Carbone D.P.,Thoracic Oncology Center |
Felip E.,University of Barcelona
Clinical Lung Cancer | Year: 2011
There is a high risk of relapse after curative-intent resection for even early-stage Non-small cell lung cancer (NSCLC), and thus adjuvant chemotherapy has been explored with the goal of eliminating occult metastases and consequently reducing the risk of recurrence. Although adjuvant chemotherapy confers a survival advantage of approximately 5% at 5 years and is now generally accepted for patients with stage II-IIIA disease, adjuvant therapy for patients with stage I disease is more controversial. In this review we describe approaches to improve treatment outcomes and ongoing research into new therapies in the adjuvant setting. In the future it is likely that patient selection on the basis of gene signatures and biomarkers will be of increasing importance in determining optimal treatment for individual patients. New targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors, angiogenesis inhibitors, and anticancer immunotherapies are showing activity in the advanced disease setting and are being studied for incorporation into multimodal adjuvant treatment approaches. It is hoped that such advances and a changing treatment paradigm will ultimately result in greater survival for patients with early NSCLC. © 2011 Elsevier Inc. All rights reserved.
Poste G.,Arizona State University |
Carbone D.P.,Thoracic Oncology Center |
Parkinson D.R.,Nodality |
Verweij J.,Erasmus Medical Center |
And 2 more authors.
Clinical Cancer Research | Year: 2012
Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts. ©2012 AACR.
Sugarbaker P.H.,Washington Cancer Institute |
Stuart O.A.,Washington Cancer Institute |
Eger C.,Thoracic Oncology Center
Gastroenterology Research and Practice | Year: 2012
In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients. © 2012 Paul H. Sugarbaker et al.
Pecot C.V.,Vanderbilt University |
Li M.,Vanderbilt University |
Zhang X.J.,Vanderbilt University |
Rajanbabu R.,Thoracic Oncology Center |
And 18 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012
Background: Current management of lung nodules is complicated by nontherapeutic resections and missed chances for cure. We hypothesized that a serum proteomic signature may add diagnostic information beyond that provided by combined clinical and radiographic data. Methods: Cohort A included 265 and cohort B 114 patients. Using multivariable logistic regression analysis we calculated the area under the receiver operating characteristic curve (AUC) and quantified the added value of a previously described serum proteomic signature beyond clinical and radiographic risk factors for predicting lung cancer using the integration discrimination improvement (IDI) index. Results: The average computed tomography (CT) measured nodule size in cohorts A and B was 37.83 versus 23.15 mm among patients with lung cancer and 15.82 versus 17.18 mm among those without, respectively. In cohort A, the AUC increased from 0.68 to 0.86 after adding chest CT imaging variables to the clinical results, but the proteomic signature did not provide meaningful added value. In contrast, in cohort B, the AUC improved from 0.46 with clinical data alone to 0.61 when combined with chest CT imaging data and to 0.69 after adding the proteomic signature (IDI of 20% P=0.0003). In addition, in a subgroup of 100 nodules between 5 and 20mm in diameter, the proteomic signature added value with an IDI of 15% (P < 0.0001). Conclusions: The results show that this serum proteomic biomarker signature may add value to the clinical and chest CT evaluation of indeterminate lung nodules. Impact: This study suggests a possible role of a blood biomarker in the evaluation of indeterminate lung nodules. ©2012 AACR.
Lyons G.,Thoracic Oncology Center |
Quadrelli S.,Thoracic Oncology Center |
Jordan P.,Thoracic Oncology Center |
Colt H.,University of California at Irvine |
Chimondeguy D.,Thoracic Oncology Center
Lung Cancer | Year: 2011
Introduction: The purpose of this study, therefore, was to evaluate the impact of the use of the present classification IASLC staging system (TNM7) on the categorization of patients and survival after resection. Methods: Between August 1985 and January 2007, 414 consecutive patients underwent pulmonary resection with a curative intention for NSCLC at the British Hospital in Buenos Aires were included in this study only if they were pathologically staged as N0-M0. Preoperative staging was performed according to the TNM classification system of the International Union Against Cancer (173 men, 58 women). Results: 231 tumours were identified as pathological N0. Mean age was 61.4 years. 173 patients (74.9%) were men. When the TNM7 was applied, 28 patients (12.1%) changed their T factor staging (14 were moved towards a higher T and 14 were moved to a lower T) and 41 patients (17.7%) changed their pathological staging by applying the TNM7: 14 patients were downstaged (6.1%) and 27 (11.7%) were upstaged. With the present T definition among 103 patients in stage IB 27 were upstaged (18 to IIA and 9 to IIB) and in the group of stage IIIB (n= 14) all of them were downstaged (5 to IIB and 9 to IIA). The current T definition showed a statistically significant difference between the two T1 subgroups (93% versus 70% 5 year survival between T1a and T1b, p= 0.027). Conclusion: This study shows that the clinical impact of the using the IASLC proposed staging system would be modest but relevant, identifying a subgroup with a better prognosis (T1a). © 2011 Elsevier Ireland Ltd.