5-year Overall Survival Of Patients Research Articles

Multiple Elements Classified Hematological Malignancies from Healthy Population

IntroductionIt is a little known about how multiple elements interacts and functions in cells, although a specific element had already reported to take a role, enzymatic, transcriptional activities, etc. Although, several metals such as cadmium, nickel, lead, and chrome were known as carcinogen, it is also not known about relations of multiple elements in disease mechanisms. To investigate the impact of multiple elements on the features of hematological malignancies, we analyzed the multiple elements in the serum of patients with hematological malignancies and healthy persons.MethodsWe obtained 47 of peripheral blood samples from 40 patients with hematological malignancies, and 102 of healthy persons: 50 persons who visited to medical check-up and 52 volunteers.Hematological malignancies were 16 acute myeloid leukemia, 5 acute lymphoblastic leukemia, 9 non-Hodgkin’s lymphoma, 9 Multiple myeloma, and 1 Chronic myeloid leukemia.Samples were centrifuged, and 1.0-1.5ml of plasma was separated. We measured 23 elements were measured using inductively coupled plasma mass spectrometry.To assess the difference of the element patterns between hematological malignancies and healthy persons, multivariate discrimination analysis was performed. Overall survival of hematological malignancies was assessed by Log-rank test.Multivariate analysis with the elements highly discriminated hematological malignancies from healthy persons’ samples. Elements data increased the accuracy to discriminate hematological malignancies from healthy persons close to 100 % in addition to clinical data such as complete blood count, albumin, total bilirubin, blood urine nitrogen, creatinine. To our knowledge, this is the first report on the successful classifying disease from healthy persons by measurements of multiple elements with more than 90% accuracy using peripheral blood serum (Table 1). Five year overall survival of patients with hematological malignancy was likely dependent on this discriminant score. Data suggested the potential interaction between multiple elements and hematological malignancies, and the possibility future applications on diagnosis and prognosis.Table 1Accuracy of cross-validated classification patients with hematological malignancies and healthy persons by discriminant analysisAccuracyClinical dataMulti-elementsMulti-elements + Clinical data%93.791.398.9 DisclosuresNo relevant conflicts of interest to declare.

The Addition of Radiation Therapy to Initial Treatment for Extramedullary Acute Myeloid Leukemia Does Not Offer a Survival Benefit When Added to Chemotherapy

Background: The presentation of acute myeloid leukemia (AML) as an extramedullary tumor occurs in up to 9% of cases, making it an uncommon event and one that poses difficulties in clinical decision-making. Current data on treatment and outcomes for myeloid sarcoma are based largely on case reports and clinician experiences involving a small number of patients. Radiation is often added to standard chemotherapy regimens in order to attempt to improve rates of complete remission, however there is a paucity of data to guide the utilization of radiation therapy in addition to chemotherapy.Aims: To determine the impact of chemotherapy, the combination of chemotherapy and radiation therapy, and transplantation on the survival of patients with myeloid sarcoma.Methods: Beginning with a PubMed search from 1985 to 2014, we performed a review of the literature on cases of isolated myeloid sarcomas (without bone marrow involvement) presenting as the initial diagnosis of AML. We identified 7 large case reports or reviews where individual patient characteristics (including treatment course, site of disease, overall survival (OS) and time to development of bone marrow involvement) were defined.We also undertook a chart review of the patients treated at Memorial Sloan Kettering Cancer Center from 1990 to July 2014 who upon initial presentation of AML demonstrated extramedullary involvement. We excluded patients with extramedullary disease at relapse, those presenting with lymph node, splenic disease or leukemia cutis in both data sets. For the MSKCC data, we included those who presented with bone marrow involvement due to the low number of patients available for analysis.Results: The literature search identified 71 analyzable patients and there was no significant difference in OS whether patients with isolated myeloid sarcoma were initially treated with radiation therapy (n= 14, 11.2 months), chemotherapy (n=40, 19 months) or the combination of chemotherapy and radiation (n=17, 24 months, p=0.41) Fig 1. The median OS of these patients was 16 months (n=71).At MSKCC, 27 patients were available for analysis. The median 3 year OS of patients presenting with AML and extramedullary involvement was 41%. There was a significant improved 1 year OS (p=0.002) if patients were treated with chemotherapy alone (n=19), as opposed to the combination of radiation and chemotherapy (n=6), 89% vs. 33%, respectively. There was no difference in OS if patients presented with bone marrow involvement or with isolated disease (35% vs. 55% at 3 years, p= 0.51). Lastly, patients who underwent allogeneic stem cell transplantation (n=13) exhibited a median 44% 3 year OS. Only seven of these patients were in first complete remission.Summary/ Conclusion: Patients with AML who present with extramedullary disease seem to derive no additional survival benefit from the inclusion of radiation therapy to chemotherapy as initial treatment. Also, presentation with isolated myeloid sarcoma does not appear to confer a worse prognosis when compared to myeloid sarcoma with bone marrow involvement and likely represents a different manifestation of the same disease process. For comparison, regarding overall survival, patients enrolled in ECOG 1900 who received standard therapy had a median OS of 15.7 months and those with intermediate risk cytogenetics and an intermediate risk mutational risk profile, as described by Patel et al in NEJM 2012, had a 3 year OS of 42% comparable to the outcomes we noted above. This suggests that patients with myeloid sarcoma do no worse than those with bone marrow only disease.The survival of patients who underwent allogeneic stem cell transplantation in our study had a similar median 3 year OS to patients with AML who undergo allogeneic stem cell transplantation studied by the CIBMT and published in Blood 2012 by Saber et al. The 3 year OS rates for patients who underwent a matched related donor transplant in this publication was 39%, and 37% for those who had a matched unrelated donor transplant.In summary, though the sample size is notably small and acknowledging the limitations of retrospective data, patients with myeloid sarcoma during the initial presentation of AML should undergo risk stratification and treatment in the same manner as patients with AML without extramedullary disease. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Increased Risk of Venous Thromboembolism in Primary Central Nervous System Lymphoma Patients Undergoing Therapy

