Abstract Introduction: Bevacizumab was approved for treatment of advanced non-squamous, non-small cell lung cancer (NSCLC) in the US in late 2006. Information on its uptake and patient and tumor factors associated with its use is lacking. Materials and methods: This was a longitudinal, retrospective cohort study of patients with stage IIIB/IV non-squamous NSCLC aged 21 years or greater diagnosed between 2005 and 2010 at four Cancer Research Network sites. Patients were categorized as receiving first-line carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) within 120 days of diagnosis. Information on patient and tumor characteristics was obtained from queries of sites’ electronic tumor registries and administrative databases. Factors independently associated with CPB use were evaluated using bivariate and multivariate logistic regression analyses. Results: A total of 1109 patients with advanced NSCLC were included with 198 (17.9%) and 911 (82.1%) patients receiving CPB and CP, respectively. Bevacizumab use increased modestly during the study period, peaking in 2008 at 18.5%. In bivariate analyses, patients who received CPB were younger with less comorbidity and well to moderately differentiated tumors while patients who received CP were more likely to have had hypertension, peripheral vascular disease, and a prior hospitalization. Factors independently associated with CPB use included younger age, well/moderately differentiated tumor grade, no prior hospitalization, and more recent study year. Conclusions: Use of bevacizumab in patients with advanced NSCLC increased rapidly then moderated. Younger patients and those with lower risks for adverse effects were more likely to receive bevacizumab.
Keywords: carcinoma; non-small-cell lung; angiogenesis inhibitors; diffusion of innovation; managed care programs; health services accessibility; population characteristics

Abstract Objective: In order to prevent and treat radiation-induced adverse events, especially oral mucositis, in patients with oral or oropharyngeal cancer receiving radiotherapy or chemoradiotherapy, a prophylactic bundle, i.e., a set of oral care management procedures, is conducted and assessed. Subjects and methods: The subjects were 30 patients with squamous cell carcinoma of the oral cavity or oropharynx who underwent radiotherapy. The patients received the prophylactic bundle to prevent radiation-induced oral mucositis during radiotherapy. Results: Severe oral mucositis, grade 3, was observed in 5 of 30 patients (17%). The occurrence of oral mucositis was lower than in previous reports. The prophylactic bundle included the use of spacers, administration of pilocarpine hydrochloride, appropriate oral care, and use of steroid ointment during radiotherapy. Conclusions: This preliminary study suggests that the prophylactic bundle, when performed in oral or oropharyngeal cancer patients, decreases severe radiation-induced oral mucositis. Further evaluation is needed in multi-centre, prospective, randomized trials.
Keywords: oral mucositis; radiotherapy; head and neck cancer; prophylactic bundle

Abstract Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV). However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA) still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1) further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3) explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1) The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013). A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001), there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001). 2) Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen concentration (median, 19 months versus 35 months; P <0.001). In addition, a similar result was observed in 194 early stage NSCLC (stage I -IIIA) (P <0.001). Univariate and multivariate analysis revealed that higher levels of fibrinogen (FIB≥4.20 g/L), age, distant metastases and pathological types were positively associated with shorter overall survival (OS). 3) In addition, there was a significant link between the elevation by more than 15% in the plasma fibrinogen level after receiving short-term chemotherapy and shorter overall survival (OS). Conclusion: 1) This study shows high plasma fibrinogen concentration is associated with lymph nodes or distant organ metastases in lung cancer. 2) Furthermore, our results indicate a significant relevance between high pre-treatment plasma fibrinogen concentration and poor prognosis in patients with lung cancer. 3) In addition, we find that the patients with a low plasma fibrinogen level will have a shorter OS if the plasma fibrinogen level increases significantly after receiving short-term chemotherapy. Interestingly, we also find that the patients with a high plasma fibrinogen level will have a longer OS if the plasma fibrinogen level decreases significantly after receiving short-term chemotherapy, which indicate the change of the plasma fibrinogen level after receiving short-term chemotherapy may be used as an independent prognostic factor.
Keywords: lung cancer; fibrinogen; overall survival; prognosis; cancer stage; short-term chemotherapy

Abstract Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The grim statistics speak for themselves with reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem guided gene therapy. Stem cells have the unique potential for self-renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we discuss various strategies to safeguard stem cell guided gene therapy against iatrogenic cancerogenesis. Defining cancer biomarkers to facilitate early diagnosis, elucidating cancer genomics and proteomics with modern tools of next generation sequencing, and analyzing patients’ gene expression profiles provide essential data to elucidate molecular dynamics of cancer and to consider them for crafting pharmacogenomics-based personalized therapies. Streamlining of these data into genetic engineering of stem cells facilitates their use as the vectors delivering therapeutic genes into specific cancer cells. In this realm, stem cells guided gene therapy becomes a promising new frontier in personalized and targeted therapy of cancer.
Keywords: cancer; stem cells; suicide gene therapy; stem cell guided delivery of therapeutics; genomic medicine; pharmacogenomics; targeted therapy; personalized therapy