Lower Overall Survival Rate Research Articles

Comparative analysis of radiofrequency ablation and resection for resectable colorectal liver metastases

To evaluate the therapeutic efficacy of radiofrequency ablation (RFA) for resectable colorectal liver metastases (CRLM) compared with that of resection. Between June 2004 and June 2009, we retrospectively analyzed 29 patients with resectable CRLMs; 17 patients underwent RFA, and 12 underwent hepatic resection. All of the patients were informed about the treatment modalities and were allowed to choose either of them. RFA including an intraoperative approach was performed by a radiologist; otherwise, hepatic resection was performed by a surgeon. Comparative analysis of the two groups was performed, including comparisons of gender, age, and clinical outcomes, such as primary tumor stage and survival rates. The mean tumor size was significantly larger in the resection group (3.59 cm vs 2.02 cm, P < 0.01), and the 5-year overall survival (OS) rate for all patients was 44.7%. There was no difference in the 5-year OS rates between the RFA and resection groups (37.8% vs 66.7%). Univariate analysis indicated significantly lower 5-year OS rates for patients with a tumor size > 3 cm. The 5-year disease-free survival (DFS) rates were 17.6% and 22.2% in the RFA and resection groups, respectively (P = 0.119). Univariate analysis revealed that in cases of male gender, age > 65 years, T stage < IV, absence of lymphatic metastasis, and tumor size > 3 cm, RFA resulted in significantly inferior 5-year DFS rates compared with surgical resection. Surgical resection revealed superior outcomes in the treatment of resectable CRLMs, particularly in cases with a hepatic tumor size > 3 cm.

Aldehyde Dehydrogenase 1 Expression in Inflammatory Breast Cancer as Measured by Immunohistochemical Staining

BackgroundInflammatory breast cancer (IBC) is a rare but aggressive type of breast carcinoma. Despite multimodality approaches, the clinical outcome of patients with IBC remains poor. Tumors arising from cancer stem cells (CSCs) are associated with drug resistance, tumor recurrence, and poor prognosis. This study aimed to evaluate expression of aldehyde dehydrogenase 1 (ALDH1), a putative stem cell marker, in IBC tumors. Materials and MethodsTissue microarrays of 74 surgically resected IBC tumors were immunohistochemically stained for ALDH1. The results were correlated with clinicopathologic parameters and survival data and were compared with findings published in the literature. ResultsThe median follow-up time of the cohort was 42.1 months, and the 5-year overall survival (OS) rate was 46%. Twenty-four tumors (32%) were positive for ALDH1 staining. However, ALDH1 expression was not significantly associated with clinicopathologic variables, including lymph node status, tumor grade, and the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Log-rank testing found that ALDH1 expression was not significantly associated with the OS rate, although there was a trend toward an association with lower OS rate (P = .07). The findings were consistent with some of the published data, but substantial inconsistency among reports was noted. ConclusionIn this IBC cohort, no significant correlation between ALDH1 expression and prognosis or other clinicopathologic variables was found. Although sample size and selection criteria may be contributory factors, inconsistent results reported in the literature raise concern regarding the reliability of immunohistochemically identified ALDH1 as a sole marker of breast CSCs. Further study is required to elucidate the significance of CSCs in IBC biology.

Prognostic Impact Of MLL5 transcript Levels On Outcome Of Patients With Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study

