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1.
Role of Dual-Energy Computed Tomography in Thoracic Oncology.
Odisio, EG, Truong, MT, Duran, C, de Groot, PM, Godoy, MC
Radiologic clinics of North America. 2018;(4):535-548
Abstract
Dual-energy CT (DECT) is an emerging technology that has potential to enhance diagnostic performance and radiologists' confidence in the evaluation of thoracic malignancies. DECT clinical applications include characterization of solitary pulmonary nodule, lung masses and mediastinal tumors. DECT-derived iodine uptake quantification may assist in characterization of tumor differentiation and gene expression. The use DECT in oncology has potential to improve lung cancer staging, therapy planning, and assessment of response to therapy as well as detection of incidental pulmonary embolism.
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2.
Complementary and Integrative Medicine in Lung Cancer: Questions and Challenges.
Frenkel, M, Slater, R, Sapire, K, Sierpina, V
Journal of alternative and complementary medicine (New York, N.Y.). 2018;(9-10):862-871
Abstract
Lung cancer represents 13% of all cancers, making it the second most common type of malignancy in the United States. Lung cancer is the leading cause of cancer death in men and women in the United States and accounts for nearly 18% of all deaths from cancer. Because of its high mortality rate, lung cancer is associated with an increased rate of distress. Patients use various strategies to cope with this distress during and after cancer treatments, and complementary and integrative medicine (CIM) has become a common coping strategy. This review covers major questions and challenges of incorporating CIM during and beyond treatment for lung cancer. The questions revolve around determining the value of nutrition and nutritional supplements, assessing the role of exercise, addressing the mind-body connection, enhancing the benefit of immunotherapy, and determining the benefit of incorporating complementary therapies such as acupuncture and homeopathy. This review may provide a basis for discussion that can enhance patient-doctor dialogue regarding the use of CIM during and after treatment for lung cancer.
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3.
Exploring the potential of NTME/GC-MS, in the establishment of urinary volatomic profiles. Lung cancer patients as case study.
Porto-Figueira, P, Pereira, J, Miekisch, W, Câmara, JS
Scientific reports. 2018;(1):13113
Abstract
The growing cancer incidence and mortality worldwide claims for the development of novel diagnostic strategies. In this study we aimed to explore the potential of an innovative methodology, based on a needle trap microextraction (NTME), combined with gas chromatography-mass spectrometry (GC-MS), as new approach to isolate and profile urinary volatile organic metabolites (VOMs) from lung cancer (LC) patients and healthy individuals (CTRL). In this context, different experimental parameters with influence of NTME extraction efficiency including, temperature, equilibration time, headspace volume, ionic strength, pH, effects of sample volume and stirring, were investigated and optimized. For the DVB/CarX/Car1000 needle trap device (NTD), the best results were obtained using 40 mL headspace of a 4-mL acidified (pH = 2) urine sample with 20% NaCl and an extraction temperature of 50 °C for 40 min of equilibration time. The stability of the isolated VOMs was investigated up to 72 h after extraction. From the VOMs identified, belonging namely to ketones, sulphur and benzene derivatives, 98 presented a frequency of occurrence above 90%. Data were processed by discriminant analysis, retrieving differentiated clusters for LC and CTRL groups. As far we are aware, this is the first study using NTME/GC-MS to establish urinary volatomic profiles. Preliminary results are very promising, as broad and comprehensive volatile profiles were obtained. Moreover, the extended storage stability of the NTD devices opens new opportunities for sampling other matrices in a wide range of applications.
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4.
The Risk for Lung Cancer Incidence with Calcium Channel Blockers: A Systematic Review and Meta-Analysis of Observational Studies.
Rotshild, V, Azoulay, L, Zarifeh, M, Masarwa, R, Hirsh-Raccah, B, Perlman, A, Muszkat, M, Matok, I
Drug safety. 2018;(6):555-564
Abstract
INTRODUCTION There are conflicting findings regarding the association between the use of calcium channel blockers (CCBs) and the risk of lung cancer. Considering the public health importance of lung cancer prevention, and emerging evidence of a significant biologic role of calcium channel regulation in the development of lung cancer, we conducted a meta-analysis to assess the risk of lung cancer in CCB users compared with non-CCB users. MATERIALS AND METHODS We conducted a comprehensive systematic search of leading medical databases for observational studies published up to December 2017 that examined CCB use and the risk of lung cancer. We used random-effects models to pool results. The impact of duration of CCB use on the estimated effect size was explored using random effects meta-regression. RESULTS Ten studies (six cohort and four case-control studies) that evaluated the overall cancer risk among 38,758 CCB users were included in the analysis. Overall risk ratio (RR) for CCB use and lung cancer was 1.15 (95% confidence interval [CI] 1.01-1.32). Subgroup analysis by duration of CCB use suggested that the observed increase in lung cancer risk was driven by the results of five studies with prolonged (≥ 4 years) exposure (RR 1.18; 95% CI 1.08-1.30). CONCLUSIONS Our analysis suggests exposure to CCBs is associated with an increased risk of lung cancer. Considering their widespread use, and the paucity of data on the long-term effects of chronic exposure to CCBs, these results are reason for concern and warrant further investigation. SYSTEMATIC REVIEW REGISTRATION The protocol for this study was registered at the PROSPERO registry of systematic reviews (registry number: CRD42017056362).
