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PurposeStudies on predictive scores for very late recurrence (VLR) (recurrence later than 12 months) after second-generation cryoballoon-based pulmonary vein isolation (CB2-PVI) are sparse. We aimed to evaluate the frequency of late recurrence (LR) (later than 3 months) and VLR, and to validate predictive scores for LR and VLR after initial CB2-PVI.MethodsA total of 288 patients undergoing initial CB2-PVI (66 ± 11 years, 46% paroxysmal) were retrospectively enrolled in the LR cohort. In the VLR cohort, 83 patients with recurrence within 3–12 months or with < 12-month follow-up were excluded. The predictive scores of arrhythmia recurrence were assessed, including the APPLE, DR-FLASH, PLAAF, BASE-AF2, ATLAS, SCALE-CryoAF, and MB-LATER scores.ResultsDuring a mean follow-up of 15.3 ± 7.1 months, 188 of 288 (65.2%) patients remained in sinus rhythm without any recurrences. Thirty-two of 205 (15.6%) patients experienced VLR after a mean of 16.6 ± 5.6 months. Comparing the predictive values of these specific scores, the MB-LATER score showed a reliable trend toward greater risk of both LR and VLR (area under the curve in LR; 0.632, 0.637, 0.632, 0.637, 0.604, 0.725, and 0.691 (p = ns), VLR; 0.612, 0.636, 0.644, 0.586, 0.541, 0.633, and 0.680 (p = 0.038, vs. BASE-AF2, respectively)). Kaplan-Meier analysis estimated patients with higher MB-LATER scores which had favorable outcomes (24-month freedom from LR; 26.0% vs. 56.7%, p < 0.0001, VLR; 53.4% vs. 82.1%, p = 0.013).ConclusionThe MB-LATER score provided more reliable predictive value for both LR and VLR. Patients with higher MB-LATER scores may benefit from more intensive long-term follow-up.

Chronic inflammation harbors a vulnerable substrate for atrial fibrillation (AF) recurrence after catheter ablation. However, whether the ABO blood types are associated with AF recurrence after catheter ablation is unknown. A total of 2106 AF patients (1552 men, 554 women) who underwent catheter ablation were enrolled retrospectively. The patients were separated into two groups according to the ABO blood types, the O-type (n = 910, 43.21%) and the non-O-type groups (A, B, or AB type) (n = 1196, 56.79%). The clinical characteristics, AF recurrence, and risk predictors were investigated. The non-O type blood group had a higher incidence of diabetes mellitus (11.90 vs. 9.03%, p = 0.035), larger left atrial diameters (39.43 ± 6.74 vs. 38.20 ± 6.47, p = 0.007), and decreased left ventricular ejection fractions (56.01 ± 7.33 vs. 58.65 ± 6.34, p = 0.044) than the O-type blood group. In the non-paroxysmal AF (non-PAF) patients, the non-O-type blood groups have significantly higher incidences of very late recurrence (67.46 vs. 32.54%, p = 0.045) than those in the O-type blood group. The multivariate analysis revealed the non-O blood group (odd ratio 1.40, p = 0.022) and amiodarone (odd ratio 1.44, p = 0.013) were independent predictors for very late recurrence in the non-PAF patients after catheter ablation, which could be applied as a useful disease marker. This work highlighted the potential link between the ABO blood types and inflammatory activities that contribute to the pathogenic development of AF. The presence of surface antigens on cardiomyocytes or blood cells in patients with different ABO blood types will have an impactful role in risk stratification for AF prognosis after catheter ablation. Further prospective studies are warranted to prove the translational benefits of the ABO blood types for the patients receiving catheter ablation.

Background To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC). Methods Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS. Results Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early ( n  = 165, 37.2%) versus late relapse ( n  = 278, 62.8%) ( p  = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p  = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p  < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p  = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p  = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p  = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p  < 0.001). Conclusions Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.

