Significant Difference In 5-year Overall Survival Research Articles

The impact of operative approaches on outcomes of middle and lower third esophageal squamous cell carcinoma.

The aim of this study was to investigate the perioperative outcomes and 3-year overall survival (OS) of 2 approaches including Sweet and open Ivor Lewis esophagectomy in the surgical treatment of middle and lower third esophageal squamous cell carcinoma. The medical records of 1,746 consecutive patients who underwent esophagectomy for middle and lower esophageal cancer between January 2009 and September 2015 at the First Department of Thoracic Oncologic Surgery of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively reviewed. The clinical variables and 3-year survival were compared between Sweet (n=1,701) and open Ivor Lewis (n=45) approaches in unmatched and propensity score matching analysis. Patients who received esophagectomy by Sweet approach had shorter duration of surgery (mean 212 vs. 390 min; P<0.001), more lymph nodes removed (mean 24 vs. 19; P=0.005), lower overall complications rate (24.4% vs. 11.7%; P=0.009), lower total hospital cost (¥77,200 vs. 106,000; P=0.045) compared with patients who received open Ivor Lewis approach. After propensity score matching analysis, Sweet approach was still associated with decreased duration of surgery (mean 210 vs. 390 min; P<0.001), more lymph nodes removed (mean 24 vs. 19; P=0.050), and lower total hospital cost (¥86,800 vs. 106,000; P=0.045) compared with Ivor Lewis approach. However, there were no significant differences in overall complication rates (24.4% vs. 24.4%; P=1.000) between two approaches. There was no significant difference in 3-year OS between Sweet and open Ivor Lewis approaches (59.9% vs. 61.4%; P=0.637) in unmatched analysis and in matched analysis (77.8% vs. 61.4%; P=0.264). In this cohort, for middle and lower third esophageal squamous cell carcinoma patients, both Sweet and open Ivor Lewis approaches are feasible in terms of perioperative outcomes and 3-year OS.

CXCR4 Overexpression is a Poor Prognostic Factor in Pediatric Acute Myeloid Leukemia With Low Risk: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group.

Overexpression of CXC chemokine receptor 4 (CXCR4+) is a poor prognostic factor in adult acute myeloid leukemia (AML); however, its prognostic significance in pediatric AML is unclear. This retrospective study examined the prognostic significance of CXCR4+ in pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. In the total cohort (n = 248), no significant differences were observed between CXCR4+ patients (n = 81) and CXCR4- patients (n = 167) in terms of 3-year overall survival (OS) (69.4% vs. 75.2%, P = 0.44). However, there was a significant difference in 3-year OS between CXCR4+ and CXCR4- patients in the low-risk (LR) group (n = 93; 79.2% vs. 98.3%, P = 0.007). CXCR4+ patients in the t(8;21) AML without KIT mutation group had a significantly worse 3-year OS than CXCR4- patients (n = 44; 76.1% vs. 100.0%, P = 0.01). Multivariate Cox regression analysis identified CXCR4+ as a poor prognostic factor for OS in LR AML patients (hazard ratio, 11.47; P = 0.01). Consistent with the data for survival analysis, CXCR4+ patients in the t(8;21) AML group had a higher incidence of splenomegaly than CXCR4- patients (25.9% vs. 5.9%, P = 0.03). These results suggest that CXCR4+ is a poor prognostic factor for LR patients, particularly t(8;21) patients without KIT mutation. The poor outcome was only applicable to OS, not relapse-free survival (RFS); thus, CXCR4+ may be associated with a poor prognosis after recurrence. Intensive therapy, including administration of CXCR4 antagonists, may be promising for pediatric AML patients with LR.

Prognostic value of computed tomography texture features in non-small cell lung cancers treated with definitive concomitant chemoradiotherapy.

