Prognosis Of Colorectal Liver Metastases Research Articles

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Macrophage Morphology Is a Strong Predictor of Prognosis in Colorectal Liver Metastases: Results from an External Validation

Introduction: Tumor-associated macrophages (TAMs), key components of tumoral microenvironment, impact prognosis in different cancer subtypes. Previously reported data from Humanitas University group showed that TAMs morphology correlates with prognosis in colorectal liver metastases (CLMs), with smaller TAMs (S-TAMs) conferring a more favourable prognosis than larger ones (L-TAMs). This study aimed to externally validate TAMs morphology as a prognostic factor in resected CLMs.

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases.

The red blood cell distribution width (RDW) level is a potential prognostic factor for solid tumours. We aimed to investigate the predictive value of pre-neoadjuvant chemotherapy (pre-NAC) RDW, preoperative RDW and the change in RDW on the pathological response and prognosis of patients with colorectal liver metastasis (CRLM), which was helpful for treatment decision-making, surveillance and prognostication. This retrospective study analyzed clinicopathologic data, treatments and outcomes of 150 CRLM patients treated with NAC followed by liver resection at our hospital. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcome was postoperative major complications. The RDW level was presented as the RDW-SD level and the RDW-CV level. The optimal cut-off of RDW level was determined by X-tile analysis. The change in RDW was scored as 0 (decreased pre-NAC RDW and decreased preoperative RDW), 2 (elevated pre-NAC RDW and elevated preoperative RDW), or 1 (all other combinations). Multivariable logistic regression analysis was performed to determine the relationships between the tumour characteristics and pathological response and the postoperative major complications. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with survival. The optimal cut-off values of the RDW-CV and RDW-SD levels for survival were 13.5% and 42.2 fl, respectively. The multivariate analysis showed that a preoperative RDW-CV ≥13.5% (OR =3.215, 95% CI: 1.299-7.958, P=0.012) significantly predicted a favorable pathological response. The multivariate analysis revealed that a pre-NAC RDW-CV ≥13.5% (OR =2.462, 95% CI: 1.080-5.615, P=0.032) significantly predicted postoperative major complications. In the multivariate analysis, an RDW-CV change =2 (HR =0.487, 95% CI: 0.309-0.768, P=0.002) was a significant predictor of better PFS. The multivariate analysis also revealed that an RDW-SD change =2 (HR =0.532, 95% CI: 0.332-0.854, P=0.009) were an independent predictor of better OS. This study revealed that pre-NAC RDW, preoperative RDW and RDW changes may be reliable markers that could predict a pathological response and prognosis in CRLM patients receiving NAC followed by liver resection.

Preoperative D-dimer and Gamma-Glutamyltranspeptidase Predict Major Complications and Survival in Colorectal Liver Metastases Patients After Resection

OBJECTIVES: To investigate the predictive value of the pre-operative D-dimer and gamma-glutamyltranspeptidase (GGT) for the prognosis in colorectal liver metastases (CRLM) patients after hepatic resection. METHODS: Two hundred and ninety-two patients between December 2008 and December 2016 and 101 patients at our center from January 2017 to December 2018 were selected as a training set and validation set, respectively. The combination of the pre-operative D-dimer and GGT status (CPDG score) was scored as follows: elevated D-dimer levels with elevated GGT levels was allocated a score of 2, decreased D-dimer levels with decreased GGT levels was allocated a score of 0, and all other combinations were allocated a score of 1. In the training set, a logistic regression was applied to explore potential predictors of major postoperative complications. A Cox proportional hazards analysis was used to analyze survival. We further verified our findings in the validation set. RESULTS: Major complications occurred in 43 (14.7%) and 25 (24.8%) patients in the training set and validation set, respectively. In the training set, multivariate analysis showed that elevated GGT levels and elevated D-dimer levels independently predicted major complications respectively. In the multivariate analyses, elevated pre-operative D-dimer levels remained independently associated with decreased overall survival (OS) (hazard ratio [HR] = 1.751, 95% confidence interval [CI]: 1.139-2.691, P = .01). The CPDG score was an independent prognostic factor for major complications and OS in the multivariate analyses. The predictive ability of the CPDG score was higher than either factor alone. A Kaplan-Meier survival analysis showed that compared with patients with CPDG score = 1 or CPDG score = 0, patients with a CPDG score = 2 had worsened OS. Furthermore, for OS comparisons, the differences between any two groups were significant. In the validation set, elevated GGT and D-dimer were also suggested to predict worse progression-free survival (PFS) and to be independently associated with major complications. CONCLUSIONS: The pre-operative D-dimer levels, GGT levels and CPDG score are reliable biomarkers to predict post-operative major complications or survival in CRLM patients after hepatic resection, which make it useful for CRLM patients in guiding surveillance approaches and prognosis assessments.

