Early Recurrence Of Colorectal Cancer Research Articles

Real-world evidence of FOLFIRI combined with anti-angiogenesis inhibitors or anti-EGFR antibodies for patients with early recurrence colorectal cancer after adjuvant FOLFOX/CAPOX therapy in Japan: A retrospective observational study using administrative database.

110 Background: Oxaliplatin-containing regimens (FOLFOX or CAPOX) are the most common adjuvant treatments after curative resection of colorectal cancer (CRC). However, real-world evidence (RWE) of treatment sequence/outcomes for patients with early recurrence CRC after receiving adjuvant chemotherapy are limited. Methods: This retrospective cohort study was based on an administrative database in Japan. The primary objective was to describe the treatment sequence for patients with early recurrence CRC and treated by combination of FOLFIRI and anti-angiogenesis inhibitors (AAIs) or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) after adjuvant FOLFOX or CAPOX therapy. The study included patients with CRC who underwent surgical resection, started adjuvant chemotherapy ≤3 months (mo) after the first surgery, had early recurrence of CRC (defined as initiation of FOLFIRI + AAIs/anti-EGFR mAbs second line [2L] regimen) within 1 year after adjuvant chemotherapy ended. Patient characteristics at baseline of 2L (60 days prior to 2L initiation) and treatment sequence were summarized descriptively; time to discontinuation (TTD) for adjuvant and 2L therapy were analyzed using Kaplan-Meier method. Cox proportional hazard model was used to identify risk factors associated with TTD of 2L regimen. Results: The cohort included 832 patients: median (range) age was 67 (24-86) years, 56.4% males, 65.5% with left-sided CRC. Most patients received CAPOX (71.3%) as adjuvant therapy. Median (95% CI) duration of adjuvant therapy was 5.4 mo (5.3-5.5). As 2L therapy, 72.5% and 27.5% of patients received FOLFIRI + AAIs (AAIs group) and FOLFIRI + anti-EGFR mAbs (anti-EGFR group), respectively. Median TTD (95% CI) of the AAIs and anti-EGFR groups in 2L were 6.2 mo (5.8-6.9) and 6.1 mo (5.2-7.4), respectively. Among patients with recurrence within 6 mo (72.6%), the median TTD (95% CI) for AAIs and anti-EGFR groups were 6.1 mo (5.5- 6.5) and 5.8 mo (5.1-7.8), respectively. Among patients with recurrence during 6 to 12 mo (27.4%), the median TTD (95% CI) of AAIs and anti-EGFR groups were 8.1 mo (6.1-9.2) and 6.2 mo (4.6-8.0), respectively. Age ≥70 years was negatively associated with TTD of 2L, HR = 1.19 (95% CI: 1.02-1.39); p=0.03. Conclusions: This is the first RWE based on administrative data on treatment sequence/ outcomes for patients with early recurrence CRC treated by FOLFIRI + AAIs/anti-EGFR mAbs after adjuvant FOLFOX/CAPOX therapy in Japan. The treatment outcomes for patients with early recurrence CRC were similar to previous clinical trials in 2L advanced CRC. The results suggested that these two 2L regimens had similar TTD; however, the timing of relapse may influence the efficacy of AAIs and anti-EGFR mAbs.

Development and validation of a novel radiomics nomogram for prediction of early recurrence in colorectal cancer

BackgroundEarly recurrence (ER) is a significant concern following curative resection of advanced colorectal cancer (CRC) and is linked to poor long-term survival. Reliable prediction of ER is challenging, necessitating the development of a novel radiomics-based nomogram for CRC patients. MethodsWe enrolled 405 patients, with 298 in the training set and 107 in the external test set. Radiomic features were extracted from preoperative venous-phase computed tomography (CT) images. A radiomics signature was created using univariate logistic regression analyses and the least absolute shrinkage and selection operator algorithm. Clinical factors were integrated into the analyses to develop a comprehensive predictive tool in a multivariate logistic regression model, resulting in a radiomics nomogram. Subsequently, the calibration, discrimination, and clinical usefulness of the nomogram were evaluated. ResultsThe radiomics signature, consisting of four selected CT features, was significantly associated with ER in both the training and test datasets (P < 0.05). Independent predictors of ER included TNM stage, carcinoembryonic antigen level and differentiation grade were identified. The radiomics nomogram, incorporating all these predictors, exhibited good predictive ability in both the training set with an area under the curve (AUC) of 0.82 (95 % confidence interval (CI), 0.74–0.90) and the test set with an AUC of 0.85 (95 % CI, 0.72–0.99), surpassing the performance of any single candidate factor alone. Furthermore, additional analysis demonstrated that the nomogram was clinically useful. ConclusionsWe have developed a radiomics-based nomogram that effectively predicts early recurrence in CRC patients, enhancing the potential for timely intervention and improved outcomes.

