Adverse Predictors Of Overall Survival Research Articles

Patients with Pulmonary Artery Reconstruction or Double Sleeve Resection Show Inferior Survival than Patients with Bronchial Sleeve Resection for Non-small Cell Lung Cancer.

Sleeve lobectomy or resection with pulmonary artery reconstruction is a technique that allows for resection of locally advanced central lung carcinoma, preserving lung function, and is associated with lower morbidity and mortality than pneumonectomy. This survey aimed to assess the long-term survival comparing different types of sleeve lobectomy and identify risk factors affecting survival.All consecutive patients who underwent anatomical resection for primary non-small cell lung cancer with bronchial sleeve or pulmonary artery reconstruction in our department between September 2003 and September 2021 were included in this study. Cases with carinal sleeve pneumonectomy were excluded. Data were evaluated retrospectively.Bronchial sleeve resection was performed in 227 patients, double sleeve resection in 67 patients, and 45 cases underwent isolated lobectomy with pulmonary artery reconstruction. The mean follow-up was 33.5 months. The 5-year survival was 58.5% for patients after bronchial sleeve, 43.2% after double sleeve, and 36.8% after resection with vascular reconstruction. The difference in overall survival of these three groups was statistically significant (p=0.012). However, the UICC stage was higher in cases with double sleeve resection or resection with vascular reconstruction (p=0.016). Patients with lymph node metastases showed shorter overall survival (p=0.033). The 5-year survival rate was 60.1% for patients with N0 and 47% for patients with N1 and N2 status. Induction therapy, vascular sleeve resection, and double sleeve resection were independent adverse predictors for overall survival in multivariate analysis.Sleeve lobectomy and resection with vascular reconstruction are safe procedures with good long-term survival. However, double sleeve resection and vascular sleeve resection were adverse predictors of survival, possibly due to a higher UICC stage in these patients.

Epidemiology and prognostic nomogram for chronic eosinophilic leukemia: a population-based study using the SEER database

Chronic Eosinophilic Leukemia (CEL), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate epidemiology and develop a prognostic nomogram for CEL patients. Utilizing the Surveillance, Epidemiology and End Results database, CEL cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL patients by incorporating these factors. The incidence rate of CEL was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL as independent and adverse predictors of overall survival. To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups. This study enhances our understanding of CEL, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL.

Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10−7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10−5) and ASCT (p = 4.8 × 10−4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10−8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10−4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10−4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

Prognostic Relevance of Truncating ASXL1 Mutations and ASXL1-Integrated Molecular Models in Proliferative CMML

