Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to evaluate the efficacy and safety of pemetrexed plus cisplatin/carboplatin in locally advanced or metastatic non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy.</p> <p>Methods</p> <p>Fifty-three locally advanced or metastatic non-small cell lung cancer patients previously treated with platinum-based chemotherapy received pemetrexed 500 mg/m²plus cisplatin 75 mg/m²or carboplatin area under the curve (AUC) 5 every 21 days, with dexamethasone, folic acid and vitamin B12 being administered.</p> <p>Results</p> <p>Median age was 52 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0-2. Thirty-eight patients had stage IV tumors. Thirty-seven patients had adenocarcinoma (including 6 alveolar carcinoma patients), and fourteen patients had squamous cell carcinoma. Thirty-four patients were treated in second line, 15 in third line, and 4 in fourth line. Seven patients (13.2%) showed partial response; Thirty-six (67.9%) had stable disease. The median progression free survival time was 6.0 months and the median overall survival time was 10.0 months. The 1-year survival rate was 40.9%. Five (9.4%) and four (7.5%) patients experienced grade 3 or 4 leukopenia and thrombocytopenia, respectively. Nonhematological toxicities included grade 3 nausea/vomiting in 1 patient (1.9%), grade 3 rash in 1 patient, grade 4 diarrhea in 1 patient (1.9%) and grade 4 creatinine increase in 1 patient (1.9%).</p> <p>Conclusion</p> <p>Locally advanced or metastatic NSCLC patients previously treated with platinum-based chemotherapy could benefit from pemetrexed plus cisplatin/carboplatin chemotherapy with tolerable adverse events.</p

Applications of Generalized Cascade Scattering Matrix on the Microwave Circuits and Antenna Arrays

The ideal lossless symmetrical reciprocal network (ILSRN) is constructed and introduced to resolve the complex interconnections of two arbitrary microwave networks. By inserting the ILSRNs, the complex interconnections can be converted into the standard one-by-one case without changing the characteristics of the previous microwave networks. Based on the algorithm of the generalized cascade scattering matrix, a useful derivation on the excitation coefficients of antenna arrays is firstly proposed with consideration of the coupling effects. And then, the proposed techniques are applied on the microwave circuits and antenna arrays. Firstly, an improved magic-T is optimized, fabricated, and measured. Compared with the existing results, the prototype has a wider bandwidth, lower insertion loss, better return loss, isolation, and imbalances. Secondly, two typical linear waveguide slotted arrays are designed. Both the radiation patterns and scattering parameters at the input ports agree well with the desired goals. Finally, the feeding network of a two-element microstrip antenna array is optimized to decrease the mismatch at the input port, and a good impedance matching is successfully achieved

Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα) expression level in postoperative NSCLC patients who received adjuvant chemotherapy.</p> <p>Methods</p> <p>Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed.</p> <p>Results</p> <p>TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopIIα (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopIIα expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopIIα expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopIIα to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy.</p> <p>Conclusions</p> <p>High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.</p

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis

AIM: To study the risk factors for liver metastasis and the prognosis in patients with human epidermal growth factor receptor 2 (HER2) over-expressing gastric cancer (GC)

Fatal Interstitial Lung Disease after Addition of Sorafenib to a Patient with Lung Adenocarcinoma Who Had Failed to Improve with Erlotinib Alone

Interstitial lung disease (ILD) induced by epidermal growth factor receptor tyrosine kinase inhibitors has been extensively documented with decreasing incidence after appropriate patient selection due to increasing awareness over the years. However, ILD induced by sorafenib was mentioned with lower frequency only in patients with hepatocellular and renal cell carcinoma living in Japan but not in patients with other carcinomas or living outside Japan, and it has been overlooked in clinical practice. In the present case, sorafenib was added to the treatment of a 60-year-old non-smoking patient with non-small cell lung cancer (NSCLC). After his failing to improve with erlotinib alone, erlotinib was continued to be given in combination with sorafenib as a salvage therapy. Although clinical signs of ILD were observed 2 weeks after the addition of sorafenib, the radiological diagnosis of ILD was only made 41 days after the initiation of the combination treatment, and the patient died 56 days after treatment onset. It was concluded that ILD was indeed induced by sorafenib. This is the first report of ILD induced by sorafenib in a patient with NSCLC living outside Japan. Oncologists should be aware of this fatal complication for its early detection in order to avoid a severe course of ILD leading to a decrease in the ILD mortality rate