Independent Predictor Of Relapse Research Articles

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study

ObjectiveIn 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study.MethodsThis retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model.Results702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028).ConclusionsLVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Abstract 5221: TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading

Abstract Background: Thyroid transcription factor 1 (TTF-1) is expressed in 70% to 80% of lung adenocarcinomas (LUAD). Several papers revealed that TTF-1 expression is associated with better patient outcomes independent of the tumor stage. However, it is unknown whether the prognostic impact of TTF-1 only results from a different growth pattern (tumor grading) or is independently associated with a biologically more aggressive phenotype. Thus, we analyzed a large bi-centric cohort of LUAD to assume the true prognostic value of TTF-1 in relation to the tumor grade. Methods: We collected a large, real-life cohort of 447 patients with completely resected LUAD from two large-volume German lung cancer centers. TTF-1 status, evaluated by IHC, and tumor grading were correlated with clinical, pathologic, and molecular data, as well as patient outcomes. Kaplan-Meier curves were used for comparison of TTF-1 status and different tumor grades in terms of the DFS. The impact of TTF-1 was measured by univariate and multivariate Cox regression. Finally, a causal graph analysis was performed to identify and account for potential confounders to improve the statistical estimation of the predictive power of TTF-1 expression for DFS in comparison to the tumor grade. Results: Kaplan-Meier curves revealed that TTF-1 positivity is associated with longer DFS independent of tumor grade, whereas a strong association of DFS with the tumor grade is observed only in TTF-1-positive patients. In univariate analysis, TTF-1 positivity was associated with significantly longer DFS (median log HR -0.83 [-1.43; -0.20]; p=0.018), whereas higher tumor grade showed a non-significant association with shorter DFS (median log HR 0.30 [-0.58; 1.60]; p=0,62 for G1 to G2 and 0.68 [-0.24; 1.89]; p=0,34 for G2 to G3). In multivariate analysis, TTF-1 positivity resulted in a significantly longer DFS (median log HR -0.65 [-1.13; -0.09]; p=0.05) independent of all other parameters, including tumor grade. Applying the adjustment sets suggested by the causal graph analysis, the superiority of TTF-1 (median log HR -0.86 [-1.25; -0.41]) over tumor grade (median log HR 0.31 [-0.32; 1.30]/0.61[-0.07; 1.65]) in terms of prognostic power was confirmed. Conclusion: This study draws three important conclusions: Firstly, it indicates that the prognostic power of tumor grade is limited to TTF-1-positive patients. Secondly, it underlines the independent prognostic value of TTF-1 expression for DFS regardless of tumor grade. Finally, our analyses reveal that the effect size of TTF-1 surpasses that of tumor grade. To transfer the results directly into the clinical area, we recommend distinguishing between TTF-1-positive and TTF-1-negative LUADs in the pathological report. Tumor grading should only be applied to TTF-1-positive LUADs (TTF-1+/G1-3). TTF-1-negative LUADs should either not be graded or always be classified as high-grade (TTF-1-/G3). Citation Format: Simon Schallenberg, Gabriel Dernbach, Mihnea Dragomir, Georg Schlachtenberger, Kyrill Boschung, Corinna Friedrich, Kai Standvoss, Lukas Ruff, Philipp Anders, Christian Grohe, Winfried Randerath, Sabine Merkelbach-Bruse, Alexander Quaas, Matthias Heldwein, Ulrich Keilholz, Khosro Hekmat, Jens Rückert, Reinhard Büttner, David Horst, Frederick Klauschen, Nikolaj Frost. TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5221.

Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study

BackgroundApproximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. ObjectiveTo determine the most important prognostic factors for relapse in CSI-NS patients. Design, setting, and participantsPopulation-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. Outcome measurements and statistical analysisHistological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell’s C-index) and calibration. ResultsOf 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from < 5% to > 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. Conclusion and relevanceThe identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INRand 3 monthly UCE and NCCwere done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.