Introduction Chronic myelomonocytic leukemia (CMML) can be classified into dysplastic (dCMML) and proliferative (pCMML) subtypes based on a white blood cell count (WBC) ≥ 13 x 10 9/L for pCMML. Though this cutoff may seem arbitrary, there is evidence that pCMML is a unique biological entity with a distinct molecular profile and worse outcomes (Carr RM, et al. Nat Commun. 2021). We hypothesized that contemporary CMML prognostic scoring systems - such as the Mayo Molecular Model (MMM; Patnaik MM, et al. Leukemia. 2014) and the CPSS-Molecular Model (CMM; Elena C, et al. Blood. 2016) - would not adequately risk-stratify pCMML patients. Moreover, while truncating ASXL1 mutations are considered a high-risk feature in CMML, their prognostic relevance in pCMML is unknown. Methods After IRB approval, we compiled a large (n = 888), molecularly-annotated database of CMML patients seen at two US medical centers (Mayo Clinic and MD Anderson) via retrospective chart review. All statistical analyses considered the clinical and laboratory parameters obtained at the time of presentation. The cohort was divided into dCMML and pCMML subgroups, which were analyzed independently alongside the entire cohort. Categorical variables were compared by Fisher exact or Pearson χ 2 tests and continuous variables by Mann-Whitney U tests. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Survival was assessed via the Kaplan-Meier method. P-values < 0.05 were considered significant. Calculations were performed using the BlueSky Statistics (v10.3.1) interface for R. Results We identified 474 (54%) dCMML cases and 410 (46%) pCMML cases with median age 71 years and 67% males. Patients with pCMML were more likely to have higher AMC (5.1 vs 1.5 x 10 9/L, p < 0.0001), circulating immature myeloid cells (IMC; 65% vs 36%, p < 0.0001) and abnormal karyotypes (37% vs 30%, p = 0.0187). They were also overrepresented in higher-risk categories of the MMM and CMM compared to dCMML (p < 0.0001 for each model). The number of somatic mutations was higher in pCMML than dCMML (mean 3.0 vs 2.6, p = 0.0050). Mutations in ASXL1 (53% vs 39%), NRAS (21% vs 11%), CBL (18% vs 12%), SETBP1 (14% vs 7%), JAK2 (10% vs 3%), CEBPA (5% vs 2%), GATA2 (3% vs 0%), and FLT3 (3% vs 1%) were more frequent while mutations in TET2 (38% vs 48%), SF3B1 (2% vs 8%), ZRSR2 (2% vs 8%), and NPM1 (1% vs 3%) were less frequent in pCMML compared to dCMML, respectively (p < 0.05 for all). Though the MMM and CMM effectively stratified the dCMML group, they did not provide meaningful risk stratification in the pCMML group (MMM p < 0.05 overall but could not distinguish between low and intermediate-1/2 or intermediate-1 and high risks; CMM p > 0.05). Likewise, there was no difference in the median overall survival (OS) or leukemia free survival (LFS) when pCMML patients were stratified by truncating ASXL1 mutations( Figure 1A). We then sought to better risk stratify pCMML. Univariate analysis identified increasing age, male gender, abnormal karyotype, and elevated WBC, ANC, and AMC as adverse predictors for OS. In addition, the presence of IMC and peripheral blood (PB) blast % were adverse factors for LFS, while age was not significant for LFS. None of the aforementioned mutations were significant in the univariate model for OS, whereas GATA2 and NPM1 mutations were significant for LFS. In multivariate analysis for OS, only male gender and AMC ≥ 10 x 10 9/L retained significance. In multivariate analysis for LFS, male gender, AMC ≥ 10 x 10 9/L, and peripheral blasts ≥ 5% remained significant; GATA2 and NPM1 mutations were not significant. These variables risk-stratified pCMML patients based on the presence of 0, 1, or ≥ 2 risk factors ( Figure 1B). In comparison, OS was 40.7 months (95% CI 35.2 - 50.1 mo.) for dCMML patients, 20.1 months (95% CI 18.2 - 22.7 mo.) for pCMML patients, and 31.8 months (95% CI 28.4 - 33.5 mo.) for the entire cohort. At last follow up, 586 deaths (66%) and 168 AML transformations (19%) were recorded in the cohort. Deaths in dCMML vs pCMML were 294 (62%) vs 291 (71%; p = 0.0067), with AML transformations in 83 (18%) vs 84 (21%; p = 0.2055) patients, respectively. Conclusions Truncating ASXL1 mutations, along with ASXL1-mutation weighted CMML prognostic models failed to effectively risk stratify pCMML patients. In pCMML, male gender and AMC ≥ 10 x 10 9/L, effectively risk stratified for OS, while these factors along with PB blasts ≥ 5% effectively risk stratified for LFS.

Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas

It is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.

Higher red blood cell distribution width at diagnose is a simple negative prognostic factor in chronic phase-chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: A retrospective study.

The aim of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict prognosis and treatment response in chronic myeloid leukemia (CML)-chronic phase (CP) patients treated with tyrosine kinase inhibitor (TKIs).We retrospectively enrolled 93 newly diagnosed CML-CP patients treated with TKIs from 2009 to 2018 at the First Hospital of Lanzhou University. Patients were divided into 2 groups using an RDW of 18.65% determined by receiver operating characteristic curve analysis. We analyzed the correlation of treatment responses and the RDW compared to common scoring systems, as well as the correlation of the RDW with disease outcome, including overall survival (OS) and progression-free survival (PFS), and demographic and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.The median age of patients was 40 years, and 51 patients (54.8%) were men. A high RDW could predict treatment response at 3 months (P = .03) and 6 months (P = .02). The RDW was significantly lower in patients who achieved molecular response by 3 months (P < .001) and complete cytogenetic response by 6 months (P = .001) than in those who did not respond. Patients with a high RDW (>18.65%, n = 35) had significantly worse 5-year OS (77.1% vs 96.6%; P = .008) and PFS (80.0% vs 98.3%; P = .002) than those with a low RDW (≤18.65%, n = 58). Multivariate analysis demonstrated that a high RDW was an adverse predictor of OS (P = .005, HR (hazard ratio) = 9.741) and PFS (P = .009, HR = 16.735).The RDW is a readily available prognostic marker of outcome in patients with CML-CP and can predict treatment response to TKIs. Further larger and prospective studies are required.

