Objective To compare single-dose and multiple instilthe patients treated with epirubicin than in the control group (24, 25 and 52%, respectively; P<0.001). In lations of epirubicin in the chemoprophylaxis of superficial bladder tumours.those receiving epirubicin, the rates of recurrence were statistically comparable (P=0.9). Patients who had a Patients and methods In a prospective randomized and controlled study, 168 evaluable patients were large tumour burden showed slightly lower recurrence rates with single-dose epirubicin than with delayed assigned to three groups after transurethral resection of bladder tumour (TURBT) and histological confirmaintenance therapy but the diÂerence was statistically insignificant. Patients with a history of bladder mation of its superficial nature (pTa and pT1). The groups were comparable for tumour stage, grade and tumours before treatment had lower recurrence rates with maintenance treatment than with a single dose other tumour characteristics. In group 1, patients received a single dose of 50 mg epirubicin in 50 mL (34.6 and 22.6% in groups 1 and 2, respectively); again this diÂerence was statistically insignificant. normal saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal saline Patients with grade 3 tumours showed a marginal diÂerence in favour of maintenance therapy. The rates 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and thereafter monthly to of progression amongst the three groups were 5.5, 3.4 and 9.3%, respectively, with no significant diÂer-complete one year of treatment; group 3 (control group) received no adjuvant therapy after TURBT.ences. The overall toxicity rates were comparable in the two treated groups (22 and 25%). The patients were assessed by cysto-urethroscopy, urine cytology and DNA flow cytometry 8 weeks Conclusion With the possible exception of grade 3 tumours, single-dose immediate epirubicin is as eÂec-after resection and then every 3 months during the first 2 years and 6 monthly thereafter during the tive as delayed maintenance therapy, with the advantage of being more cost-eÂective. next 2 years. Intravenous urography was performed annually and when otherwise indicated.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of patients with HCC remain very poor. This study was conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients with chemotherapy -naïve, advanced hepatocellular carcinoma. 23 patients with unrespectable HCC who had received no prior systemic chemotherapy with objectively measurable tumors were enrolled on this study. The mistletoe preparation for the study is an aqueous injectable solution. It contains one milliliter of viscum fraxini in dilution stage -2 (15 mg extract of 20 mg mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate, ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules. 2 ampoules of viscum fraxini -2 were administered subcutaneously once weekly. As assessed by conventional imaging criteria, 3 (13.1%) patients have achieved complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%) had progressive disease while 9 (39.1%) patients didn't have evaluation of response due to early death. The median overall survival time for all patients was 5 months (range 2 -38 months), for those who achieved a CR was 29 months (range 12 -38 months) and, for those who achieved a PR was 6.5 months (range 6 -7 months). The median progression free survival for all patients was 2 months (range 1 -38 months), for those who achieved a CR, it was 29 months (range 8 -38 months) and for those who achieved a partial response, it was 5 months (range 4 -6 months). No hematologic toxicity has been encountered. The spectrum of non-hematologic toxicity was mild. The WHO toxicity criteria grade 3 -4 were 34.8% drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of injection. No drug related discontinuation or toxic deaths have occurred. Viscum fraxini-2 seems to be particularly promising in patients with advanced HCC, it shows antitumor activity and low toxicity profile. Further studies in combination with other active agents are clearly warranted.

This study demonstrates that epirubicin has better efficacy and lower toxicity than doxorubicin when used as an intravesical agent.

Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m² doxorubicin-loaded nanoparticles (30 mg/m² group), 20 mg/m² doxorubicin-loaded nanoparticles (20 mg/m² group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693.

Background. Breast tumors are composed of phenotypically diverse groups of cells; however, it is unclear which of these cells contribute to tumor development. Breast cancer management usually targets proliferating cells, but as breast cancer stem cells are slowly cycling, they may escape these targets whenever they are not actively proliferating. This may explain the occurrence of recurrences and failure of the treatment. Aim. To assess the impact of the BCSC expression on progression-free survival (PFS), overall survival (OS), and tumor response in metastatic breast cancer patients and to correlate the BCSC expression with different clinicopathological parameters. Material. This prospective study enrolled 76 de novo metastatic breast cancer patients recruited from the Oncology Center, Mansoura University, Egypt, with a minimum age 31 years and a maximum of 70 years. Pretreatment BCSC markers (CD44 and CD24) were assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissues from a primary or metastatic site. Patients received different lines of treatment, hormonal or chemotherapy, according to their biological subtypes. Anti-Her2 was added for Her2-positive patients. Results. Thirty-three patients (43.4%) were premenopausal and 43 patients (56.6%) were postmenopausal. Bone-only metastasis was seen in 12 patients (15.7%), however, visceral ± bone metastasis was seen in 64 patients (84.3%). BCSC markers (CD44+ve and CD24−ve) were expressed in 32 patients (42.1%), while 44 patients (57.9%) were not expressing BCSC markers. Out of 32 patients expressing BCSC, 22 patients (68%) were premenopausal and 28 patients (87.5%) were with high-grade (GIII) disease. BCSC was significantly presented in triple negative subtype breast cancer as there were 32 patients with the BCSC expression, and out of them, 15 patients (46.9%) had triple negative disease, 10 patients (31.3%) had luminal subtype, and seven patients (21.9%) were Her2-amplified, while there were 44 patients without BCSC expression, and out of them, 30 patients (68.2%) were of the luminal subtype, no patient (20.5%) had triple negative disease, and five patients (11.4%) were Her2-amplified (P 0.006). Twenty-four patients (31.5%) presented with visceral crisis; out of them, 17 patients (70.1%) were expressing BCSC which also denoted more aggressive disease. Seventy-four patients were candidates for the response assessment. BCSC-expressing patients showed poor response compared to non-BCSC (16.1% responsive versus 51.2%, respectively), with a significance relation (P 0.003). The BCSC expression was associated with both significant short PFS (median, 18 months vs. 35 months; P=0.001) and short OS (median, 26 months vs. 43 months; P=0.003). In multivariate analysis; BCSC expression was an independent prognostic factor for poor OS (P=0.055) along with the molecular subtype (P=0.012), Her2 status (P=0.011), and histologic grade (P=0.037). Conclusion. This study further validates the BCSC expression as a poor prognostic biomarker correlated with poor response, short PFS and OS. So, it could be used as a marker for tailoring treatment with different lines of therapies in further studies. The BCSC expression was highly presented in the triple negative subtype which is an aggressive disease that lacks different targets. So, targeting BCSC may carry a hope in future for this group of patients.