RNA-seq–based miRNA signature as an independent predictor of relapse in pediatric B-cell acute lymphoblastic leukemia

AbstractAberrant micro-RNA (miRNA) expression profiles have been associated with disease progression and clinical outcome in pediatric cancers. However, few studies have analyzed genome-wide dysregulation of miRNAs and messenger RNAs (mRNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To identify novel prognostic factors, we comprehensively investigated miRNA and mRNA sequencing (miRNA-seq and mRNA-seq) data in pediatric BCP-ALL samples with poor outcome. We analyzed 180 patients, including 43 matched pairs at diagnosis and relapse. Consensus clustering of miRNA expression data revealed a distinct profile characterized by mainly downregulation of miRNAs (referred to as an miR-low cluster [MLC]). The MLC profile was not associated with any known genetic subgroups. Intriguingly, patients classified as MLC had significantly shorter event-free survival (median 21 vs 33 months; log-rank P = 3 ×10−5). Furthermore, this poor prognosis was retained even in hyperdiploid ALL. This poor prognostic MLC profiling was confirmed in the validation cohort. Notably, non-MLC profiling at diagnosis (n = 9 of 23; Fisher exact test, P = .039) often changed into MLC profiling at relapse for the same patient. Integrated analysis of miRNA-seq and mRNA-seq data revealed that the transcriptional profile of MLC was characterized by enrichment of MYC target and oxidative phosphorylation genes, reduced intron retention, and low expression of DICER1. Thus, our miRNA-mRNA integration approach yielded a truly unbiased molecular stratification of pediatric BCP-ALL cases based on a novel prognostic miRNA signature, which may lead to better clinical outcomes.

TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading

ObjectivesThyroid transcription factor 1 (TTF-1) is a well-established independent prognostic factor in lung adenocarcinoma (LUAD), irrespective of stage. This study aims to determine if TTF-1′s prognostic impact is solely based on histomorphological differentiation (tumor grading) or if it independently relates to a biologically more aggressive phenotype. We analyzed a large bi-centric LUAD cohort to accurately assess TTF-1′s prognostic value in relation to tumor grade. Patients and methodsWe studied 447 patients with resected LUAD from major German lung cancer centers (Berlin and Cologne), correlating TTF-1 status and grading with clinical, pathologic, and molecular data, alongside patient outcomes. TTF-1′s impact was evaluated through univariate and multivariate Cox regression. Causal graph analysis was used to identify and account for potential confounders, improving the statistical estimation of TTF-1′s predictive power for clinical outcomes. ResultsUnivariate analysis revealed TTF-1 positivity associated with significantly longer disease-free survival (DFS) (median log HR −0.83; p = 0.018). Higher tumor grade showed a non-significant association with shorter DFS (median log HR 0.30; p = 0,62 for G1 to G2 and 0.68; p = 0,34 for G2 to G3). In multivariate analysis, TTF-1 positivity resulted in a significantly longer DFS (median log HR −0.65; p = 0.05) independent of all other parameters, including grading. Adjusting for potential confounders as indicated by the causal graph confirmed the superiority of TTF-1 over tumor grading in prognostics power. ConclusionsTTF-1 status predicts relapse and survival in LUAD independently of tumor grading. The prognostic power of tumor grading is limited to TTF-1-positive patients, and the effect size of TTF-1 surpasses that of tumor grading. We recommend including TTF1 status as a prognostic factor in the diagnostic guidelines of LUAD.

Prognostic Factors for Relapse in Patients With Clinical Stage I Testicular Seminoma: A Nationwide, Population-Based Cohort Study.

Approximately 20% of patients with clinical stage I seminoma relapse. Tumor size and rete testis invasion have been identified as risk factors for relapse. However, the level of evidence supporting the use of these risk factors in clinical decision making is low. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We assessed prognostic factors for relapse in an unselected nationwide population-based setting with centralized pathology review. Patients with clinical stage I seminoma diagnosed from January 2013 to December 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histologic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified potential clinical and histopathologic prognostic factors and relapse was assessed by the use of Cox regression analysis. Of 924 patients included, 148 (16%) patients relapsed during a median follow-up of 6.3 years. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated preorchiectomy levels of β-human chorionic gonadotropin and lactate dehydrogenase were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors to 62% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the prognostic model had an overall concordance statistic of 0.70. The provided prognostic factors could replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study