Neo-adjuvant Chemotherapy-Induced Neutropenia Is Associated with Histological Responses and Outcomes after the Resection of Colorectal Liver Metastases

BackgroundNeutropenia, the major adverse event in chemotherapy, is associated with favourable clinical outcome in several solid tumours. We aimed to investigate the predictive value of neo-adjuvant chemotherapy (NAC)–induced neutropenia for the pathological response and prognosis in colorectal liver metastases (CRLM) patients. MethodsA retrospective review was performed in 141 CRLM patients receiving NAC followed by liver resection. A logistic regression was applied to analyse potential predictors. A Cox proportional hazards analysis was used to analyse survival. ResultsNeutropenia due to NAC was observed in 42.6% (60/141) of all patients, and grade 3/4 neutropenia was noted in 31.7% (19/60). A pathological response (tumour regression grade (TRG) 1–3) was reported in 46.1% (65/141) of patients. Multivariate analysis showed that neutropenia significantly predicted the favourable pathological response (OR = 3.718, 95% CI 1.716–8.329, P = 0.001), as well as targeted therapy, good differentiation and preoperative CEA < 10 ng/ml as independent predictors of favourable histological response. Of the patients, 54.6% (77/141) had postoperative complications, including 28 major complications (28/77, 36.4%). Severe neutropenia significantly predicted postoperative major complications in multivariate analysis (OR = 4.077, 95% CI 1.184–14.038, P = 0.026). Compared to patients without neutropenia, patients with neutropenia had significantly better progression-free survival (PFS) (P = 0.007; mPFS, 10.2 months vs. 6.7 months). Patients with histological response had significantly better PFS than patients with no histological response (P = 0.001; mPFS, 10.0 months vs. 5.5 months). According to multivariate analyses, neutropenia was a significant predictor for better PFS (HR = 0.613, 95% CI 0.406–0.925, P = 0.020) but not OS. ConclusionsFor CRLM patients receiving NAC followed by liver resection, NAC-induced neutropenia was a significant predictor of favourable pathological response, postoperative major complications and better prognosis, which makes it useful for CRLM patients in guiding treatment approaches and prognosis assessments.

Impact of fresh frozen plasma transfusion on postoperative inflammation and prognosis of colorectal liver metastases

BackgroundBlood transfusion has been reported to be associated with immunomodulation and poor oncologic outcomes in several malignancies. The aim of the study is to investigate the influence of the use of fresh frozen plasma (FFP) on long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. Materials and methodsThe study comprised 127 patients who had undergone first hepatic resection for CRLM between April 2000 and December 2013. We retrospectively investigated the influence of the use of FFP on disease-free survival as well as overall survival and assessed the impact of such a practice on postoperative inflammation markers. ResultsIn multivariate analysis, more than four lymph node metastases of the primary cancer (P = 0.001), bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005) were independent risk factors for cancer recurrence, while more than four lymph node metastases of the primary cancer (P < 0.001), presence of neoadjuvant chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were independent risk factors for poor overall survival. In patients who underwent FFP transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of operation (P = 0.039), and intraoperative blood loss (P < 0.001) were significantly greater. Moreover, FFP transfusion was associated with a higher white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010) and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and day 3 (P = 0.017). ConclusionsPerioperative FFP transfusion is independently associated with poor long-term outcomes in patients with CRLM after hepatic resection. FFP may have an influence on postoperative inflammation because of its immunosuppressive effects.

Utility or futility of prognostic scoring systems for colorectal liver metastases in an era of advanced multimodal therapy

Objectives To assess the general applicability of prognostic scores for colorectal liver metastases (CRLM). Methods Review of English language studies from 1980 to 2008 (Medline and Embase). Search keywords included “Colorectal neoplasms”, “liver metastases”, “liver resection”, “prognostic scoring system”. Results Six scoring systems and fourteen prognostic factors within these studies were identified. No prognostic factor was common in all scoring methods. Five scores retained the number of metastases as a prognostic factor. Size of metastases and time between the onset of the primary tumor and the discovery of metastases were present in four scores. Three scores predicted 5-year survival using carcinoembryonic antigen (CEA) and R1 resection. Only two scores were assessed preoperatively. Successive scoring methods had improved predictive accuracy compared to earlier systems. However, their applicability in general populations remains debatable. An evaluation of the scores applicability to different patient populations demonstrated that the models were minimally effective in predicting disease-specific survival and recurrence, suggesting that stratification of patients by clinical and pathologic factors alone, may be clinically unreliable and not applicable for selection of patients for surgery. Conclusion The utility of prognostic models on general populations is inconsistent. Current clinicopathologic factors may be inadequate to determine disease prognosis in CRLM. Future attempts to develop prognostic scores should include additional biologic and clinical variables, and be validated in larger populations.

Does Repeated Surgery Improve the Prognosis of Colorectal Liver Metastases?

Hepatic resection for colorectal metastases was performed for 188 patients. Overall survival rates after the first hepatectomy are 41.4% and 32.7% for 5 and 10 years, respectively. The survival rate of 116 cases with unilobar hepatic metastases (H1) is significantly higher than those of 48 cases with two to four bilobar metastases (H2) and 24 cases with more than four (H3), respectively. However, the differences between the survival rates from H1 with multiple metastases, H2, and H3 are not significant, even though the H3 group has no 10-year survivors. The 5-year survival rates after the second hepatectomy (30 patients) and the resection of the lung (26 patients) are 30.3% and 35.2%, respectively, in this series. In those patients, the 5-year survival rates from the first metastasectomy are 43.4% and 50.3%, respectively. There are 14 5-year survivors with multiple metastases and 8 of those patients underwent multiple surgeries. There are 13 patients with three or more repeat resections of the liver and/or lung. The 5-year survival rates of the patients from the first and third metastasectomy are 53.9% and 22.5%, respectively. Repeat operations for the liver and the lung contribute to the improving prognosis.