BackgroundThe aim of this study is to compare the effectiveness of 131I therapy between three groups of DTC patients who received 30, 60 or 100 mCi for thyroid remnant ablation after total thyroidectomy and were postoperatively judged with low risk of cancer recurrence.MethodsThe project was designed as a two-stage, prospective randomized clinical trial. In 1998-2001 in a randomized prospective study the early comparison of treatment with 30 mCi vs 60 mCi suggested the lower 131I activity to be less effective, whereas in 2003-2005 the comparison between 60 vs 100 mCi showed no significant differences. The present study comprises the long-term assessment of the disease course in 3 study groups.ResultsA group of 309 DTC patients (285 women and 24 men) with no clinical, histopathological, sonographical or biochemical signs of persistent disease were included after total thyroidectomy and appropriate extent of neck lymph node dissection (265 with papillary and 44 with follicular thyroid cancer). For radioiodine thyroid remnant ablation, 30 mCi of 131I was applied in 86 patients, whereas 60 mCi in 128 and 100 mCi in 95 patients. The median follow-up was 10 years (2-12) for subjects treated with 30 mCi and 60 mCi and 6 years (2-6) for patients treated with 100 mCi of 131I. In the first evaluation, published previously, we observed that because of incomplete thyroid remnant ablation, the second 131I treatment was necessary in 10% patients, without difference between groups treated with 60 and 100 mCi and in 22% patients treated with 30 mCi. All patients entered full remission. To evaluate the long-term outcome of the adjuvant 131I treatment, the course of the follow-up and the most recent disease status were assessed by sonography, radiological examinations and serum Tg estimation (on LT4-suppressive treatment). Within the whole observation period local relapse was stated in 2 (2.4%), 4 (3%) and 3 (3%) patients treated with 131I activities of 30 mCi, 60 mCi and 100 mCi respectively and serum Tg concentration on LT4-suppressive treatment was low, without differences between groups.ConclusionsNo significant differences in the 5 years efficacy of thyroid remnant radioiodine ablation using 30, 60 and 100 mCi were observed in low-risk DTC patients operated by total thyroidectomy and neck lymph node dissection. However, patients treated initially with 30 mCi, required second course of radioiodine in 22%, while this was necessary only in 13,3% and 11,2% of patients treated with 60 mCi and 100 mCi respectively.

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Polymorphisms in DNA repair genes may modulate not only an individual DNA repair capacity, DNA damage levels and cancer risk but also clinical outcome after DNA damage-inducing anticancer therapy. In this study, we analyzed the association between the XPA -4G>A, XPD Asp312Asn, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC2 -4234G>C, XRCC3 -4541A>G and Thr241Met polymorphisms and prognosis in 250 inoperable non-small cell lung cancer (NSCLC) patients treated with radiotherapy and platinum-based chemotherapy. In univariate model, the XPA-4A and XRCC1 399Gln alleles alone and in combination influenced survival only in stage III group. In multivariate analysis, the XPA-4 GA/AA was associated with poor survival (HR 1.55, p 5 0.011 overall and HR 1.72, p 5 0.008 in stage III). In chemoradiotherapy group, the XPA-4A carriers were at increased risk of death and progression (HR 1.73, p 5 0.013 and HR 1.65, p 5 0.016, respectively), especially in stage III (p 5 0.008). Moreover, individuals with ! 2 XPA/XRCC1 adverse alleles showed a higher risk of death (HR 1.46, p 5 0.036 overall; HR 1.85, p 5 0.004 in stage III and HR 1.71, p 5 0.022 in chemoradiotherapy group) and progression (HR 1.75, p 5 0.011 overall and HR 1.93, p 5 0.005 in stage III). The XPA-4 GA/AA genotype individually and together with the XRCC1 399Gln was an independent unfavorable prognostic factor in our study. Thus, our findings indicate a prognostic potential of the XPA-4G>A in unresected NSCLC treated with radiotherapy and chemoradiotherapy. The results require validation in an independent population.

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Almost all participants from each country want to participate in their treatment decisions. Although there are country-specific differences in the amount of information required, wide variation within each country suggests that information that patients feel is essential or desired for DM should be addressed on an individual basis in all countries.

Certain common inherited variations in genes involved in tumor angiogenesis, progression and metastasis may contribute to cancer therapy outcome and prognosis by altering the gene expression and protein activity. In this report, we examined the effect of functional polymorphisms in MMP-1, MMP-2, MMP-3, VEGF, VEGFR2, FGFR4 and COX-2 genes on overall (OS) and progression-free survival (PFS) of 350 Caucasian patients with inoperable non-small cell lung cancer (NSCLC). The results of multivariate analysis indicated that VEGFR2 -906C and COX-2 -1195G alleles were strongly associated with poor OS and PFS (p 5 0.002 and 0.015, respectively, for OS; p 5 0.009 and 0.015, respectively, for PFS), while MMP-2 -1306 T allele carriers had significantly reduced PFS (p 5 0.010). Moreover, an increased risk of death and progression was significantly associated with the number of adverse alleles for VEGFR2/COX-2 (p 5 0.0005 for OS and 0.0006 for PFS in >1 adverse allele carriers) and VEGFR2/COX-2/MMP-2 combinations (p 5 0.0003 for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2 TC/CC, COX-2 AG/GG and MMP-2 CT/TT genotypes as well as "at risk" allele combinations were identified as independent predictors of unfavorable OS and PFS in the group. In conclusion, the data suggest that selected VEGFR2, COX-2 and MMP-2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated with radiotherapy with or without chemotherapy, although further validation studies are warranted to confirm our observations.The majority of non-small cell lung cancers (NSCLC) are inoperable at initial diagnosis due to advanced stage and/or comorbidities. The choice of treatment in inoperable NSCLC depends mainly on clinical stage and, most frequently, is limited to radiation therapy, chemotherapy or a combination of both. The prognosis, however, remains unsatisfactory because of relatively low response rates and high metastatic potential. Large inter-individual variability is also observed in the clinical course and treatment outcomes, being a result of molecular heterogeneity of the tumor and host factors.1 Therefore, there is a need for novel prognostic and predictive markers that can be detected in blood and used in a large group of NSCLC patients for whom tumor tissue is not readily accessible.Lung cancer progression, including tumor growth, invasion and metastasis, depends on extracellular matrix (ECM) remodeling in which matrix metalloproteinases (MMPs) play an active role. They are multifunctional zinc endopeptidases being important regulators of the tumor microenvironment controlling cell proliferation, migration, inflammation and apoptosis.2 Some MMPs, such as MMP-1, -2, -3, -7 or -9, also contribute to angiogenesis, for example, MMP-2 and -9 are known to release vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) from ECM that, in turn, up-regulate the MMP expression. Angiogenesis is a complex, dynamic process of new blood vessels formation in which VEGF and VEGF receptor 2 (VEGF...

PCI in the current series was well tolerated and associated with a relatively low toxicity.

BackgroundSeveral studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer.MethodsBronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B.ResultsMore than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen’s κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p<0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p = 0.03, RR = 2.11) expression on overall survival in a group of 60 patients with NSCLC.ConclusionThese results show the feasibility of multiple gene expression analysis in bronchoscopy obtained cancer specimens as prognostic markers in radiotherapy and chemotherapy for advanced lung cancer. A limiting factor was relatively high proportion of samples from which sufficient amount of RNA could not be isolated.