BackgroundType 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation.MethodsWe analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18–36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors.ResultsAfter discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001).ConclusionsA high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Minimal effective dose of maintenance steroid therapy for relapse of cryptogenic organizing pneumonia

BackgroundLong-term maintenance steroid therapy (MST) is frequently required for repeated relapses of cryptogenic organizing pneumonia (COP); however, the optimal minimal dose has not been clarified. Therefore, this study evaluated the minimal MST dose required to prevent repeated relapses and identify relapse predictors. MethodsWe retrospectively reviewed the medical records of patients with steroid-treated COP and compared background factors between the non-relapse and relapse groups. We also reviewed the treatment course in the relapse group and determined the minimal effective steroid dose based on the MST dose at relapse events and the current relapse prevention dose. ResultsIn total, 48 patients were identified, including 27 (56%) in the non-relapse group and 21 (44%) in the relapse group. Receiver operating characteristic curve analysis identified prednisolone at 5 mg/day as the optimal cut-off value in the relapse group. Relapse-free time in patients with relapsed COP was significantly longer in the MST dose ≥5 mg/day group than in the <5 mg/day group (log-rank P = 0.003; hazard ratio, 0.19; 95% confidence interval [CI], 0.04–0.60). Multivariate logistic regression analysis demonstrated that a high eosinophil percentage and CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) were predictors of relapse (odds ratio [OR], 1.12; 95% CI, 1.02–1.23; P = 0.008 and OR, 3.87; 95% CI, 1.29–11.6; P = 0.008, respectively). ConclusionsOur results indicate that 5 mg/day of prednisolone may be the minimal effective dose for preventing repeated relapses, and a high BALF eosinophil percentage and CD4/CD8 ratio are independent predictors of relapse.

Prognostic factors for relapse in patients with clinical stage I testicular seminoma: A nationwide, population-based cohort study.

5041 Background: Approximately 20% of patients with clinical stage I testicular seminoma will relapse after orchiectomy. No robust prognostic factors for relapse exist which challenges risk assessment and counselling for patients. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We therefore assessed prognostic factors for relapse in a large unselected nationwide population-based setting with centralized pathology review. Methods: Patients with clinical stage I seminoma diagnosed in Denmark between 2013 and 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, microscopic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified clinical and histopathological prognostic factors and relapse were assessed by use of Cox regression analysis. Potential prognostic factors included age, pre-orchiectomy values of β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH), tumor size, tumor multifocality, tumor necrosis, lymphovascular invasion, pagetoid rete involvement, and invasion of rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis. Results: In total, 924 patients were included. During a median follow-up of 6.3 years, 148 (16%) patients relapsed. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated pre-orchiectomy levels of β-hCG and LDH were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors, to 64% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the model had an overall concordance statistic of 0.70. Conclusions: The provided prognostic factors allow a long-awaited opportunity to make more informed treatment decisions about post-orchiectomy management in patients with clinical stage I seminoma. These should replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies. [Table: see text]

Solid Pseudopapillary Neoplasms of the Pancreas: Clinicopathologic Analysis and a Predictive Model

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare. They are considered low-grade malignancies, and a small percentage of patients experience recurrence or metastasis. It is critical to investigate associated biological behavior and identify patients at a risk of relapse. This was a retrospective study of 486 patients with SPNs who were diagnosed between 2000 and 2021. Their clinicopathologic features, including 23 parameters and prognoses were analyzed. Six patients (1.2%) presented with synchronous liver metastasis. A total of 21 patients experienced recurrence or metastasis postoperatively. The overall and disease-specific survival rates were 99.8% and 100%, respectively. The 5- and 10-year relapse-free survival (RFS) rates were 97.4% and 90.2%, respectively. Tumor size, lymphovascular invasion, and the Ki-67 index were independent predictors of relapse. Furthermore, a Peking Union Medical College Hospital–SPN risk model was built to evaluate the risk of relapse and compared it with the American Joint Committee on Cancer tumor staging system (eighth edition, 2017). Risk factors included 3 parameters: tumor size (>9 cm), lymphovascular invasion status (presence), and Ki-67 index (>1%). Risk grades were available for 345 patients, who were divided into 2 groups: (1) low risk (n = 124) and (2) high risk (n = 221). The group with no risk factors was designated as low risk and had a 10-year RFS of 100%. The group associated with 1 to 3 factors was designated as high risk, with a 10-year RFS of 75.3%. Receiver operating characteristic curves were generated, and the area under the curve was 0.791 for our model and 0.630 for the American Joint Committee on Cancer with respect to the cancer staging system. We validated our model in independent cohorts and demonstrated a sensitivity of 98.3%. In conclusion, SPNs are low-grade malignant neoplasms that rarely metastasize, and the 3 selected pathologic parameters can be used to predict their behavior. A novel Peking Union Medical College Hospital–SPN risk model was proposed for routine application to guide the patient counseling in clinical practice.

