Trajectory patterns and cumulative burden of CEA during follow-up with non-small cell lung cancer outcomes: A retrospective longitudinal cohort study.

BACKGROUND: Previous studies of non-small cell lung cancer (NSCLC) focused on CEA measured at a single time point, ignoring serial CEA measurements. METHODS: This retrospective cohort included 2959 patients underwent surgery for stage I-III NSCLC. CEA trajectory patterns and long-term cumulative CEA burden were evaluated using the latent class growth mixture model. RESULTS: Four CEA trajectory groups were identified, named as low-stable, decreasing, early-rising and later-rising. Compared with the low-stable group, the adjusted hazard ratios associated with death were 1.27, 4.50, and 3.68 for the other groups. Cumulative CEA burden were positively associated with the risk of death in patients not belonging to the low-stable group. The 5-year overall survival (OS) rates decreased from 62.3% to 33.0% for the first and fourth quantile groups of cumulative CEA burden. Jointly, patients with decreasing CEA trajectory could be further divided into the decreasing & low and decreasing & high group, with 5-year OS rates to be 77.9% and 47.1%. Patients with rising CEA trajectory and high cumulative CEA were found to be more likely to develop bone metastasis. CONCLUSIONS: Longitudinal trajectory patterns and long-term cumulative burden of CEA were independent prognostic factors of NSCLC. We recommend CEA in postoperative surveillance of NSCLC.

Prediction models of colorectal cancer prognosis incorporating perioperative longitudinal serum tumor markers: a retrospective longitudinal cohort study.

BACKGROUND: Current prognostic prediction models of colorectal cancer (CRC) include only the preoperative measurement of tumor markers, with their available repeated postoperative measurements underutilized. CRC prognostic prediction models were constructed in this study to clarify whether and to what extent the inclusion of perioperative longitudinal measurements of CEA, CA19-9, and CA125 can improve the model performance, and perform a dynamic prediction. METHODS: The training and validating cohort included 1453 and 444 CRC patients who underwent curative resection, with preoperative measurement and two or more measurements within 12 months after surgery, respectively. Prediction models to predict CRC overall survival were constructed with demographic and clinicopathological variables, by incorporating preoperative CEA, CA19-9, and CA125, as well as their perioperative longitudinal measurements. RESULTS: In internal validation, the model with preoperative CEA, CA19-9, and CA125 outperformed the model including CEA only, with the better area under the receiver operating characteristic curves (AUCs: 0.774 vs 0.716), brier scores (BSs: 0.057 vs 0.058), and net reclassification improvement (NRI = 33.5%, 95% CI: 12.3 ~ 54.8%) at 36 months after surgery. Furthermore, the prediction models, by incorporating longitudinal measurements of CEA, CA19-9, and CA125 within 12 months after surgery, had improved prediction accuracy, with higher AUC (0.849) and lower BS (0.049). Compared with preoperative models, the model incorporating longitudinal measurements of the three markers had significant NRI (40.8%, 95% CI: 19.6 to 62.1%) at 36 months after surgery. External validation showed similar results to internal validation. The proposed longitudinal prediction model can provide a personalized dynamic prediction for a new patient, with estimated survival probability updated when a new measurement is collected during 12 months after surgery. CONCLUSIONS: Prediction models including longitudinal measurements of CEA, CA19-9, and CA125 have improved accuracy in predicting the prognosis of CRC patients. We recommend repeated measurements of CEA, CA19-9, and CA125 in the surveillance of CRC prognosis.

Influence of the initial recurrence site on prognosis after radical surgery for colorectal cancer: a retrospective cohort study.

BACKGROUND & AIMS: In this retrospective study, we aimed to elucidate how the initial recurrence site influences the post-recurrence survival (PRS) after the curative resection of colorectal cancer. PATIENTS AND METHODS: We collected samples from patients with stage I-III colorectal adenocarcinoma who were admitted to Yunnan Cancer Hospital from January 2008 to December 2019. Four hundred and six patients who developed recurrence after radical resection were included. The cases were classified according to the original site of recurrence as follows: liver metastases (n = 98), lung metastases (n = 127), peritoneum (n = 32), other individual organ (n = 69), two or more organs or sites (n = 49), and local recurrence (n = 31). Kaplan-Meier survival curves were used to compare the PRS of patients with different initial sites of recurrence. The influence of the initial recurrence site on PRS was analyzed using the Cox proportional hazards model. RESULTS: The 3-year PRS of simple liver metastasis was 54.04% (95% CI, 45.46%-64.24%), and the 3-year PRS of simple lung metastasis was 50.05% (95% CI, 42.50%-58.95%). No significant difference was observed between simple liver metastasis or simple lung metastasis and local recurrence with a 3-year PRS of 66.99% (95% CI, 53.23%-84.32%). The 3-year PRS for peritoneal metastases was 25.43% (95% CI, 14.76%-43.82%), and the 3-year PRS for two or more organ sites was 34.84% (95% CI, 24.16%-50.24%). The peritoneal (hazard ratio [HR], 1.75; 95% CI, 1.10-2.79; P = 0.0189) and metastasis to two or more organs or sites (HR, 1.59; 95% CI, 1.05-2.43; P = 0.0304) were PRS-independent adverse prognostic factors. CONCLUSION: The prognosis of patients with peritoneum and multiple organs or sites recurred was poor. This study suggests early monitoring of peritoneal and multiple organ or site recurrence after surgery. This part of patients should receive comprehensive treatment as early as possible to improve their prognosis.

Effect of initial recurrence site on the prognosis of different tissue types of non-small cell lung cancer: a retrospective cohort study.

PURPOSE: To explore the correlation between the initial recurrence site and survival after recurrence (PRS) in non-small cell lung cancer (NSCLC). METHODS: We collected 588 stages I-III NSCLC patients with recurrence after radical resection in Yunnan Cancer Hospital from January 2013 to December 2018. We used Kaplan-Meier survival curves to compare PRS in patients with different site recurrences. The univariate and multivariate Cox proportional hazard models were used to analyze the impact of the initial recurrence site on PRS. RESULTS: The recurrence site included the lung (n = 109), brain (n = 113), bone (n = 79), abdomen (n = 28), pleura (n = 24), lymph node (n = 81), and multisite (n = 154). In the total population, patients with multisite recurrence had substantially worse PRS (24.8 months, 95% confidence interval [CI]: 17.46-32.20) than that of patients without multiple sites recurrence (42.2 months, 95% CI 32.24-52.10) (P = 0.026). However, patients with lung recurrence had better RFS (63.1 months, 95% CI 51.13-74.00) than those who did not (31.0 months, 95% CI 25.10-36.96) (P < 0.001). In adenocarcinoma, patients with pleural recurrence had substantially worse PRS (21.3 months, 95% CI 15.07-27.46) than that of patients without pleural recurrence (46.9 months, 95% CI 35.07-58.80) (P = 0.031). Multivariate Cox proportional hazards regression analysis revealed that lung recurrence (HR 0.58, 95% CI 0.40-0.82; P = 0.003) was independent protective prognostic factor for PRS in the total population, while pleural recurrence (HR 2.18, 95% CI 1.14-4.17; P = 0.018) was independent adverse prognostic factors for PRS in adenocarcinoma patients. CONCLUSION: The initial recurrence site was associated with PRS in NSCLC patients. Identification of recurrence sites could guide the subsequent treatment.

Significance of tumor deposits combined with lymph node metastasis in stage III colorectal cancer patients: a retrospective multi-center cohort study from China.

PURPOSE: The study aimed to explore the value of tumor deposits in stage III colorectal cancer (CRC) and verify whether patients with more tumor deposit numbers have higher risk of recurrence. METHODS: The retrospective cohort analysis was performed at two cancer centers of China. Stage III CRC patients who underwent radical resection at the center between April 2008 and February 2019 were identified. The Univariate/Multivariate Cox regression, Kaplan-Meier analysis, and PSM were recurrence-free survival (RFS) used. RESULTS: Total 1080 stage III CRC patients (634 [58.7%] men; median [IQR] age, 60 [50-68] years) who underwent radical surgical resection were identified for inclusion in this study. Patients with tumor deposits had a 12.8% lower 3-year RFS (n = 236 [69.9%]) than the patients without tumor deposits (n = 844 [82.7%]) (P ≤ 0.0001). The 3-year RFS of patients with stage N2 (n = 335 [61.2%]) was 18.6% lower (P ≤ 0.0001) than the original cohort of patients with stage N1 (n = 745 [79.8%]), but it was similar to the RFS of patients with 4 or more tumor deposits plus lymph node metastases (n = 58 [61.4%]) (P = 0.91). The RFS for patients with 4 or more tumor deposits plus number of lymph node metastases (n = 58 [61.4%]) was 15.8% lower than the cohort of patients with 1-3 tumor deposits + number of lymph node metastases (n = 687 [77.2%]) (P = 0.001). Multivariate analysis confirmed that patients with 4 or more tumor deposits + the number of lymph node metastases (hazard ratio [HR], 1.88; 95% CI, 1.24-2.87) were independently associated with a shorter RFS. CONCLUSION: The number of tumor deposits is an indicator of poor postoperative prognosis. It is necessary to incorporate the number of tumor deposits combined with the number of lymph node metastases to stratify postoperative stratification of stage III CRC, which may provide a new theoretical basis for adjuvant therapy for patients with N1 stage CRC after surgery.

Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study.

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients' recurrence free survival (RFS). The Kaplan-Meier method was used to create the patients' RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0-88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5-86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1-93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22-2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5-96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8-71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51-49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.

ZNF326 as a potential prognostic and predictive biomarker in stage II colorectal cancer.

Background: Adjuvant chemotherapy is considered for stage II colorectal cancer (CRC) patients with poor prognostic risk factors. However, current stratification algorithms are still insufficient to identify high-risk patients. Methods: We conducted a screening strategy to define ZNF326 based on quantitative proteomics in 11 paired CRC patients selected by a nested case-control design, and tested the association between ZNF326 expression level with the prognosis of stage II CRC patients and the benefit from adjuvant chemotherapy in public datasets; further investigation was conducted through subgroup analyses. Results: We found that low ZNF326 expression was significantly associated with a lower 5-year overall survival (OS) rate among stage II patients in both the discovery [P=0.008; hazard ratio (HR): 3.13, 95% confidence interval (CI): 1.29-7.58] and validation (P=0.025; HR: 1.98, 95% CI: 1.08-3.65) cohorts. In the Cox multivariable analysis, low ZNF326 expression was both associated with shorter OS after adjustment for age, sex, and adjuvant chemotherapy in the discovery and validation data sets. Subgroup analyses yielded largely similar results. In a pooled database, the rate of 5-year OS was higher among stage II ZNF326-high tumors who were treated with adjuvant chemotherapy than it was among those who were not treated with adjuvant chemotherapy (P=0.011; HR: 0.28, 95% CI: 0.10-0.80). Conclusions: ZNF326 has the potential to be used in clinical practice for risk classification. ZNF326-low expression level identified a subgroup of patients with high-risk stage II CRC who appeared to less benefit from adjuvant chemotherapy.

Prognostic Value of the Lung Immune Prognostic Index for Metastatic Non-Small Cell Lung Cancer Patients: A Chinese Cohort Study.

Background: Most cancer-related deaths around the globe are caused by lung cancer. The present treatments for metastatic non-small cell lung cancer (mNSCLC) are cytotoxic chemotherapy (CCT), targeted therapy (TT) and immunotherapy, but the benefit of the same regime varies greatly. Hence, it is important to identify biomarkers to predict the efficacy of modalities. Previous literature suggested certain parameters might be predictive factors. Nevertheless, the utility of these parameters is limited due to the types of solid tumors. Purpose: The study aimed to examine whether the lung immune prognostic index (LIPI) was related to outcomes of CCT, immune checkpoint inhibitors (ICIs) and TT for mNSCLC patients. Materials and Methods: A retrospective cohort study between September 2012 and May 2020 was conducted on 350 Chinese mNSCLC patients, including 147 patients receiving ICIs, 103 TT, and 100 CCT. The data were examined to analyze the prognostic value of LIPI among various treatments. Main Outcomes and Measures: The associations between PFS and good, intermediate, or poor prognostic LIPI scores in ICIs, TT, and CCT were determined, respectively. Results: In univariable analyses, there was a relevance between a good LIPI score and better PFS among patients receiving ICIs (HR, 0.81; 95% CI, 0.44-1.51), TT (HR, 0.35; 95% CI, 0.16-1.74), and CCT (HR, 0.39; 95% CI, 0.19-0.80). In multivariable analyses, the intermediate LIPI score was linked to better PFS only in patients receiving TT (HR, 0.31; 95% CI, 0.17-0.92) rather than ICIs (HR, 1.12; 95% CI, 0.66-2.45) or CCT (HR, 1.24; 95% CI, 0.49-4.55). Conclusion: Baseline LIPI value is an important prognostic biomarker for mNSCLC patients treated with TT. Shorter PFS with TT was associated with poor baseline LIPI. Poor LIPI score may be considered as a promising indicator showing which patients are unlikely to respond well to TT. The prognostic value of LIPI can be more clearly determined through prospective clinical study.

Effect of oral pre-emptive analgesia on pain management after total knee arthroplasty: a protocol for systematic review and meta-analysis.

