Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.

We hypothesized improved inter-laboratory comparability of estrogen receptor (ER) and progesterone receptor (PgR) across different assay methodologies with adjunctive statistical standardization, akin to bone mineral density (BMD) z-scores. We examined statistical standardization in MA.12, a placebo-controlled pre-menopausal trial of adjuvant tamoxifen with locally assessed hormone receptor +/- tumours, and in a cohort of post-menopausal British Columbia (BC) tamoxifen-treated patients.

The causes of meningiomas are not well understood. Folate metabolism gene polymorphisms have been shown to be associated with various human cancers. It is still controversial and ambiguous between the functional polymorphisms of folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) and risk of adult meningioma. A population-based case–control study involving 600 meningioma patients (World Health Organization [WHO] Grade I, 391 cases; WHO Grade II, 167 cases; WHO Grade III, 42 cases) and 600 controls was done for the MTHFR C677T and A1298C, MTRR A66G, and MTR A2756G variants in Chinese Han population. The folate metabolism gene polymorphisms were determined by using a polymerase chain reaction–restriction fragment length polymorphism assay. Meningioma cases had a significantly lower frequency of MTHFR 677 TT genotype [odds ratio (OR) = 0.49, 95 % confidence interval (CI) 0.33–0.74; P = 0.001] and T allele (OR = 0.80, 95 % CI 0.67–0.95; P = 0.01) than controls. A significant association between risk of meningioma and MTRR 66 GG (OR = 1.41, 95 % CI 1.02–1.96; P = 0.04) was also observed. When stratifying by the WHO grade of meningioma, no association was found. Our study suggested that MTHFR C677T and MTRR A66G variants may affect the risk of adult meningioma in Chinese Han population.

To investigate the prognostic role of major matrix metalloproteinase (MMP) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with chemoradiotherapy. Four hundred twenty-one consecutive NPC patients were prospectively recruited. Two hundred patients were randomly selected as the training cohort, and the remaining 221 patients were the validation cohort. Twelve polymorphisms in the MMP-1, 2, 3, 7, 8, and 9 genes were genotyped by ligase detection reaction-PCR. MMP-9 rs2250889 PR/RR (HR = 2.287, 95% CI 1.400-3.735) and rs17576 RQ/QQ (HR = 2.347, 95% CI 1.431-3.849) genotypes were significantly related with increased death risk in the training cohort. Analysis of the validation cohort confirmed these results (rs2250889: HR = 2.231, 95% CI 1.281-3.886; rs17576: HR = 2.987, 95% CI 1.674-5.330). Multivariate analysis showed that rs17576 (HR = 2.284, 95% CI 1.123-4.643, P = 0.023) was still an independent prognostic factor. The MMP-9 rs17576 is a novel independent prognostic marker in patients with locoregionally advanced NPC treated with chemoradiotherapy.

Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer.

The Wilms' tumor gene (WT1) has been identified as an oncogene in many malignant diseases, and aberrant WT1 expression has been linked to development, progression, and prognosis of non-small-cell lung cancer (NSCLC). We sought to investigate the underlying mechanism of WT1 and metastasis in NSCLC.

Five-year overall survival (OS) for children with B-cell precursor acute lymphoblastic leukemia (B-ALL) exceeds 90% with risk-adapted therapy. Age, initial WBC count, genetic aberrations, and minimal residual disease (MRD) are used for risk stratification. Intrachromosomal amplification of a region of chromosome 21 (iAMP21; three or more extra copies of RUNX1 on an abnormal chromosome 21) is a recently identified recurrent genomic lesion associated with inferior outcome in some studies. We investigated the impact of iAMP21 in a large cohort treated in contemporary Children's Oncology Group (COG) ALL trials.

To explore the activity and safety of two schedules of ixabepilone, as first line chemotherapy, in patients with metastatic breast cancer previously treated with adjuvant chemotherapy, a randomized non-comparative phase II study was conducted. From November 2008 until December 2010, 64 patients were treated with either ixabepilone 40 mg/m(2) every 3 weeks (Group A, 32 patients) or ixabepilone 20 mg/m(2) on days 1, 8 and 15 every 4 weeks (Group B, 32 patients). Overall response rate (the primary end point) was 47% in Group A and 50% in Group B. The most frequent severe adverse events were neutropenia (32% vs. 23%), metabolic disturbances (29% vs. 27%) and sensory neuropathy (12% vs. 27%). Two patients in Group A and 3 in Group B developed febrile neutropenia. After a median follow-up of 22.7 months, median progression-free survival (PFS) was 9 months in Group A and 12 months in Group B. Median survival was 26 months in Group A, whereas it was not reached in Group B. Multiple genetic and molecular markers were examined in tumor and peripheral blood DNA, but none of them was associated with ORR or drug toxicity. Favorable prognostic markers included: the T-variants of ABCB1 SNPs c.2677G/A/T, c.1236C/T and c.3435C/T, as well as high MAPT mRNA and Tau protein expression, which were all associated with the ER/PgR-positive phenotype; absence of TopoIIa; and, an interaction between low TUBB3 mRNA expression and Group B. Upon multivariate analysis, tumor ER-positivity was a favorable (p = 0.0092) and TopoIIa an unfavorable (p = 0.002) prognostic factor for PFS; PgR-positivity was favorable (p = 0.028) for survival. In conclusion, ixabepilone had a manageable safety profile in both the 3-weekly and weekly schedules. A number of markers identified in the present trial appear to deserve further evaluation for their prognostic and/or predictive value in larger multi-arm studies.

Loss of phosphatase and tensin homologue (PTEN) expression may be prognostic in colorectal cancer (CRC) and may have a correlation with vascular endothelial growth factor (VEGF) expression via hypoxia-inducible factor 1 (HIF-1) alpha, and the PI3K/mTOR pathways. We therefore have explored the prognostic association of PTEN loss and the potential that PTEN loss may be predictive of outcome with bevacizumab. Patients enrolled in the AGITG MAX trial, a randomized Phase III trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C [M]) with available tissues were analyzed for PTEN expression (loss vs. no loss) as assessed using a Taqman® copy number assay (CNA). Of the original 471 patients enrolled, tissues from 302 (64.1%) patients were analyzed. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. PTEN status was not prognostic for progression-free survival (PFS) or overall survival (OS) in multivariate analyses adjusting for other baseline factors; loss versus no loss PFS hazard ratio (HR) 0.9 (0.7-1.16), OS HR 1.04 (0.79-1.38). PTEN was not prognostic when assessed by KRAS and BRAF status. By using the comparison of C versus CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS. PTEN status was not prognostic for survival in advanced colorectal cancer, irrespective of KRAS or BRAF status. PTEN status did not significantly predict different benefit with bevacizumb therapy.

Inherited functional single-nucleotide polymorphisms (SNPs) in DNA repair genes may influence the capability of DNA repair and contribute to the risk of breast cancer. We therefore performed a case-control study to investigate the association of three in excision repair cross-complimentary group 1 (ERCC1) and three in xeroderma pigmentosum complementation group F (XPF) with the risk of breast cancer. Genotyping of ERCC1 (rs2298881, rs3212986, and rs11615) and XPF (rs2276465, rs6498486, and rs2276466) was performed in a 384-well plate format on the MassARRAY(®) platform. Odds ratios and their corresponding 95% confidence intervals were used to assess the effect of each SNP on breast cancer risk. The ERCC1 rs11615 variant A/A genotype was associated with increased breast cancer risk in codominant, dominant, and recessive models, and XPF rs6498486 variant C/C genotype carriers have a significantly increased breast cancer risk in codominant, dominant, and recessive models. Individuals with both the ERCC1 rs11615 A allele and XPF rs6498486 C allele had a heavy increased risk of breast cancer compared to double wild-type homozygotes. The present study shows that the ERCC1 rs11615 and XPF rs6498486 polymorphisms are associated with breast cancer risk in a Chinese population. Further large-scale studies are required to elucidate whether these ERCC1 and XPF SNPs interact with environmental factors in the development of breast cancer.

Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored.

The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML.

The prognosis of patients with anaplastic oligodendrogliomas (AOD) and oligoastrocytomas (AOA) is variable. Biomarkers might be helpful to identify more homogeneous disease subtypes and improve therapeutic index. The aim of this study is to develop new clinical, pathological and molecular prognostic models for locally diagnosed anaplastic gliomas with oligodendroglial features (AOD or AOA).

This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving.

Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer.

Inactivation of von Hippel-Lindau (VHL) gene in clear-cell renal cell carcinoma (RCC) leads to increased levels of hypoxia-inducible factors (HIF) and overexpression of HIF target genes, such as VEGF and others. VEGF-targeted agents are standard in advanced clear-cell RCC but biomarkers of activity are lacking.

We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer.

Sequences of human endogenous retroviruses (HERVs) are members of the long terminal repeat (LTR) retrotransposon family. Although the expression of HERV has long been a topic of investigation, HERV-insertion polymorphisms are not well known, and a genetic association between HERV-insertion polymorphisms and cancer has never been reported. To identify novel HERV loci in the genome from cancer tissues, we carried out the inverse PCR method targeting a conserved LTR region of HML-2, which is the most recently acquired HERV group. Novel two insertions, HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally polymorphic solo LTRs. Furthermore, a significant prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60 years and over who had lung adenocarcinoma [versus the other genotyping; odds ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort consisting of female never-smoking patients with lung adenocarcinoma, a prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged 60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29), whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11-0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent manner and that other HERV polymorphisms related to human diseases might remain to be identified in the human genome.

Tivozanib is a potent selective tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. This Phase Ib study investigated the safety/tolerability, pharmacokinetics (PK), and activity of tivozanib with weekly paclitaxel in metastatic breast cancer (MBC). MBC patients with no prior VEGFR TKI treatment received daily oral tivozanib (3 weeks on, 1 week off) with weekly paclitaxel 90 mg/m(2). Standard 3 + 3 dose escalation was used; tivozanib cohorts (C) included C1 0.5 mg, C2 1.0 mg, and C3 1.5 mg. Assessments included Response Evaluation Criteria in Solid Tumors response, PK, and vascular function. Eighteen patients enrolled. Toxicities in >20 % of patients included fatigue, alopecia, nausea, diarrhea, peripheral sensory neuropathy, and hypertension. Grade 3/4 toxicities in >15 % of patients included fatigue and neutropenia. Maximum tolerated dose was tivozanib 1.5 mg with paclitaxel 90 mg/m(2). Four patients withdrew because of toxicity and one due to progressive disease. Thirteen patients were evaluable for response: four (30.8 %) had confirmed partial response; four had stable disease ≥6 months (30.8 %). PK data suggest no influence of paclitaxel on tivozanib concentrations. Tivozanib plus weekly paclitaxel was tolerable at all dose levels, supporting their combination at full dose. Activity in this small population was encouraging.

This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of βIII-tubulin as a predictive marker was also evaluated.