Relapse-free survival in Sudanese women with non-metastatic breast cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and a major cause of cancer mortality in Sudan. However, there is lack of data related to BC relapse. Therefore, this study was undertaken to estimate the 5-year relapse free survival (RFS) rate and factors related to BC relapse in Sudanese women with non-metastatic BC. Data of BC women with BC diagnosed and treated at the National Cancer Institute-University of Gezira during 2012 were retrieved from medical records. The cases were followed-up through hospital records and telephone contact. Survival functions were calculated using Kaplan-Meier method and compared by log-rank test. The prognostic factors were tested using univariate and multivariable Cox regression analyses. We included 168 women with median age of 45years (range, 22-83years). 53.5%of women had stage III at time of diagnosis, whereas 4.2% and 42.3% of women presented with stage I and stage II, respectively. At the end of 5years follow-up, with median follow-up period of 64months, 94 (56.0%) women were alive in remission, 11 (6.5%) were alive with BC relapse, 49 (29.2%) were dead, and survival status was unknown in 14 (8.3%) women. Most of the occurred relapses were distant relapses. The 5-year RFS was 59%. The independent predictors of relapse were: larger primary tumor size (HR:1.84, 95% CI: 1.54-5.48, p=0.018); involved axillary lymph nodes with tumour (HR: 2.91, 95% CI: 1.53-7.91, p=0.001); not receiving adjuvant radiotherapy (HR: 2.2, 95% CI: 1.22-3.95, p=0.009); and not receiving hormone therapy (HR: 1.67, 95% CI: 1.01-2.76, p= 0.046). We found a high risk of BC relapse in our resource-constrained settings. Advanced stages, not receiving adjuvant radiotherapy, and not receiving adjuvant hormone therapy were independent predictors associated with worse 5-year RFS. Therefore, enhancing the early diagnosis of BC and improving timely access to appropriate treatments represent key approaches to achieving better treatment outcomes.

Predictors of relapse in granulomatosis with polyangiitis: a multi-center study

BackgroundGranulomatosis with polyangiitis (GPA) is a rare systemic vasculitis. Its severity ranges from indolent disease to fulminant that may cause death. With treatment, remission is seen in more than 80% of cases, although relapse is still common. There have been studies showing that there may be factors to predict relapse in GPA. Based on relapses, the decision to start treatment and/or to monitor the patients more closely is made. Therefore, predicting the relapse of GPA can be effective in controlling the disease. Our aim was to investigate possible factors for relapse in GPA.We recruited 254 patients diagnosed with GPA who were under treatment at Alzahra hospital affiliated to Isfahan University of Medical Sciences (from 2013 to 2020) and Amir Alam Hospital affiliated to Tehran University of Medical Sciences (from 2020 to 2022) to plan a retrospective study. Chi-squared or Fisher’s exact tests were performed to compare categorical variables, while the Mann–Whitney U test was used to compare continuous variables.ResultsAnalysis of our patients (aged 20–80,122 females) showed that 147 patients (57.9%) experienced relapse. Mean age in relapse group was 43.8 ± 16.6 and in no-relapse group was 45.6 ± 15.1 (P > 0.05). Among many potential predictors, we observed in multivariate analysis that positive PR3-ANCA (proteinase 3-antineutrophilic cytoplasmic antibodies) (P = 0.007, OR:2.62,CI:1.29–5.31),nose manifestations (P = 0.004, OR 3.00, CI 1.43–6.26), mucosal membranes involvement (P = 0.009, OR 4.21, CI 1.43–12.38), and gastrointestinal tract (GI) complications (P = 0.03, OR 5.64, CI 1.14–27.90) were significant predictors of GPA relapse.ConclusionAmong clinical and laboratory features we studied, positive PR3-ANCA, nose manifestations, mucosal membranes involvement, and GI complications were independent predictors of relapse in patients with GPA.