To identify factors associated with post-recurrence survival (PRS), we examined our institutional recurrence patterns following definitive resection for rectal cancer. We reviewed all patients with rectal cancer diagnosed at three hospitals in the east of Iran from 2011 to 2020. The optimal cut-off value was determined by receiver operating characteristic (ROC) analysis to determine early recurrence. The effect of recurrence time was evaluated on PRS. 326 eligible patients with a mean ± SD age of 56 ± 12.8 years were included in this study. In a median (IQR: Inter-quartile range) follow-up time of 76 (62.2) months, 106 (32.5%) patients experienced at least any recurrence (locoregional or distant metastasis) following primary resection. The median (IQR) time from initial surgery to recurrence was 29.5 (31.2) months. Based on ROC analysis, early recurrence was specified at ≤ 29 months. However, for the patients who experienced only locoregional recurrence, 33 months was the cut-off to define early recurrence. Recurrence time and recurrence management were both significant variables on PRS. Moreover, TNM staging was significantly associated with early recurrence ( P  = 0.003). In this research, recurrence time, recurrence management and TNM staging were found to be correlated with PRS.

To determine an optimal cut-off value for distinguishing early and late recurrence in patients with laryngeal cancer after initial surgery and to evaluate the risk factors for early recurrence. This retrospective study included 328 patients with laryngeal cancer who underwent initial resection in our hospital from January 2014 to April 2018. A minimum P -value approach was used to determine the optimal cut-off value to divide patients into early and late recurrence groups. The clinicopathological characteristics were compared between the two groups. The risk factors for early recurrence were evaluated using logistic regression analysis. The optimal cut-off value to identify between early recurrence ( n  = 51, 50.5%) and late recurrence ( n  = 50, 49.5%) was 17 months ( p  < 1e −17 ). The overall survival of the late recurrence group (48.36 ± 16.02 months) was longer than the early recurrence group (32.61 ± 19.65 months) significantly ( p  < 0.001). Lymphovascular invasion ( p  = 0.038), patients without adjuvant radiotherapy ( p  = 0.043), advanced tumor, node, metastasis (TNM) stage ( p  = 0.035), and positive surgical margins ( p  = 0.045) were independent risk factors for early recurrence. The best cut-off value to identify early recurrence after initial surgery for laryngeal cancer was 17 months. Intensive follow-up and adjuvant radiotherapy may be beneficial for patients with risk factors for early recurrence.

Background Operable breast cancer patients may experience late recurrences because of reactivation of dormant tumor cells within the bone marrow (BM). Identification of patients who would benefit from extended therapy is therefore needed. Methods BM samples obtained pre- and post-surgery were previously analysed for presence of disseminated tumor cells (DTC) by a multimarker mRNA quantitative reverse-transcription PCR assay. Updated survival analyses were performed on all patient data ( n  = 191) and in a subgroup of patients alive and recurrence-free after 5 years ( n  = 156). DTC data were compared to the mitotic activity index (MAI) of the primary tumors. Median follow-up time was 15.3 years. Results Among the 191 patients, 49 (25.65%) experienced systemic relapse, 24 (49%) within 5–18 years after surgery. MAI and pre- and post-operative DTC status had significant prognostic value based on Kaplan–Meier analyses and multiple Cox regression in the overall patient cohort. With exclusion of patients who relapsed or died within 5 years from surgery, only pre-operative DTC detection was an independent prognostic marker of late recurrences. High MAI (≥10) did not predict late recurrences or disease-specific mortality. Conclusion Pre-operative DTC detection, but not MAI status, predicts late recurrences in operable breast cancer.

