Independent Predictor Of Poor Survival Research Articles

Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival. Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p= 0.0006, area under the curve= 0.78). Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence.

Primary appendiceal lymphoma: clinical characteristics and outcomes of 116 patients

BackgroundPrimary appendiceal lymphoma (PAL) is extremely rare with limited data available in literature. In this study, we sought to describe clinical features and identify factors affecting survival in patients with PAL using a large population cohort. MethodsSurveillance, Epidemiology, and End Results database was queried for patients with PAL between 1973 and 2012. Patient demographics, tumor characteristics, and outcomes were assessed. ResultsOne hundred sixteen patients with PAL were included. The mean age (standard deviation) at diagnosis was 48 y (±22). PAL primarily afflicted males and white race. Diffuse large B-cell lymphoma was the most common histologic subtype (34.5%). Patients with Burkitt lymphoma presented at an earlier age compared with follicular lymphoma and diffuse large B-cell lymphoma (33 versus 59 and 53 y, respectively, [P < 0.001]). Mean overall survival (OS) for the whole cohort was 185 mo with a 5-y survival rate of 67%. No statistically significant survival difference was observed between gender, race and histologic subtypes. Right hemicolectomy conferred no survival benefit over appendectomy and/or partial colectomy (P = 0.501). In multivariate analysis, increasing age at diagnosis (P < 0.001) was associated with increased hazards of death while gender, race, tumor histology, disease stage, and nature of resection were not significantly associated with OS. ConclusionsThis is the largest series of PALs. Our results demonstrate that age at diagnosis is an independent predictor of poor survival. Gender, race, histologic subtypes have no effect on OS, and hemicolectomy provides no survival benefit over appendectomy and/or partial colectomy. Additional prospective, multicenter studies including details about chemotherapy and immunotherapy are needed to guide management.

Advance care planning for 600 Chinese patients with end-stage renal disease

Background/purposeThere is increasing recognition of the need to integrate advance care planning (ACP) into end-stage renal disease (ESRD) care with attention to medical, ethical, psychosocial, and spiritual issues but publications comparing patients who chose renal replacement therapy (RRT) and renal palliative care (RPC) is scarce. We here share our experience on ACP for ESRD patients in a center with renal replacement and palliative programs in place. MethodsFrom June 2006 to December 2011, ESRD patients were empowered to make an informed choice of future medical care in a structured ACP that was emphasized to be an ongoing process. Patients who opted for RRT and RPC would be followed up at the predialysis clinic and the one-stop multidisciplinary RPC clinic, respectively. This was a single-center study in a secondary care hospital. A total of 600 patients (265 RRT, 335 RPC) were enrolled and followed up over a median of 782 days. ResultsThe majority of patients and relatives declined dialysis because of perceived physical burden. Only 1.6% of palliative care patients changed their decision and commenced dialysis. Baseline characteristics differed between patients who chose RRT or RPC. Survival declined according to the modified Charlson Comorbidity Index scores. Older age, mental incompetence, hyperlipidemia, high modified Charlson Comorbidity Index, low estimated glomerular filtration rate, and low albumin were important independent predictors of poor survival. Factors affecting the ACP decision were discussed in the Chinese culture context. ConclusionA structured ACP could empower the patient to make an informed decision on the management of ESRD. 背景於未期腎病患者的照顧中加入關注身心社靈和倫理問題的預設照顧計劃(ACP)受到日益重視，但有關比較接受腎替代療法和接受腎臟紓緩治療文獻討論為數不多。作為同時提供腎透析服務以及腎臟紓緩治療的部門，本文旨在分享我們為未期腎病者討論預計照顧計劃的經驗。 方法自二零零六年六月至二零一零五月間，透過有組織的預設照顧計劃討論，未期腎病患者會被鼓勵就未來的治療計劃作出知情選擇。選擇腎透析和腎臟紓緩治療的病人會分別於透析預備門診和一站式跨科際腎臟紓緩治療門診去覆診。本研究於一家二級醫院進行。總共有六百病人參與此研究，當中265名接受腎透析，335名接受腎臟紓緩治療，其中位跟進日數為782日。 結果大部份病人和家屬之所以拒絕腎透析是由於預計的身體負累，只有百分之一點六接受腎臟紓緩治療會改變主義而接受腎透析。選擇腎透析和腎臟紓緩治療的病人在基本的身體狀況有明顯分別。生存率亦隨著修改版查爾森共病量表的分數而下降。年長、精神自主能力缺欠、高血脂、修改版查爾森共病量表分數高、腎小球濾過率低、白蛋白低均屬重要暨獨立的因素以預計較差的生存率。本文亦會探討在中國文化處境下影響預設照顧計劃討論的因素。 結論有組織的預設照顧計劃討論能幫助病人在未期腎病的醫療方向作出知情的選擇。