Major Histotypes in Skin Melanoma: Nodular and Acral Lentiginous Melanomas Are Poor Prognostic Factors for Relapse and Survival.

The histological subtype is not considered one of the major prognostic factors in melanoma, yet it is known to have an impact on survival. The aim of this study was to investigate the clinical significance of histological subtypes and the possible impacts of clinicopathological factors on the course of melanoma patients of all stages. A total of 1017 cutaneous melanoma patients were analyzed retrospectively. Four major melanoma histotypes that were studied in this study were as follows: (1) superficial spreading melanoma (SSM), (2) nodular melanoma (NM), (3) acral lentiginous melanoma (ALM), and (4) lentigo maligna melanoma (LMM). Unlike SSMs and LMMs, there were statistically significant correlations between NMs and ALMs and most aggressive histopathological prognostic indicators, such as higher Clark level ( P = 0.0001), thick Breslow depth ( P = 0.0001), presence of ulceration ( P = 0.0001), and lymphovascular invasion ( P = 0.0001). Furthermore, NMs and ALMs were also associated with advanced clinical stages, that is, node involvement and metastasis. Relapse rates for nonmetastatic melanomas were higher in NMs (39.6%) and ALMs (35.3%) than in SSMs (24.3%) and LMMs (10.3%) ( P = 0.0001). Additionally, 5-year relapse-free survival rates were 90.5%, 70.5%, 55.7%, and 50.5% in LMMs, SSMs, ALMs, and NMs, respectively ( P = 0.0001). Moreover, 5-year overall survival rates plummeted from 84.3% in LMMs to 74.8%, 64.3%, and 46% in SSMs, ALMs, and NMs, respectively ( P = 0.0001). In conclusion, we observed that the histologic subtype was an independent predictor for relapse and outcome for cutaneous melanoma patients. Both NM and ALM had unfavorable prognoses, and they were associated with known poor pathological and clinical indicators.

Cancer Stem Cells and Cell Cycle Genes as Independent Predictors of Relapse in Non-small Cell Lung Cancer: Secondary Analysis of a Prospective Study.

PurposeCancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. It has been shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (NCT04634630). We recently described an overexpression of CSCs recurrence-related genes (RG) in lung cancer. This study aims to investigate CSC frequency and RG expression as predictors of disease-free survival in lung cancer.Experimental DesignThis secondary analysis of a prospective cohort study involved 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages ACL and SCCL. Cell population frequency analysis of ALDHhigh (CSCs) and ALDHlow (cancer cells) was performed on each tumor specimen. In addition, RG expression was assessed for 31 target genes separately in ALDHhigh and ALDHlow populations. CSCs frequency and RG expression were assessed as predictors of disease-free survival by Cox analysis.ResultsCSCs frequency and RG expression were independent predictors of disease-free survival. CSC frequency was not related to disease-free survival in early-stage patients (HR = 0.84, 95%CI = 0.53-1.33, P = .454), whereas it was a risk factor for locally advanced-stage patients (HR = 1.22, 95%CI = 1.09-1.35, P = .000). RG expression—if measured in CSCs—was related to a higher risk of recurrence (HR = 1.19, 95%CI = 1.03-1.39, P = .021). The effect of RG expression measured in cancer cells on disease-free survival was lower and was not statistically significant (HR = 1.12, 95%CI = 0.94-1.33, P = .196).ConclusionsCSCs frequency and RG expression are independent predictors of relapse in lung cancer. Considering these results, CSCs and RG may be considered for both target therapy and prognosis.

Incidence and Predictors of Relapse After Stopping Antiviral Therapy in Pediatric Chronic Hepatitis B.