Risk and prognostic factors of breast cancer with liver metastases

BackgroundLiver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).MethodsData on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.ResultsYoung age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88–3.66; P < 0.001) and HR−/HER2+ (HR = 3.43; 95% CI = 2.28–5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58–0.95; P < 0.001).ConclusionsBreast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.

High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.

To investigate the use of high-dose therapy and autologous stem cell transplantation (ASCT) for relapsed or high-risk diffuse large B-cell lymphoma (DLBCL) between 1990 and 2007, we conducted a nationwide survey using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Of the 1222 patients in the database, 576 (47%) received ASCT in first complete remission (CR1), 140 (12%) in first partial remission, 281 (23%) in sensitive relapse, 150 (12%) in resistant or sensitivity-unknown relapse, and 75 (6%) in primary refractory status. With a median follow-up of 22months, the 2-year overall survival (OS) and progression-free survival rates were 71% and 68%, respectively. The cumulative incidences of 2-year non-relapse mortality and relapse/progression were 6% and 26%, respectively. Relapse/progression after ASCT in the rituximab era (2002-2007) was significantly lower than that in the pre-rituximab era (1990-2001; P < 0.001). Older age, male gender, poor performance status at ASCT, non-CR1 at ASCT, ASCT performed in 1990-2001, and LEED or MCEC regimen were adverse predictors of OS. Because ASCT for newly diagnosed high-risk DLBCL has not been performed recently, a registry database study to assess the impact of ASCT for relapsed or refractory DLBCL in the rituximab era is warranted.

Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy

AimThis study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. MethodsClinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. ResultsThe overall median follow-up period was 2.6 years (0.2–17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). ConclusionsMUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.

Surgical Outcomes of Patients With Stage III Thymoma in the Japanese Nationwide Database

To investigate the clinical characteristics and therapeutic outcomes of patients who underwent surgery for stage III thymoma in Japan. Using the Japanese nationwide database, which contains the records of 2,835 patients with thymic epithelial tumors who underwent treatment between 1991 and 2010, we extracted and analyzed the records of those who underwent surgery for stage III thymoma. A total of 310 patients (170 males, 140 females; median age, 58 years) were analyzed. Involved sites were the lung in 194 (62.6%), the pericardium in 151 (48.7%), the great vessels in 126 (40.6%), the phrenic nerve in 84 (27.1%), and the chest wall in 7 (2.3%). Complete resection (R0) was achieved in 247 (79.7%) cases. Induction therapies were administered to 42 (13.5%) patients, and postoperative therapies were administered to 147 (47.4%). In R0 cases, 68 (27.5%) experienced recurrence. The pleural space was the most frequent site of recurrence (46; 18.6%). The 10-year overall and disease-free (in R0) survival rates were 80.2% and 51.6%, respectively. Multivariate analyses revealed that age (p= 0.002), male sex (p= 0.017), induction therapy (p < 0.001), and type B histology (p= 0.037) were independent adverse predictors for overall survival. Chest wall invasion was the only independent adverse predictor for disease-free survival, although the factor analysis was marginal for overall survival. The outcomes of surgery for patients with stage III thymoma were favorable unless chest wall invasion was present; however, the role of complete resection and appropriate multimodal treatment plan require further investigation.

Impact of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mechanical mitral valve replacement for rheumatic mitral valve disease