A population-based study of large granular lymphocyte leukemia.

Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen. Population-based studies have not been reported in LGL leukemia. We present clinical characteristics, natural history and risk factors for poor survival in patients with LGL leukemia using the Surveillance, Epidemiology, and End Results Program (SEER) and the United States National Cancer Data Base (NCDB). LGL leukemia is an extremely rare disease with the incidence of 0.2 cases per 1 000 000 individuals. The median age at diagnosis was 66.5 years with females likely to be diagnosed at 3 years earlier compared with males. Analysis of patient-level data using NCDB (n=978) showed that 45% patients with T-LGL leukemia required some form of systemic treatment at the time of diagnosis. T-LGL leukemia patients have reduced survival compared with general population, with a median overall survival of 9 years. Multivariate analysis showed that age >60 years at the time of diagnosis and the presence of significant comorbidities were independent predictors of poor survival.

Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas.

BackgroundSynovial sarcoma (SS) is a soft tissue sarcoma of unknown histogenesis. Most metastatic or unresectable cases are incurable. Novel antitumor agents and precise prognostication are needed for SS patients. The protein forkhead box M1 (FOXM1), which belongs to the FOX family of transcription factors, is considered to be an independent predictor of poor survival in many cancers and sarcomas, but the prognostic implications and oncogenic roles of FOXM1 in SS are poorly understood. Here we examined the correlation between FOXM1 expression and clinicopathologic and prognostic factors, and we investigated the efficacy of FOXM1 target therapy in SS cases.MethodsImmunohistochemical study of 106 tumor specimens was conducted to evaluate their immunohistochemical expression of FOXM1. An in vitro study examined the antitumor effect of the FOXM1 inhibitor thiostrepton and small interference RNA (siRNA) on two SS cell lines. We also assessed the efficacy of the combined use of doxorubicin (DOX) and thiostrepton.ResultsUnivariate and multivariate analyses revealed that FOXM1 expression was associated with poor prognosis in SS. The cDNA microarray analysis using clinical samples revealed that the expression of cell cycle-associated genes was correlated with FOXM1 expression. FOXM1 inhibition by thiostrepton showed significant antitumor activity on the SS cell lines in vitro. FOXM1 interruption by siRNA increased the chemosensitivity for DOX in both SS cell lines.ConclusionFOXM1 expression is a novel biomarker, and its inhibition is a potential treatment option for SS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2542-4) contains supplementary material, which is available to authorized users.

Downregulated long non-coding RNA CLMAT3 promotes the proliferation of colorectal cancer cells by targeting regulators of the cell cycle pathway.

Over-expression of long non-coding RNA (lncRNA)-CLMAT3 is significantly associated with colorectal liver metastasis and is an independent predictor of poor survival for colorectal cancer patients. However, as little is known regarding the role of this gene in the proliferation of colorectal cancer in vitro, we investigated the involvement of lncRNA-CLMAT3 in colorectal cancer cell proliferation. In this study, we demonstrate that lncRNA-CLMAT3 expression was significantly increased in colorectal cancer cells compared with a normal intestinal mucous cell line and that inhibition of lncRNA-CLMAT3 suppressed colorectal cancer cell proliferation in vitro. We also found that this reduced colorectal cancer cell proliferation due to lncRNA-CLMAT3 knockdown is associated with G0/G1 cell-cycle arrest induction and apoptosis enhancement. Furthermore, lncRNA-CLMAT3 knockdown enhanced Cdh1 expression and resulted in p27Kip accumulation via increased Skp2 protein ubiquitination. Taken together, our findings suggest that reducing lncRNA-CLMAT3 inhibits colorectal cancer cell proliferation by affecting cell cycle components.

Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.

Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD (HR = 1.31, P < 0.0001) than in patients with NASH (HR = 1.73, P < 0.0001) or HCV (HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease (MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT.

Predictors of death among drug-resistant tuberculosis patients in Kuala Lumpur, Malaysia: A retrospective cohort study from 2009 to 2013.

The emergence of drug-resistant tuberculosis (TB) is a major public health threat. However, little is known about the predictors of death in drug-resistant TB in Malaysia. This study aimed to determine the predictors of death in drug-resistant TB patients, including multidrug-resistant TB (MDR-TB), in Kuala Lumpur, Malaysia. This study adopted a retrospective cohort study design and involved laboratory-confirmed drug-resistant TB patients (n=426) from January 2009 to June 2013. A Cox regression model and Kaplan-Meier curves were used to model the outcome measure. Data were analysed by using SPSS v.20.0 for Windows. In this study, 15.3% (n=65) of the patients died. Among the study patients, 70.9% were monoresistant TB cases, 9.4% were poly-resistant TB and 19.7% were MDR-TB. MDR-TB [adjusted hazard ratio (aHR)=2.23, 95% confidence interval (CI) 1.26-3.95], ethnicity [Malay (aHR=5.95, 95% CI 2.30-15.41), Chinese (aHR=4.01, 95% CI 1.38-11.66) and Indian (aHR=3.76, 95% CI 1.19-11.85)], coronary heart disease (aHR=6.82, 95% CI 2.16-21.50), drug abuse (aHR=3.79, 95% CI 2.07-6.93) and treatment non-compliance (aHR=1.81, 95% CI 1.01-3.27) were independent predictors of poorer survival in the multivariate Cox regression analysis. This study suggests that MDR-TB, local ethnicity, coronary heart disease, history of drug abuse and treatment non-compliance are factors predicting poor survival in drug-resistant TB patients. More emphasis should be given to the management of drug-resistant TB patients with these characteristics to achieve better treatment outcomes.

Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma

BackgroundIt is now widely recognized that outcomes in cancer patients are not determined by their tumor characteristics alone. In this study, we retrospectively analyzed the clinical data of esophageal cancer patients to evaluate the impact of red blood cell distribution width (RDW), platelet distribution width (PDW), and mean platelet volume (MPV) on cancer-specific survival (CSS).Study designWe retrospectively reviewed a database of 144 consecutive patients who underwent curative esophagectomy for esophageal squamous cell carcinoma at our institute between 2006 and 2014.ResultIn multivariate analysis, pathological stage (pStage) (p = 0.0002) and a high RDW (p = 0.0300) were found to be independently associated with poor survival. Patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.004).Among non-elderly patients, multivariate analysis demonstrated that pStage (p = 0.0120), and a high RDW (p = 0.0092) were independent risk factors for a worse prognosis. In addition, non-elderly patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.0003).On the other hand, univariate analysis demonstrated that pStage (p = 0.0008) was the only significant risk factor for a poor prognosis in elderly patients.ConclusionsWe confirmed that a high RDW was significantly associated with the CSS of esophageal cancer patients after curative esophagectomy. Furthermore, in non-elderly patients, a high RDW was a significant and independent predictor of poor survival.

Hepatic resection and prognosis for patients with single hepatocellular carcinoma larger than 5 cm

Purpose: This study aimed to determine the factors that affect on the prognosis of hepatic resection for HCC larger than 5 cm. Methods: A total of 421 patients underwent hepatic resection for the HCC at Keimyung University Dong-San Medical Center between January, 2001 and November, 2013, we analyzed 114 patients underwent resection with single HCC larger than 5 cm, retrospectively. Results: During median follow-up period was 26.4 months (range), 3- and 5- year disease-free survival rates of 42%, 30%. Iin univariate analysis, positive hepatitis B surface antigen, AFP of 2000 ng/mL or higher, PIVKA-II of 200 mIU/mL or higher, Edmonson grade III/IV, the presence of macrovascular invasion, the presence of microvascular invasion, and the presence of satellite nodule were all significant predictors of poor prognosis. However, tumor size larger than 10 cm and surgical margin status were not associated with a poor prognosis. In multivariate analysis, positive hepatitis B surface antigen, PIVKA-II 200 mIU/ml, macrovascular invasion, and microvascular invasion remained independent predictors of poor survival. Conclusion: After resection of the tumors larger than 5 cm in diameter, more restrict application of surveillance modalities, imaging studies and tumor markers, is recommended to detect earlier recurrence for the patients who have poor prognostic factors.