The aim of this study was to investigate whether the computed tomography (CT) texture features of primary tumors are associated with the overall survival (OS) of non-small cell lung cancer (NSCLC) patients undergoing definitive concomitant chemoradiotherapy (CCRT). In this retrospective study, 98 patients (83 men and 15 women; mean age, 61.9 ± 8.0 years) with unresectable NSCLCs (stage IIIA, 45; stage IIIB, 53) underwent definitive CCRT at our institution from January 2006 to December 2011. Patients were followed up for 3 years or until death. The CT texture parameters of primary tumors were extracted from contrast-enhanced CT images taken before CCRT using an in-house software program. Each texture parameter was dichotomized based on their optimal cutoff values obtained from receiver operating characteristics curve analysis. Three-year OS was compared between the dichotomized subgroups using Kaplan-Meier analysis and the log-rank test. Multivariate Cox regression analysis was performed to determine significant prognostic factors. The 3-year cumulative survival rate was 0.51. The mean 3-year OS was 24.0 months (95% confidence interval, 21.5-26.6 months). There were no significant differences in 3-year OS according to tumor stage or histologic subtypes. However, entropy (P = 0.030), skewness (P = 0.021), and mean attenuation (P = 0.030) were shown to be significantly associated with 3-year OS. Multivariate Cox regression analysis revealed that higher entropy (adjusted hazard ratio [HR],2.31; P = 0.040), higher skewness (adjusted HR,1.92; P = 0.046), and higher mean attenuation (adjusted HR,1.93; P = 0.028) were independent predictors of decreased 3-year OS. Computed tomography texture features have the potential to be used as prognostic biomarkers in unresectable NSCLC patients undergoing definitive CCRT.

Evaluating the fate of patients who undergo resections of very large, node-negative lung cancers using the National Cancer DataBase

To determine whether there are differences in survival associated with different treatment modalities among patients with lymph node-negative, very large non-small-cell lung cancers (NSCLCs). The National Cancer DataBase was used to identify patients diagnosed with NSCLCs >7 cm (T3) without lymph node involvement (N0) or metastatic disease (M0) from 1999 to 2006. Surgical therapy included surgery alone, neoadjuvant chemoradiation therapy or chemotherapy, surgery followed by adjuvant chemoradiation therapy or chemotherapy and surgery followed by postoperative radiation therapy (PORT). The 5-year overall survival (OS) was estimated by the Kaplan-Meier method and comparisons were made using log-rank tests and Cox regression models. Of the 2296 patients identified with cT3N0M0 disease, 45% underwent surgical therapy. The 5-year OS rate was 38%. Across the different treatment regimens, there was a significant difference in 5-year OS. Neither neoadjuvant chemoradiation therapy or chemotherapy nor adjuvant chemoradiation therapy was associated with improved 5-year OS. The use of adjuvant chemotherapy was associated with improved OS relative to surgery alone [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.54-0.91, P = 0.008]. PORT alone was associated with a detrimental effect on 5-year OS relative to surgery alone [HR 2.04; 95% CI 1.38-3.03, P < 0.001]. Large T3N0 NSCLCs appear to be optimally treated with surgical resection followed by adjuvant chemotherapy.

Preoperative serum VEGF-A levels to predict survival for Caucasian and Asian patients undergoing resection for gastric adenocarcinoma.

81 Background: Clinical trials in gastric adenocarcinoma (GC) patients of vascular endothelial growth factor A (VEGF-A) targeted therapies have suggested these therapies may be more effective in Caucasians (CA) than in Asians (AS). Methods: Levels of VEGF-A in serum were measured in CA and AS treated at two institutions prior to potentially curative surgical resection for GC, and levels were correlated with overall survival (OS). Results: There were significant differences in CA (n=118) and AS (n=115) in terms of age (median 66 vs. 59), use of neoadjuvant (52% vs. 14%) and adjuvant therapy (27% vs. 18%), tumor location (58% upper/GE junction vs. 80% distal/middle), Lauren classification (57% vs. 46% intestinal), and TNM status (65% stage II or III vs. 55% stage I). CA had a median VEGF-A levels that was 95% higher than that of AS as well as a much higher standard deviation (88.1 + 6206 vs. 45.2 + 76.3 pg/ml, p&lt;0.001). CA with proximal/nondiffuse tumors had significantly higher VEGF-A levels than those with distal/nondiffuse or diffuse tumors (median 120 vs. 71 and 50 pg/ml; p=0.016). The 5-year OS for CA with low vs. high VEGF-A levels was 72.4% vs. 43.4% (p=0.001). In AS, there was no significant difference in 5-year OS according to VEGF-A level (77.4%% vs.85.6%, p=0.236). On multivariate analysis, tumor size, location, grade, N stage, and serum VEGF-A level were independent predictors of OS in CA. Conclusions: In patients with resectable GC, higher circulating VEGF-A levels are independently associated with decreased OS in CA but AS, suggesting varying importance of this angiogenic factor in GC progression among different races.