BackgroundThe MLL5 gene encodes a histone methyltransferase implicated in positive control of several genes related to hematopoiesis. Its close relationship with retinoic acid–induced granulopoiesis suggests that the deregulated expression of MLL5 might lead acute promyelocytic leukemia (APL) blasts to become less susceptible to differentiation-inducing ATRA effects. Here, we retrospectively determined the MLL5 transcript levels in samples from APL patients enrolled in the International Consortium on Acute Promyelocytic Leukemia (IC-APL) trial and analyzed its relationship with clinical and laboratory features, hematologic recovery, relapse, and survival. The results of the IC-APL have been previously reported (Blood 2013, 121(11) pp: 1935). In brief, complete hematological remission (CR) was achieved by 153/180 patients enrolled in Brazil, Mexico, Chile and Uruguay and after a median follow up of 28 months, the 2-year cumulative incidence of relapse (CIR), overall survival (OS) and disease-free survival (DFS) were 4.5%, 80% and 91%, respectively.Design and MethodsOne hundred and twenty-one APL patients (age, 15-73y) from seven different Brazilian institutions and treated according to the IC-APL protocol were included. The treatment schedule was identical to that adopted in the PETHEMA/HOVON LPA2005 trial, except for the replacement of idarubicin by daunorubicin. ATRA treatment was initiated immediately in all cases in which the diagnosis of APL was suspected based on morphology. As normal controls, total bone marrow (BM, n=8) and peripheral blood (PB, n=101) cells from healthy donors (age, 18-60y) were collected and mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation. Additionally, 28 CBF-leukemia samples were included. Gene expression profile was analyzed by real-time quantitative PCR using the ABL FusionQuant Standard Kit as an endogenous control. Based on the continuous distribution of MLL5/ABL expression on APL samples (Figure 1), we adopted the median value of MLL5/ABL expression as cut-off to dichotomize APL patients in “low” and “high” MLL5 transcript levels.ResultsMLL5 expression was not different between APL, CBF-leukemia and healthy donors samples (Figure 1; P=0.19). There was no relevant difference between APL patients with low (n=62) and high (n=59) MLL5 transcript levels with respect to clinical and laboratory features, although high MLL5 transcript levels were more likely to be present in female gender (P=0.029). Overall, 102 (84%) achieved CR. Patients with low MLL5 transcript levels had significantly lower CR rate than patients with high MLL5 transcript levels (74% vs 95%; P=0.002). Twelve patients (10%) experienced early mortality (i.e., death during induction therapy) due to hemorrhage (n=6; 50%), disease progression (n=1; 8.3%), thrombosis (n=1; 8.3%), therapy-related infection (n=3; 25%) and differentiation syndrome (n=1; 8.3%); MLL5 transcript levels had no impact on early mortality (P=0.155). With a follow-up of 33 months among survivors (range, 1-72 months), patients with low MLL5 transcript levels had significantly lower 2-year OS (P=0.005) and 2-year DFS rate (P=0.037) than patients with high MLL5 transcript levels. Up to January 2013, a total of six relapses (5%) had been recorded. The 2-year CIR among patients with low and high MLL5 transcript levels was 14% (95%CI: 5% to 27%) and 2% (95%CI: 0.1% to 11%), respectively (P=0.04). We have further evaluated the prognostic impact of MLL5 transcript levels in those patients who remain alive after induction therapy (107 patients). Low MLL5 transcript levels were predictive of lower CR rate (P=0.042) and 2-year OS rate (P=0.009), but had no impact on DFS (P=0.106).ConclusionOur results show that MLL5 transcript levels may predict lower remission rate, short survival and higher risk of relapse in APL patients treated with ATRA and anthracycline-based chemotherapy. This is the first report describing the MLL5 expression as a prognostic factor in APL; nevertheless, our results should be confirmed in an independent cohort. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Low WT1 Expression At Diagnosis Is a Strong Predictor On Poor Outcome In Patients With t(8;21) Acute Myeloid Leukemia

IntroductionAcute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. The dynamic patterns of AML1-ETO transcript levels during treatment and clinical outcome of patients vary greatly. Our AML05 trial revealed that minimal residual disease (MRD)status and treatment strategy were independent risk factors for outcome and that risk stratification treatment directed by MRD may improve the outcome of t(8;21) AML in CR1 (Blood 2013; 121:4056). As for pretreatment parameters, c-KIT mutation is a well-established adverse predictor on survival. However, a subset of t (8;21) AML patients without c-KIT mutation still showed poor clinical outcome. The prognostic value of WT1 transcript levels at diagnosis in AML has been investigated and the results were controversial. We wondered if WT1 expression associated with outcome in t (8;21) AML patients. MethodsA total of 101 patients were included. They all were eligible cases who enrolled into AML05 trial from June 2005 to December 2012, and had available bone marrow samples at diagnosis. After 1 or 2 induction therapy and 2 cycles of intermediate-dose cytarabine-based consolidation therapy, fifty-seven patients continued cytarabine-based consolidation chemotherapy or received autologous-hematopoietic stem-cell transplantation (auto-SCT) and were defined as CT group, the remaining 44 patients received allogeneic SCT (allo-SCT) and defined as SCT group.WT1 and ABL transcript were tested by real time quantitative PCR, and WT1 transcript levels were calculated as WT1copies/ABL copies in percentage. The upper limit of normal bone marrows (NBMs) was 0.5%. c-KIT mutations in exon 8 and 17 were screened by direct sequencing. ResultsThe median follow-up time was 25 (6-93) months for 73 alive patients. The cumulative incidence of relapse (CIR) at 3 years was 35.3%. The 3-year disease free survival (DFS) and overall survival (OS) rates were 57.2% and 62.8%, respectively. The median WT1 transcript levelsssof all patients were 9.1% (0.02%-99.3%). c-KIT mutation was detected in 31 patients. Receiver operating characteristics (ROC) curves revealed that WT1 transcript levels of 5.0% (1-log increase compared to the upper limit of NBM) were the best cutoff values to discriminate patients with different outcome. WT1 transcript levels of ≤5.0% were significantly associated with c-KIT mutation (23/42 vs 8/59, P<0.001), but didn't related to other pretreatment parameters (all P>0.05). In CT group, patients with WT1≤5% (n=19) had significantly higher CIR rate at 3-year, lower 3-year DFS and OS rate than those with WT1>5% (n=38), respectively (89.5% vs 27.9%, P<0.0001; 10.5% vs 66.1%, P<0.0001; 28.5% vs 66.5%, P=0.0062). Furthermore, patients with WT1≤5% and c-KIT mutation (-) had similar CIR, DFS and OS rate to both patients with WT1≤5% and c-KIT mutation (+) and patients with WT1>5% and c-KIT mutation (+) (all P >0.05, Figure 1). Therefore, they were merged into one group (n=24). Thus, patients with WT1≤5% and/or KIT mutation (+) had significantly higher CIR rate at 3-year, lower 3-year DFS and OS rate than those with WT1>5% and c-KIT mutation (-) (n=33) in CT group, respectively (89.4% vs 27.4%,P<0.0001; 10.6% vs 72.6%, P<0.0001; 26.1% vs 72.2%, P=0.0013). For patients ith WT1≤5%, allo-SCT significantly lowered CIR rate at 3-year, improved 3-year DFS rate and tended to improve OS rate compared to chemotherapy/auto-SCT by landmark analysis, respectively (11.5% vs 88.2%, P<0.0001; 65.4% vs 11.8%, P=0.0001; 60.6% vs 32.6%, P=0.10. Figure 2). Multivariate analysis revealed that WT1 transcript levels (≤5% vs >5%) and treatment (chemotherapy/auto SCT vs allo-SCT) instead of other pretreatment parameters were independent prognostic factors for relapse (hazard ratio (HR) 0.20, 95% CI 0.093¨C0.44; 0.096, 95% CI 0.033¨C0.28. all P<0.0001) , DFS (HR 0.22, 95% CI 0.11¨C0.44; 0.23, 95% CI 0.11¨C0.49. all P<0.0001) and OS (HR 0.30, 95% CI 0.14¨C0.66, P=0.003; 0.37, 95% CI0.16¨C0.82, P=0.014).▪▪ ConclusionLess than 1-log increase of WT1 transcript levels at diagnosis is a strong predictor on poor outcome in patients with t (8;21) AML, and allo-SCT could significantly improve outcome of such patients. Grant SupportBejing Municipal Science & Technology Commission(Z111107067311070) and Nature Science Foundation of China (81170483). Disclosures:No relevant conflicts of interest to declare.