Risk Factors of Colorectal Cancer Recurrence After Curative Resection Surgery: A Systematic Review and Meta-analysis

Context: According to the World Health Organization, colorectal cancer (CRC) is the third most prevalent cancer globally, with the highest mortality rate after lung cancer. Some studies predicted risk factors provoking CRC recurrence. However, no single study discussed CRC recurrence. Objectives: This study aimed to quantitatively estimate the influence of several risk factors toward early recurrence of CRC. Methods: We utilized four medical databases, including Pubmed, Cochrane, Wiley library, and ScienceDirect, and a range of literature searches between July to October 2020 with output study, odds ratio (OR), and some risk factors. We used PRISMA protocol along with several relevant keywords with NOS method was utilized to assess the quality of the study. Fixed- and randomized effect model were utilized to control each numerical analysis’ bias. Results: We found six studies that compared the risk factor of CRC recurrence after curative resection with curative-intention encompassing a total of 15.457 patients. We found seven risk factors of colorectal cancer recurrence, including vascular invasion (OR 2.3; IK95%: 01.56 - 3.4; P &lt; 0.0001), depth of invasion (T stage) (OR 2.27; IK95%: 1.14 - 4.51; P = 0.02), pre-operative CEA serum (OR 2.24 IK95%: 1.57 - 3.2; P &lt; 0.0001), post-operative CEA serum (OR 5.97 IK95%: 3.04 - 11.74; P &lt; 0,0001), pre-operative CA19-9 serum (OR 3.03; IK95%: 1.74 - 5.25; P &lt; 0.0001), and regional nodal metastasis (N stage) (OR 2.56; IK95% 1.41 - 4.62; P = 0.002). Conclusions: Risk factors of earlier CRC recurrence were diversely reviewed. The elevation of post-operative CEA serum was assumed as the main factor in this study; however, most of the studied parameters were statistically significant.

Efficacy of PRR11, HMGA2, and ANXA10 in predicting early recurrence of colorectal cancer after total mesorectal resection

Efficacy of PRR11, HMGA2, and ANXA10 in predicting early recurrence of colorectal cancer after total mesorectal resection

Predictive Nomogram for the Prediction of Early Recurrence of Colorectal Cancer.

AimThe prognosis of colorectal cancer (CRC) individuals after curative resection is not satisfactory due to the early recurrence. We sought to identify the affecting features of early recurrence in CRC patients.MethodsA total of 3500 CRC patients underwent curative resection were retrospectively incorporated into our study. Among them, 246 patients exhibited tumor recurrence: 121 had early recurrence (≤1 year after operation) and 125 had late recurrence (>1 year after operation). A total of 246 CRC patients with recurrence were randomly assigned into the training group (N=177) or validation group (N=69) based on the ratio of 7:3. LASSO COX regression and support vector machine (SVM) were utilized to screen for the significant clinical indexes associated with the presence of early recurrence. Recurrent nomogram was created based on the above informative parameters to predict the probability of early recurrence.ResultsProportion of advanced TNM stage, platelet count, systemic immune-inflammation index (SII), mean corpuscular hemoglobin concentration (MCHC), CA-199, CA-125, lactate dehydrogenase, total bile acid (TBA), urea nitrogen were significantly higher in early recurrence group compared with that in late recurrence group. Results from LASSO COX regression and support vector machine (SVM) revealed that TNM stage, CA-199, CA125, SII and TBA were strong predictors for the presence of early recurrence among postoperative CRC patients in the training group. The recurrent nomogram based on the five predictors exhibited good predictive performance as calculated by C-index (0.846, 95% CI 0.789–0.902 in the training group and 0.799, 95% CI 0.697–0.902 in the validation group) for the prediction of early recurrence. Moreover, the recurrent nomogram exhibited not only encouraging calibration ability, but also great clinical utility both in the training group and validation group.ConclusionTNM stage, CA-199, CA125, SII and TBA were closely correlated with the presence of early recurrence of CRC patients. The recurrent nomogram held well predictive ability for the identification of CRC patients with early recurrence.