Introduction: Primary CNS Lymphoma (PCNSL) is a rare and aggressive NHL associated with poor prognosis. Age, performance status, serum LDH and monocytosis at diagnosis as well as tumor location are reported to be associated with outcomes. We conducted a retrospective review of PCNSL patients to evaluate outcomes and the influence of known prognostic factors.Methods: Patients diagnosed with PCNSL between 06/2006 and 06/2014 at University Hospitals Seidman Cancer Center (Cleveland, OH) were eligible. Five patients that did not receive treatment because of very poor performance status or significant comorbidities were included. Treatment regimens included high dose methotrexate (HD-MTX) based regimens (DeAngelis LM, et al J Clin Oncol 20: 4643-8, 2002; and Ferreri AJ, et al. Lancet 374(9700):1512-20, 2009) and temozolomide plus rituximab (Wong ET, et al. Cancer 101: 139-45, 2004). In patients younger than 60 years, whole brain radiation therapy (WBRT) was administered based on patient and physician preference. Overall survival (OS) and progression free survival (PFS) were calculated from date of diagnosis to death or progression, respectively. Survival outcomes were analyzed with the Kaplan Meier method and compared between groups using the log-rank test.Results: Thirty patients were included. Patient characteristics are summarized in table 1. Median age at diagnosis was 64.5 (18-82) years. None of these patients had received a prior solid organ transplant or had prior diagnosis of lymphoma. One patient had HIV infection diagnosed at the time of PCNSL diagnosis. Lymphoma subtype was predominantly diffuse large B cell lymphoma (n=25; 83%). High-dose methotrexate (HD-MTX)-containing regimens (with or without high dose cytarabine) were used in 20 patients (66.6%).After a median follow-up of 16 months, estimated 2-year overall survival (OS) for all patients was 66.4%. Patients ineligible to receive any treatment had dismal OS (median 1.5 months), significantly inferior than patients who received any type of treatment (p < 0.0001). Two year OS for patients receiving treatment was 77%; there was no difference in OS among patients treated with different treatment regimens. Rituximab was not associated with longer OS. Two year PFS for patients treated with HD-MTX containing regimens was 85.7% vs. 37.5% for patients treated without HD-MTX (p=0.08). Use of WBRT was not associated with prolonged OS or PFS. On univariate analysis, elevated CSF protein was associated with inferior OS (p = 0.03); age, ECOG performance status, serum LDH at diagnosis, tumor location within the CNS, neutrophil and lymphocyte count at diagnosis and monocyte counts did not predict for OS or PFS. Among patients receiving HD-MTX based regimens 6/20 (30%) had a venous thromboembolic (VTE) episode, all occurred during HD-MTX based regimens; median time from diagnosis to VTE was 70 days (range 24 – 154), and occurred after a median of 2 cycles of chemotherapy (range 1 – 5).Conclusions: Treatment of PCNSL can result in improved outcomes and prolonged survival. Patients treated with lower intensity treatments such as temozolomide and rituximab have better OS than those not capable of tolerating even these therapies. We observed a high incidence of VTE in patients receiving HD-MTX treatment for PCNSL. The risk factors for this complication include frequent hospitalizations, use of central venous catheters and decreased mobility. Close monitoring and surveillance should be done and prophylactic measures to prevent VTE should be considered. A larger case – control study is planned to identify the specific risk factors for VTE compared with other CNS neoplasms and non – PCNSL lymphomas. Table 1Baseline patient charachteristicsVariablePatient Number (%)Gender (Male / Female)22/8Median Age (Range)64.5 (18-82) yearsLymphoma subtype DLBCL MZL T cell lymphoma Unclassifiable25 (83.3%) 2 (6.6%) 1 (3.3%) 2 (6.6%)PCNSL location in CNS Cortex Deep brain Structures13 (43.3%) 17 (56.6%)CSF involvement9 (30%)Elevated protein in CSF14 (46.6%)Elevated serum LDH8/30 (26.6%)ECOG performance status at diagnosis 0 1 2 3 47 (23.3%) 15 (50%) 5 (16.6%) 1 (3.3%) 2 (6.6%)Age > 60 years21 (70%)Elevated WBC (>10,000/mcl) at diagnosis13 (43.3%)Hemoglobin (<10 g/dl) at diagnosis8 (26.7%)Treatment High dose Methotrexate - based Temozolomide – based No treatment20 (66.6%) 5 (16.6%) 5 (16.6%)Rituximab15 (50%)Whole brain radiation therapy11 (36%) DisclosuresNo relevant conflicts of interest to declare.