INTRODUCTION: Total knee arthroplasty (TKA) is currently regarded as an effective treatment for knee osteoarthritis, relieving patients' pain and significantly enhancing their quality of life and activity levels, allowing them to return to work and daily life after surgery. However, some TKA patients suffer from varying degrees of postoperative residual pain and opioid abuse, which negatively impacts their recovery and quality of life. It has been reported that preoperative treatment with multimodal analgesics improves postoperative pain and reduces opioid consumption. However, there is no conclusive evidence that pre-emptive analgesia provides the same benefits in TKA. In order to inform future research, this protocol focuses on the efficacy and safety of oral analgesics used in TKA pre-emptive analgesia. METHODS AND ANALYSIS: We will search the literature on the involvement of pre-emptive analgesia in the management of pain in TKA from the PubMed, EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, from their inception to 1 February 2023. Additionally, clinical registry platforms will be investigated to collect data for ongoing studies. Using the Cochrane Risk of Bias Tool, the quality assessment will be conducted. RevMan V.5.4 will be used for the meta-analysis. The statistic I 2 will be used to measure the percentage of total variability due to heterogeneity between studies. Where appropriate, subgroup and sensitivity analyses, assessment of evidence quality and publication bias will be conducted. ETHICS AND DISSEMINATION: No ethical approval and consent is required for this systematic review. Moreover, the results of this systematic review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022380782.

The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II-III Colorectal Cancer: A Retrospective Multi-Center Cohort Study.

Background: It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy. Purpose: The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II-III colorectal cancer (CRC). Methods: The retrospective cohort analysis was performed on patients with stage II-III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II-III CRC. Results: A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80-2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52-3.70; log-rank P=0.66). Conclusion: Patients over the age of 75 with stage II-III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II-III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.

DNA methylation age acceleration is associated with age of onset in Chinese spinocerebellar ataxia type 3 patients.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado Joseph disease (MJD), is a common dominantly inherited ataxia, and has heterogeneous clinical features and variable age of onset, ranging from 10 to 78 years. Repeats variability of ATXN3, HTT, ATN1 and ATXN2 can explain partially but not fully SCA3 age of onset heterogeneity. Aging is a reported modifier of SCA3 severity and closely linked to DNA methylation (DNAm). DNAm age acceleration was associated with disease risk and/or variable disease phenotypes in several repeat associated neurodegenerative diseases (such as Huntington's disease and Amyotrophic lateral sclerosis). To understand if DNAm age acceleration is associated with SCA3 age of onset, we performed a genome-wide DNAm study of a Chinese SCA3 family with variable age of onset and clinical presentations. All patients showed unsteady gait, deterioration of extremities coordination, speech (dysarthria) and swallowing problems (dysphagia, choking on eating and/or drinking) and oculomotor abnormalities, with variable age of onset ranging from 27 to 52 years. We found that DNAm age acceleration is associated with age of onset (p-value = 0.0023, B = -1.26), suggesting that every 5 year increase in DNAm-age acceleration is corresponding to a 6.3 year earlier disease onset. This association remains significant after the adjustment to ATXN3 CAG repeats (adjusted p-value = 0.037, adjusted B = -1.0). In an independent SCA3 cohort (n = 40), we also observed the association between DNAm age acceleration and age of onset (adjusted p-value = 0.007, adjusted B = -0.69). Of note, we found no significant association between DNAm of single-CpG locus and/or CpG-SNPs and SCA3 age of onset in the current family or the SCA3 cohort. Our findings suggested that DNAm age acceleration might be a SCA3 age of onset modifier, and encourage further investigations in extended SCA3 cohorts to clarify the role of epigenetic aging in modifying disease onset.

Relationship Between Preoperative and Postoperative Serum Carcinoembryonic Antigen and Prognosis of Patients with Stage I-III Rectal Cancer: A Retrospective Study of a Multicentre Cohort of 1022 Rectal Cancer Patients.