Up-regulated expression of scavenger receptor class B type 1 (SR-B1) is associated with malignant behaviors and poor prognosis of breast cancer

Scavenger receptor class B type 1 (SR-B1) is an integral membrane protein that is expressed in numerous cells and tissue types. The primary role of SR-B1 is to facilitate uptake of cholesteryl esters from high-density lipoproteins (HDL) in the liver. Altered SR-B1 expression contributes to human diseases. This study assessed association of SR-B1 expression in breast tissue specimens with breast cancer development and prognosis. Tissue specimens from 30 cases of adjacent normal breast tissues, ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDCA) were subjected to Western blot analysis, and 135 cases of DCIS and IDCA were used for quantitative immunohistochemical analysis of SR-B1 expression. The data showed that SR-B1 was significantly overexpressed in IDCA tissues compared to normal breast and DCIS tissues. SR-B1 expression was associated with pre-menopausal status, tumor size, and worse overall survival of patients. The data from this ex vivo study suggests that up-regulated SR-B1 protein expression is associated with malignant behaviors of breast cancer and that SR-B1 is an independent predictor for poor survival in breast cancer patients.

Migration-inducing gene 7 promotes tumorigenesis and angiogenesis and independently predicts poor prognosis of epithelial ovarian cancer.

Epithelial ovarian carcinomas (EOC) cause more mortality than any other cancer of the female reproductive system. New therapeutic approaches to reduce EOC mortality have been largely unsuccessful due to the poor understanding of the mechanisms underlying EOC proliferation and metastasis. Progress in EOC treatment is further hampered by a lack of reliable prognostic biomarkers for early risk assessment. In this study, we identify that Migration-Inducting Gene 7 (MIG-7) is specifically induced in human EOC tissues but not normal ovaries or ovarian cyst. Ovarian MIG-7 expression strongly correlated with EOC progression. Elevated MIG-7 level at the time of primary cytoreductive surgery was a strong and independent predictor of poor survival of EOC patients. Cell and murine xenograft models showed that MIG-7 was required for EOC proliferation and invasion, and MIG-7 enhanced EOC-associated angiogenesis by promoting the expression of vascular endothelial growth factor. Inhibiting MIG-7 by RNA interference in grafted EOC cells retarded tumor growth, angiogenesis and improved host survival, and suppressing MIG-7 expression with a small molecule inhibitor D-39 identified from the medicinal plant Liriope muscari mitigated EOC growth and invasion and specifically abrogated the expression of vascular endothelial growth factor. Our data not only reveal a critical function of MIG-7 in EOC growth and metastasis and support MIG-7 as an independent prognostic biomarker for EOC, but also demonstrate that therapeutic targeting of MIG-7 is likely beneficial in the treatment of EOC.

Predictors of survival for patients with cancer after cryptogenic stroke.

Patients with active cancer experience ischemic stroke via cryptogenic mechanisms, with cancer-associated hypercoagulability being considered a major contributor to such strokes. Despite the remarkably shortened survival of these patients, the clinical predictors of survival are poorly understood. We determined the clinical factors including D-dimer levels serving as the predictors of overall survival in these patients. Retrospective study was conducted on cancer patients who visited our hospital for acute ischemic stroke with cryptogenic mechanisms from April 2012 through November 2014. Demographics, clinical characteristics, imaging and laboratory results including coagulation markers were collected, and overall survival was calculated from the patient medical records and a governmental national database. A high D-dimer level was defined as a D-dimer level exceeding the median value from the study population (>5.50μg/ml). A total of 93 patients were identified, with a median survival of 62days (interquartile range 32-223days). A high D-dimer level (p=0.004; hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.21), systemic metastases (p=0.02; HR 2.08, 95% CI 1.11-3.90), and diabetes mellitus (p=0.03; HR 1.78, 95% CI 1.03-3.10) were identified as independent predictors of poor overall survival using multivariate Cox proportional hazard analysis. Most of the patients (87%) were primarily treated with low-molecular-weight heparin (dalteparin, n=49; enoxaparin, n=32). The type of low-molecular-weight heparin had no association with survival. A high D-dimer level, systemic metastases, and diabetes are independent predictors of poor survival in cancer patients with cryptogenic stroke.

