Anna Fabisiewicz

Evaluation of Prognostic Significance of Circulating Tumor Cells Detection in Rectal Cancer Patients Treated with Preoperative Radiotherapy: Prospectively Collected Material Data

The aim of this study was to evaluate the prognostic value of circulating tumor cells (CTC) in nonmetastatic rectal cancer patients treated with short-term preoperative radiotherapy. In this single-center trial, 162 patients with rectal cancer after preoperative short-term radiotherapy (5 × 5 Gy) were recruited from January, 2008 to September, 2011. Clearance of CTC was determined in 91 patients enrolled in the molecular analysis. CTC presence was evaluated with real-time reverse transcription polymerase chain reaction assay (qPCR) based on the expression of three tumor genetic markers: carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), and/or cancer stem cells marker CD133 (CEA/CK20/CD133). We found that CTC detection 7 days after surgery was of prognostic significance for the local recurrence (P value = 0.006). CTC detected preoperatively and 24 hours after resection had no prognostic value in cancer recurrence; however, there was a significant relationship between CTC prevalence 24 hours after surgery and lymph node metastasis (pN1-2). We also confirmed a significant clearance of CTC in peripheral blood (PB) 24 hours after surgery. Preoperative sampling is not significant for prognosis in rectal cancer patients treated with short-term radiotherapy. Detection of CTC in PB 7 days after surgery is an independent factor predicting local recurrence in this group of patients.

FcγRIIA and FcγRIIIA polymorphisms do not influence survival and response to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy in patients with diffuse large B-cell lymphoma

Rituximab in combination with chemotherapy significantly improves outcome compared to chemotherapy alone, and therefore it has become a new standard for the treatment of non-Hodgkin lymphomas (NHLs). The precise mechanism of action of this anti-CD20 antibody is still unknown. In vitro studies suggest that rituximab may induce lysis of Blymphoma cells through the mechanisms of antibody-dependent cellular cytotoxicity (ADCC) [1,2], complement-dependent cytotoxicity [3], or direct signaling leading to apoptosis [4]. In ADCC, the antibody binds lymphoma cells and then is recognized by effector cells via their receptors (FcgRs) for immunoglobulin G (IgG), which leads to eradication of tumor cells. FcgRs have polymorphic alleles that can influence the binding of antibody and efficacy of the immunoresponse. Natural killer (NK) cells bearing homozygous FcgRIIIA-158V/V have higher affinity to IgG1 than cells with F/F or F/V alleles, and mediate ADCC more effectively [5,6]. Recently, it has been shown that the FcgRIIIA-158V allele is associated with rituximab-induced neutropenia [7]. Reports on the influence of FcgRIIA and FcgRIIIA single nucleotide polymorphisms (SNPs) on the survival of patients with diffuse large B-cell lymphoma (DLBCL) are inconsistent. The study by Mitrovic et al. [8] reported the absence of correlation of FcgRIIA and FcgRIIIA polymorphisms with response and survival of patients with DLBCL treated with rituximab (R) and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. In contrast, Kim et al. [9] reported that this polymorphism is predictive in the response to R-CHOP in Korean patients with DLBCL, but does not influence survival. In terms of the FcgRIIA polymorphism, only one study demonstrated that the H/H genotype is correlated with response to rituximab in patients with non-Hodgkin lymphoma, but no difference in survival was found [10]. Encouraged by these findings, we examined the possible correlation between FcgRIIA-131H/R and FcgRIIIA-158V/F polymorphisms and the response rate and survival of patients with DLBCL. We studied 87 patients with DLBCL treated with R-CHOP between 2004 and 2007 at the Institute of Oncology. The median age of patients was 57 years (range 25–81) and the male/female ratio 41/46, and Ann Arbor stage was III–IV in 74%, lactate dehydrogenase (LDH) was4normal in 48%, extranodal sites were involved in 59%, and the International Prognostic Index (IPI) score was 0–2 in 76% of patients. Patients were treated with a median 6 cycles of R-CHOP (range 4–8). During a median observation time of 40 months, 21 patients had disease progression (median time to progression 9 months). There were 17 deaths. The study was approved by the Ethics Committee and all patients gave informed consent. Genotyping