IDH1and IDH2 Mutations Confer An Adverse Effect In Patients With Acute Myeloid Leukemia Lacking The NPM1 Mutation

PurposeRecurrent mutations in the genes coding the isocitrate dehydrogenases IDH1 and IDH2 have recently been identified in patients with acute myeloid leukemia (AML). However, the prognostic importance of IDH1 and IDH2 mutations is not consistent among several studies. In the present study, we examined the incidence and prognostic impacts of IDH1 and IDH2 mutations in Japanese adults with AML. Patients and MethodsA total of 233 adults with AML were subjected to the study. Age ranged from 15 to 86 years, with a median of 57.0 years. Patients with aged 69 or less were treated with the protocols of Japan Adult Leukemia Study Group (JALSG). Patients with aged 70 or more were treated with low dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) (Suzushima et al. Leuk Res 2010). DNA was extracted from bone marrow or peripheral blood mononuclear cells of AML patients at diagnosis and subjected to PCR amplification and direct sequencing of the IDH1 and IDH2 genes. NPM1, FLT3 and CEBPA gene mutations were also analyzed. The study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the tenets of the revised Declaration of Helsinki. ResultsIDH1 R132 mutations were detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%; 17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive and were most frequent in the cytogenetic intermediate-risk group. In addition, IDH1 and IDH2 mutations were mutually exclusive with the CEBPA mutation. Moreover, IDH1 and IDH2 mutations were associated with NPM1 mutations. Of 39 patients with IDH mutations, 17 (44%) had the NPM1 mutation, whereas 36 of 194 (19%) lacking an IDH mutation had an NPM1 mutation (P = 0.001). There was no significant correlation of the IDH mutation with FLT3-ITD. Of 226 patients evaluable for treatment outcome, there was no significant difference in 5-year overall survival (OS) between patients with and those without IDH1 mutations (25.1% vs. 29.9%, P = 0.3089). In contrast, 5-year OS rates were significantly lower (6.2%) in patients harboring the IDH2 mutation than in patients lacking the IDH2 mutation (31.5%) in the entire cohort of AML (P = 0.0026). Because IDH1 and IDH2 mutations were associated with NPM1 mutations, we compared OS in patients with and those without IDH1 or IDH2 mutations among patients with and those without NPM1 mutations. Of 51 patients with NPM1 mutations, there was no significant difference in 5-year OS between patients with and those without the IDH1 or IDH2 mutation. In contrast, among 175 patients lacking the NPM1 mutation, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than in those without such mutations (0% vs. 32.4%, P = 0.0023 and 0% vs. 32.6%, P = 0.0001, respectively). Moreover, among patients with the wild-type of NPM1, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than that in those with the CEBPA mutation, FLT3-ITD, or the wild-type of CEBPA, FLT3, IDH1 and IDH2 (P=0.0002). ConclusionsFrequent mutations in IDH1 and IDH2 are also found in Japanese adults with AML. Our data strongly suggest that IDH1 and IDH2 mutations confer adverse prognostic effect in NPM1 wild-type AML. On the other hand, an adverse effect of IDH1 and IDH2 mutations may be negated among patients with NPM1 mutations, because NPM1 mutations generally have a higher complete remission rate and more favorable OS. Disclosures:No relevant conflicts of interest to declare.

Consolidation with High Dose Therapy and Autologous Stem Cell Transplant Improves Survival for Patients with Mantle Cell Lymphoma

Abstract 2006 Background:Mantle cell lymphoma (MCL) comprises 5–7% of all non-Hodgkin lymphomaand remains incurable with conventional chemotherapeutic approaches. Some clinical series and trials suggest that outcomes are improved with intensive induction containing cytarabine (Ara-C) and/or the use of high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) once patients (pts) achieve remission. What is not apparent are the contributions of each and which prognostic factors influence outcomes. We examined our single center experience with initial management strategies for pts diagnosed with MCL between 1995 and 2011 and compared outcomes of CHOP±R (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone), an intensive induction regimen HCVAD±R (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate/cytarabine) in patients who subsequently underwent observation or HDT/ASCT. Methods:To examine the effectiveness of CHOP±R, HCVAD±R and HDT/ASCT, and the contributions of each to overall survival (OS), we conducted an IRB-approved retrospective review of consecutive cases of MCL identified from our database. Responsesfollowing the first management strategy were retrospectively assessed using International Working Group Criteria (JCO 1999). Descriptive statistics for the baseline characteristics of pts who received CHOP±R and HCVAD±R were compared using Chi-square tests. Kaplan–Meier estimation was used to evaluate OS and the treatment regimens were compared with the log-rank test. Toevaluate prognostic factors and the effects of treatment on OS, Cox proportional hazards models were used controlling for sex, race, stage, presence of B-symptoms, MIPI score, and those who underwent consolidation with HDT/ASCT. Results:103 ptswere identified with a median age of 58 (range 32–79 years), 27% were ≥65 years of age, 80% were male, 77% were white, 96% had an ECOG PS ≤1, 93% were advanced stage (III/IV), and the majority had a low risk MIPI score (53%). 43% (N=44) received CHOP±R (mean # of cycles 5.3, median 6, range 1–8) and the remaining 57% received HCVAD±R (N=59, mean # of cycles 4.5, median 4, range 1–12). 65% of HCVAD pts and 27% of CHOP pts received R. No significant differenceswere observed in the baseline characteristics of the two groups: age (59 years CHOP±R vs. 57 HCVAD±R, p=0.06), presence of B symptoms (32% vs. 31%, p=0.77), stage (III/IV, 91% vs. 95%, p=0.69), or MIPI score (low 50% vs. 56%, p=0.97). Of the pts who were consolidated with a transplant (N=47), median age was 58, 85% were male, 32% had B-symptoms, all had an ECOG PS ≤1, 26% had an LDH>ULN, 51% had a low MIPI, and 81% received HCVAD±R as induction. In comparison to those observed, the only significant differences were ECOG PS (8% ≥2, p=0.05) and induction regimen (63% CHOP±R, p<0.001). There were no significant differences in 5-year OS for CHOP±R: 64% (95% CI 44–79%) and HCVAD±R:68% (52–80%). There was a significant difference in 5-year OS for patients who underwent HDT/ASCT vs. those who did not consolidate with transplant (74% vs. 59%, p=0.03). 5-year OS for those treated with HCVAD±R + HDT/ASCT was not significantly different from the rest of the pts74% vs. 61% (p=0.19). After controlling for clinical confounders including sex, race, stage, presence of B-symptoms, consolidation with HDT/ASCT was associated with superior OS (HR 0.46 95% CI 0.22–0.93) while having a high MIPI score was associated with inferior OS (HR 3.79, 95% 1.59–9.01). Conclusions:Our single institution experience for untreated MCL pts demonstrates favorable 5-year OS independent of induction chemotherapy. Patients who underwent consolidation with HDT/ASCT had superior OS compared to those who did not. Disclosures:Flowers:Genentech/Roche (unpaid): Consultancy; Millennium (unpaid): Consultancy; Celgene: Consultancy; Celgene: Research Funding; Spectrum: Research Funding; Millennium: Research Funding; Gilead: Research Funding; Janssen: Research Funding.

Clinical Significance of Mixed Phenotype in Adult Patients with Philadelphia Chromosome-Positive Acute Leukemia–no Prognostic Impact in the Imatinib Era.