The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma.

Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL).Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR.Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group.Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL.

Abstract P3-07-55: Predictive value of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene methylation in triple-negative breast cancer patients receiving carboplatin

Abstract Background: The epigenetic profile of triple-negative breast cancer (TNBC) showed a wide prevalence of MGMT promoter methylation.Aberrant methylation of MGMT seems to be an independent predictor of poor survival in patients with basal-like breast cancer. Moreover, patients with MGMT-negative basal-like tumors who received cyclophosphamide had asignificantly improved DFS and OS compared with MGMT-positive tumors.However, the impact of MGMT methylation in the context of modern therapy concepts is not clear. Methods: We retrospectively evaluated 174 TNBC tumors of patients enrolled into the neoadjuvantGeparSixtotrial from 08/2011 to 12/2012. Patients were randomized to receive 18 weeks of neoadjuvant treatment with paclitaxel (80mg/m2/week) and non-pegylated liposomal doxorubicin (20mg/m2/week) with or without addition of carboplatin (AUC 2.0-1.5/week).Hormone-receptor status, HER2status, and Ki67 were centrally confirmed prior to randomization. We defined pathological complete response (pCR)as ypT0/is ypN0. MGMT promoter methylation status was determined by PCR using EZ DNA Methylation Kit™ (Zymo Research); TNBCtumors were considered to be methylated if they had an average methylation ≥10%, some tumors were considered borderline due to high heterogeneity among GpC islands.We investigated the effect of MGMT methylation on pCR and its correlation with baseline characteristics. Results: A total of210 tumors from the TNBC cohort of the GeparSixtotrial(n=315) were available with a tumor content &amp;gt;20%. In 174 tumors the methylation assay was performed successfully. The number of tumorswith methylated MGMT was similar in carboplatin vs. non-carboplatin treated cohorts. In the carboplatin group 19.3% (17/88) of TNBC were methylated, 65.5% (58/88)unmethylated, and 14.8% (13/88) borderline.In the non-carboplatin group 20.9% (18/86) of TNBC were methylated, 62.8% (54/86)unmethylated, and 16.3% (14/86) borderline.In the entire cohort,there was no association between MGMT methylation status and pCR (p=0.522).Non-carboplatin cohort: 33.3% (6/18) of patients with methylated MGMT achieved pCR vs. 51.9% (28/54) of unmethylatedand 21.4% (3/14) of borderline (p=0.079).Carboplatin cohort: 52.9% (9/17) of patients with methylated MGMT achieved pCR vs. 55.2% (32/58) of unmethylatedand 76.9% (10/13) of borderline (p=0.320). In TNBC patients with methylated MGMT, the addition of carboplatin resulted in a 20% increased pCR rate (p=0.241). Conclusion: In this study no statistically significant association between MGMT methylation andpCR was found.Patients with MGMT methylation seemed to have a lower possibility to achieve a pCR and the addition of carboplatin seemed to reverse this effect. However, a clear classification of the borderline MGMT samples and further studies in larger series of TNBC are warranted. Citation Format: Fontanella C, Gehlhaar C, Denkert C, Schneeweiss A, Heppner B-I, Koch I, Blohmer J-U, Jackisch C, Lederer B, Fasching PA, Müller V, Untch M, Aprile G, Puglisi F, Nekljudova V, Heppner F, von Minckwitz G, Loibl S. Predictive value of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene methylation in triple-negative breast cancer patients receiving carboplatin. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-55.

