Survival analysis of patients with locally advanced non-small cell lung cancer treated at the Nu-Med Radiotherapy Center in Elbląg

Introduction.  The study aimed to report the efficiency of radical radiotherapy and chemoradiotherapy in patients with non-small cell lung cancer (NSCLC) treated in the Nu-Med Radiotherapy Center in Elbląg. Material and methods.  Ninety-two patients diagnosed with NSCLC treated between 2013 and 2016 were included in the analysis. Overall survival (OS) was estimated by the Kaplan-Meier method. Results.  The 2-year OS for all patients was 36% (median 1.5 years). Two prognostic factors had a significant impact: tre­atment method and performance status (PS). Patients who underwent concurrent radiochemotherapy and were treated sequentially had a better 2-year OS in comparison with those treated with radiotherapy alone (respectively 46% and 37% vs. 25%, p ≤ 0.05). Patients with PS 0–1 had better OS (median 1.6 years) compared with PS 2 (median 0.7 years, p = 0.04). Other prognostic factors analysed had no impact on OS in our study. Conclusions.  The treatment results of our patients are comparable to those in published trials and meta-analyses

PDR brachytherapy: a report on one – year clinical experience at the Medical University of Gdańsk

PurposeOne-year clinical experience with pulse dose rate (PDR) brachytherapy is presented.Material and methodsBetween March 1999 and June 2000 intracavitary, intraluminal, and interstitial PDR brachytherapy was performed in 119 patients with a variety of malignancies. The dose per pulse of 0.5–4 Gy, repeated each hour, or 6 Gy per application was administered, up to the total dose of 6–70 Gy, using a microSelectron-PDR remote afterloading system with a 192Ir source of 1 Ci nominal activity. The planning system PLATO BPS (version 13) was used for dose calculations. Depending on individual applications, the algorithms of the dose point, the geometrical volume, or the geometrical point dose distribution optimization in PDR treatment planning were performed. In 40 patients therapy was given with a curative intent, and 74 cases were treated palliatively. In the remaining five patients PDR was applied as salvage therapy in the previously irradiated area.ResultsWith a median follow-up of 11 months (range 1–18 months) local control was maintained until the last follow-up or death in 39 out of 40 patients treated with radical intent. The subjective improvement was achieved in more than a half of patients with advanced esophageal and lung carcinomas presenting dysphagia and dyspnoe. Significant acute toxicity (severe esophagitis precluding subsequent POR application) occurred in only one patient. Delayed vaginal cuff necrosis was observed in one woman who received prior pelvic irradiation for gynaecological cancer.ConclusionThe PDR brachytherapy is a safe and clinically effective method in a variety of malignancies. The possibility of programme optimization combined with the use of relatively wide range of pulse doses makes it possible to deliver an optimal brachytherapy scheme

Survival analysis of patients with locally advanced non-small cell lung cancer treated at the Nu-Med Radiotherapy Center in Elbląg

Introduction.  The study aimed to report the efficiency of radical radiotherapy and chemoradiotherapy in patients with non-small cell lung cancer (NSCLC) treated in the Nu-Med Radiotherapy Center in Elbląg. Material and methods.  Ninety-two patients diagnosed with NSCLC treated between 2013 and 2016 were included in the analysis. Overall survival (OS) was estimated by the Kaplan-Meier method. Results.  The 2-year OS for all patients was 36% (median 1.5 years). Two prognostic factors had a significant impact: tre­atment method and performance status (PS). Patients who underwent concurrent radiochemotherapy and were treated sequentially had a better 2-year OS in comparison with those treated with radiotherapy alone (respectively 46% and 37% vs. 25%, p ≤ 0.05). Patients with PS 0–1 had better OS (median 1.6 years) compared with PS 2 (median 0.7 years, p = 0.04). Other prognostic factors analysed had no impact on OS in our study. Conclusions.  The treatment results of our patients are comparable to those in published trials and meta-analyses.Introduction.  The study aimed to report the efficiency of radical radiotherapy and chemoradiotherapy in patients with non-small cell lung cancer (NSCLC) treated in the Nu-Med Radiotherapy Center in Elbląg. Material and methods.  Ninety-two patients diagnosed with NSCLC treated between 2013 and 2016 were included in the analysis. Overall survival (OS) was estimated by the Kaplan-Meier method. Results.  The 2-year OS for all patients was 36% (median 1.5 years). Two prognostic factors had a significant impact: tre­atment method and performance status (PS). Patients who underwent concurrent radiochemotherapy and were treated sequentially had a better 2-year OS in comparison with those treated with radiotherapy alone (respectively 46% and 37% vs. 25%, p ≤ 0.05). Patients with PS 0–1 had better OS (median 1.6 years) compared with PS 2 (median 0.7 years, p = 0.04). Other prognostic factors analysed had no impact on OS in our study. Conclusions.  The treatment results of our patients are comparable to those in published trials and meta-analyses

