routine chemiluminescent immunometric assay (normal range 0-37 KU/l). Progression-free survival (PFS) and overall (OS) crude, adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were estimated using Cox regression analysis. CA19-9 and CEA were included as log2-transformed continuous variables and adjustment included mutually between CA19-9 and CEA in addition to primary tumor location, sex and age. Results: In 3LT median pretreatment CEA levels were higher than in 1LT (59 µg/l [IQR 14-288] vs. 23[6-153] P < 0.01) while CA19-9 values were similar (112 KU/l [23-626] vs. 98[19-390]). In patients treated with 3LT univariate analysis showed that high levels of CA19-9 and CEA were associated with short PFS (CA19-9: HR = 1.06, 95% CI 1.02-1.10, P < 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT neither CA19-9 nor CEA were significantly associated with PFS. In a multivariate analysis, none of the biomarkers were significantly associated with PFS. In patients treated with 3LT univariate analysis showed that high levels of CA 19-9 and CEA were associated with short OS (CA19-9: HR = 1.11, 1.07-1.16, P < 0.01; CEA: HR = 1.1, 1.06-1.16, P < 0.01). In patients treated with 1LT high levels of CA-19-9 but not CEA was significantly associated with a shorter OS (HR = 1.07, 1.00-1.14, P = 0.04). In 3LT multivariate analyses showed that high levels of CA19-9 and CEA were the only factors associated with a shorter OS (CA19-9: HR = 1.08, 1.03-1.13, P < 0.01; CEA: HR = 1.07, 1.01-1.14, P < 0.01), while there was no significant association to OS in 1LT. Conclusions: Serum CA19-9 may be a valuable prognostic biomarker in combination with CEA in mCRC patients receiving third line therapy.

The prognostic value of serum IL-6 and YKL-40 in patients with metastatic colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15060-e15060
Author(s):  
Benny Vittrup Jensen ◽  
Mathias Holsey Gramkow ◽  
Camilla Stedstrup Mosgaard ◽  
Christian Dehlendorff ◽  
Per Pfeiffer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Metastatic Colorectal Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Continuous Variables ◽  
Female Ratio ◽  
Cox Regression Analysis ◽  
L 14

e15060 Background: The prognostic value of serum IL-6, YKL-40 and CEA before first (1) and third line therapy (3LT) in metastatic colorectal cancer (mCRC) is lacking and was evaluated in this study. Methods: From 2004 to 2015 serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 years (range 33-87) and male/female ratio 243(59%)/172(41%). Serum IL-6 (R&D, UK) and YKL-40 (Quidel, USA) were determined by ELISA. Progression-free (PFS) and overall survival (OS), crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated with Cox regression analysis. CEA, IL-6 and YKL-40 were included as log2-transformed continuous variables with mutual adjustment between CEA, IL-6 and YKL-40, primary tumor location, sex and age. Results: In 3LT IL-6, YKL-40 and CEA levels were higher (P < 0.001) than in 1LT (IL-6: 9.5 pg/ml [IQR4.2-18.5] vs. 4.6 [2.5-10.5]; YKL-40: 140 ng/ml [77-272] vs. 101 [62-172]; and CEA: 59 ug/l [14-288] vs. 23[5.8-153]). In 3LT univariate analysis showed that increased levels of IL-6, YKL-40 and CEA were associated with shorter PFS (IL-6: HR = 1.19, 95% CI 1.07-1.31, P < 0.01; YKL-40: HR = 1.13, 1.04-1.24, P = 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT only high IL-6 was associated with shorter PFS (HR = 1.09, 1.01-1.17, P = 0.03). In a multivariate analysis only high IL-6 was significantly associated with shorter PFS in 3LT (HR = 1.15, 1.03-1.29, P < 0.01) and none of the biomarkers in 1LT. In 3LT univariate analysis showed that increased levels of all 3 biomarkers were associated with a shorter OS (IL-6: HR = 1.36, 1.23-1.51, P < 0.01; YKL-40: HR = 1.21, 1.10-1.33, P < 0.01; CEA: HR = 1.11, 1.06-1.16, P < 0.01). In 1LT high levels of IL-6 (HR = 1.17, 1.08-1.27, P < 0.01) and YKL-40 (HR = 1.18, 1.00-1.38, P = 0.05), but not CEA, were associated with short OS. In 3LT the multivariate analysis showed that both higher IL-6 (HR = 1.34, 1.20-1.50, P < 0.01) and CEA (HR = 1.09, 1.03-1.14, P < 0.01), but not YKL-40 were significantly associated with a shorter OS. In 1LT only higher IL-6 was associated with a shorter OS (HR = 1.19, 1.08-1.31, P < 0.01) Conclusions: Serum IL-6 and YKL-40 may be useful prognostic biomarkers in combination with CEA in patients with mCRC