Circulating tumor DNA as a promising biomarker of relapse risk for stage II-III colorectal cancer.

4079 Background: About 30-50% colorectal cancer patients undergoing a curative resection will experience disease recurrence ultimately. Early detection of recurrence is of great significance for improving the prognosis of colorectal cancer patients. Circulating tumor DNA (ctDNA) has been suggested to be a promising biomarker for postoperative surveillance and prognosis prediction in various cancers including colorectal cancer. However, its performance in predicting early recurrence of colorectal cancer as well as appropriate testing procedures still needs large-scale prospective studies to evaluate. Methods: A total of 246 patients with stage II-III colorectal cancer and underwent curative resection from three clinical centers of China were enrolled in this multicenter prospective cohort study. Tissue samples as well as serial plasma samples before surgery, 7 days and 6 months after surgery and 3 months interval afterwards until recurrence were collected, and subjected to deep targeted-panel sequencing containing 425 cancer-related genes. ctDNA baseline genomic alterations and dynamic changes were analyzed. Its performance in predicting early recurrence was evaluated and compared with other clinical routine investigations, including serum biomarkers CEA and CA199, and CT examination. Results: The ctDNA positive rates at baseline (before surgery) and 7 days after surgery were 72.9% and 18.1% respectively. Among 199 patients with complete survival data, 18 patients were recurrent during follow up period with a median disease-free survival of 280.5 days (114-461 days). At baseline, high clinical stage (p = 0.035), and PTEN mutation (p = 0.009) were significantly associated with increased recurrent risk; while APC mutation (p = 0.04) predicted a decreased recurrent risk. Detection of ctDNA 7 days after surgery [HR: 5.9 (1.94-17.97); p = 0.0004] or any time point before clinical recurrence [HR: 6.14 (2.3-16.38); p &lt; 0.0001] was associated with a significantly higher recurrent risk, and the HR increased accordingly with ctDNA mutation level. In multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathological risk factors. CEA status was not significantly (p &gt; 0.4) associated with disease-free survival. A risk scoring model comprising of clinical variables and ctDNA detection after surgery was constructed and can predict 18-month recurrence with an AUC of 0.77. Conclusions: ctDNA is a promising marker of risk stratification, and early relapse detection in resected stage II/III CRC patients. Clinical trial information: NCT03312374 .

2078 Prognosis and predictive factors of early-recurrence in colorectal cancer

2078 Prognosis and predictive factors of early-recurrence in colorectal cancer

The value of trefoil factor 3 expression in predicting the long‑term outcome and early recurrence of colorectal cancer.

The trefoil factor (TFF) family comprises three thermo-stable and protease-resistant proteins (TFF1, TFF2 and TFF3) and plays an essential role in gastrointestinal mucosa protection and regeneration, and TFFs have recently been found to be involved in the development and progression of various types of cancer. However, the clinical significance of TFFs in colorectal cancer (CRC) patients remains unclear. The present study determined the relationship between TFF expression and clinicopathological findings, as well as long-term outcome in CRC patients. The mRNA expression levels of TFFs were examined in the excised CRC specimens obtained from 154 consecutive CRC patients who underwent surgical resection between 2005 and 2007 at our institution. TFF3 expression was significantly associated with the presence of distant metastasis (p=0.017), although neither TFF1 nor TFF2 expression was associated with the clinicopathological features. Survival rate of the patients with positive TFF3 was significantly worse compared to those with negative TFF3 (p=0.011). A multivariate analysis revealed that the expression of TFF3, lymph node metastasis, and vascular invasion were independent prognostic factors for disease-specific survival. Furthermore, among 134 patients with no clinical findings of metastasis at surgery, the patients with positive TFF3 experienced recurrence within one year more frequently than those with negative TFF3 (p=0.039). In conclusion, TFF3 is not only a useful biomarker for a long-term surgical result in CRC patient, but also may be a risk factor of early recurrence.

CD133-positive tumor cell content is a predictor of early recurrence in colorectal cancer.