There are no definite end-points for stopping therapy in pediatric chronic hepatitis B (CHB). The study objective was to evaluate the incidence of relapse after stopping antiviral therapy and to identify its predictors. All hepatitis B surface antigen (HBsAg) positive children presenting to our hospital, who had been on antivirals for at least 2 years with undetectable hepatitis B virus-deoxyribonucleic acid (HBV-DNA) and normal alanine aminotransferase (ALT) on 3 consecutive occasions over last 12 months were included. Antivirals were stopped if liver biopsy showed histological activity index <5 and fibrosis (Ishak) <3. Virological relapse was defined as the elevation of HBV-DNA (>2000 IU/mL) and biochemical relapse as a rise in ALT levels to >2 times the upper limit of normal. Those having biochemical relapse were started on pegylated interferon alpha-2b-based sequential therapy. Of the 114 children with CHB screened, 31 HBsAg-positive children fulfilled inclusion criteria and antivirals were stopped in them. Virological and biochemical relapse was seen in 12 (38.7%) and 5 (16.1%) children within 12 months of stopping antiviral treatment. On Cox regression, hepatitis B e antigen (HBeAg) positive status at the time of stopping antiviral therapy (HR: 6.208, 95% CI: 1.630-23.638) and longer time taken for HBV-DNA to become undetectable while on antivirals (HR: 1.027, 95% CI: 1.000-1.055) were the independent predictors of relapse. Discontinuation of antiviral treatment in children with CHB resulted in relapse in one-third of the patients. Relapse was frequent in those who were HBeAg-positive at the time of stopping therapy and in those who required longer therapy for HBV-DNA to become undetectable.

Clinical and pathological predictors of relapse in IgG4-related disease

ObjectivesIn IgG4-related disease, the relationship between pathological findings and relapse has not been well established. This study aimed to identify the clinical and pathological predictors of disease relapse in IgG4-RD.MethodsPatients with newly diagnosed IgG4-RD (n = 71) were enrolled between January 2011 and April 2020; all cases were pathologically confirmed. The clinical and pathological features were recorded in a database at baseline and each follow-up visit. Patients were followed up at least once a month via outpatient clinic examinations and telephone calls. Univariate and multivariate Cox regression analyses and receiver operating curve (ROC) analysis were used to identify the predictors of disease relapse and to assess their predictive value.ResultsOver a median follow-up of 26 (range, 6–123) months, 3/71 (4.2%) patients died. Of the remaining 68 patients, 47 (69.1%) patients had achieved clinical remission and 21 (30.9%) had suffered relapse at the last follow-up. The independent predictors of relapse were IgG4 ≥ 6.5 g/L (HR = 2.84, 95% CI: 1.11–7.23), IgG ≥ 20.8 g/L (HR = 4.11, 95% CI: 1.53–11.06), IgG4-RD responder index (RI) ≥ 9 (HR = 3.82, 95% CI: 1.28–11.37), and severe IgG4+ plasma cell infiltration (HR = 6.32, 95% CI: 1.79–22.41). A prognostic score developed using three of the identified predictors (IgG ≥ 20.8 g/L, IgG4-RD RI ≥ 9, and severe IgG4+ plasma cell infiltration) showed good value for predicting impending relapse (AUC, 0.806).ConclusionsIn patients with IgG4-RD, IgG4 ≥ 6.5 g/L, IgG ≥ 20.8 g/L, IgG4-RD responder index (RI) ≥ 9, and severe IgG4+ plasma cell infiltration are predictors of relapse.

Predictors of diabetes relapse after metabolic surgery in Asia.