Abstract 2574 Background:Mixed phenotype acute leukemia (MPAL) has historically been known as biphenotypic acute leukemia (BAL), and novel diagnostic criteria for this disease entity are described in the World Health Organization (WHO) classification 4th edition. As the most common recurrent genetic abnormality observed in MPAL is the bcr-abl fusion gene, Philadelphia chromosome-positive MPAL (Ph+MPAL) has been recognized as one distinctive disease entity. The prognosis of Ph+B-cell acute lymphoblastic leukemia (Ph+B-ALL) has been dramatically improved with the introduction of imatinib, and the goal of this study was to determine whether imatinib results in a survival benefit in the context of Ph+MPAL. Patients and Methods:We retrospectively analyzed 42 consecutive adult patients who were diagnosed with Ph+AL between January 2001 and March 2012 at Gunma University Hospital and Saiseikai Maebashi Hospital in Gunma, Japan. Ph+AL was diagnosed based on detection of the bcr-abl fusion gene with the polymerase chain reaction method and the presence of more than 20% of blasts in the peripheral blood and/or bone marrow. Patients with a previous history of chronic myelogenous leukemia were excluded. The lineage of leukemia cells was defined according to the WHO classification 4th edition. All patients received intensive chemotherapy and concurrent administration of imatinib. The c2-test was used for comparison of binary variables. The Mann-Whitney U test was used for comparison of continuous variables. Overall survival (OS) rate was estimated by the Kaplan-Meier method and were compared using the log-rank test. P < 0.05 was considered as statistically significant. Results:According to the WHO classification 4th edition, 13 (31%) patients were categorized as Ph+MPAL (positive for both myeloid and B-cell lineage), 27 (64%) patients were categorized as B-cell lineage acute lymphoblastic leukemia (Ph+B-ALL), and two (5%) patients were categorized as acute myeloid leukemia (Ph+AML). Patients with Ph+AML were excluded from this study, as the number of patients was relatively small. Of the 40 Ph+AL patients, 23 patients were men, and 17 were women, and the median age was 53 years (range, 16–75 years). Age, sex, white blood cell counts, lactate dehydrogenase levels, and the prevalence of additional cytogenetic abnormalities at diagnosis were not significantly different when comparing the groups, although patients with Ph+MPAL showed significantly higher frequency of major bcr-abl gene than those with Ph+B-ALL (69% and 19%, respectively; p < 0.01). Immunophenotypic analysis revealed that Ph+MPAL patients expressed CD10 and CD34 with significantly lower frequency than Ph+B-ALL patients. Notably, positivity of myeloid antigens (CD13 and 33) was similar between both groups. The complete response (CR) rates after the initial induction therapy were not significantly different when comparing Ph+MPAL and Ph+B-ALL (100% vs. 85%, respectively, p = 0.14). Likewise, the 5-year-OS rate was similar when comparing patients with Ph+MPAL and Ph+B-ALL (55% vs. 53%, respectively, p = 0.87). Of the 13 patients with Ph+MPAL, six patients received AML-type chemotherapy, and seven patients received ALL-type chemotherapy as the initial induction therapy. All patients achieved CR after the initial induction therapy, and there was no significant difference in 5-year OS according to the therapeutic strategy (AML-type vs. ALL-type), (50% vs. 63%, respectively, p = 0.71). Among 12 patients younger than 65 years old who were alive at >3 months after the diagnosis, eight patients underwent allogeneic hematopoietic stem cell transplantation (allo SCT). The 5-year OS was significantly better for patients who underwent allo-SCT than for those who received chemotherapy alone (58% vs. 20%, respectively, p = 0.05). Conclusion:Among adult Ph+AL patients, mixed phenotype was more frequently observed than expected, and Ph+MPAL patients showed unique clinical features, including immunophenotype and the type of bcr-abl fusion gene. Although BAL has been considered as a negative prognostic factor, Ph+MPAL patients showed comparable prognosis to those with Ph+B-ALL who received imatinib-containing intensive chemotherapy. Therefore, the established theory that mixed phenotype is associated with poor outcomes should be revisited among these patients. Disclosures:No relevant conflicts of interest to declare.

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

Influence of the in situ component in 389 infiltrating ductal breast carcinomas

Our aim was to evaluate and compare lymph node involvement, as well as disease-free survival (DFS) and overall survival (OS), between infiltrating ductal carcinoma with (group 1) and without (group 2) intraductal carcinoma component in order to determine the prognostic value of the intraductal component. Data from 389 cases of infiltrating ductal carcinoma of the breast were included in the study by means of reviewing medical charts and pathology slides. There was no statistically significant difference between both groups regarding node status. The 5-year DFS rate was 90.7% in group 1 and 81.8% in group 2 (p=0.014), with a median follow-up of 73.2months (95% CI 68.3-77.4). There was no statistically significant difference in 5-year OS between groups (98% group 1 vs. 93% group 2) with a median global survival of 134months (95% CI 131-137). The presence of intraductal component in the infiltrating carcinoma seems to increase DFS and may be an independent and favorable prognostic factor for breast cancer.

IDH2 Mutations Have An Unfavorable Impact in Elderly Patients with Acute Myeloid Leukemia

Abstract 2519 Purpose:Recurrent mutations in the genes coding the isocitrate dehydrogenases, IDH1 and IDH2, have recently been demonstrated in patients with acute myeloid leukemia (AML). However, it remains to be determined how frequently IDH1 and IDH2 mutations occur in Asian AML patients and whether IDH1 and IDH2 mutations are associated with clinical profiles and outcome. In this study, we examined the incidence and prognostic impacts of IDH1 and IDH2 mutations in Japanese adults with AML. Patients and Methods:A total of 190 adults with AML were subjected to the study. Age ranged from 15 to 86 years, with a median of 57.0 years. Patients with aged 69 or less were treated with the protocols of Japan Adult Leukemia Study Group (JALSG). Patients aged 70 or more were treated with low dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) (Suzushima et al. Leuk Res 2010). DNA was extracted from bone marrow or peripheral blood mononuclear cells of AML patients at diagnosis and subjected to PCR amplification and direct sequencing of the IDH1 and IDH2 genes. NPM1, FLT3 and CEBPA gene mutations were also analyzed. The study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the tenets of the revised Declaration of Helsinki. Results:IDH1 R132 mutations were detected in 16 patients (8.4%). IDH2 mutations were found in 18 patients (9.5%; 17 with R140 and one with R172). IDH1 and IDH2 mutations had mutually exclusively occurred. IDH1 mutation was associated with higher platelet counts and was more frequent with M1 in FAB classification. IDH2 mutation was associated with ages, lower leukocyte counts and was more frequent with M0. Median age of patients with IDH2 mutation was 63.5 years, while that with wild type was 55.5 years (P=0.036). No IDH2 mutation was observed in patients aged 39 or less. Both IDH1 and IDH2 mutations were most frequent in cytogenetically normal AML and cytogenetic intermediate-risk group. Although IDH1 mutations were not significantly associated with mutations in NPM1 and FLT3, IDH2 mutations were associated with NPM1 mutations. Of 15 IDH2 mutations, 8 (53%) had NPM1 mutation, whereas 26 of 121 (21%) lacking IDH2 mutation had NPM1 mutation (P=0.012). Interestingly, both IDH1 and IDH2 mutations were mutually exclusive with CEBPA mutations. There was no significant difference in 5-year overall survival (OS) between patients with and without IDH1 mutation (32.6% vs. 26.7%, P=0.7377). In contrast, 5-year OS rates were 6.6% for patients harboring IDH2 mutation and 34.5% for patients lacking IDH2 mutation in the entire cohort of AML (P=0.0020). This unfavorable effect was also found in cytogenetically normal AML (P=0.0383). Of patients aged 59 or less, there was no significant difference in 5-year OS between IDH2 mutations (14.3%) and wild-type (43.3%) (P=0.1440). On the other hand, among patients aged 60 or older, 5-year OS rates were 0% for patients carrying IDH2 mutation and 21.6% for patients lacking IDH2 mutation (P=0.0100). Conclusions:Frequent mutations in IDH1 and IDH2 are also found in Japanese adults with AML. Our study indicates that IDH2 mutation has an unfavorable impact on the treatment outcome in adult patients with AML, especially in older (age ≥60 years) patients. These data suggest that IDH2 mutation confer a significant adverse impact on elderly patients with AML. Disclosures:No relevant conflicts of interest to declare.

Prognostic value of serum CA(125) level change during chemotherapy post-surgery in patients with advanced epithelial ovarian carcinoma