Characteristics of Mesenchymal Multipotent Stromal Cells Determine Their Effectiveness for Acute Graft Versus Host Disease Prophylaxis after Allogeneic Bone Marrow Transplantation

IntroductionAllogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, among which the most challenging is graft-versus-host disease (GVHD). As the conventional methods of GVHD prophylaxis are often inefficient new method involving the use of donors’ multipotent mesenchymal stromal cells (MSC) was developed. In some cases prophylaxis of acute GVHD (aGVHD) failed. The reasons of the failure could be either the result of particular qualities of donor-recipient interaction, patient status or characteristics of MSC samples. The results of the aGVHD prophylaxis with donors’ MSC injections after allo-BMT in patients with hematological malignancies included in the randomized clinical trial (Clinicaltrials.gov NCT01941394) were analyzed. In order to discriminate between effective and ineffective for aGVHD prophylaxis MSC samples were thoroughly analyzed. The growth and differentiation characteristics, relative expression levels of different genes were investigated in all MSC samples.MethodsThe study included 77 patients who received allo-BMT from related donors after informed consent. The patients were randomized into 2 groups: the first received standard prophylaxis of aGVHD and the second were additionally infused with MSC from the bone marrow of corresponding hematopoietic stem cells donor at day of WBC reconstitution >1*109/l. MSC were cultivated in aMEM with 4% donors’ platelet lysate. MSC were administered intravenously when the blood counts indicated recovery (peripheral blood leukocytes reached 1x109/l). MSCs and colony-forming unit-fibroblasts (CFU-Fs) from the bone marrow of those donors were analyzed. For this purpose MSC were cultivated in standard conditions (aMEM, 10% fetal calf serum) for 5 passages. Relative expression level (REL) of 30 genes involved in proliferation, differentiation and immunomodulation was estimated by RT-qPCR in all MSC samples.ResultsThe infusion of MSC reduced the incidence of aGVHD 2 times and increased the 5 years overall survival of patients (p=0.047). Four of 39 MSC samples have been ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index), the MSC properties of these donors (growth parameters, REL of 30 genes involved in proliferation, differentiation and immunomodulation) found no significant differences between the MSC, effective and ineffective for preventing aGVHD. However the analysis revealed that cumulative MSC production and CFU-F concentrations in bone marrow decreased with donor age. MSC populations revealed the hierarchy that changed during cultivation, resulting in an increase in the impact of mature cells and a decrease in the subpopulation of cells with high proliferation potential.The combination of predictors that characterize the most suitable for the prevention of aGVHD MSC samples was revealed by multiple logistic regression analysis. A model calculating the probability of the success of MSC samples application was proposed:logit(P)=0,75+10,897*FGFR1-4,272*PPARG-2,014*IGF1,where logit(P) = ln[P/(1-P)], P – probability of successful prophylaxis, FGFR1, PPARG and IGF1 – REL of corresponding genes in tested MSC sample. Chi-square goodness of fit test p= 0.0053. The calculated efficiency of this model was 94%.The following parameters of MSC were essential for the success of aGVHD prophylaxis: increased REL of FGFR1 combined with reduced REL of PPARG and IGF1 genes. Depending on the chosen value for probability of successful application of MSC, this model can correctly predict the outcome of the use of MSC in 82-94% of cases.ConclusionsThese data confirm the presence of hierarchy as well as heterogeneity in MSC population. The high variability of all analyzed characteristics among MSC from different donors was shown. The mathematical model revealed the combination of parameters enabling to distinguish effective and ineffective MSC samples. By means of the proposed model ineffective MSC samples could be discharged and replaced by effective MSC sample from the third part donor. Such strategy hopefully will prevent the development of aGVHD in the maximum number of patients. DisclosuresNo relevant conflicts of interest to declare.

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

BackgroundEpidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN.Materials and methodsThe patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan–Meier statistical method.ResultsWe demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4–193.4; P=0.002).ConclusionIn this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.

Gallbladder cancer.

Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities-inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract.

Association Between Radiation Therapy Dose and Survival in Patients With Stage I Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiation Therapy