Limited studies have focused on diabetes relapse after metabolic surgery, especially among Asians. To identify the predictors of diabetes relapse following initial postoperative remission in Asia. Four tertiary hospitals METHODS: We assessed 342 patients (age, 41.0 ± 10.8 yr; body mass index [BMI], 39.6 ± 7.3 kg/m2) with complete diabetes data before and 1 and 3 years after metabolic surgery. A total of 290 (84.8%) and 277 (81.0%) patients had diabetes remission at 1 and 3 years after surgery. Logistic regressions were performed to identify the independent predictors of diabetes relapse. Two published predictive models for diabetes remission were also tested for relapse. Of the 290 patients with 1-year diabetes remission, 29 (10%) experienced a relapse at 3 years after surgery. The area under the receiver operating characteristic curve of the ABCD score in predicting 1-year remission, 3-year remission, and 3-year relapse were .814, .793, and .795, while those of the DiaRem2 score were .823, .774, and .701, respectively. The baseline age, BMI, and insulin use were independent predictors for relapse. The most powerful predictive model for relapse was composed of preoperative insulin use, 1-year A1C, and a change in BMI between the first and third year (C-statistic: .919). The ABCD score predicted both mid-term postoperative diabetes remission and relapse in Asians. Initial older age, lower BMI, insulin use, higher 1-year A1C, and weight regain were independent predictors of relapse. Personalized strategies should be proposed for those at risk of relapse to optimize diabetes outcomes after surgery.

Outcomes of a combined vs non-combined endo-epicardial ventricular tachycardia ablation strategy.

Direct comparisons of combined (C-ABL) and non-combined (NC-ABL) endo-epicardial ventricular tachycardia (VT) ablation outcomes are scarce. We aimed to investigate the long-term clinical efficacy and safety of these 2 strategies in ischemic heart disease (IHD) and non-ischemic cardiomyopathy (NICM) populations. Multicentric observational registry included 316 consecutive patients who underwent catheter ablation for drug-resistant VT between January 2008 and July 2019. Primary and secondary efficacy endpoints were defined as VT-free survival and all-cause death after ablation. Safety outcomes were defined by 30-day mortality and procedure-related complications. Most of the patients were male (85%), with IHD (67%) and mean age of 63 ± 13years. During a mean follow-up of 3 ± 2years, 117 (37%) patients had VT recurrence and 73 (23%) died. Multivariate survival analysis identified electrical storm (ES) at presentation, IHD, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class III / IV, and C-ABL as independent predictors of VT recurrence. In 135 patients undergoing repeated procedures, only C-ABL and ES were independent predictors of relapse. The identified independent predictors of mortality were C-ABL, ES, LVEF, age, and NYHA class III / IV. C-ABL survival benefit was only seen in patients with a previous ablation (P for interaction = 0.04). Mortality at 30days was similar between NC-ABL and C-ABL (4% vs. 2%, respectively, P = 0.777), as was complication rate (10.3% vs. 15.1%, respectively, P = 0.336). A combined or sequential endo-epicardial VT ablation strategy was associated with lower VT recurrence and lower all-cause death in IHD and NICM patients undergoing repeated procedures. Both approaches seemed equally safe.

Causes, frequencies, and predictors of relapse in patients with ulcerative colitis on long-term follow-up in a tertiary care hospital of Northern India

Context: Ulcerative colitis (UC) initially thought to be a disease of developed world is equally common in India. Surprisingly, there are very scant data from India. The study was undertaken to find the frequency of relapse and to determine factors predictor of relapse in Indian population. Subjects and Methods: This study was conducted at a tertiary care center of New Delhi for a period of 1 year. Patients were included if they had a diagnosis of UC based on accepted historical, endoscopic, histological, and/or radiologic criteria. Detailed past/present history, baseline clinical examination, dietary details, and psychological analysis using shortened Depression Anxiety Stress Scale score, biochemical tests, inflammatory markers, endoscopic, and histopathological analysis were done at baseline and regular intervals. The outcome was clinical relapse or continued remission. Results: Out of 86 patients screened, 50 patients were included in the study according to inclusion criteria and were followed up. The frequency of relapse was 32%. Univariate analysis showed higher relapse frequency, frequency of steroid received in past, patients on immunomodulator therapy, presence of acute or chronic inflammatory cells on histology, and disease activity at baseline as predictors of relapse. There was no significant difference between anxiety, stress, and depression relapsers and those who maintained remission. On multivariate analysis, disease activity at baseline was the only independent predictor of relapse. Conclusions: Stringent control of disease activity with mucosal healing should be the aim, as mucosal healing is the only predictor for prolonged remission.