The aims of this study were to demonstrate the tumorigenicity of CD133+ colon cancer cells in vitro, analyze the correlations between spheroid formation and clinicopathologic variables, and screen for overexpressed genes in CD133+ colon cancer stem cells. Moreover, the aim of this study was to establish a living tumor tissue bank using surgically resected specimens. Using LoVo cell line, we isolated CD133+ cells and performed clonogenic assay and animal experiment to test tumorigenicity of CD133+ cells. Twenty-nine surgical samples were freshly collected from 27 patients who received curative or palliative surgery, and the samples were mechanically and enzymatically dissociated into single cells. We confirmed the enhanced tumorigenicity of CD133+ cells isolated from LoVo cell line both in vitro and in vivo. Of these 29 samples, 8 (28%) contained >3% CD133+ cells. Sphere formation was significantly higher in samples from patients with lymphatic invasion than in those without lymphatic invasion [54.5% (6/11) vs. 12.5% (2/16); P=0.033] and in samples containing >3% of CD133+ cells than in those containing ≤3% of CD133+ cells [36.4% (4/11) vs. 0% (0/16); P=0.019]. These findings indicate that CD133 is a valid marker for identifying cancer stem cells from fresh surgically resected colorectal cancer tissues. Furthermore, we successfully established a living tumor tissue bank using surgically resected colorectal tissues with a viability of >70%.

Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection.

PurposeBecause predicting recurrence intervals and patterns would allow for appropriate therapeutic strategies, we evaluated the clinical and pathological characteristics of early and late recurrences of colorectal cancer.MethodsPatients who developed recurrence after undergoing curative resection for colorectal cancer stage I-III between January 2000 and May 2006 were identified. Early recurrence was defined as recurrence within 2 years after primary surgery of colorectal cancer. Analyses were performed to compare the clinicopathological characteristics and overall survival rate between the early and late recurrence groups.ResultsOne hundred fifty-eight patients experienced early recurrence and 64 had late recurrence. Multivariate analysis revealed that the postoperative elevation of carbohydrate antigen 19-9 (CA 19-9), venous invasion, and N stage correlated with the recurrence interval. The liver was the most common site of early recurrence (40.5%), whereas late recurrence was more common locally (28.1%), or in the lung (32.8%). The 5-year overall survival rates for early and late recurrence were significantly different (34.7% vs. 78.8%; P < 0.001). Survival rates after the surgical resection of recurrent lesions were not different between the two groups.ConclusionEarly recurrence within 2 years after surgery was associated with poor survival outcomes after colorectal cancer recurrence. An elevated postoperative CA 19-9 level, venous invasion, and advanced N stage were found to be significant risk factors for early recurrence of colorectal cancer.

The Functional Significance of MicroRNA-29c in Patients with Colorectal Cancer: A Potential Circulating Biomarker for Predicting Early Relapse

BackgroundThe recurrence of colorectal cancer (CRC) is frequent within the first year of curative resection surgery and may be unavoidable. microRNAs have been suggested to play roles in carcinogenesis and cancer recurrence. We recently identified microRNA-29c (miRNA-29c) as a predictor of early recurrence in CRC. In the present study, we further investigated the functions and serum level of miRNA-29c in relation to early recurrence of CRC.MethodsFirst we further confirmed overexpression of miRNA-29c in non-early relapse subjects. Gain-of-function in vitro studies were used to evaluate the effect of miRNA-29c on cell proliferation, migration, invasion, and cell cycle progression. The colon cancer cell line Caco2 and a stable clone overexpressing miRNA-29c were xenografted to evaluate the in vivo effect of miRNA-29c in null mice. Finally, circulating miRNA-29c was investigated as a potential biomarker for identifying early relapse.ResultsmiRNA-29c expression significantly decreased during early relapse compared to non-early relapse in UICC stage II and III CRC patients (P = 0.021). In vitro studies showed that overexpression of miRNA-29c inhibited cell proliferation and migration. The cell cycle studies also revealed that miRNA-29c caused an accumulation of the G1 and G2 population. In vivo, miRNA-29c suppressed tumor growth in null mice. The serum miRNA-29c increased significantly in early relapsed patients compared to non-early elapsed patients (P = 0.012).ConclusionsmiRNA-29c shows anti-tumorigenesis activity, and preoperative circulating miRNA-29c levels can be used to predict postoperative early relapse of CRC.

Proliferating cell nuclear antigen (PCNA) and silver binding nucleolar organizing regions (AgNOR) as predictors of early recurrence in colorectal cancer (CRC): [formula omitted], MA Mahkri, E Lee, M Gesell, and GD Luk. Dallas VA and UT Southwestern, Dallas, TX

Proliferating cell nuclear antigen (PCNA) and silver binding nucleolar organizing regions (AgNOR) as predictors of early recurrence in colorectal cancer (CRC): [formula omitted], MA Mahkri, E Lee, M Gesell, and GD Luk. Dallas VA and UT Southwestern, Dallas, TX