Systemic inflammation in colorectal cancer: Underlying factors, effects, and prognostic significance

Tuomisto, Anne; Mäkinen, Markus J.; Väyrynen, Juha P.

doi:10.3748/wjg.v25.i31.4383

Cited by 205 publications

(201 citation statements)

References 195 publications

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“…CRC patients are often accompanied by a low level of systemic inflammatory response, including an increased proinflammatory cytokines and acute phase proteins entering the circulation, which ultimately leads to systemic malignant tumor wasting cachexia in various aspects [23] . Numerous articles had analyzed the relationship between inflammatory cytokines and the CRC progression and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Li¹,

Wu²,

Xing³

et al. 2020

J. Cancer

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Background: Many indicators of peripheral blood in routine blood test (BRT) results of colorectal cancer (CRC) patients are related to prognosis. Currently, indexes such as NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte ratio) evaluate the survival risk of patients by assessing the inflammatory-immune status of CRCs. These indexes are more comprehensive and accurate than independent estimates. We hope to design more effective indexes through fully considering the correlation and significance between BRT indicators and prognosis, so as to play a guiding role in clinical malignant estimation of CRCs. Methods: 701 CRCs in training set and 256 CRCs in test set were included in the study samples, and their clinical data, tumor pathology results and peripheral blood routine results were collected. The prognosis, progression, and survival status of all patients were determined after follow-up. Above data were used for statistical analysis and designing new indexes. Results: It was found that high NE, MONO, RDW-CV/SD and PLT in peripheral blood indicated poor prognosis of DFS and OS. Conversely, CRCs with postoperative tumor progression or death had lower LY, EO, RBC, HGB, HCT, MCV, MCH, MCHC, PDW, and P-LCR. IRR, ARR and CRR related to infection, anemia and coagulation were designed respectively using the largest AUC indicators (P<0.05) selected by ROC curve. The formula: IRR= (NE*MONO)/(LY*EO); ARR= (HGB*MCHC)/RDW-CV; CRR=PLT/PDW. Results of Kaplan-Meier survival analysis and multivariate COX proportional hazard analysis adjusted for age, gender, TNM stage, infiltration, adhesion showed IRR, ARR, CRR were all able to be used as the evaluation standard of survival of CRC. The result was also authenticated in the test set. Conclusion: We designed three different prognostic indexes of colorectal cancer, IRR, ARR and CRR, which could be used as risk indicators of CRC prognosis, tumor progression and survival.

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Section: Discussionmentioning

confidence: 99%

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Li¹,

Wu²,

Xing³

et al. 2020

J. Cancer

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“…In our study, we evaluated the prognostic and predictive value of a set systemic in ammation markers that have been previously described elsewhere [4], and used them to create a prognostic score tool. PLR and NLR have been studied as prognostic factors in most tumor types [23], and hypoalbuminemia has been identi ed as a prognostic indicator in CRC [24].…”

Section: Discussionmentioning

confidence: 99%

“…Molecular classi cations of colorectal cancer show that patients with BRAF mutations cluster together on the CMS1 subgroup, which is also characterized by high immune activation and in ltration and the co-occurrence of microsatellite instability (MSI) [3]. Systemic in ammation is also known to be prognostic of poor clinical outcomes in patients with CRC [4].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Antiangiogenic-Based Treatment and Systemic Inflammatory Factors on Outcomes in Patients With BRAF v600-Mutated Metastatic Colorectal Cancer: A Real-World Study in Spain

Montes

Rúa

Vázquez

et al. 2020

Preprint

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Background Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC.Methods/patients This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1–3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin <3.6 g/dL.Results Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1–3, but not PLR. Patients with SIS 1–3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit.Conclusions Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy.Trial registration GIT-BRAF-2017-01.

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“…Generally, chronic in ammation has emerged as a hallmark of different types of cancer, including CRC [10]. Particularly, clinically silent systemic in ammation is manifested during disease onset [11], whereas overt in ammation occurs throughout its progression [12]. Strong epidemiological evidence suggests that low-dose aspirin, and other non-steroidal anti-in ammatory drugs, are powerful chemo-preventive agents for reducing rates and cancer-related deaths [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

Ying

Sun

Wang

et al. 2020

Preprint

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Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.

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Systemic inflammation in colorectal cancer: Underlying factors, effects, and prognostic significance

Cited by 205 publications

References 195 publications

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Effect of Antiangiogenic-Based Treatment and Systemic Inflammatory Factors on Outcomes in Patients With BRAF v600-Mutated Metastatic Colorectal Cancer: A Real-World Study in Spain

Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

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