PURPOSE: Based on a multi-centered and a large sample size, this study aims to analyze the relationship between preoperative and postoperative serum CEA and recurrence of rectal cancer without preoperative therapy. METHODS: This retrospective cohort study enrolled stage I to III rectal cancer patients without preoperative therapy (N = 1,022) who received radical resection of rectal cancer from 2 hospitals in China. Based on the preoperative and postoperative serum carcinoembryonic antigen, the patients were subdivided into 3 groups ie, normal preoperative CEA (≤5.0 ng/mL, N = 627), elevated preoperative (>5.0 ng/mL) but normalized postoperative CEA (normalized postoperative CEA, N = 255), as well as elevated preoperative and postoperative CEA (elevated postoperative CEA, N = 67). The generalized additive model was used to assess the relationship between carcinoembryonic antigen and the risk of recurrence. Further, the Cox regression model was used to evaluate the relationship between carcinoembryonic antigen and 3-year recurrence-free survival (RFS) after adjusting for potential confounders. RESULTS: The 3-year RFS of patients with elevated postoperative CEA was 45.8% (95% CI, 35.2% -59.5%), which was significantly lower compared to the other two groups of patients (normalized postoperative CEA: 75.9%, 95% CI, 70.8%-81.4%; and normal preoperative CEA: 84.9%, 95% CI, 82.2%-87.8%) (P <0.001). Based on multivariable Cox model analysis, the elevated postoperative CEA was a prognostic factor for 3 years RFS (hazard ratio [HR], 3.08; 95% CI, 2.05-4.66; P<0.001). At the same time, normalized postoperative CEA was insignificantly correlated with 3-year RFS (HR, 1.38; 95% CI, 1.00-1.92; P = 0.05) and was not an independent risk factor. CONCLUSION: We found that preoperative and postoperative serum CEA of rectal cancer patients were related to the 3-year recurrence-free survival rate. Moreover, the risk of recurrence in the normalized postoperative CEA group of patients was insignificantly different from that of the normalized preoperative CEA patients. Therefore, it is necessary to combine preoperative and postoperative CEA to predict the prognosis of patients with rectal cancer, rather than using it alone.

Trajectories of Perioperative Serum Tumor Markers and Colorectal Cancer Outcomes: A Retrospective, Multicenter Longitudinal Cohort Study.

BACKGROUND: The dynamic monitoring of perioperative carcinoembryonic antigen (CEA) is recommended by current colorectal cancer (CRC) guidelines, while the benefits of additional measurements of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) have remained controversial. METHODS: This retrospective longitudinal cohort included 3539 CRC patients who underwent curative resection. Distinct trajectory groups were identified by the latent class growth mixed model. Patients were grouped into subgroups jointly by CEA, CA19-9, and CA125 according to preoperative levels and longitudinal trajectories, respectively. The end points were overall survival (OS) and recurrence-free survival (RFS). FINDINGS: Three distinct trajectory groups were characterized for serum CEA, CA19-9, and CA125: low-stable, early-rising, and later-rising. Jointly, patients were grouped into six preoperative (trajectory) joint groups. Compared with the three-low group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) associated with death were 1.87 (1.29-2.70), 3.82 (2.37-6.17), 1.87 (0.97-3.61), 2.81 (1.93-4.11), and 4.99 (2.80-8.86) for the CEA-high, CA19-9-high, CA125-high, two-high, and three-high group, respectively. And compared with the three-stable trajectory group, the corresponding HRs (95% CIs) were 1.59 (1.10-2.30), 1.55 (0.77-3.10), 6.25 (4.02-9.70), 4.05 (2.73-6.02), and 12.40 (5.77-26.70) for the five rising trajectory groups, respectively. Similar associations between joint groups and RFS were observed. Notably, the trajectory joint group still had prognostic significance after adjusting for preoperative levels. The CA19-9-high group (HR: 3.82, 95% CI: 2.37-6.17) was associated with higher risk of death than the two-high group (HR: 2.81, 95% CI: 1.93-4.11). Likewise, for the CA125-rising trajectory group and two-rising trajectory group, the HRs (95% CIs) were 6.13 (3.75-10.00) and 3.99 (2.63-6.05) for death, and 3.08 (2.07-4.58) and 2.10 (1.52-2.90) for recurrence. INTERPRETATION: In addition to CEA, the dynamic measurements of CA19-9 and CA125 are recommended to monitor the prognosis of CRC patients. FUNDING: National Natural Science Foundation of China [81973147, 82001986, 81960592, 82073569, 81660545].

Predictive Value of Postoperative Peripheral CD4+ T Cells Percentage in Stage I-III Colorectal Cancer: A Retrospective Multicenter Cohort Study of 1028 Subjects.

OBJECTIVE: Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer (CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients. PATIENTS AND METHODS: Consecutive stage I-III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed. RESULTS: A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3% [95% CI 65.7-75.2%] vs 77.6% [95% CI 73.7-81.7%] and unadjusted hazard ratio [HR] 1.36 [95% CI 1.04-1.78], P=0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12-0.72], P=0.008). CONCLUSION: Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy.