Low-dose CT for lung cancer screening: position paper from the Italian college of thoracic radiology.

Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices.

T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.

The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

Changes in plasma mass-spectral profile in course of treatment of non-small cell lung cancer patients with epidermal growth factor receptor tyrosine kinase inhibitors.

INTRODUCTION: Our previous study showed that pretreatment serum or plasma Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry may predict clinical outcome of non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, plasma proteomic profiles of NSCLC patients were evaluated in the course of EGFR TKIs therapy. MATERIALS AND METHODS: Plasma samples were collected at baseline, in the course of gefitinib therapy and at treatment withdrawal. Samples were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Acquired spectra were classified by the VeriStrat test into "good" and "poor" profiles. The association between VeriStrat classification and progression-free survival (PFS) and overall survival (OS), and types of clinical progression, was analyzed. RESULTS: Plasma samples from 111 NSCLC patients treated with gefitinib were processed. VeriStrat "good" classification at baseline correlated with longer PFS (hazard ratio [HR], 0.54; 95% confidence interval, 0.35-0.83; p = 0.005) and OS (HR, 0.40; 95% confidence interval, 0.26-0.61; p < 0.0001), when compared with VeriStrat "poor." Multivariate analysis confirmed longer PFS (HR, 0.52; p = 0.025) and OS (HR, 0.44; p = 0.001) in patients classified as VeriStrat "good", when VeriStrat was considered as a time-dependent variable. About one-third of baseline "good" classifications had changed to "poor" at the time of treatment withdrawal; progression in these patients was associated with the development of new lesions. CONCLUSIONS: Our findings support the role of VeriStrat in the assistance in treatment selection of NSCLC patients for EGFR TKI therapy and its potential utility in treatment monitoring.

Phase I study of NGR-hTNF, a selective vascular targeting agent, in combination with cisplatin in refractory solid tumors.

PURPOSE: NGR-hTNF exploits the tumor-homing peptide asparagine-glycine-arginine (NGR) for selectively targeting TNF-α to an aminopeptidase N overexpressed on cancer endothelial cells. Preclinical synergism with cisplatin was displayed even at low doses. This study primarily aimed to explore the safety of low-dose NGR-hTNF combined with cisplatin in resistant/refractory malignancies. Secondary aims included pharmacokinetics (PKs), pharmacodynamics, and activity. EXPERIMENTAL DESIGN: NGR-hTNF was escalated using a doubling-dose scheme (0.2-0.4-0.8-1.6 µg/m(2)) in combination with fixed-dose of cisplatin (80 mg/m(2)), both given intravenously once every three weeks. PKs and circulating TNF-receptors (sTNF-Rs) were assessed over the first three cycles. RESULTS: Globally, 22 patients (12 pretreated with platinum) received a range of one to ten cycles. Consistently with the low-dose range tested, maximum-tolerated dose was not reached. No dose-limiting toxicities (DLTs) were observed at 0.2 (n = 4) and 0.4 µg/m(2) (n = 3). One DLT (grade 3 infusion-related reaction) was observed at 0.8 µg/m(2). This dose cohort was expanded to six patients without further DLTs. No DLTs were noted also at 1.6 µg/m(2) (n = 3). NGR-hTNF exposure increased dose-proportionally without apparent PK interactions with cisplatin. No shedding of sTNF-Rs was detected up to 0.8 µg/m(2). At the dose level of 0.8 µg/m(2), expanded to 12 patients for activity assessment, a platinum-pretreated lung cancer patient achieved a partial response lasting more than six months and five patients maintained stable disease for a median time of 5.9 months. CONCLUSIONS: The combination of NGR-hTNF 0.8 µg/m(2) with cisplatin 80 mg/m(2) showed favorable toxicity profile and promising antitumor activity.