Early and late recurrences in lymph node-negative gastric cancer: a retrospective cohort study

BACKGROUND: Predictors of recurrence in patients with lymph node-negative gastric cancer (GC) who have undergone curative resection have been widely investigated, but not the effects of predictors on timing of recurrence. OBJECTIVE: Determine the factors associated with early and late recurrence in patients with node-negative GC. DESIGN: Retrospective cohort. SETTING: Academic tertiary care center. PATIENTS AND METHODS: The study included patients with node-negative GC after curative resection between 2008 and 2018 at two institutions. Early and late recurrences were determined using a minimum P value approach to evaluate the optimal cutoff for recurrence-free survival (RFS). A competing risk model and landmark analysis were used to analyze factors associated with early and late recurrences. MAIN OUTCOME MEASURES: Recurrence-free survival and factors associated with survival. SAMPLE SIZE: 606. RESULTS: After a median follow-up of 70 months, 50 (8.3%) patients experienced recurrent disease. The optimal length of RFS for distinguishing between early (n=26) and late recurrence (n=24) was 24 months ( P =.0013). The median RFS in the early and late recurrence groups was 11 and 32 months, respectively. Diffuse tumors (hazard ratio 3.358, P =.014), advanced T stage (HR 8.804, P =.003), perineural invasion (HR 10.955, P <.001), and anemia (HR 2.351, P =.018) were independent predictors of early recurrence. Mixed tumor location (HR 5.586, P =.002), advanced T stage (HR 5.066, P <.001), lymphovascular invasion (HR 5.902, P <.001), and elevated CA19-9 levels (HR 5.227, P <.001) were independent predictors of late recurrence. Similar results were obtained in the landmark analysis. CONCLUSIONS: Individualized therapeutic and follow-up strategies should be considered in future studies because of distinct patterns in predictors of early and late recurrence. LIMITATIONS: Retrospective design, small sample size. CONFLICT OF INTEREST: None.

Predictors of early and late recurrence of atrial fibrillation after catheter ablation: two sides of the same coin?

Background Recurrence of atrial fibrillation (AF) after catheter ablation (CA) is estimated to be between 20% and 45%. Recurrent AF early after ablation is generally classified as benign as a part of a blanking period, but recently has been associated with later recurrent AF. The prediction of early and late AF recurrence after CA remains challenging as well as the predictive value of early AF recurrence in the blanking period. Purpose We aimed to determine the clinical and procedural factors associated with early and late recurrence of AF after CA. Methods Single-centre retrospective study that included all patients who underwent AF CA between January 2017 and October 2019. Ablation procedures included radiofrequency and second-generation cryoballoon CA. Early recurrence of AF (ERAF) was defined as any recurrence of AF &gt;30 seconds within 90 days after CA and late recurrence (LR) was defined as any recurrence of AF &gt;30 seconds after 90 days of CA. The independent association between clinical and procedural variables and AF recurrence was evaluated with logistic regression analysis. Results We included 399 patients, 64,7% male, with a mean age of 56,8±11,6 years, most of them had paroxysmal AF with a mean duration until CA of 3,5±3,4 years. Early recurrence of AF occurred in 51 patients (12,8%). After multivariate logistic regression, we identify left atrium (LA) diameter [odds ratio (OR) 1,1, 95% confidence interval (CI) 1,03–1,18; p=0,007] as the only independent predictor associated with recurrent AF. Late recurrence of AF was observed in 104 patients (26,1%), on average, 12,8±8,7 months after CA. After multivariable adjustment, LA diameter (OR 1,1, 95% CI 1,01–1,12; p=0,032) and intraprocedural electric cardioversion (OR 1,8, 95% CI 1,03–3,12; p=0,040) were independently associated with recurrent AF. Regarding patients with ERAF, most of them also had late recurrent AF (64,7%), whereas in patients without ERAF, only 20,4% had LR (p&lt;0,001). After including ERAF in the multivariate logistic regression, we identify ERAF as the only independent predictor of late recurrence of AF (OR 5,23, 95% CI 2,56–10,72; p&lt;0,001). Conclusions In our cohort, late recurrence of AF after catheter ablation was significantly higher in patients with recurrence within the blanking period, which was the only independent predictor of AF late recurrence. FUNDunding Acknowledgement Type of funding sources: None.