L1CAM is an independent predictor of poor survival in endometrial cancer — An analysis of The Cancer Genome Atlas (TCGA)

BackgroundL1-cell adhesion molecule (L1CAM) was previously reported to carry a poor prognosis in Stage I, low-risk endometrial cancer (EC). We evaluated the role of L1CAM among all stages and histologies in ECs in The Cancer Genome Atlas (TCGA). MethodsClinical information and RNA-Seq expression data were derived from TCGA uterine cancer cohort. Associations between L1CAM expression and clinical factors were tested with linear and logistic regression. Differences in survival between “high” and “low” expression groups (defined by median expression) of L1CAM were compared using Cox regression analysis, with p-values calculated via log-rank test. Kaplan-Meier curves were tested with the log-rank test. ResultsPatient characteristics of 545 primary tumors with RNA-Seq gene expression data were analyzed. Median age was 64years (range 31–90). Stage I, II, III, and IV comprised 62%, 10%, 23%, and 5%, respectively. 75% were endometrioid; 21% serous. Grade 1, 2, and 3 comprised 18%, 22%, and 60%, respectively. Median follow-up was 23.0months. High L1CAM expression was associated with advanced stage (OR 3.2), high grade (OR=6.8), serous histology (OR=16.3), positive cytology (OR=3.5), positive pelvic (OR=21.8) and para-aortic lymph nodes (OR=10.3) (all p≤0.001). High L1CAM was associated with a median overall survival (OS) of 107months, versus not reached for low L1-expressing ECs (HR=3.46, CI 1.97–6.07, p<0.001). On multivariate analysis, L1CAM expression remained an independent prognostic variable in predicting OS in EC. ConclusionsL1CAM expression is an independent predictor of poor survival in endometrial cancer, and is associated with advanced stage, high-risk endometrial cancer.

Reduction of prostaglandin transporter predicts poor prognosis associated with angiogenesis in gastric adenocarcinoma.

Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE2 in tissues is determined by a balance of PG biosynthesis and degradation pathways, which involve the PG transporter (PGT). We investigated PGT in gastric adenocarcinoma by determining its expression pattern and examining associations of PGT with prognosis and tumor angiogenesis. PGT expression was determined by immunohistochemistry in advanced gastric adenocarcinoma specimens obtained from 96 patients who underwent surgical resection. Correlations between PGT expression level and clinicopathological factors were statistically analyzed. Angiogenesis in the tumor tissue was evaluated by counting the number of microvessels. The role of PGT in mRNA and protein expression of vascular endothelial growth factor (VEGF) was examined in gastric cancer cells stimulated by PGE2 . Based on multivariate and Kaplan-Meier analyses, negativity for PGT expression was an independent poor prognostic factor. There were more microvessels in PGT-negative tumors than in PGT-positive tumors. Transfection of AGS and MKN7 gastric cancer cells with PGT-specific siRNA led to increased VEGF mRNA and protein expression accompanied by increased PGE2 in the culture media. PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.

Clinical significance of GRHL3 expression in diffuse large B cell lymphoma.

In the present study, we assessed the GRHL3 expression in 967 patients with diffuse large B cell lymphomas to identify the potential prognostic value and the development of specific therapeutic strategies. All patients enrolled were from a previous study by Hao Zhang et al. (BMC Cancer 14:333, 2014). GRHL3 expression status was evaluated by immunohistochemical analysis. Survival analysis using the Kaplan-Meier method and multivariate analysis were conducted to adjust the effect of GRHL3 expression as a potential independent prognostic factor. In the enrolled 967 patients, GRHL3 expression was detected in 398 (41.16%) patients under immunohistochemical analysis. The 5-year survival rate in patients with GRHL3 expression was significantly lower than that in those without GRHL3 expression (37.8 vs 52.8%, P < 0.001). Multivariate analysis identified GRHL3 expression as an independent predictor of poor survival. The sensitivity and specificity of GRHL3 for the diagnosis of germinal center B cell (GCB)/non-GCB was 89.2% (182/204) and 82.1% (174/212), respectively. GRHL3 expression may be useful as a prognostic factor and for the diagnosis GCB/non-GCB of diffuse large B cell lymphoma.