To investigate the prognostic value of the changes in serum CA(125) level during chemotherapy post-surgery in patients with advanced epithelial ovarian carcinoma. A retrospective analysis was conducted on 142 patients with stage III - IV epithelial ovarian carcinoma who had primary treatment in the Cancer Center of the Sun Yat-sen University during January 1998 to December 2003. The changes in CA(125) levels during chemotherapy post-surgery in patients were analyzed. The survival outcomes of patients with various levels of CA(125) were studied using Kaplan-Meier method. Multivariate Cox regression model was used to assess the correlations between survival and the change in CA(125) level during chemotherapy and other prognostic factors. The 3-year overall survival (OS) was 64%, 71%, and 64% respectively in patients with different pretreatment CA(125) levels (< or = 500, > 500 - 1500 and > 1500 kU/L; P > 0.05). The CA(125) level was normalized (0 - 35 kU/L) in 77 (54.2%) patients after three cycles of postoperative chemotherapy. It revealed significant differences in 3-year OS (84% vs. 42%) and 5-year OS (56% vs. 15%) between the patients with normalized and elevated CA(125) levels (n = 48) after three cycles of chemotherapy (P < 0.01). Multivariate analysis showed that residual tumor size > 1 cm (P < 0.01) and elevated CA(125) after three-cycle postoperative chemotherapies (P < 0.01) were two independent factors related to survival. In the subgroup of optimal cytoreduction (residual tumor size < or = 1 cm), the 3-year and 5-year OS rate were 88% and 64% for patients with normalized CA(125) level after three cycles of chemotherapy respectively, while only 52% and 18% for patients with elevated CA(125) level (P < 0.01). Similarly, even in the suboptimal cytoreduction group, the 3-year and 5-year OS were also significantly increased for patients with normalized CA(125) level after three cycles of chemotherapy post-surgery, as compared with patients with elevated CA(125) level (74% vs. 33% in 3-year OS, 32% vs. 13% in 5-year OS; P < 0.01). CA(125) level after three cycles of chemotherapy post-surgery is an independent predictor of survival for advanced ovarian carcinoma. Whatever the patients undergo, optimal or suboptimal cytoreduction, if the CA(125) becomes normalized after three cycles of chemotherapy, they would have more favorable prognosis than those with elevated CA(125) after three cycles of chemotherapy.

The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-analysis

The prognostic relevance of lymphatic micrometastases in colorectal carcinoma is unclear. To determine the prognostic significance of micrometastases in colorectal cancer, a meta-analysis was performed on all studies, which reported 3-year disease-free survival (DFS) and overall survival (OS). Published studies selected for meta-analysis contained sufficient data from which to extrapolate estimates of 3-year DFS and/or OS. From 1991-2003, 25 studies re-examined N0 lymph nodes by serial sectioning and immunohistochemical (IHC) staining or reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Eight studies (566 patients) with IHC detected micrometastases and three (173 patients) with RT-PCR micrometastases were used to determine DFS and OS. Weighted estimates of 3-year survival were combined across studies within each group, and the combined survival estimates were compared across groups using a binomial test. Micrometastases were identified in all IHC studies; upstaging, including N1, N1mi and N0(i+), was achieved in 32% (179/566 patients). All RT-PCR studies identified micrometastases; upstaging to N0(mol+) was achieved in 37% (64/173 patients). There was a statistically significant difference in 3-year OS between RT-PCR positive N0(mol+) patients (77.8%) and those for whom micrometastases were not detected (96.6%) (P < .001). The prognostic value of micrometastases detected retrospectively by RT-PCR is significant in AJCC stage II colorectal patients. Studies utilizing RT-PCR performed a more complete nodal analysis when compared to studies using IHC techniques. RT-PCR may also be more specific for the detection of clinically relevant micrometastases compared to IHC detected cytokeratins. Prospective studies are needed to evaluate the potential benefit of systemic chemotherapy in patients with molecular metastases.

A Comparison of Endometrial Cancer Outcomes in Ontario

Objective: To compare endometrial cancer treatment strategies and outcomes across the province of Ontario, Canada.Methods: A retrospective cohort study was conducted of 195 women diagnosed with endometrial cancer in Ontario between 1996 and 1998, as a sample of the population. The women’s charts were randomly selected by the medical records departments at 5 tertiary care centres in Ontario. The outcomes measured included 5-year overall survival (OS) and disease-free survival (DFS), use of adjuvant radiotherapy, treatment complications, and prognostic factors for survival.Results: The 2 main treatment strategies were (1) total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO) and (2) surgical staging (defined as TAH BSO and pelvic lymph node dissection with or without cytology, peritoneal biopsies, and omentectomy). Surgical staging rates across the province ranged from 0% to 88%. Stratified survival analysis revealed a significant difference in OS among centres (log rank P = .039). Crude survival analysis revealed no difference in 5-year OS or DFS between the 2 treatment strategies. The Cox proportional hazards model identified advanced stage of tumour as being the most predictive factor of DFS, and the woman’s age at diagnosis and tumour grade as predictive of OS.Discussion: There was a significant difference in 5-year OS among the 5 tertiary care centres. There was no significant difference between surgical staging and TAH BSO with respect to 5-year DFS or OS.Conclusion: As there were significant differences in the treatment of endometrial carcinoma and OS across the province, a population-based study of endometrial cancer treatment strategies and outcomes is required.