Usefulness of postoperative surveillance MR for women after breast-conservation therapy: Focusing on MR features of early and late recurrent breast cancer

Purpose To investigate the imaging characteristics of early and late recurrent breast cancer and the detectability of mammography, ultrasonography, and breast magnetic resonance imaging (MRI) in patients who underwent breast-conservation therapy (BCT). Materials and methods Total of 1312 women with 2026 surveillance breast MRI after BCT between January 2014 and September 2018 were studied. Early recurrence was defined as newly diagnosed breast cancer and/or axillary metastasis within 12 months of surgery. Late recurrence was defined as recurrence after 12months of surgery. We assessed the detectability of recurrent lesions in each postoperative imaging modality and evaluated characteristics of recurrent lesions on postoperative MRI by comparing early and late recurrence groups. Result Of the 2026 cases, 103 were confirmed as recurrent breast cancer by biopsy or surgery. Thirty-one cases were early recurrence, and 72 cases were late recurrence. MRI showed significantly higher detectability for recurrent lesions (102 cases, 99%) than mammography (59.4%, p < 0.001) or ultrasound (68.9%, p < 0.001), or both mammography and ultrasound (81.6%, p < 0.001). The recurrent lesions did not have typical malignant morphologic features, but variable features on MRI. However, early recurrent lesions showed fast enhancement in early dynamic phase regardless of the kinetic pattern of delayed dynamic phase; and late recurrence lesions showed early fast enhancement and delayed washout pattern. There were 19 cases which were not detected on mammography or ultrasound but could only be detected with MRI. Conclusion Postoperative breast MRI showed significantly higher detectability for recurrent lesions than mammography and ultrasound. Early fast enhancement is the most important feature of recurrent lesions on postoperative breast MRI for both early and late recurrence groups. Due to its high possibility of recurrence, further work-up should be considered regardless of their morphologic features.

Clinicopathological and Molecular Features of Patients with Early and Late Recurrence after Curative Surgery for Colorectal Cancer

Background: Few reports have investigated genetic alterations between patients with early and late recurrence following curative surgery for colorectal cancer (CRC). Methods: A total of 1227 stage I–III CRC patients who underwent curative resection were included retrospectively. Among them, 236 patients had tumor recurrence: 139 had early (<2 years after surgery) and 97 had late (≥2 years after surgery) recurrence. Clinicopathological features and genetic alterations were compared between the two groups. Results: Compared to those with late recurrence, patients with early recurrence were more likely to have advanced pathological node (N) categories; tumor, node, metastasis (TNM) stages; adjuvant chemotherapy treatment; liver metastases; APC mutations; and worse five-year overall survival rates. Patients with right-sided colon cancer were more likely to develop early recurrence than were those with left-sided colon cancer or rectal cancer. Regarding rectal cancer, patients with early recurrence were more likely to be at advanced pathological N categories and TNM stages than those with late recurrence. Multivariate analysis revealed old age, early recurrence, multiple-site recurrence, and BRAF and NRAS mutations to be independent prognostic factors. Conclusion: CRC patients with early recurrence have a worse OS rate and more APC mutations than those with late recurrence.

Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.

Defining early recurrence in patients with resected primary colorectal carcinoma and its respective risk factors

Purpose There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors. Methods A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery. Patient data were retrieved from a prospectively maintained institutional database. Included patients underwent resection for primary, non-metastatic colorectal carcinomas with curative intent between 1995 and 2010. Aims of the study were (1) to define the optimal cut-off point of recurrence-free survival based on overall survival using a minimum p value approach and (2) to identify patterns of initial recurrence and putative risk factors for early recurrence using regression models. Results Recurrence was diagnosed in 412 of 1893 patients. Statistical analysis suggested that a recurrence-free survival of 16 months could be used to distinguish between early and late recurrence based on overall survival (p < 0.001). Independent risk factors for early recurrence included advanced pT categories (pT3,4/ypT3,4) and positive lymph node status (pN+/ypN+). Early recurrence was independent of site of recurrence and was associated with worse prognosis. Conclusions Recurrence of colorectal carcinoma within 16 months after primary treatment should be labeled as “early.” Tumor categories pT3,4/ypT3,4 and positive lymph node status pN+/ypN+ are predictive of early recurrence.