PDR brachytherapy: a report on one – year clinical experience at the Medical University of Gdańsk

SummaryPurposeOne-year clinical experience with pulse dose rate (PDR) brachytherapy is presented.Material and methodsBetween March 1999 and June 2000 intracavitary, intraluminal, and interstitial PDR brachytherapy was performed in 119 patients with a variety of malignancies. The dose per pulse of 0.5–4 Gy, repeated each hour, or 6 Gy per application was administered, up to the total dose of 6–70 Gy, using a microSelectron-PDR remote afterloading system with a 192Ir source of 1 Ci nominal activity. The planning system PLATO BPS (version 13) was used for dose calculations. Depending on individual applications, the algorithms of the dose point, the geometrical volume, or the geometrical point dose distribution optimization in PDR treatment planning were performed. In 40 patients therapy was given with a curative intent, and 74 cases were treated palliatively. In the remaining five patients PDR was applied as salvage therapy in the previously irradiated area.ResultsWith a median follow-up of 11 months (range 1–18 months) local control was maintained until the last follow-up or death in 39 out of 40 patients treated with radical intent. The subjective improvement was achieved in more than a half of patients with advanced esophageal and lung carcinomas presenting dysphagia and dyspnoe. Significant acute toxicity (severe esophagitis precluding subsequent POR application) occurred in only one patient. Delayed vaginal cuff necrosis was observed in one woman who received prior pelvic irradiation for gynaecological cancer.ConclusionThe PDR brachytherapy is a safe and clinically effective method in a variety of malignancies. The possibility of programme optimization combined with the use of relatively wide range of pulse doses makes it possible to deliver an optimal brachytherapy scheme

Increased Insulin-Like Growth Factor 1 Receptor Protein Expression and Gene Copy Number in Small Cell Lung Cancer

PurposeIdentification of new therapies in small cell lung cancer (SCLC) is urgently needed. Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. Knowledge about IGF1R protein expression, gene copy number, and the prognostic relevance of these features in SCLC is limited.MethodsWe analyzed IGF1R protein expression and gene copy number in primary tumors from 90 patients with SCLC (67 men and 23 women) who underwent pulmonary resection. IGF1R expression assessed by immunohistochemistry with H scores from 0 to 400 was evaluable in 84 patients and IGF1R gene copy number assessed by silver in situ hybridization technique in 81 patients.ResultsMedian H score for IGF1R protein expression was 88 (range, 0–400), and the proportion of positive immunostaining using cutoff H score of 10 was 74%. Increased IGF1R gene copy number (an average of four or more copies per cell) was found in 15 cases (18.5%), five of whom (6.2%) showed gene amplification. There was a significant correlation between protein expression and gene copy number (r = 0.49, p < 0.005). IGF1R expression and gene copy number did not associate with clinicopathological factors such as patient age, tumor size, lymph node involvement, stage, and survival.ConclusionsSCLC is characterized by frequent high-IGF1R protein expression, increased gene copy number, and occasional occurrence of true gene amplification. These features may have important implications for future anti-IGF1R therapeutic approaches