scholarly journals Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review

2020 ◽  
Vol 12 ◽  
pp. 175883592094093
Author(s):  
Yinying Wu ◽  
Yangwei Fan ◽  
Danfeng Dong ◽  
Xuyuan Dong ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Second Line ◽  
Efficacy And Safety ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods: A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion: Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.

Safety and Efficacy Of Bendamustine In Patients With Aggressive Non-Hodgkin Lymphomas (NHL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4371-4371 ◽  
Author(s):  
Jakob Hammersen ◽  
Michael Sommer ◽  
Christin Gössel ◽  
Ulf Teichgräber ◽  
Sabine Hahnfeld ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Sustained Remission ◽  
Cox Regression Analysis ◽  
Line Therapy

Abstract Introduction Frail patients with aggressive NHL frequently do not qualify for CHOP-based chemotherapy. Alternatives are required urgently. Bendamustine has been well established as a standard treatment of indolent lymphomas. Its use in high grade lymphoma has been suggested as a promising option. However, which patients benefit most effectively requires further clarification. Methods We retrospectively characterized 51 unselected consecutive patients (39,2% female, 60,8% male, median age 70 years, range 32 - 92 years) with aggressive NHL treated with bendamustine +/- rituximab. They were analyzed for baseline characteristics (histological type, IPI, ABC/GCB-subtypes, age, ECOG, comorbidity (CIRS-G), outcome (ORR, PFS, OS), and toxicity (CTCAE)). Results 21 patients with aggressive NHL received Bendamustin as 1st-line therapy and 30 patients beyond 1st-line. Of the 1st line patients 14 suffered from diffuse large cell B cell lymphoma (DLCBL), 5 from mantle cell lymphoma (MCL), and 2 from other subtypes. In 1st line patients median age was 82 years, ECOG-status was ≥ 2 in 38%. Median international prognostic index (IPI) was 3 (range 1-4). Comorbidity assessment by CIRS-G revealed median 3 (range 1 to 5) severely or very severely affected organs. The overall response rate (ORR) in 1st line treatment was 91%, with a median progression free survival (PFS) of 6 months and a median overall survival (OS) of 15 month. In DLBCL 5 GCB- and 6 ABC-lymphomas were differentiated. GCB-patients showed an ORR of 80% (2 complete remission (CR), 2 partial remission PR)), a median PFS 8 month and OS of 15 months, respectively. ABC-patients had an ORR 67% (no CR, 4 PR, 2 SD), a median PFS of 6 month and OS of 8 months, respectively (n.s.). 7 patients achieved a long term-remission >5 years. Univariate analysis of prognostic variables showed significance for ECOG (p<0.0001) and CIRS-G (p=0.002) for OS, Cox-regression analysis showed significance for ECOG (p=0.016). No significance was shown for disease stage or LDH activities. The ORR in patients beyond 1st-line therapy (median age 64 years, ECOG-status ≥ 2 in 17%) was 66% with a median PFS of 8 month and OS of 24 month. Median cumulative dose was 540 mg/m2 in median 4 cycles. Toxicity in the 1st-line cohort was moderate, mainly grade 1 & 2. Three patients showed grade 3 leukocytopenia. Other side effects primarily were: inappetence, weight-loss, fever. Conclusion Bendamustine shows high efficacy in aggressive NHL, even sustained remission was achieved by a subgroup, which requires further definition. Toxicity was well manageable. Defining prognostic parameters we showed GCB-subtype of DLBCL might predict a better outcome in bendamustine treated patients. Remarkably, performance and comorbidity assessment is of crucial prognostic value with a greater impact on outcome compared to classic parameters. Currently, the BRENDA trial (NCT01686321) prospectively investigates the role of bendamustine in aggressive NHL. Disclosures: Off Label Use: Use of Bendamustine in aggressive NHL. Wedding:Roche: Speakers Bureau; Amgen: Speakers Bureau; Chugai: Speakers Bureau; Janssen-Cilag: Speakers Bureau; Novartis: Speakers Bureau; Cephalon: Speakers Bureau; Prostarkan: Speakers Bureau; Pfizer: Speakers Bureau. La Rosée:Mundi Pharma: Honoraria.