Long‐term prognosis of childhood acute promyelocytic leukaemia with arsenic trioxide administration in induction and consolidation chemotherapy phases: a single‐centre experience

The efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (As2 O3 ) as induction therapy for adult acute promyelocytic leukaemia (APL) has been documented in several clinical trials. However, the role of ATRA/As2 O3 combination in induction and consolidation therapy in children remains unclear. Here, we report the efficacy of combined treatment with As2 O3 and ATRA as induction and consolidation chemotherapy to treat newly diagnosed childhood APL. From 1998 to 2011, 43 children with newly diagnosed APL received induction and consolidation chemotherapy with ATRA and As2 O3 (Protocol B). Rates of complete remission (CR), event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) and drug toxicity were compared between children treated with Protocol B and 25 others treated previously with ATRA alone as induction chemotherapy (Protocol A). Of 43 patients treated with Protocol B, 41 (95.4%) achieved CR (two died of intracranial haemorrhage on day 10 and 14). In contrast, only 20 (80%) of 25 patients treated with Protocol A achieved CR. Thus, the CR rate was significantly lower in patients receiving induction chemotherapy with Protocol A than in those treated with Protocol B (P = 0.045, χ(2) = 6.508). Of the 41 patients who achieved CR on induction therapy with Protocol B, 40 also received consolidation therapy. Molecular relapse, but no overt morphological relapse, occurred in one patient at 25 months after diagnosis; this patient regained CR status with As2 O3 treatment. With a median follow-up period of 75 months, estimated EFS, DFS and OS rates were 92.5 ± 4.2%, 97.1 ± 2.9% and 95.3 ± 3.2%, respectively, for Protocol B. In contrast, with a median follow-up of 127 months, the EFS, DFS and OS rates at 75 months were 70.4 ± 9.4%, 76.4 ± 9.2% and 70.4 ± 9.4%, respectively, for Protocol A. Thus, patients treated with Protocol A showed significantly lower EFS (P = 0.021) and OS (P = 0.007) rates than those treated with Protocol B. Application of As2 O3 and ATRA as induction and consolidation chemotherapy resulted in excellent outcomes and improved long-term prognosis in children with newly diagnosed APL.

Clinical effects of concurrent radiochemotherapy followed by radical surgery and radical radiotherapy with concurrent chemotherapy: a comparative study of 243 patients with FIGO stage IIB cervical cancer

Objective To compare concurrent radiochemotherapy (CRCT) followed by radical surgery and radical radiotherapy (RT) with concurrent weekly cisplatin in terms of survival rates and longterm toxicities in patients with FIGO stage ⅡB cervical cancer.Methods A retrospective analysis was performed on 243 patients with FIGO stage ⅡB cervical cancer who were admitted to our hospital from November 2004 to November 2011.Of the 243 patients,121 patients received CRCT followed by radical surgery (group 1),and 122 received radical RT with concurrent chemotherapy (weekly cisplatin,40 mg/m2) (group 2).The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for survival difference analysis ; the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％ in groups 1 and 2.34 and 33 patients were followed up for at least 3 years in groups 1 and 2.The 3-year progression-free survival (PFS) rates,overall survival (OS) rates,and local control rates for groups 1 and 2 were 91.5％ vs 82.0％ (P =0.013),95.5％ vs 89.2％ (P =0.085),and 96.7％ vs 93.4％ (P =0.375),respectively.In group 1,the patients with a tumor diameter of ≥6 cm and an age of ≤35 years had a significantly lower 3-year PFS rate than those with a tumor diameter of ＜ 6 cm and an ageof＞35 years (68.2％ vs 93.8％,P=0.004;74.1％ vs 93.2％,P=0.037).In group 2,the patients with non-squamous cell carcinoma and a tumor diameter of ≥6 cm had a significantly lower 3-year PFS rate than those with squamous cell carcinoma and a tumor diameter of ＜ 6 cm (50.0％ vs 83.0％,P =0.013 ;25.0％ vs 86.0％,P =0.002).In groups 1 and 2,the patients with a tumor diameter of ≥6 cm had a significantly lower 3-year OS rate than those with a tumor diameter of ＜ 6 cm (78.8％ vs 97.0％,P =0.033 ;46.9％ vs 92.6％,P =0.007).Leg edema occurred more frequently in group 1 than in group 2 (33.1％ vs 8.2％,P=0.000),while radiation enteritis more frequently in group 2 than in group 1 (31.2％ vs 5.0％,P =0.000).Conclusions CRCT followed by radical surgery may lead to better PFS than radical RT with weekly cisplatin in patients with FIGO stage ⅡB cervical cancer.Tumor diameter is the common prognostic factor for PFS in patients who receive the two treatments. Key words: Cervical neoplasms/surgery; Cervical neoplasms/concurrent chemoradiotherapy; Prognosis

Patterns of recurrence and second primary tumors in oral squamous cell carcinoma treated with surgery alone

The aim of the present study is to review the recurrence patterns and incidence of second primary tumors (SPTs) in patients with oral squamous cell carcinoma (OSCC) who underwent surgery alone without postoperative adjuvant therapy. Data on patients recorded in the head and neck cancer registry of Cathay General Hospital were reviewed. A total of 72 patients with T1-3N0 OSCC who underwent surgery alone were included. Among the 72 patients, 44 had T1 tumors, 22 had T2 tumors, and 6 had T3 tumors. The 5-year overall survival (OS) rate was 77.3%, the recurrence-free survival rate was 74.1%, and the SPT-free survival rate was 73%. Eighteen (25%) patients had disease recurrence (regional recurrence in nine patients, local recurrence in seven patients, and locoregional recurrence in two patients). Most patients with local recurrence alone (6/7 patients, 85.7%) could be salvaged with treatment. However, locoregional control was obtained in only five (45.5%) of 11 patients with neck recurrence after surgical salvage therapy. At the time of analysis, 20 patients developed SPTs, and 15 (75%) of the SPTs were in the oral cavity. The annual incidence of SPT was 5%. Neck recurrence and SPT were associated with 48.4% and 24.4% lower 5-year OS rates, respectively. Multivariate analysis revealed that neck recurrence was a significant risk factor for low OS (p = 0.008). Neck recurrence was the most important prognostic factor for OS. The incidence of SPT development was high. Regular and long-term monitoring for recurrence and development of SPTs is necessary to improve the survival rate.

Clinical analysis and prognostic significance of hepatitis B virus infections for diffuse large B-cell lymphoma with or without rituximab therapy

The aim of this study was to analyze the clinical features of hepatitis B surface antigen (HBsAg)-positive and negative diffuse large B-cell lymphomas (DLBCLs) and to compare the outcomes and serum hepatitis B virus (HBV)-DNA loads of patients treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimens with rituximab (RCHOP) or without. A total of 451 DLBCL patients, of which 90 were HBsAg-positive and 361 were HBsAg-negative, were retrospectively reviewed. We compared onset age, gender, Ann Arbor stage, international prognostic index (IPI), lactate dehydrogenase (LDH) and β2-microglobulin (β2-M) levels, as well as overall survival (OS) rates and HBV-DNA loads under CHOP or RCHOP regimens. The OS rate of the HBsAg-positive DLBCL patients was significantly lower than that of HBsAg-negative DLBCL patients and the HBsAg-positive DLBCL patients had an earlier median onset age. HBsAg-positive DLBCL patients had poorer OS rates compared with HBsAg-negative patients (62.2% HBsAg-positive vs. 76.2% HBsAg-negative, P=0.018). HBsAg-positive DLBCL patients with HBV-DNA loads >103 cps/ml during chemotherapy had significantly lower OS rates than those with lower HBV-DNA loads (48.4% HBV-DNA elevated vs. 71.2% HBV-DNA normal, P=0.037). HBsAg-positive DLBCL patients treated with RCHOP had a significantly higher OS rate (79.6%) compared with the 41 CHOP-treated patients (43.9%; P<0.001). HBsAg-positive DLBCL patients with an earlier median onset age and elevated HBV-DNA during chemotherapy had poorer prognoses. HBsAg and HBV-DNA during chemotherapy may be used as prognostic indicators for patients with DLBCL. Rituximab improves the outcome of HBsAg-positive DLBCL patients when administered in combination with anti-viral lamivudine.

Abstract 3472: Excision repair cross complementing group 1 (ERCC1) and regulatory subunit of Ribonucleotide Reductase (RRM1) as prognostic and predictive markers for ovarian cancer.

Abstract Background: Ninety percent of ovarian cancers are epithelial in nature (EOC); the standard approach for treatment is surgery followed by platinum and taxane based chemotherapy. Gemcitabine has been evaluated recently in combination with platinum and taxane for platinum sensitive recurrence and as a single agent for platinum refractory or resistant recurrent EOC. ERCC1 and RRM1 are involved in DNA synthesis and repair derived from genotoxic stress, and they have also been reported as predictive markers for therapeutic efficacy in patients with lung and pancreatic cancers. Their expression, association and clinical significance in ovarian carcinoma remain uncertain. Design: 198 archived cases of epithelial cell ovarian cancer were reviewed and divided into three subtypes: borderline tumor (BLT), Type I and Type II. 2mm TMAs were developed with duplicate cores per case. Immunofluorescence combined with Automated Quantitative Analysis (AQUA) was used to assess the expression of ERCC1 and RRM1. The average of duplicate cores was used for analysis and Greedy search was used for establishing the high and low score cutoff points. Results: 44 cases (22%) were BLT, 29 (15%) were Type I tumors, 121 (61%) were Type II tumors, and 4 cases (4%) were unclassified. Type II tumors were significantly higher among elderly Caucasian women (p&amp;lt;0.001) as compared to African American women. Kaplan Meier curves showed no statistically significant difference in overall survival (OS) between Type I and Type II cancers. Low ERCC1 scores were significantly associated with lower OS rates (hazard ratio (HR) = 1.46), when compared with high ERCC1 scores. In contrast, low RRM1 scores were associated with better overall survival (HR = 0.36). Scores for both markers were not significantly associated with tumor type, histology grade or stage. On multivariate analysis including ERCC1, RRM1, tumor stage, tumor type, age and race; only age and tumor type (BLT I&amp;II) persisted as independent prognostic factors for poor overall survival. Conclusion: Our study suggests that low expression of ERCC1 and high expression of RRM1 are associated with poor survival in ovarian cancer patients. Large studies are warranted to elucidate whether or not the expression of ERCC1 and RRM1 can be used as prognostic or predictive markers. Citation Format: Jun Zhou, Quratulain Ahmed, Wei Chen, Xin Li, Robert Morris, Rouba Ali-Fehmi, Gerold Bepler. Excision repair cross complementing group 1 (ERCC1) and regulatory subunit of Ribonucleotide Reductase (RRM1) as prognostic and predictive markers for ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3472. doi:10.1158/1538-7445.AM2013-3472

1430 PRE-CYSTECTOMY SERUM CARBOHYDRATE ANTIGEN 19-9, CARBOHYDRATE ANTIGEN 125, AND CARCINOEMBRYONIC ANTIGEN: PROGNOSTIC VALUE IN UROTHELIAL CARCINOMA OF BLADDER