Fibroblast Growth Factor Receptor 1 and Related Ligands in Small-Cell Lung Cancer

Introduction: Small-cell lung cancer (SCLC) accounts for 15% of all lung cancers and has been understudied for novel therapies. Signaling through fibroblast growth factors (FGF2, FGF9) and their high-affinity receptor has recently emerged as a contributing factor in the pathogenesis and progression of non-small-cell lung cancer. In this study, we evaluated fibroblast growth factor receptor 1 (FGFR1) and ligand expression in primary SCLC samples. Methods: FGFR1 protein expression, messenger RNA (mRNA) levels, and gene copy number were determined by immunohistochemistry (IHC), mRNA in situ hybridization, and silver in situ hybridization, respectively, in primary tumors from 90 patients with SCLC. Protein and mRNA expression of the FGF2 and FGF9 ligands were determined by IHC and mRNA in situ hybridization, respectively. In addition, a second cohort of 24 SCLC biopsy samples with known FGFR1 amplification by fluorescence in situ hybridization was assessed for FGFR1 protein expression by IHC. Spearman correlation analysis was performed to evaluate associations of FGFR1, FGF2 and FGF9 protein levels, respective mRNA levels, and FGFR1 gene copy number. Results: FGFR1 protein expression by IHC demonstrated a significant correlation with FGFR1 mRNA levels (p < 0.0001) and FGFR1 gene copy number (p = 0.03). The prevalence of FGFR1 mRNA positivity was 19.7%. FGFR1 mRNA expression correlated with both FGF2 (p = 0.0001) and FGF9 (p = 0.002) mRNA levels, as well as with FGF2 (p = 0.01) and FGF9 (p = 0.001) protein levels. There was no significant association between FGFR1 and ligands with clinical characteristics or prognosis. In the second cohort of specimens with known FGFR1 amplification by fluorescence in situ hybridization, 23 of 24 had adequate tumor by IHC, and 73.9% (17 of 23) were positive for FGFR1 protein expression. Conclusions: A subset of SCLCs is characterized by potentially activated FGF/FGFR1 pathways, as evidenced by positive FGF2, FGF9, and FGFR1 protein and/or mRNA expression. FGFR1 protein expression is correlated with FGFR1 mRNA levels and FGFR1 gene copy number. Combined analysis of FGFR1 and ligand expression may allow selection of patients with SCLC to FGFR1 inhibitor therapy

Phospholipids mediated conversion of HDLs generates specific apoA-II pre-β mobility particles

Apolipoproteins (apo)A-I and A-II are major proteins of human HDL. The cycling of apoA-I between lipid-poor and lipid-rich forms of HDL plays a key role in the transport of cholesterol by these particles. ApoA-II resides only in part of HDL particles, and little is known about its role in HDL metabolism. Our study investigates the redistribution of apoA-II after HDL remodelling induced by exogenous phospholipids (PL). During incubation with egg yolk lecithin (EYL) liposomes, human HDL became PL-enriched and free cholesterol (FC)-depleted, and lost small amounts of apoA-I and apoA-II. The loss of FC and apolipoproteins correlated with the rise of PL content in HDL. Agarose gel electrophoresis demonstrated the appearance of new pre-β mobility fractions containing apoA-I and apoA-II in liposomes and HDL mixtures. Two-dimensional nondenaturing 2–27% PAGE has shown that the pre-β mobility fraction that appeared at initial liposome-PL/HDL-PL ratio 5:1 consisted of two distinct heterogeneous subpopulations of particles containing either apoA-I or apoA-II. Our study provides evidence that during HDL conversion mediated by PL apoA-II dissociated from HDL particles yielding apoA-II-specific pre-β mobility particles. This observation supports the hypothesis that apoA-II in plasma, like apoA-I, may cycle between lipid-poor and lipid-rich forms of HDL