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Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: A dose-response PRISMA meta-analysis.
Wei, H, Jing, H, Wei, Q, Wei, G, Heng, Z
Medicine. 2018;(37):e12282
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Abstract
The associations of the risk of lung cancer with the vitamin D intake and serum level are controversial. We performed a comprehensive dose-response meta-analysis to evaluate the precise relationships between the above mentioned parameters.We performed a web search of the PubMed, Medline, and Embase databases to identify potential studies that evaluated the relationships between vitamin D intake or serum 25-hydroxyvitamin D (25([OH]D) levels and the risk of lung cancer on December 5, 2017. According to the inclusion and exclusive criteria, 16 studies were included in this meta-analysis. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. A dose-response analysis was conducted to quantitate the relationship between the serum 25(OH)D or vitamin D intake and the risk of lung cancer.The pooled RR (highest level vs lowest level) showed that the serum 25(OH)D level was not associated with the risk of lung cancer (RR = 1.046, 95% CI = 0.945-1.159). A high vitamin D intake was inversely correlated with the lung cancer risk (RR = 0.854, 95% CI = 0.741-0.984). No significant dose-response relationship was observed between the serum 25(OH)D level and the lung cancer risk. The linearity model of the dose-response analysis indicated that with every 100 IU/day increase in vitamin D intake, the risk of lung cancer decreased by 2.4% (RR = 0.976, 95% CI = 0.957-0.995, P = .018).A high vitamin D intake provides limited protection against lung cancer carcinogenesis.
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Spectral CT Analysis of Solitary Pulmonary Nodules for Differentiating Malignancy from Benignancy: The Value of Iodine Concentration Spatial Distribution Difference.
Wu, L, Cao, G, Zhao, L, Tang, K, Lin, J, Miao, S, Lin, T, Sun, J, Zheng, X
BioMed research international. 2018;:4830659
Abstract
OBJECTIVE The objective is to assess the value of spatial distribution difference in iodine concentration between malignant and benign solitary pulmonary nodules (SPNs) by analyzing multiple parameters of spectral CT. METHODS Sixty patients with 39 malignant nodules and 21 benign nodules underwent chest contrast CT scans using spectral imaging mode during pulmonary arterial phase (PP), arterial phase (AP), and venous phase (VP). Iodine concentrations of proximal and distal regions in pulmonary nodules on iodine-based material decomposition images were recorded. Normalized iodine concentration (NIC) and the differences in NIC between the proximal and the distal regions (dNIC) were calculated. The two-sample t-test and Mann-Whitney U-test were performed to compare the multiple parameters generated from spectral CT between malignant and benign nodules. Receiver operating characteristic (ROC) curves were generated to calculate sensitivity and specificity. RESULTS NIC in the proximal region (NICpro) and NIC in the distal region (NICdis) between malignant and benign nodules at AP (NICpro, P=0.012; NICdis, P=0.024), and VP (NICpro, P=0.005; NICdis, P =0.004) were significantly different. NICpro at PP (P = 0.037) was also found significantly different between malignant and benign nodules; however, no significant differences were found in NICdis at PP (P = 0.093). In addition, the dNIC of malignant nodules was significantly higher than that of benign ones at PP (median and interquartiles (0.31, 0.11, 0.57 versus -0.26, -0.5, -0.1); p≤0.001), AP (mean dNIC, 0.093 ±0.094 versus -0.075±0.060; p≤0.001), and VP (mean dNIC, 0.171±0.137 versus -0.183±0.127; p≤0.001). The sensitivity and specificity (93%, 95%, respectively) of dNIC during VP were higher than other parameters, with a threshold value of -0.07. CONCLUSIONS Spectral CT imaging with multiple parameters such as NICpro, NICdis, and dNIC may be a new method for differentiating malignant SPNs from benign ones.
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The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers.