The prognostic significance of preoperative atrial fibrillation on mitral valve replacement remains unclear. The aim of this study was to explore the effects of the presence of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mitral valve replacement for rheumatic valve disease. A retrospective analysis was performed on a total of 793 patients who underwent mitral valve replacement with or without tricuspid valve repair in our hospital. The patients selected were divided into two groups according to preoperative rhythm status. Patients with preoperative atrial fibrillation were assigned to the AF group, while patients in preoperative sinus rhythm were assigned to the SR group. Postoperative follow-up was performed by outpatient visits, as well as by telephone and written correspondence. Data gathered included survivorship, postoperative complications, left ventricular function and tricuspid regurgitation. For patients with atrial fibrillation vs those in sinus rhythm, there was no difference in postoperative mortality and morbidity. Follow-up was a mean of 8.6 ± 2.4 years. For patients with preoperative atrial fibrillation, 10-year survival from a Kaplan-Meier curve was 88.7%, compared with 96.6% in patients with preoperative sinus rhythm (P = 0.002). Multivariate analysis identified low left ventricular ejection fraction, older age, large left atrium and preoperative atrial fibrillation as significant adverse predictors for overall survival. Freedom from thromboembolism complications at 13 years was lower for patients with preoperative atrial fibrillation without maze procedure and left atrial appendage ligation, compared with that for patients with preoperative sinus rhythm without maze procedure and left atrial appendage ligation, and patients with concomitant maze procedure and left atrial appendage ligation (76.3 vs 94.8 vs 94.0%, respectively; P = 0.001). On echocardiography, the proportion of patients with significant tricuspid regurgitation was 38.7% (atrial fibrillation patients) vs 25.4% (patients in sinus rhythm; P < 0.001). Left ventricular ejection fraction measured 5 years after surgery increased by an average of 1.2% in the AF group, while it increased by 5.3% in the SR group (P = 0.028). Preoperative atrial fibrillation is a risk factor for long-term mortality, thromboembolism complications and tricuspid regurgitation, and it also has an adverse effect on the degree of improvement when considering left ventricular function.

Vasculogenic mimicry is a marker of poor prognosis in prostate cancer

We investigated the role of vasculogenic mimicry (VM) in the progression of prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for treatment of PCa and for whom a complete record of clinical and follow-up data were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were detected by immunohistochemical staining in frozen tissue sections. Relationship between VM and clinicopathological variables was analyzed statistically. Multivariate analyses were performed to assess the prognostic significance of VM. Results showed that out of the 96 PCa cases studied here, VM was detectable in 24 (25%) and was positively correlated with preoperative prostate-specific antigen (PSA) level, Gleason score, pathological stage, lymph node metastasis, seminal vesicle invasion, distant metastasis and PSA doubling time (PSADT). Univariate analysis showed that VM, PSA level, Gleason score, distant metastasis and PSADT were correlated with overall survival (OS), while VM, Gleason score, distant metastasis, local recurrence and PSADT were correlated with disease-free survival (DFS). Multivariable analysis indicated that the presence of VM, higher Gleason score and distant metastasis were the adverse predictors of OS and DFS. A higher widespread staining for MMP-2 was correlated with the VM-positive subgroup. In conclusion, VM mainly exists in the high risk PCa patients and is an independent marker of poor prognosis.

Preoperative metastatic status, level of thrombus and body mass index predict overall survival in patients undergoing nephrectomy and inferior vena cava thrombectomy

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known about the prognostic impact of body mass index (BMI) and obesity on patients with locally advanced kidney cancer. Previous studies suggest that clinical/pathological stage, the proximal extent of the tumour thrombus, direct vascular wall invasion, and preoperative performance status may all constitute important prognostic factors within this patient population. The present study shows that a patient's metastatic status, higher level of tumour thrombus, and lower BMI all constitute adverse predictors of overall survival in patients who have RCC with inferior vena cava tumour thrombus. • To determine which clinical variables, including body mass index (BMI), predict overall survival (OS) after nephrectomy with inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with tumour thrombus. • After institutional review board approval, a retrospective analysis of all patients (N= 100) undergoing nephrectomy and IVC thrombectomy for RCC from 1989 to 2010 were reviewed. One patient was excluded owing to missing clinical information leaving 99 patients in the study cohort. • Patients were placed into one of two subgroups, based on their preoperative BMI (BMI ≤30 kg/m(2) or BMI >30 kg/m(2) ). • Complications, blood loss, level of tumour thrombus, side of tumour and follow-up data were tabulated. • Fifty-six patients had a BMI ≤30 kg/m(2) and 43 patients had a BMI >30 kg/m(2) . Intraoperative complications occurred in 14% of those with BMI >30 kg/m(2) and 5.4% of those with a BMI ≤30 kg/m(2) (P= 0.171). • On multivariate analysis, a higher thrombus level (III/IV vs I/II) and the presence of metastatic disease at time of diagnosis was associated with a worse OS (P= 0.041 and P < 0.001, respectively). • The subgroup with a higher preoperative BMI had a significantly better OS (hazard ratio 0.42; 95% confidence interval 0.22-0.80, P= 0.009). • Similarly, our Kaplan-Meier survival analysis showed an improved OS in the patient cohort with a BMI >30 kg/m(2) (P= 0.016). • Important predictors of outcome in patients undergoing nephrectomy with IVC thrombectomy for RCC with tumour thrombus include preoperative BMI, level of IVC tumour thrombus, and metastatic status at time of surgery.

Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML

AbstractIncreased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.

Malignant Gastric Polyps - An Analysis of 7,284 Cases

Purpose: Gastric polyps are encountered in up to 5% of upper endoscopies. Although there is consensus on the management of the majority of this heterogeneous group of lesions, no guidelines exist for malignant gastric polyps (MGP). While many MGP can be removed endoscopically, the risk of lymph node metastases remains. Aim: To define selection criteria for the endoscopic resection of MGP and to investigate factors influencing survival outcomes using a cancer registry. Methods: The Surveillance Epidemiology and End Result (SEER) database was used to identify patients diagnosed with MGP from 1998-2007. Multivariate logistic regression analysis was used to identify predictors of lymph node metastases and Cox regression analysis to identify adverse predictors of overall survival. Results: 7,284 patients were identified. 60% were men. The mean age was 71 years ± 0.1 and mean polyp size was 2.6 cm ± 0.4. The number of MGP increased from 2.2% in 1988 to 9.3% in 2007. The most frequent treatment was surgical resection (72%), followed by no surgery (17%), and endoscopic resection (10%). In patients undergoing surgical resection, high tumor grade, patient's age and tumor size predicted lymph node metastases (Table). For low grade MGP < 2 cm, only 4.9% had positive lymph nodes following surgery. Predictors of adverse survival included: size > 2 cm (HR 1.39, 95% CI 1.24-1.57), race other than Asian (White HR 1.48, 95% CI 1.32-1.66, Black HR 1.71, 95% CI 1.46-2.01), positive lymph nodes (N1 HR 1.57, 95% CI 1.38-1.79), and no resection (HR 4.22, 95% CI 3.58- 4.99) or endoscopic resection (HR 1.29, 95% CI 1.04- 1.62).Table: Predictors of lymph node metastasesConclusion: The optimal treatment for MGP remains surgical resection. However, for low grade, proximally located MGP < 2 cm, endoscopic resection may be adequate treatment due to the low risk of lymph node metastases. Assuming these selection criteria are confirmed by other studies, endoscopic resection is under-utilized in the management of MGP. This research was not supported by any industry grant.

Lens culinaris agglutinin‐reactive fraction of AFP is a useful prognostic biomarker for survival after repeat hepatic resection for HCC

Repeat hepatic resection for recurrent hepatocellular carcinoma (HCC) is effective in improving long-term outcome in selected patients. In the present study, we attempted to identify the prognostic factors influencing overall and recurrence-free survival after the second hepatic resection. From 1 September 1997 to 30 September 2009, 329 consecutive patients with HCC underwent surgical exploration at Yamanashi University Hospital, Japan. Of these, 35 patients underwent curative, second hepatic resection. The survival results in the 35 patients were analyzed retrospectively, and prognostic factors were determined. The univariate analysis revealed that Child-Pugh B, a Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) value more than 15%, and multiple tumors, were associated with significantly worse overall survival (P=0.010, P=0.0003, and P=0.037, respectively) and only AFP-L3 >15% was associated with significantly worse recurrence-free survival after the second hepatic resection (P=0.008). By multivariate analysis, only AFP-L3 >15% was an independent predictor of adverse overall survival. The 1-, 3-, and 5-year survival rates after the second hepatic resection of 27 HCC patients with low AFP-L3 (≤15%) were 100%, 100%, and 91.7%, respectively, whereas the corresponding survival rates of eight HCC patients with high AFP-L3 (>15%) were 100%, 47.6%, and 23.8%, respectively. The preoperative AFP-L3 level was a useful prognostic biomarker for survival after repeat hepatic resection.

Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma

Autologous stem cell transplantation (autoSCT) has improved the outcome of patients with mantle cell lymphoma (MCL) considerably. However, little is known about the patterns and outcome of MCL recurrence after autoSCT. The authors conducted a retrospective study of 118 patients with MCL who underwent autoSCT from August 1992 to August 2008 at 3 different referral centers in Germany. Fifty-two relapses occurred for a cumulative incidence of 46% after 5 years. Only 3 patients relapsed after 5 years (at 90 months, 91 months, and 171 months) after undergoing autoSCT. A Cox regression analysis of the incidence of relapse identified not receiving rituximab before autoSCT and undergoing salvage autoSCT as predictive factors for relapse, whereas cytosine arabinoside intensification; a total body irradiation-based, high-dose regimen; patient age; and year of transplantation had no influence. The median overall survival (OS) after relapse was 23 months. Twenty patients (39%) underwent allogeneic stem cell transplantation (alloSCT) for relapse, and 11 of those patients remained in ongoing complete remission at the time of the current report. It is noteworthy that there were 4 long-term survivors who lived for >5 years after relapse even without undergoing alloSCT. A Cox regression analysis of OS after relapse revealed that the response duration after autoSCT was an adverse predictor of OS, whereas alloSCT was associated with a significantly longer OS after relapse. The current results indicated that autoSCT was capable of inducing long-term remission up to 16 years after treatment, but the outcome of patients with MCL who relapsed after autoSCT was poor, especially if their response duration after autoSCT was short. However, for a subset of patients with relapsed MCL, alloSCT may offer the possibility of durable survival, and individual patients can enjoy long-term survival after relapse even without undergoing alloSCT.

Abstract A110: Factors affecting cervical cancer survival for patients referred to a tertiary care center in Kentucky

Abstract Objectives: The aim of this research was to identify prognostic factors influencing cervical cancer recurrence and survival in Kentucky. Methods: A cohort study was performed to assess predictive survival factors of cervical cancer patients referred to the University of Kentucky using the University of Kentucky database and the Kentucky Cancer Registry from January 2001 to May 2010. Eligibility criteria include those at least 18 years old, a history of cervical cancer, and no prior history of malignancy. Descriptive statistics were compiled for age, race, insurance status, tobacco use, Appalachian or non-Appalachian residence using the Appalachian Regional Commission classification of county, co-morbid risk factors, BMI, and pathologic characteristics. Univariable and multivariable Cox proportional hazard analysis were performed to assess associations with cervical cancer recurrence and overall survival. Results: 380 patients met entry criteria. 91 % were Caucasian (N=346), 43% were uninsured (N=163), and 64% (N=242) lived in Appalachia. While 48% (N=184) of the population had no co-morbid risk factors, 41 % (N=156) had one or two risk factors. The following covariates were not associated with recurrence free or overall survival: race, BMI, Appalachian residence, insurance status, months between last normal cervical cytology and diagnosis, histology (squamous cell carcinoma vs. adenocarcinoma vs. other), and tumor grade. The univariable analysis revealed age [HR1.02 (95%CI 1.01,1.04)], having more than two co-morbid risk factors [HR 2.8 (95%CI 1.1, 7.2)], and diagnosis in disease stages II, III, and IV [HR 5.0 (95% 2.3,10.9); 11.0 (5.2,23.1); 43.7 (19.0,100.3)] were associated with a worse recurrence-free survival while age [HR 1.03 (95%CI 1.02,1.04)], having more than two co-morbid risk factors [HR 3.7 (95%CI 1.8, 7.9)], smoking status [HR 1.4 (95%CI 1.0,2.5)], and diagnosis in disease stages II, III, and IV [HR 4.0 (95%CI 2.2, 7.1); 7.3 (95%CI 4.1,12.9); 32.7 (16.8,63.8)] all significantly decreased overall survival. After controlling for all significant variables, Stage IV disease was a significant predictor of progression-free survival [HR 3.6 (95%CI 2.0,6.4)] while stages II, III, and IV [HR 3.0 (95%CI 1.6,5.7); 6.0 (95%CI 3.3,11.0); 38.9 (95%CI 18.0,84.0)] and having more than two co-morbid risk factors [HR 2.3 (95%CI 1.0,5.2)] remained significant adverse predictors for overall survival. Conclusions: Co-morbid risk factors and stage influence cervical cancer survival. Future cervical carcinoma research should consider medical co-morbidities as an important factor impacting survival. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A110.

Positive Postradiotherapy Planned Neck Dissection is Strongly Associated with Increased Distant Metastasis Rather Than Regional Relapse

Positive Postradiotherapy Planned Neck Dissection is Strongly Associated with Increased Distant Metastasis Rather Than Regional Relapse

Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma

Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC. The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival. Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN.