Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients treated with chemotherapy

Purpose

Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes.

Patients and methods

This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin–etoposide or cyclophosphamide–epirubicin–vincristine chemotherapy. To determine the ABCB1 genotype, allelic specific TaqMan^? probes were used in a RT-PCR .

Results

Patients carrying the G2677T/A TT?+?TA?+?AA genotypes (24?%) or the C3435T CT?+?TT genotypes (72?%) or the 2677T/A-3435T haplotype (40?%) had a longer PFS (Cox regression, P?=?0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P?=?0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT?+?TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P?=?0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P?=?0.051), but its independent value was not confirmed (Cox regression, P?=?0.071).

Conclusions

Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.     

Sileneoside H, a new phytoecdysteroid from Silene brahuica

Sileneoside H (1), a new phytoecdysteroid, has been isolated from the roots of Silene brahuica and identified as 22-O-alpha-D-galactosylintegristerone A 25-acetate by MS and NMR analysis.     

Breast reconstruction following mastectomy for invasive breast cancer by free flaps from the abdomen is oncologically safe

Aims

To report the long-term results of oncological safety of breast reconstruction by autologous tissue following mastectomy for invasive breast cancer.

Methods

One-hundred-fifty-six consecutive patients with invasive breast cancer treated with mastectomy and reconstruction by autologous tissue were reviewed throughout (from 1987 to 2003 with median follow up time of 66 months).

Results

Median patient age was 45.9 years (range 26–68). The 157 observed tumors had mean diameter of 25 ± 19 mm, 70 of them were poorly differentiated, and 137 were invasive ductal carcinoma. Multifocal disease was present in 44 patients. Breast reconstruction was carried out only by autologous tissue (free flaps were used in 95% and free TRAM flap transfer was the most common reconstructive procedure). There was only one local recurrence as first site of recurrence, thus yielding a local recurrence rate of 0.6%.

Conclusions

Breast reconstruction by autologous tissue following mastectomy for invasive breast cancer is an oncologically safe procedure.     

Lymph node revealing solution: a rapid method for the fixation of cystectomy specimens

The objective of this study was to describe the use of the lymph node revealing solution (LNRS) for rapid fixation of total cystectomy specimens, and to compare it with formalin fixation. LNRS is a mixture of 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin (65:20:5:10 v/v) prepared under a fume-hood. Sixteen consecutive cystectomy specimens were fixed for two hours either in LNRS or in buffered formalin. Representative sections were embedded in paraffin, sectioned and stained with H&E, periodic acid Schiff, alcian-blue, and immunostained for cytokeratins 20, high and low molecular weight cytokeratins, prostatic specific antigen, Factor VIII related antigen, s-100 protein, and protein kinase C isoenzymes. Results showed that the tissues were well fixed after 2 hours in LNRS, and were not fixed after 2 hours in formalin. Processing and sectioning of the paraffin blocks of the LNRS fixed tissue was excellent; it was impossible in the sections fixed for 2 hours in formalin. All the stains were excellent after LNRS fixation. We conclude that fixation of cystectomy specimens in LNRS requires only two hours and results in excellent stained slides. It is therefore recommended for cystectomy specimens.     

The evolving practice of intrauterine cervix brachytherapy in Canada: A medical physics perspective

PurposeTo determine the current equipment, technology, and treatment planning methods used in Canadian cancer centers for intrauterine cervix brachytherapy.Methods and MaterialsA questionnaire was developed to survey medical physicists in Canada regarding technical aspects of intrauterine cervix brachytherapy. A response was obtained from one physicist at each radiotherapy facility in Canada.ResultsA total of 32 of the 41 Canadian radiotherapy facilities perform intrauterine brachytherapy. Most (88%) use high-dose-rate brachytherapy. Images used for treatment planning are two-dimensional (2D) X-rays (63%), CT (66%), MRI (13%), and cone beam CT (9%). Patients are moved to another room to obtain images at 66% of the centers. Dose is prescribed to a volume at 28% of centers, and dose–volume histogram information is used in evaluating dose to the organs at risk (47%) and target (31%). Manual optimization was the most common optimization method (81%). A total of 69% of the institutions made significant changes within the past 5 years, and 66% plan major changes within the next 2 years.ConclusionsIntrauterine brachytherapy treatment for cervical cancer is rapidly evolving in Canada, with centers moving toward 3D image-based methods. Often these imaging modalities are not located in the brachytherapy room, so studies on immobilization and verification would be useful. Access to MRI is increasing, but remains low, correlating with a low adoption of volume-based parameters for evaluating target coverage. National treatment guidelines would be useful for centers making the transition from 2D to 3D methods and for encouraging access to MRI.     

The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study

INTRODUCTION : We recently found that DNA methylation of S100A2, spleen tyrosine kinase (SYK), and Stathmin-1 (STMN1) correlates with response to tamoxifen therapy in metastatic breast cancer. In this retrospective study, we investigated immunohistochemically whether these three markers are predictors of relapse in early breast cancer (EBC) patients treated with adjuvant tamoxifen alone. METHODS : Immunohistochemical staining was performed for S100A2, SYK and STMN1 on a tissue microarray containing ER-positive invasive breast carcinomas from a study cohort of 215 operable breast cancer patients, who underwent radical local therapy and who were treated with adjuvant tamoxifen monotherapy. Cox regression was used to correlate staining intensity of the three markers with main endpoints in our study; disease-free survival (DFS), and disease-specific survival (DSS). RESULTS : In univariate analysis, only STMN1 staining intensity strongly correlated with DFS (P = 0.014) and DSS (P = 0.002). In the groups of low and high STMN1 intensity, DFS was 84% and 63%, and DSS was 89% and 70%. STMN1 retained its prognostic value for DFS (P = 0.002) and DSS (<0.001) in the multivariate model together with lymph node status. We found also a trend to better DFS in patients with low STMN1 intensity in both lymph node-positive (P = 0.001) and -negative patients (P = 0.065). As the tumour cells did not express S100A2 (except in one case) the potential prognostic value of this marker was not evaluated. CONCLUSIONS : Staining intensity of STMN1, but not SYK, predicted outcome in our collective of ER- positive tamoxifen treated EBC patients.