Vishwanathan, K, Dickinson, PA, Bui, K, Cassier, PA, Greystoke, A, Lisbon, E, Moreno, V, So, K, Thomas, K, Weilert, D, et al
Journal of clinical pharmacology. 2018;(4):474-484
Abstract
Two phase 1, open-label studies assessed the impact of food or gastric pH modification (omeprazole) on the exposure and safety/tolerability of osimertinib and its metabolites. The food effect study was an open-label, 2-period crossover study in patients with advanced non-small-cell lung cancer, randomized into 2 treatment sequences: single-dose osimertinib 80 mg in a fed then fasted state or fasted then fed. The gastric pH study was an open-label, 2-period fixed sequence study assessing the effect of omeprazole on osimertinib exposure in healthy male volunteers. In period 1, volunteers received omeprazole 40 mg (days 1-4), then omeprazole 40 mg plus osimertinib 80 mg (day 5). In period 2, volunteers received osimertinib 80 mg alone (single dose). Blood samples were collected at prespecified time points for pharmacokinetic analyses. Safety/tolerability was also assessed. In the food effect study 38 patients were randomized to fed/fasted (n = 18) or fasted/fed (n = 20) sequences with all patients completing treatment. Coadministration with food did not affect osimertinib exposure (geometric least-squares mean ratios [90% confidence intervals]: 106.05% [94.82%, 118.60%] [area under the plasma concentration time curve from zero to 72 hours] and 92.75% [81.40%, 105.68%] [maximum plasma concentration]). In the gastric pH study (n = 68 received treatment, n = 47 completed the study), coadministration with omeprazole did not affect osimertinib exposure (geometric least-squares mean ratios 106.66% [100.26%, 113.46%] [area under the concentration-time curve], 101.65% [94.65%, 109.16%] [peak concentration]). Osimertinib was well tolerated in both studies. Osimertinib may be administered without regard to food. Dose restriction is not required in patients whose gastric pH may be altered by concomitant agents or medical conditions. ClinicalTrials.gov: NCT02224053, NCT02163733.
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A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer.
Kondo, R, Watanabe, S, Shoji, S, Ichikawa, K, Abe, T, Baba, J, Tanaka, J, Tsukada, H, Terada, M, Sato, K, et al
Oncology. 2018;(4):223-232
Abstract
OBJECTIVE Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. RESULTS Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5-59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). CONCLUSIONS This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.
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Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab.
Dumenil, C, Massiani, MA, Dumoulin, J, Giraud, V, Labrune, S, Chinet, T, Giroux Leprieur, E
PloS one. 2018;(4):e0195945
Abstract
INTRODUCTION The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in 'real life' patients with advanced NSCLC. METHODS Clinical and histological characteristics, therapies and survival data of all consecutive patients with advanced NSCLC included prospectively and treated by nivolumab in two French academic hospitals between February 2015 and December 2016 were examined. RESULTS Sixty-seven patients were included, mostly male (69%), current or former smokers (87%) with PS <2 (73%). Median age was 68.5 years and 42% were aged ≥70 years. According to uni- and multi-variate analyses, only PS 2 (OR = 0.17, 95% CI 0.03-0.99, p = 0.049) and number of previous treatment lines (OR = 0.33, 95% CI 0.13-0.85, p = 0.022) were significantly negatively associated with tumor control. Worse progression-free survival (PFS) was significantly associated with PS 2 (HR = 5.17, 95% CI 1.99-13.43, p = 0.001) and use of steroids (HR = 3.27, 95% CI 1.39-7.69, p = 0.006). Worse overall survival was associated with symptomatic brain metastasis (HR = 3.15, 95% CI 1.23-8.85, p = 0.029). Treatment-related adverse events occurred in 47 patients (70%), symptomatic brain metastasis being significantly associated with Grade ≥3 toxicity (OR = 8.13, 95% CI 1.21-55.56, p = 0.031). Age and nutritional status were not associated with response, PFS, OS or toxicity. CONCLUSION Our results suggest that nivolumab is not beneficial or safe for patients with PS 2 and symptomatic brain metastases.
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10.
An MRM-Based Cytokeratin Marker Assay as a Tool for Cancer Studies: Application to Lung Cancer Pleural Effusions.
Perzanowska, A, Fatalska, A, Wojtas, G, Lewandowicz, A, Michalak, A, Krasowski, G, Borchers, CH, Dadlez, M, Domanski, D
Proteomics. Clinical applications. 2018;(2)
Abstract
PURPOSE The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis, and therapy monitoring. Second, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. EXPERIMENTAL DESIGN A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity. The potential clinical applicability was demonstrated by the analysis of 118 PE samples. RESULTS The MRM assay was evaluated for endogenous detection, linearity, precision, upper and lower limits of quantification, selectivity, reproducibility and peptide stability, and is generally applicable to any epithelial cancer study. A set of 118 patients with known pathologies allowed us to define the range of CK levels in clinical PE samples. Specific CKs were able to differentiate cancer-related PEs from those caused by benign ailments. In addition, they allowed to differentiate between PEs from subjects with small cell lung cancer versus non-small cell lung carcinoma, and to further differentiate the latter into its two subtypes, adenocarcinoma and squamous cell carcinoma. CONCLUSION AND CLINICAL RELEVANCE An MRM-based CK assay for carcinoma studies can differentiate between the three lung cancer histological types using less-invasive PE sampling providing potential therapy-guiding information on patients that are inoperable.