Angiogenesis is an important event in the survival and progression of solid tumors. The angiogenic status and the exact role of the angiogenic cytokines in lymphoid leukemia has not been fully elucidated. We have investigated the profile of the systemic components of angiogenic regulation in B-lineage acute lymphoblastic leukemia (B-ALL) and B-chronic lymphocytic leukemia (B-CLL), namely vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), endostatin and matrix metalloproteinase-9 (MMP-9) using enzyme-linked immunosorbent assay (ELISA). In B-ALL patients, sVEGF, and MMP-9 were significantly lower than control levels at diagnosis (p < 0.001) and increased to near control levels in remission (p>0.05). Both serum TNF-alpha and endostatin levels showed no significant difference at diagnosis (p>0.05) and in remission (p>0.05) compared to control levels. VEGF, TNF-alpha, MMP-9 and endostatin levels were not significantly correlated with peripheral white cell count or bone marrow blast cell count, but were positively correlated with platelet count. In B-CLL patients, serum VEGF, MMP-9 and TNF-alpha were significantly higher (p < 0.001 = 0.009, 0.007, respectively) and decreased to near control levels in remission (p>0.05 for all). Serum endostatin levels showed no significant difference at diagnosis and in remission compared to control levels (p>0.05). A significant positive correlation between VEGF, TNF-alpha, MMP-9 and peripheral white cell counts, bone marrow lymphocytic count and platelets count were found. In conclusion, our data suggest that the driving forces of angiogenic factors (VEGF, TNF-alpha and MMP-9) in adult B-ALL appears different from that in B-CLL patients.

Nucleophosmin (NPM1) and fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutations represent the most frequent molecular aberrations in patients with cytogenetically normal-acute myeloid leukemia (CN-AML). We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by polymerase chain reaction and GeneScan assays of bone marrow samples obtained from newly diagnosed 104 CN-AML patients. FLT3-ITD+ and NPM1mut were detected in 36 (34.6%) and 30 (28.8%) out of 104 subjects, respectively, 16 cases (15.4%) had double NPM1mut/FLT3-ITD+. The incidence of FLT3-ITD+ was significantly higher in the NPM1mut group than in the NPM1 wild (NPM1wt) group (P = 0.018). Statistical analysis revealed that isolated NPM1mut group had a better clinical outcomes in terms of higher complete response (CR) rate (P = 0.01) and a trend towards favorable overall survival (OS) and disease-free survival (DFS) (P = 0.28, 0.40, respectively). In contrast, the isolated FLT3-ITD+ group had an unfavorable outcome in terms of lower CR rate (P = 0.12), shorter OS, and DFS (P < 0.0001 for both). The NPM1mut/FLT3-ITD-group had the best OS and DFS, while the NPM1wt/FLT3-ITD+ group had the worst OS and DFS than other groups (NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-) (P < 0.0001 for both). Multivariate Cox regression analysis showed that age and FLT3/ITD+ were independent poor prognostic factors for OS (P = 0.006, <0.0001, respectively), while FLT3/ITD+ was independent predictor for DFS (P = 0.04). However, NPM1mut did not have a significant impact on OS and DFS. In conclusion, adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Patients with NPM1mut/FLT3-ITD- had the best prognosis in terms of higher CR, OS, and DFS, while those with NPM1mut/FLT3-ITD+ had the worst CR rate, and NPM1wt/FLT3-ITD+ had the lowest OS and DFS.

It has been known that the insertion/deletion mutation of CALR gene is the second deriver mutation in myeloproliferative neoplasm (MPN) of essential thrompocythemia (ET) and primary myelofibrosis (PMF). As the molecular workup has been incorporated for the prospective screening and diagnosis of MPN in our Oncology Center. An Egyptian 87 cohort of patients with non-mutated JAK2 (58 ET and 29 MF) were investigated using polymerase chain reaction (PCR) as a pilot study. We found that 37 out of 87 patients (42%) were carrying CALR mutations (30 out of ET (52%) and 7 out of MF (24%)). Sanger sequencing was used to determine the type of CALR mutations in all positive patients and we found that 13 out of 37 (35%) had type 1/type 1-like and 36 out of 37 (97%) with type 2/type 2-like. This CALR mutation profile in Egyptian patients appear different from the western status as type2/type 2-like is the highest in our patients (97%) versus 35-45% and type1/type 1-like was 35% versus 55-65% compared to western results. Meanwhile, the clinical course and phenotype of our cohort of patients is not similar to that in western as there is no significant difference of overall survival between type1/type1-like and type2/type2-like. This finding might be due to the different environmental and genetic backgrounds of Egyptian population. A part of it might be related to the HCV infection as 12 out of 37 (32%) had HCV infection. Further study is in progress on a large number of patients to correlate that with the clinicopathological status, response to therapy and the mechanistic pathway of oncogenic transformation. Disclosures No relevant conflicts of interest to declare.