Safety and tolerability profile of raltitrexed in Chinese patients with locally advanced or recurrent and metastatic colorectal cancer: A phase IV trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 571-571
Author(s):  
Shukui Qin ◽  
Jin Li ◽  
Yunpeng Liu ◽  
Yin Chen ◽  
Nong Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Locally Advanced ◽  
Chinese Patients ◽  
Tolerability Profile ◽  
Second Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Phase Iv

571 Background: The clinical benefit and safety profile associated with raltitrexed in patients with advanced colorectal cancer (CRC) were established. However, safety information of raltitrexed in Chinese patients is rare. We aimed to assess the safety of raltitrexed monotherapy in Chinese patients with advanced CRC. Methods: This single-arm, open-label, multi-center, phase IV trial was conducted in 13 hospitals across China between March 2011 and July 2014. Patients with locally advanced or recurrent and metastatic colorectal cancer (mCRC) received raltitrexed (3mg/m2) as a 15-min infusion on day 1, every 21 days. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was safety and the secondary objectives were disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: A total of 215 patients were enrolled, and the safety was assessed in 205 patients. 92 patients had 394 Adverse events (AEs) during the study. A majority (94.4%) of AEs was grade 1/2 and only 5.3% was grade 3/4. Most AEs were either resolved spontaneously or treated successfully with standard medical interventions. Severe AEs were reported by 5.8% (12/205) of patients. The most commonly reported AEs were increase of transaminases, leukopenia, nausea and vomiting. Serum transaminase elevation, an important safety concern associated with raltitrexed therapy, were transient, self-limiting and manageable. No deaths were reported during the study. The DCR in second-line and third-line therapy by raltitrexed reached 49.5% and 37.4%, respectively. The median PFS in second-line and third-line therapy was 1.43 months and 1.47 months, respectively. The median OS was 13.6 months and 8.9 months, respectively. Conclusions: Raltitrexed monotherapy is a safe, well-tolerated and convenient therapy option for Chinese patients. The treatment-associated toxicity is manageable and does not lead to discontinuation of treatment in oncology practice.

scholarly journals Phase II trial of biweekly cetuximab and irinotecan as third‐line therapy for pretreated KRAS exon 2 wild‐type colorectal cancer

2018 ◽  
Vol 109 (8) ◽  
pp. 2567-2575 ◽  
Author(s):  
Hiroki Osumi ◽  
Eiji Shinozaki ◽  
Tetsuo Mashima ◽  
Takeru Wakatsuki ◽  
Mitsukuni Suenaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Wild Type ◽  
Exon 2 ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Kras Exon

scholarly journals A Novel Signature Constructed by Immune-Related LncRNA Predicts the Immune Landscape of Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengyu Sun ◽  
Tongyue Zhang ◽  
Yijun Wang ◽  
Wenjie Huang ◽  
Limin Xia
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Univariate Analysis ◽  
The Cancer Genome Atlas ◽  
High Morbidity ◽  
Cox Regression Analysis ◽  
Chemotherapy Drugs

Colorectal cancer (CRC) has the characteristics of high morbidity and mortality. LncRNA not only participates in the progression of CRC through genes and transcription levels, but also regulates the tumor microenvironment and leads to the malignant phenotype of tumors. Therefore, we identified immune-related LncRNAs for the construction of clinical prognostic model. We searched The Cancer Genome Atlas (TCGA) database for original data. Then we identified differentially expressed irlncRNA (DEirlncRNA), which was paired and verified subsequently. Next, univariate analysis, Lasso and Cox regression analysis were performed on the DEirlncRNA pair. The ROC curve of the signature was drawn, and the optimal cut-off value was found. Then the cohort was divided into a high-risk and a low-risk group. Finally, we re-evaluated the signature from different perspectives. A total of 16 pairs of DEirlncRNA were included in the construction of the model. After regrouping according to the cut-off value of 1.275, the high-risk group showed adverse survival outcomes, progressive clinicopathological features, specific immune cell infiltration status, and high sensitivity to some chemotherapy drugs. In conclusion, we constructed a signature composed of immune-related LncRNA pair with no requirement of the specific expression level of genes, which shows promising clinical predictive value in CRC patients.

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