Purpose/Objective(s): Although stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is associated with high local control rates, the optimal dose-fractionation regimen is unknown, as prospective and retrospective data argue for different dosing paradigms. Whether increasing stereotactic radiation therapy dose can compensate for larger tumor volume is an open question. We aimed to determine the comparative effectiveness of different SBRT dosing regimens using a large national database, focusing on the relative impact of dose as a function of tumor stage. Materials/Methods: Patients in the National Cancer Database with clinical T1-2 N0 NSCLC who were treated with SBRT were eligible for inclusion in this cohort. Patient survival data were only available for those with a minimum of 5 years of follow-up, and therefore the analysis was restricted to those diagnosed between 2003 and 2006. Median follow-up and overall survival (OS) were defined from the date of diagnosis to last contact. The biologically equivalent dose (BED) was calculated based on the linear quadratic formula using an alpha/beta ratio of 10. All patients received a minimum BED of 70 Gy. Highversus lower-dose (HD vs LD) SBRT was defined as BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods. Cox proportional hazard multivariable analysis (MVA) was used to estimate hazard ratios (HR), adjusting for age, sex, T stage, BED, facility type (academic vs community practice), insurance status, year of diagnosis, comorbidities, race, and histology. Results: A total of 498 patients (T1 Z 67%, T2 Z 33%) met inclusion criteria. The median follow-up was 3 years (range, 3 months-8.6 years) for the entire cohort and 5.6 years for surviving patients. The 5 most common dose fractionation schemes (% of cohort) utilized were 20 Gy x 3 (34%), 12 Gy x 4 (16%), 18 Gy x 3 (10%), 15 Gy x 3 (10%), and 10 Gy x 5 (2.6%). The median BED was 150 Gy (inter-quartile range 106 Gy 166 Gy). The 3and 5-year overall survival for the entire cohort was 50% and 30%. The 3 year OS for T1 vs T2 disease was 61% vs 30% (log rank p < 0.0001). The 3 year OS for patients who received HD vs LD was 55% vs 46% (log rank pZ 0.03). On subset analysis of the T1 cohort, there was no association between BED and 3-year OS (61% vs 60% with HD vs LD, p Z 0.9). Among the T2 cohort, patients receiving HD experienced superior 3 year OS (37% vs 24%, p Z 0.01). On MVA, the only factors independently prognostic for mortality were female gender (HR Z 0.76, p Z 0.01), T1 tumor (HR Z 0.51, p Z 0.0001), and HD (HR Z 0.78, p Z 0.01). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I NSCLC suggests higher doses are associated with a significant survival benefit, especially in patients with a larger burden of disease. Prospective data are needed to determine the optimal dose-fractionation regimen as a function of tumor volume. Author Disclosure: M. Koshy: None. R. Malik: None. D.J. Sher: None.

Impact of perioperative chemotherapy on Nigerian patients with locally advanced and metastatic gastric cancer.

e15180 Background: The overall 5-year survival of patients with gastric cancer is only 14% in Nigeria as compared to 23% in the United States of America and 60% in Japan [1-3]. The possible reasons...

Survival analysis of patients with unilateral and bilateral primary breast cancer in Northeast China

Previous reports have shown that patients with bilateral primary breast cancer (BPBC) had comparable or moderately poor survival compared with patients experiencing unilateral primary breast cancer (UPBC). However, studies are conflicting in their analyses of correlations between survival and clinicopathological and prognostic characteristics in BPBC patients. The aim of our study was to compare the clinicopathological features and prognoses of BPBC and UPBC patients in Heilongjiang Province, northeast China. We retrospectively reviewed the records of 2,695 patients who underwent modified radical mastectomy or lumpectomy from 2005 to 2008 in the Tumor Hospital of Harbin Medical University. Eighty-one patients (3.0%) had BPBC and 2,614 patients had UPBC. Multivariate analysis was performed using Cox's proportional hazards model. There were significant differences between patients with BPBC and UPBC in the age of onset (referring to the age when the first tumor in BPBC was diagnosed), T stage, menopause status (referring to the age when the second tumor in BPBC was diagnosed), and breast cancer family history. The overall 5-year survival of patients with BPBC was 70.1% compared with 87.1% for patients with UPBC (p=0.004). Furthermore, multivariate analysis showed that HER-2 status, menopause status, and mammary disease history were significant factors affecting survival among the patients with BPBC. Our results confirmed previous findings that BPBC patients had moderately poor survival. However, when T stages were matched, BPBC patients had a survival rate similar to UPBC patients. Premenopause status, HER-2 positivity and family history of breast cancer were major risk factors for BPBC.

Outcomes In Splenic Marginal Zone Lymphoma: Analysis Of 108 Patients Treated In British Columbia (BC)

▪ IntroductionSplenic marginal zone lymphoma (SMZL) is uncommon and accounts for less than 1% of all non-Hodgkin lymphomas. The optimal treatment for SMZL is unknown. We describe the outcome of 108 patients with SMZL treated in British Columbia. MethodsAll patients with SMZL diagnosed between 1985 and June 2012 were identified in the BC Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Overall survival (OS) was measured from time of diagnosis to death or last follow-up. Progression-free survival (PFS) was measured from the date of diagnosis to the date of lymphoma recurrence or transformation, or death. Time to transformation (TTT) was calculated from date of diagnosis to date of transformation to aggressive lymphoma. Results108 patients were identified with a diagnosis of SMZL. Baseline patient characteristics: median age 67 years (range 30-88), male 41%, stage IV 98%, B symptoms 17%, performance status ≥2 22%, splenomegaly 93%, bone marrow involvement 93%, peripheral blood involvement 87%. Hepatitis C serology was positive in 5 of 60 patients with available data.As initial treatment, 53 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 with a rituximab-containing regimen), 2 received antiviral therapy for hepatitis C, and 15 were observed. Of the 43 patients who had splenectomy alone, 9 subsequently received chemotherapy upon progression, 1 had excision for a soft tissue mass, and 4 transformed to diffuse large B cell lymphoma (DLBCL). Of the 38 who received chemotherapy first line, 6 subsequently received combined chemotherapy and splenectomy, 1 splenectomy alone, 4 chemotherapy alone, and 7 transformed to DLBCL. Neither of the 2 patients who received antivirals had further progression.With a median follow-up of 7 years (range 3 months to 18 years) for living patients, the 5 and 10 year OS were 65% and 48%, respectively. The 5 and 10 year PFS were 38% and 18%, respectively. The 5 year OS for patients who had a splenectomy as their first-line therapy compared to other treatments was 76% vs 53% (p=0.01); and the 5 year OS for patients who received chemotherapy alone as first-line compared to other treatments was 52% vs 72% (p=0.04). There was no difference in outcomes between those treated with rituximab containing chemotherapy as first line compared to other treatments (p=0.65). The 5 and 10 year PFS after first-line splenectomy were 52% and 18%, respectively. A total of 14 patients transformed to DLBCL with a median TTT of 3.2 years (range 6 months to 11.9 years). The 5, 10, 15 year rates of transformation were 9%, 21% and 35%, respectively. ConclusionsSplenectomy remains a reasonable treatment option for patients with SMZL. Patients selected for splenectomy as initial management of symptomatic disease experience improved outcomes. The transformation rate in SMZL is similar to that of other indolent lymphomas. Disclosures:Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Skinnider:Roche Canada: Research Funding. Gascoyne:Roche Canada: Research Funding. Sehn:Roche Canada: Research Funding. Savage:Roche Canada: Research Funding. Slack:Roche Canada: Research Funding. Shenkier:Roche Canada: Research Funding. Klasa:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding. Villa:Roche Canada: Research Funding.