You have accessJournal of UrologyBladder Cancer: Invasive (I)1 Apr 20131430 PRE-CYSTECTOMY SERUM CARBOHYDRATE ANTIGEN 19-9, CARBOHYDRATE ANTIGEN 125, AND CARCINOEMBRYONIC ANTIGEN: PROGNOSTIC VALUE IN UROTHELIAL CARCINOMA OF BLADDER Hamed Ahmadi, Hooman Djaladat, Jie Cai, Gus Miranda, and Siamak Daneshmand Hamed AhmadiHamed Ahmadi Los Angeles, CA More articles by this author , Hooman DjaladatHooman Djaladat Los Angeles, CA More articles by this author , Jie CaiJie Cai Los Angeles, CA More articles by this author , Gus MirandaGus Miranda Los Angeles, CA More articles by this author , and Siamak DaneshmandSiamak Daneshmand Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2784AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We present the results of the largest study on prognostic value of pre-cystectomy carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) levels in urothelial carcinoma of bladder (UCB). METHODS From 2004 and 2009, preoperative stored serum samples of 186 patients with UCB who underwent radical cystectomy at USC were randomly selected to measure CA19-9, CA125, and CEA levels. Reference laboratory cut-off point values were used to define abnormal marker levels (CA 19-9>35 U/mL, CA125>35 U/mL, CEA>3.8 U/mL). Pathologic stage was categorized as organ confined (OC) (pT1, pT2), extravesical (EV) (>pT2), and lymph node positive (LN+) UCB. Cox regression model was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). RESULTS The mean age of patients were 70 years (ranges, 36-91) and the median follow-up was 4 years (ranges, 0.1?7.2 years). 94 (50.5%) patients had OC, 45 (24%) had EV, and 47 (25.5%) had LN+ UCB. The mean CA 19-9, CA125, and CEA levels were14 (0.6?278) U/mL, 11.8 (3?79) U/mL, and 2.3 (0.3?30) ng/mL. 30/186 (16%) patients had at least one abnormal marker. 4-year RFS and OS were 66% and 65%, respectively. After controlling for pathologic T stage, pathologic nodal status, age, and adjuvant chemotherapy; Abnormal CA19-9 and CEA were independent predictors of worse 4-year OS (HR: 2.7; P=0.04 and HR: 2; P=0.03). (Figure1A) Abnormal CA 19-9 was also an independent predictor of worse 5-year RFS (HR: 2.8; P=0.05). (Figure1B) Pre-cystectomy CA 125 level had no correlation with oncological outcome. CONCLUSIONS In patients with UCB, abnormal precystectomy serum CA19-9 is an independent predictor of worse oncological outcome. Abnormal precystectomy CEA may also predict lower OS rate. However, precystectomy CA 125 showed no significant predictive value regarding oncological outcome. Prospective studies are encouraged to elucidate the clinical value of these serum markers. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e586 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hamed Ahmadi Los Angeles, CA More articles by this author Hooman Djaladat Los Angeles, CA More articles by this author Jie Cai Los Angeles, CA More articles by this author Gus Miranda Los Angeles, CA More articles by this author Siamak Daneshmand Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Non metastatic cell protein 1 expression and clinical significance in prostate cancer

Objective To explore the role of non metastatic cell protein 1 (NME1) in diagnosing prostate cancer (PCa) and judging early metastasis of PCa.Methods The gene chip was used to screen NME1 in PCa and benign prostatic hyperplasia (BPH) tissues,the differential expression of NME1 prostein in PCa and adjacent tissues was analyzed by using fluorescence 2-D difference gel electrophoresis (2DDIGE) technology,and validated by using immunohistochemistry (IHC).The NME1 IHC score and clinicopathological parameters of PCa patients were analyzed.Results Relative to BPH tissues the expression of NME1 was down-regulated in PCa tissues by gene chip screening (P ＜ 0.01),and relative to adjacent tissues the same phenomenon was observed in PCa tissues by using 3D-DIGE technology (P ＜0.01).The expression of NME1 was negatively correlated with serum PSA levels (P ＜ 0.05),Gleason score (P ＜0.01) and TNM stage (P ＜ 0.05),positively correlated with metastasis (P ＜ 0.01),but not correlated with age (P ＞ 0.05).NME1-positive PCa patients had a lower overall survival rate (Log Rank =11.117,P ＜0.01),but there was no significant difference in biochemical recurrence rate between NMEl-negative and NMEl-positive PCa patients (Log Rank =0.247,P ＞ 0.05).Conclusion The low expression of NME1 is closely related with the malignancy of PCa,and the loss of NME1 may promote tumor cell growth.Serum PSA levels in combination with NME1 levels can be used to diagnose PCa early and judge the degree of the malignancy of PCa.The high expression of NME1 may promote PCa metastasis. Key words: Non metastatic cell protein 1 gene; Prostate carcinoma; Diagnosis

Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years

To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients. We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2007 in our center. Patients were categorized into three groups: younger group (age < 50 years), middle-aged group (50-69 years), and elderly group (≥ 70 years). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The log-rank test was used to assess statistical differences between curves. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of age on survival at each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. We analyzed the potential prognostic factors for patients aged ≥ 70 years. Finally, the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated. In the elderly group, there was a male predominance. At the same time, cancers of the upper third of the stomach, differentiated type, and less-invasive surgery were more common than in the younger or middle-aged groups. Elderly patients were more likely to have advanced tumor-node-metastasis (TNM) stage and larger tumors, but less likely to have distant metastasis. Although 5-year overall survival (OS) rate specific to gastric cancer was not significantly different among the three groups, elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients (elderly vs middle-aged vs younger patients = 22.0% vs 36.6% vs 38.0%, respectively). In the TNM-stratified analysis, the differences in OS were only observed in patients with II and III tumors. In multivariate analysis, only surgical margin status, pT4, lymph node metastasis, M1 and sex were independent prognostic factors for elderly patients. The 5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection, and these patients benefited little from chemotherapy. Age ≥ 70 years was an independent prognostic factor for gastric cancer after gastrectomy. D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.

Tumor size as a prognostic factor in patients with node-negative gastric cancer invading the muscularis propria and subserosa (pT2-3N0M0 stage).

To explore the impact of tumor size on outcomes in patients with pT2-3N0M0 stage. ROC curve analysis was used to determine the appropriate cut-off value for tumor size in 115 patients of pT2-3N0M0 stage gastric cancer. Based on this cut-off value, patients were divided into two groups. The five-year overall survival (OS) rates in the two groups were compared according to the independent prognostic factors. Using this cut-off value of 3.7cm, 62 patients had large-sized tumors (LSTs, tumor size >3.7cm) and 53 had small-sized tumors (SSTs, tumor size <3.7cm). Patients with LSTs had a significantly lower five-year OS rate than those with SSTs (60.7% vs. 88.4%, p=0.000). Depth of tumor invasion, histological type and tumor size were independent prognostic factors. In patients with pT2N0M0 stage tumors or pT2-3N0M0 stage patients with undifferentiated type tumors, five-year OS rates were significantly lower for LSTs than for SSTs (p<0.05 each). Tumor size is a prognostic factor in patients with pT2-3N0M0 stage. Especially for pT2N0M0 stage gastric cancer and pT2-3N0M0 stage gastric cancer with undifferentiated type tumors, the prognosis was poorer in patients with tumor size >3.7cm than that in patients with tumor size <3.7cm.

Detection of circulating tumor cells in peripheral blood of colorectal cancer patients without distant organ metastases

Recently, the detection of circulating tumor cells (CTCs) in peripheral blood has become an important tool for the non-invasive assessment of micrometastases and to predict clinical outcome. The objective of this study was to investigate if the presence of CTCs in peripheral blood influences the prognosis in colorectal cancer (CRC) patients without distant organ metastases. The GCC mRNA and CK20 mRNA levels in peripheral blood and the serum levels of CEA of 92 CRC patients without distant organ metastasis were analyzed by quantitative RT-PCR and ELISA, respectively. Its associations with overall survival (OS) and disease-free survival (DFS) rates were analyzed. Univariate analyses showed that lower OS and DFS rates were significantly associated with GCC and CK20 mRNA levels, the presence of lymph node metastases, the presence of mesenteric root lymph node metastases, and the presence of tumor emboli in vessels (p < 0.05), but not with CEA levels. Multivariate analyses showed a significant association between 1) OS and GCC mRNA levels and differentiation types and 2) DFS and the presence of tumor emboli in the vessels. Kaplan-Meier curves showed that DFS was significantly associated with the presence of poorly differentiated cells, the presence of mesenteric root lymph node metastases having received prior chemotherapy, and the presence of tumor emboli in vessels. The detection of CTCs in peripheral blood may be useful for the prediction of clinical outcome in CRC patients without distant organ metastases.

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% ± 9.4% vs. 35.4% ± 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33-5.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms.

Preliminary clinical outcome in patients with glioblastoma treated with precise radiotherapy plus concomitant temozolomide

Objective To investigate the clinical outcomes and toxicity for patients with glioblastoma multiforme (GBM) who underwent precise radiotherapy combined with temozolomide (TMZ).Methods The records of 54 patients with newly - diagnosed GBM from July 2009 to December 2010 were reviewed.The patients underwent postoperative intensity - modulated radiotherapy (IMRT) or three -dimensional conformal radiotherapy (3D -CRT) with concurrent and adjuvant TMZ.Results The median follow - up was 13 months.Of the 54 patients,50 completed the combined modality treatment.The overall survival rate was significantly different between patients with good performance status( KPS ≥70) and those with worse performance status ( KPS ＜ 70) ( 86.8％ VS.50.8％,P =O.005 ).Patients who underwent partial resection had lower overall survival rate compared with those who underwent total resection,but no reach statistically significant (84.4％ vs.70.5％,P =0.067).The pattern of failure was predominandy local. Grade 3 -4 toxicity was limited to 2 patient with leukopenia during concurrent chemoradiotherapy.Conclusions These results indicate that precise radiotherapy combined with TMZ is effective and safe treatment for GBM patients. Performance status and extent of surgery were prognostic factors for overall survival. Key words: Glioblastoma, multiforme; Three -dimensional conformal radiotherpy; Intensity -modulated radiotherapy; Temozolomide

Adjuvant postoperative radiochemotherapy for patients with gastric carcinoma: a single institution experience