Induction therapy followed by surgical resection in Stage-III thimic epithelial tumors: Long-term results from a multicentre analysis of 108 cases

IntroductionSo far no specific oncological strategies have been validated for locally-advanced epithelial thymic tumors (TETs). We herein report the long-term results of a large multicentric experience adopting a multimodal treatment. MethodsFrom 01/1990 to 12/2010, the clinical data of 108 Masaoka Stage-III TETs patients surgically treated after induction therapy (IT) were retrospectively reviewed. Different IT-regimens were administered: ADOC (32pts); PAC (38pts); CEE (38pts). Radiotherapy was concurrently used in 5 patients only. The end-points of the study were the evaluation of: (1) resectability; (2) overall long-term survival (LTS) and disease-free survival (DFS); and (3) independent prognostic factors. The Mann–Whitney and Fisher’s exact tests were applied to test the associations. Survival analysis was performed by the Kaplan–Meier method and log-rank test. ResultsMean age and male/female ratio were 51±13 years and 61/47, respectively. World Health Organization (WHO) histotype was: A in 6pts (5.6%), AB in 18 (16.7%), B1 in 15 (13.9%), B2 in 26 (24.1%), B3 in 23 (21.3%), and thymic carcinoma in 20 (18.5%). Thirty-day mortality was 1.8%. A total of 81 (75%) had R0-resection, 11 (10.2%) R1 and 16 (14.8%) R2-resection. Adjuvant therapy was performed in 71 patients. During the follow-up a relapse of disease was observed in 38pts(35.2%). Five-years DFS and LTS were 69.3% and 79.3%, respectively. At univariate analysis, WHO-type B3/C (“high-risk”) TETs (p=0.001) and recurrence of disease (p=0.02) were predictors of poor LTS while only a slight correlation was found for R-status and “CHT-regimen type” (p=0.097 and p=0.067, respectively). At multivariate analysis WHO “high-risk” TETs (H.R.5.73;C.I.:1.77–18.57) and ADOC-regimen (H.R.2.84;C.I.:1.37–5.86) were independent predictors of poor survival. ConclusionsA multimodal treatment for Stage-III thymic tumors may achieve a rewarding survival. WHO-Histology seems to be the most important prognostic factor.

The role of fPSA, [-2]proPSA and the Prostate Health Index for the early prediction of outcome in patients with metastatic castration resistant prostate cancer on therapy with abirateroneacetate.

241 Background: Abiraterone acetate (AA) prolongs overall survival (OS) in pre- and post-chemotherapy setting in patients with metastatic castration resistant prostate cancer (mCRPC). Biomarkers to predict response to therapy are limited. Prostate-specific antigen (PSA) and lactate dehydrogenase (LDH) are commonly used as response-indicators but are often misleading during early therapy. Assays for circulating tumor cells, which can be surrogate for poor survival, are not routinely available at most places. In this retrospective study we evaluated the role of the PSA-derivatives free PSA (fPSA), [-2]proPSA (p2PSA) and the prostate health index (PHI) in addition to PSA as indicators of response during early AA-therapy. Methods: Twenty-five men with mCRPC receiving AA between March 2012 and July 2015 at the University Hospital of Muenster were included and analyzed. The PSA response rate (RR) was monitored according to PCWG2-criteria. Dynamic PSA-, fPSA-, p2PSA- and PHI-changes at 8-12 weeks under therapy were analyzed as predictors of progression free survival (PFS) and OS using Kaplan-Meier-analysis (KMA) and uni- and multivariate cox-regression analysis (UVA and MVA). Results: Twenty men were chemotherapy naïve, 5 pretreated with docetaxel. The PSA RR was 44%. In patients with &lt; or ≥ 12 months of PFS the relative change of median PSA and fPSA at 8-12 weeks compared to baseline differed significantly (p = 0.022 and 0.030). For men with ≤ or &gt; 15 months of OS there was a trend for a difference in relative change of median fPSA (p = 0.058). In KMA declining fPSA at 8-12 weeks was associated with a median OS of 32 months compared to 21 months in men with rising fPSA. In UVA rising PSA and fPSA were non-significant predictors of poor OS (Hazard ratio (HR) = 1.3 and 2.5 (p = 0.717 and 0.159)). In MVA PSA and fPSA were independent predictors of poor survival (HR 6.7 and 12.8 (p = 0.050 and 0.012)). Conclusions: fPSA is easily available and cheap. When added to PSA information, change of fPSA at 8-12 weeks of AA therapy may be a promising therapy control marker to help physicians to make decisions weather to stop or to continue AA therapy in men with mCRPC.