Trends In Outcomes In Core Binding Factor Acute Myeloid Leukemia: A SEER Database Analysis

▪Acute myeloid leukemia with chromosomal alterations impacting the core binding factor transcription complex (CBF-AML), specifically t(8;21) and inv(16), are associated with a greater responsiveness to cytarabine-based chemotherapies and a more favorable prognosis. The latter has been primarily gleaned from outcomes of large clinical trials of AML. However, to date, there is limited population-based outcomes data on CBF-AML. We therefore performed an epidemiologic retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to assess survival trends for CBF-AML at the population level between 2000 and 2010. Patients and MethodsPatients with a diagnosis of CBF-AML between 2000 and 2010 were identified using the SEER 18 registries database. We included patients with a diagnosis code of inv(16)/t(16;16) AML (Code 9871) or t(8;21) AML (Code 9896) diagnosed between January 2000 and December 2010. Patients were divided into cohorts based on age at diagnosis: 15-44 years old, 45-64 years old, 65-74 years old, and 75-84 years old. Disease incidence was calculated, as were early mortality rates, defined as death within 1 month. Overall survival (OS) was estimated using the method of Kaplan and Meier. Cox regression was performed to estimate predictors of survival by specific CBF-AML type, age cohorts, race/ethnicity, gender, year of diagnosis, number of primary malignancies, and residence. ResultsWe identified 777 patients with a new diagnosis of CBF-AML between 2000 and 2010. The incidence of CBF-AML increased with advancing age (ages 15-44, 0.06 per 100,000 people; ages 45-64, 0.13; ages 65-74, 0.25; ages 75-84, 0.28). Median OS for all patients was 22 months, and the combined 3-year OS was 44.3% (Fig. 1). Median OS increased from 16 months during the period encompassing 2000 and 2002 to 25 months during the period from 2006 to 2008 (p=0.002) (Fig. 2). The rate of early death was 13%, which increased with age (15-44 5%, 45-64 10%, 65-74 20%, 75-84 33%; P<0.0001). OS also worsened with advancing age; patients ages 75-84 had a 3 year OS of 9.3% and an increased HR for mortality compared to patients ages 15-44, who had a 3 year OS of 68.7% (HR 5.61, P<0.0001) (Fig. 3). Of note, worsening OS with advancing age was observed even among the subset of patients alive at 1 month. Black race was associated with an increased HR for mortality compared to white non-Hispanic patients (HR 1.50, P=0.03). Patients with inv(16) disease had an improved OS compared to patients with t(8;21) disease (HR for mortality 0.65, P<0.0001). The 3 year OS for patients with inv(16) disease was 57.3%, while for those with t(8;21) disease it was only 35.5% (Fig. 1). [Display omitted] [Display omitted] [Display omitted] ConclusionIn spite of historically favorable prognoses associated with CBF-AML in clinical trials, we found poorer survival in the general population. Unlike inv(16) disease, patients with t(8;21) CBF-AML did not appear to have a favorable OS. Survival was significantly worse among African Americans and the elderly. The reason for these differences is unknown, and merits further evaluation. Disclosures:Chen:Otsuka Pharmaceuticals, Inc.: Research Funding; Seattle Genetics: Consultancy, Research Funding; Bayer / Onyx: Research Funding. Fathi:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Millenium: Research Funding.

Functioning Adrenocortical Carcinoma with Extension upto the Right Atrium Producing Cushing's Syndrome

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Surgery is the only curative therapy available and overall 5-year survival for patients who undergo a complete resection is 32% to 48%. They are known to produce intravascular invasion and into the inferior vena cava (IVC) and in rare cases they may reach the right atrium. We report a case of functioning ACC extending into the inferior vena cava and right atrium in a female with Cushing's syndrome.

Abstract 1781: Whole-genome and RNA sequencing identify a novel recurrent translocation in adrenocortical carcinoma.