The suboptimal outcome after surgery alone for gastric cancer indicated the necessity of adjuvant treatment for potentially resectable carcinoma of the stomach. In 2001, postoperative adjuvant radiochemotherapy started to be implemented in the NCI, Cairo, Egypt. However, the fear of the acute complication hindered its use as a standard treatment with some staff didn’t follow the SWAG’s adjuvant protocol. The aim of this report is to verify this issue. In the period from 1999 to 2009, 320 out of 581 patients with gastric carcinoma, underdid potentially curative surgery. Adjuvant postoperative radiochemotherapy for stage ≥ IIA started since 2001. Radiation (45 Gy, 1.8 Gy/f) was targeted to the tumor bed, anastomosis site, duodenal stump, remnant stomach and regional lymph node together with 4–5 cycles chemotherapy (SWOG protocol). Survival analysis was performed and comparison between survival curves was done to analysis different prognostic factors. The patients’ age ranged from 17 to 86 years [mean (54 ± 12.5) years]. About 1/3 of the patients had a diffuse lesion. Adenocarcinoma was the most common pathology (60.4%). High grade pathology constituted 59.1% of the cases. About one fifth of the patients had metastatic disease at presentation. Only 351 (75%) of the patients had potentially curative gastrectomy. The median number of lymph node (LN) dissected was 12 (ranged from 0–45) with a median number of the positive LN of 3.5 (ranged from 0–40). Postoperative mortality was 12%. The median follow up period was 21.9 months (ranged from 3–129.4 months). For the 257 patients who had curative surgery, 164 (62.8%) patients were alive at the end of follow up. During follow up period, 30 patients had loco-regional relapse, and 26 patients had metastasis, and 39 patients had both pattern of failure. The overall survival (OS), loco-regional control (LRC), and metastasis free survival (MFS) rates, at median follow up period of 22 months, were 61.2%, 66.7% and 71%, respectively. At 3 and 5 years the corresponding values were: OS (42% and 28%), LRC (64% and 50.4%) and MFS (56.3% and 49%), respectively. Only stage and degree of nodal involvement had an adverse effect on all survival rates. Proximal lesion had poor OS rates. As regard LR control rate, mucinous cell type, and high grade had a bad effect. Although patients with less than D1 dissection had low OS and LRC rate, it didn’t reach significant level. There was a significant improved 5-year OS rate for concurrent chemoradiotherapy (CCRTh, 55%) versus no or single adjuvant modality (27%), P = 0.035. A subgroup analysis according to CTH regimen showed a trend for all survival rates with ECF compared to bolus 5FU/LV. However, none was statistically significant. In operable gastric carcinoma, postoperative concomitant radiochemotherapy with 5FU and LV is feasible with acceptable toxicity with a significant increase of locoregional control. A well designed phase III clinical trial — with ECF regimen and conformal radiotherapy — is worth to start to increase local control and decrease toxicity.

The Impact of Diabetes Mellitus on Prognosis of Early Breast Cancer in Asia

Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer-specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer. The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003-2004. DM status and other comorbidities were retrieved from Taiwan's National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan-Meier method. Cox's proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality. In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups. In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.

Optimal therapy for IB2 and IIA2 cervical cancer: surgery or chemoradiotherapy?

Optimal therapy for IB2 and IIA2 cervical cancer: surgery or chemoradiotherapy?

Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach

To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox's proportional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC = 0.795, 95%CI: 0.751-0.839, P = 0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size < 4.8 cm). Tumor size was significantly correlated with histological type (P = 0.039), Borrmann type (P = 0.000), depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.000), tumor-nodes metastasis stage (P = 0.000), mean number of metastatic lymph nodes (P = 0.000) and metastatic lymph node ratio (P = 0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with SSTs (37.1% vs 63.3%, P = 0.000). Univariate analysis showed that depth of tumor invasion (χ² = 69.581, P = 0.000), lymph node metastasis (χ² = 138.815, P = 0.000), tumor size (χ² = 78.184, P = 0.000) and metastatic lymph node ratio (χ² = 139.034, P = 0.000) were significantly associated with 5-year OS rate. Multivariate analysis revealed that depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.019) and tumor size (P = 0.000) were independent prognostic factors. Gastric cancers were divided into 12 subgroups: pT2N0; pT2N1; pT2N2; pT2N3; pT3N0; pT3N1; pT3N2; pT3N3; pT4aN0; pT4aN1; pT4aN2; and pT4aN3. In patients with pT2-3N3 stage tumors and patients with pT4a stage tumors, 5-year OS rates were significantly lower for LSTs than for SSTs (P < 0.05 each), but there were no significant differences in the 5-year OS rates in LST and SST patients with pT2-3N0-2 stage tumors (P > 0.05). Using a tumor size cutoff value of 4.8 cm, tumor size is a prognostic factor in patients with pN3 stage or pT4a stage advanced gastric cancer located in the lower third of the stomach.