Identifying high-risk of late recurrence (beyond 10 years) in patients with hormone receptor-positive HER2-negative early breast cancer (EBC) is crucial. The Clinical Treatment Score post-5 years (CTS5) score assesses recurrence risk after 5 years of endocrine therapy (ET). This study validated CTS5 as a prognostic tool for late recurrence by examining its association with Distant Recurrence-Free Survival using GEICAM study data and evaluating model calibration. We retrospectively analyzed 5739 hormone receptor-positive HER2-negative EBC patients from the El Álamo IV registry (N = 3509, diagnosed between 2002 and 2005) and 4 adjuvant GEICAM studies (N = 2680, conducted between 1996 and 2006). All patients were distant recurrence-free and alive 5 years after starting adjuvant ET. The CTS5 classified 43.9% of patients as low-risk, 32.2% as intermediate-risk, and 23.9% as high-risk. Significant differences in DR were observed: hazard ratio (HR) for intermediate- vs. low-risk was 2.55 (95% CI, 1.85-3.51, P < .0001), and HR for high- vs. low-risk was 5.77 (95% CI, 4.28-7.78, P < .0001). Similar results were found across subgroups by menopausal status, duration of adjuvant ET, and prior adjuvant chemotherapy (CT). Calibration showed CTS5 overestimated DR rates in low-risk (P = .0314) and high-risk (P < .0001) patients compared to observed rates. The CTS5 categorized patients based on late DR risk regardless of menopausal status, ET duration, or CT treatment. However, the model tended to overestimate events, particularly in high-risk groups, especially among those treated with ET for less than 60 months or not receiving CT.

Purpose Recurrent hepatocellular carcinoma (rHCC) patients with early recurrence usually suffer a poorer prognosis than those with late recurrence. We aimed to compare the treatment efficacy of repeat hepatectomy (RH) and percutaneous ablation (PA) in early-stage rHCC patients with early or late recurrence. Methods This retrospective study enrolled 268 patients diagnosed with early-stage rHCC who received RH and PA. Overall survival (OS) and repeat recurrence-free survival (rRFS) were compared using log-rank analysis. Propensity score matching (PSM) was used to reduce the confounding bias. Results Among the 268 patients with early-stage rHCC, 79 underwent RH and 189 underwent PA. Early (n = 174) and late (n = 94) recurrence was defined as recurrence within and after 2 years following initial hepatectomy, respectively. For patients with early recurrence, RH and PA provided similar 5-year OS (71.5% versus 74.4%, P = 0.87) and rRFS rates (24.7% versus 24.9%, P = 0.73). For patients with late recurrence, RH resulted in comparable 5-year OS (73.1% versus 86.1%, P = 0.62) and rRFS rates (36.6% versus 27.8%, P = 0.34) as PA. After PSM, RH continued to share similar 5-year OS and rRFS rates with PA in patients with early recurrence, and comparable efficacy of RH and PA was also observed in patients with late recurrence. Conclusion RH can offer comparable OS and rRFS rates as PA for early-stage rHCC patients, regardless of whether they experience early or late recurrence. Therefore, both RH and PA are feasible treatment options for early-stage rHCC patients.

Background Risk of recurrence from primary ER+ breast cancer continues for at least 20 years. We aimed to identify clinical and molecular features associated with risk of recurrence after 10 years. Methods ER+ breast cancers from patients with and without recurrence were analysed with the BC360 NanoString Panel and an 87 gene targeted-exome panel. Frequency of clinical, pathologic and molecular characteristics was compared between cases (recurred between 10 and 20 years) and controls (no recurrence by 20 years) in the Very Late Recurrence (VLR) cohort. Analogous data from METABRIC were examined to confirm or refute findings. Results VLR cases had larger tumours and higher node positivity. Both VLR and METABRIC cases had higher clinical treatment score at 5 years (CTS5). There was a trend for fewer GATA3 mutations in cases in both VLR and METABRIC but no statistically significant differences in mutation frequency. Cell cycle and proliferation genes were strongly expressed in VLR cases. Immune-related genes and cell cycle inhibitors were highly expressed in controls. Neither of these changes were significant after correction for multiple testing. Conclusions Clinicopathologic features are prognostic beyond 10 years. Conversely, molecular features, such as copy number alterations, TP53 mutations and intrinsic subtype which have early prognostic significance, have little prognostic value after 10 years.

Background Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer. Method Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected. Result With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS. Conclusion TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.