Abstract Adrenocortical carcinoma (ACC) is a lethal tumor of the adrenal cortex with limited treatment options. The only possibility for cure is complete surgical resection, but 50-70% of patients present with metastatic disease, precluding curative surgery. The outcome for patients with ACC has remained unchanged in the past 25 years, with the overall 5-year survival of patients undergoing surgical resection being ∼40%. Patients that present with advanced disease fare considerably worse with 5-year survival rates of 10-20%. The standard chemotherapy regimen of mitotane (the only approved agent), etoposide, doxorubicin, and cisplatin, has a response rate of 23.2%. A better understanding of pathobiology is needed to improve the treatment results for this disease. Previous genomic studies combined with expression microarray studies have implicated lack of H19 expression coupled with IGF2 over-expression, beta-catenin activation, and loss of p53 pathway function as important events in ACC, but no single alteration has been seen in all ACC. We used a combination of whole genome sequencing, exome sequencing, and RNA-sequencing on three tumor/normal pairs from patients. Using data from spectral karyotyping of the two ACC cell lines, SW-13 and NCI-H295R, we mined the sequencing data for structural rearrangements in regions of common breakpoints. We identified a novel recurrent translocation, t(4;8)(p16.2;p23.1) in all three tumors that was not present in the normal sequence. Using fluorescent in situ hybridization (FISH) we validated the translocation in the three tumors and both SW-13 and H295R. An additional five of five ACC scored positive for the translocation, as did three malignant non-ACC tumors (malignant pheochromocytoma, pancreatic neuroendocrine tumor, and carcinoid) suggesting that this finding has implications beyond ACC. The recurrent translocation t(4;8) (p16.2; p23.1) involves two genes of unknown function, BC042823 (uc003gho.2, IMAGE:5275587) on chromosome 4 and BC030294 (ucoo3wrb.1, IMAGE:5396854) on chromosome 8. RNA- sequencing data and RT-PCR with primers designed to both derivative chromosomes revealed transcription from both derivative chromosomes. The cDNA products were sequenced by Sanger sequencing and show partial homology to a non-coding RNA, LOC100506990, at chr8:12,338,893-12,452,929. RNA-sequencing data revealed this locus is highly transcribed in normal adrenal gland but reduced in expression in the three ACCs. In contrast to other recurrent translocations previously found in other cancers, this translocation is only present in 18-30% of the tumor nuclei scored by FISH, suggesting that it is a necessary alteration in malignant progression, but underscoring the question of how it might cooperate with events in other sub-clones to initiate tumor formation and progression. Citation Format: Michael J. Demeure, Kaiti Schwartz, Aditi Bapat, Claire Linnehan, Hollie Benson, Rebecca Reiman, Lori Phillips, Christophe Legendre, Raghu Metpally, Ahmet Kurdoglu, David Craig, John Carpten, Winnie S. Liang, Waibhav Tembe, Kimberly J. Bussey. Whole-genome and RNA sequencing identify a novel recurrent translocation in adrenocortical carcinoma. [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 1781. doi:10.1158/1538-7445.AM2013-1781

Influence of Treatment Modality in Outcomes for Different Stages of Resectable Esophageal Adenocarcinomas

There is no consensus on the most effective modality for the treatment of resectable esophageal adenocarcinomas (EAC). We theorized that treatment modality may influence survival differently depending on the stage of disease. A single-institution, retrospective examination of resectable EAC between 2000 and 2008 was performed. Resectable EAC were stratified into early disease (stage 2a or less) and late disease (stage 2b or more) based on pretreatment endoscopic ultrasound (EUS). Patients with T4, >N2, and/or distant disease were excluded. A total of 156 patients were included in this study. Most patients were white (97 %), male (83 %), and over 60 years of age (51 %). Patients with early disease on pretreatment EUS exhibited improved overall survival compared to patients with late disease (P < 0.001). Irrespective of treatment modality, there were no significant differences in overall 5-year survival for patients with early or late disease. Early and late disease patients whose disease responded to neoadjuvant chemotherapy (NAC) had significantly improved overall survival compared to nonresponsive disease (P < 0.05). The only negative independent predictors of overall 5-year survival were late stage disease on pretreatment EUS (hazard ratio 2.402, 95 % confidence interval 1.24-4.67, P = 0.01) and late stage disease on final pathological stage (hazard ratio 2.29, 95 % confidence interval 1.22-4.31, P = 0.01). Our data lack statistical power but reveal no difference in survival with the addition of neoadjuvant therapies to surgery for early or late resectable EAC. However, patients with disease that responded to NAC had improved outcomes at 5 years for both groups. Therefore, the prognosis for patients undergoing NAC may be optimized by immediate surgical resection if neoadjuvant therapies do not result in a dramatic clinical response.

Case report and review of the literature: Rectal linitis plastica secondary to the lipoid cell variant of transitional cell carcinoma of the urinary bladder

The overall 5-year survival of patients with urothelial carcinoma of the bladder (UC) is about 78%; however, there are some rare subtypes. One of these is the lipoid cell subtype, which bears a very poor prognosis. Another rare disease entity with a poor prognosis is metastasis to the lower gastrointestinal tract in the form of secondary linitis plastica of the rectum. We describe an extremely rare and unique case of rectal linitis plastica secondary to the rare lipoid cell variant of UC.

Case report and review of the literature: Rectal linitis plastica secondary to the lipoid cell variant of transitional cell carcinoma of the urinary bladder.

The overall 5-year survival of patients with urothelial carcinoma of the bladder (UC) is about 78%; however, there are some rare subtypes. One of these is the lipoid cell subtype, which bears a very poor prognosis. Another rare disease entity with a poor prognosis is metastasis to the lower gastrointestinal tract in the form of secondary linitis plastica of the rectum. We describe an extremely rare and unique case of rectal linitis plastica secondary to the rare lipoid cell variant of UC.

Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model

BackgroundRegardless of the availability of therapeutic options, the overall 5-year survival for patients diagnosed with pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have been used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions. Both frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit anti-neoplastic activity, and have been investigated as potential anti-cancer agents. The goals of this study are to identify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to evaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model.MethodsBoswellia sacra gum resins were hydrodistilled at 78°C; and essential oil distillate fractions were collected at different durations (Fraction I at 0–2 h, Fraction II at 8–10 h, and Fraction III at 11–12 h). Hydrodistillation of the second half of gum resins was performed at 100°C; and distillate was collected at 11–12 h (Fraction IV). Chemical compositions were identified by gas chromatography–mass spectrometry (GC-MS); and total boswellic acids contents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated pancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic (subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability of Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic activities in animals were assessed by immunohistochemistry.ResultsLonger duration and higher temperature hydrodistillation produced more abundant high molecular weight compounds, including boswellic acids, in frankincense essential oil fraactions. Human pancreatic cancer cells were sensitive to Fractions III and IV (containing higher molecular weight compounds) treatment with suppressed cell viability and increased cell death. Essential oil activated the caspase-dependent apoptotic pathway, induced a rapid and transient activation of Akt and Erk1/2, and suppressed levels of cyclin D1 cdk4 expression in cultured pancreatic cancer cells. In addition, Boswellia sacra essential oil Fraction IV exhibited anti-proliferative and pro-apoptotic activities against pancreatic tumors in the heterotopic xenograft mouse model.ConclusionAll fractions of frankincense essential oil from Boswellia sacra are capable of suppressing viability and inducing apoptosis of a panel of human pancreatic cancer cell lines. Potency of essential oil-suppressed tumor cell viability may be associated with the greater abundance of high molecular weight compounds in Fractions III and IV. Although chemical component(s) responsible for tumor cell cytotoxicity remains undefined, crude essential oil prepared from hydrodistillation of Boswellia sacra gum resins might be a useful alternative therapeutic agent for treating patients with pancreatic adenocarcinoma, an aggressive cancer with poor prognosis.

Prognostic Impact of Serum Soluble Interleukin-2 Receptor Values Just After Completion of R-CHOP in Diffuse Large B-Cell Lymphoma

Abstract 1591 IntroductionThe use of fluorodeoxyglucose-positron emission tomography (PET) to aid the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) after treatment with rituximab-containing combination chemotherapy was investigated. Several studies report that less than 20 % of patients who are PET-negative and more than 85 % of PET-positive patients will experience lymphoma recurrence. Since therapy for DLBCL recurrence remains a major problem, the ability to accurately predict the risk of relapse in PET-negative DLBCL patients after chemotherapy would be extremely beneficial. In this study we focused on levels of serum soluble interleukin-2 receptor (sIL-2R) since several reports indicate that sIL-2R at the time of diagnosis is closely linked to the prognoses of DLBCL patients. We measured sIL-2R levels in DLBCL patients shortly after R-CHOP therapy and investigated whether there was any correlation with patient prognoses. Patients and MethodsThis was a retrospective pooled analysis of DLBCL patients treated with R-CHOP in our institute. Patients were included if they were under the age of 80, had an International Prognostic Index (IPI) score of more than two, and had received R-CHOP with curative intent. Patients who received salvage chemotherapies due to insufficient responses to R-CHOP were also included. We excluded patients with low IPI scores as their sIL-2R levels at the time of diagnosis were usually in the normal range. Patients were also excluded if R-CHOP could not be continued for reasons other than disease progression. sIL-2R and PET analyses were performed when patients first visited the institute after completing 6–8 cycles of R-CHOP. Patients were divided into three groups: Group A consisted of patients who had completed R-CHOP, were PET-negative and whose sIL-2R levels had returned to normal (<600 mg/dl); Group B consisted of patients who had completed R-CHOP and were PET-negative, but whose sIL-2R levels had remained high (>=600mg/dl); Group C consisted of patients who had switched to salvage therapies as well as those who remained PET-positive after completing R-CHOP. Overall survival (OS) was assessed using the Kaplan-Meier method and the log-rank test was used for comparisons within each group. A multivariate Cox regression analysis was used to adjust for IPI scores. ResultsFrom January, 2006 to January, 2012, a total of 178 DLBCL patients aged less than 80 years were referred to our institution, and 70 of these patients were included in this analysis. The median age of patients was 68 years (range 37–79 years), 96 % had advanced stage DLBCL, and 77 % had elevated lactate dehydrogenase levels. 30% of patients had ECOG performance status (PS) less than 2. The median sIL-2R level at the time of diagnosis was 2676 mg/dl (range 612–48000 mg/dl). The numbers of patients assigned to groups A, B, and C were 28 (40 %), 18 (26 %), and 24 (34 %), respectively. A Fisher’s exact test showed no significant differences in IPI scores between the three groups (p=0.453). A Mann-Whitney test showed no significant differences in sIL-2R levels at the time of diagnosis between the three groups (A; median 2660 mg/dl, range 612–19000 mg/dl, B; 2905 mg/dl, 970–37100 mg/dl, C; 4347 mg/dl, 734–48000 mg/dl). Patients in groups A and B received 6–8 cycles of R-CHOP (median 7 cycles). Patients in group C received 1–4 salvage treatments (median 2 treatments) before or after completion of R-CHOP (median 6 cycles, range 2–8 cycles). After a median follow-up time of 36 months (range 5–60 months), 24 deaths had occurred (including 20 due to lymphoma), and the 3 year OS rate for the entire cohort was 65.5 % [95 % confidence interval (CI), 51.7–76.2 %]. The 3 year unadjusted OS rate of patients in groups A, B, and C was 95.2% [95%CI, 70.7–99.3%], 60.7% [95%CI, 31.3–80.6%] and 30.6% [95%CI, 12.5–51.0%], respectively (log-rank, p<0.001), (group A vs B; hazard ratio (HR), 10.8; 95%CI, 1.33–88.1; p=0.026, group B vs C; HR, 2.24; 95%CI, 0.91–5.54; p=0.079). Multivariate analysis including IPI score, revealed that 3 year OS for patients in group B was significantly inferior to that for patients in group A (HR, 6.26; 95%CI, 1.29–30.4; p=0.023), but was comparable with that for patients in group C. ConclusionDLBCL patients with an IPI score of more than 2 had an increased risk of relapse if their sIL-2R levels failed to return to normal following R-CHOP treatment, even if they completed 6–8 cycles of R-CHOP and were PET-negative. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Recent advances in treatment of metastatic colorectal cancer

Metastatic colorectal cancer is the second leading cause of cancer-related death in the Western population. New therapies have been developed at a rapid pace in the past 15 years with six new agents being approved since 1996, with the most recent addition approved in August 2012. These new cytotoxic and biologic agents have increased median overall survival from 12 to 24 months. Over 50 experimental agents are currently in clinical trials with one expected to be approved by the US FDA in the next year. The overall 5-year survival in patients with liver-isolated metastasis has improved with more aggressive surgical approaches and new chemotherapy regimens. Elderly patients with a good performance status are increasingly being given chemotherapy for metastatic disease with recent studies showing them to benefit in a similar manner to younger patients from combinations of chemotherapy and biological agents with similar toxicities.

Złośliwe gruczolaki wielopostaciowe ślinianki przyusznej w materiale Kliniki Otolaryngologii Warszawskiego Uniwersytetu Medycznego

Pleomorphic adenoma (PA), or benign mixed tumor, is the most common salivary gland neoplasm. One of the factors influencing the management strategy in parotid PA is the risk of malignant transformation of this tumor. The objective of this study was the clinical and pathological analysis of malignant mixed tumors treated surgically at the Department of Otolaryngology, Medical University of Warsaw. Retrospectively analysed clinical material included 12 patients with malignant mixed tumors selected from the group of 423 patients who underwent surgical treatment for parotid pleomorphic adenoma at the Department of Otolaryngology, Medical University of Warsaw, between January 1988 and June 2010. There were 7 women and 5 men; age ranged from 39 to 67 years, with a mean of 56 years. The following parameters were analysed: demographic data, symptoms and disease duration, results of diagnostic tests, intraoperative data, results of histopathological examination, and adjunctive therapy. Four patients with a follow-up shorter than 5 years were excluded from the analysis of treatment results. A group of 12 patients with malignant mixed tumours included 10 (83.3%) cases of a primary tumor and 2 (16.7%) cases of a recurrent tumor. In the complete study sample (n = 423), patients with malignant mixed tumor comprised: 2.8% of all patients, 2.5% of patients with primary PA and 5.1% of patients with recurrent PA. Patients with malignant mixed tumor were significantly older than patients with benign PA (an average patient age was 56.0 and 43.2 years, respectively p < 0.001). 83.3% (n = 10) patients were older than 50 years. An average disease duration was longer in patients with malignant tumors. Considering all data from preoperative patient assessment (medical history, physical examination, FNAB, imaging studies), a preliminary diagnosis of malignant disease was made in 6 (50%) patients. All patients were treated surgically and 10 also had radiation therapy. The group of patients (n = 8), subjected to evaluation of treatment results, included three patients with non-invasive carcinoma and five patients with invasive carcinoma. All patients with non-invasive carcinoma were free from disease symptoms during the follow-up of 9 to 21 years after the treatment. Five-year survival was 80% (4 of 5 patients) in a group of patients with invasive carcinoma. The rate of death for the underlying disease was the same (80%). An overall 5-year survival in patients with malignant mixed tumor was 87.5%. 1. Malignant transformation of pleomorphic adenoma more frequently occurs in recurrent tumors and in older patients. 2. Uncharacteristic clinical picture of malignant mixed tumors allows to make an accurate initial diagnosis only in half of the patients. 3. Extracapsular cancer invasion is a vital prognostic factor. Overall 5-year survival for invasive and noninvasive carcinoma was 80% and 100%, respectively.