Lung Cancer

13 Sep

Posted at 19:58h in Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania
MedicalResearch.com Interview with: [caption id="attachment_27877" align="alignleft" width="132"]Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Dr. Erica Carpenter[/caption] Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients' tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy. Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn's Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.

13 Sep

Posted at 19:37h in Author Interviews, Chemotherapy, Immunotherapy, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27869" align="alignleft" width="95"]Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital Dr. Chih-Hsin Yang[/caption] Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy. A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).

11 Sep

Posted at 21:03h in Author Interviews, Biomarkers, Cancer Research, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27803" align="alignleft" width="200"]Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 Dr. Karen Reckamp[/caption] Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 MedicalResearch.com: What is the background for this study? What are the main findings? Response: • Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation. • A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy. • The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies. • This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.

09 Sep

Posted at 03:14h in Author Interviews, Brigham & Women's - Harvard, Cancer Research, Colon Cancer, End of Life Care, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27780" align="alignleft" width="253"]Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114 Dr. Joseph Greer[/caption] Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many patients with advanced cancer have a high symptom burden, increased depression symptoms, misperceptions about their prognosis, and difficulties in making decisions about care at the end of life. To address these challenges and improve care for this vulnerable population, our research team initially conducted a small, single-group pilot study of early palliative care integrated with standard oncology care for patients with advanced lung cancer. This study showed that the model of integrated care was feasible and acceptable to patients and their families. Specifically, the majority of patients in the study were able to meet with a palliative care clinician at least monthly from the time of diagnosis of metastatic lung cancer, in order to receive help with managing symptoms as well as support for coping with the disease and making decisions about treatment. We then conducted a follow-up randomized controlled trial of early, integrated palliative care in a sample of approximately 150 patients with metastatic non-small cell lung cancer. This study was published in the New England Journal of Medicine in 2010 and showed that those patients who received early palliative care reported significantly improved quality of life, mood, prognostic awareness, and end-of-life care compared to those who received standard oncology care alone. To confirm the findings of our prior research and to determine whether the benefits of early integrated palliative care would apply to a larger sample of patients with diverse malignancies, we recently completed another randomized trial of this same model of care in a sample of 350 patients with incurable lung and gastrointestinal cancers. In this trial, we observed that patients who received the early palliative care intervention reported higher quality of life and improved mood by 24 weeks but not at the primary end-point of 12 weeks. Our team was surprised to find that the trajectory of quality of life and depression symptoms over time was different for individuals with incurable lung versus gastrointestinal cancers in this study. As expected, the palliative care intervention positively buffered the decline in quality of life by 12 weeks for patients with incurable lung cancer, as we had seen in our prior trial. However, the group of patients with gastrointestinal cancers reported an improvement in their quality of life by the 12-week time point regardless of whether they received the palliative care intervention. We are still exploring possible reasons for this difference, such as whether changes in cancer therapy may have reduced symptoms and improved quality of life in the group of patients with gastrointestinal cancer. In addition, we were pleased to learn that the early integrated palliative care intervention led to improvements in how patients cope with their illness. For example, compared to patients in the usual oncology care group, those who received early, integrated palliative care were more likely to learn ways to accept their diagnosis and to take positive actions to make their lives better. So, in addition to treating patients’ symptoms, the palliative care clinicians in this study were bolstering people’s adaptive coping skills.

19 Aug

Posted at 17:38h in Author Interviews, CT Scanning, Lung Cancer, PLoS, Radiology
MedicalResearch.com Interview with: [caption id="attachment_27200" align="alignleft" width="150"]Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida Dr. Matthew Schabath[/caption] Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study is a post-hoc analysis of data from a large randomized clinical trial (RCT) called the National Lung Screening Trial (NLST). The NLST found that lung cancer screening with low-dose helical computed tomography (LDCT) significantly reduced lung cancer deaths by 20 percent compared to screening with standard chest radiography (i.e., X-Ray). In our publication, we performed a very detailed analysis comparing outcomes of lung cancer patients screened by LDCT according to their initial (i.e., baseline), 12 month, and 24 month screening results. We found that patients who had a negative baseline screening but tested positive for lung cancer at the 12- or 24-month screen had lower survival and higher mortality rates than patients who had a positive initial screen that was a non-cancerous abnormality but developed lung cancer in subsequent screens.

05 Aug

Posted at 22:43h in Author Interviews, Beth Israel Deaconess, Biomarkers, Lung Cancer, Science
MedicalResearch.com Interview with: [caption id="attachment_26759" align="alignleft" width="200"]Dr. Elena Levantini, PhD Beth Israel Deaconess Medical Center Instructor, Medicine, Harvard Medical School Research Associate, Hematology-Oncology Beth Israel Deaconess Medical Center Dr. Elena Levantini[/caption] Dr. Elena Levantini, PhD Beth Israel Deaconess Medical Center Instructor, Medicine, Harvard Medical School Research Associate, Hematology-Oncology Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lung cancer is one of the deadliest cancers in the world, accounting for 30% of tumor-related deaths. Like many solid tumours, lung cancer is very heterogeneous (consisting of cancer cells which behave and respond differently) and hence there is currently no single efficient drug which is able to treat all patients. Levantini and colleagues previously showed that non-small cell lung cancer (NSCLC) tumor cells frequently express too little or none of a transcription factor called C/EBPα, a protein that regulates gene expression and cell proliferation in lung tissues. It’s also known to play a role in a form of leukemia, as well as liver cancer, squamous cell skin carcinomas, squamous cell cancers of the head and neck and other cancers. In their previous work, the scientists suspected that C/EBPα may act as a tumor suppressant in normal cells, but the mechanism by which its absence promoted lung cancer tumors remained unclear. Dr. Levantini went on to develop a mouse model in which deleting C/EBPα resulted in NSCLC. Analysis of this model led to the discovery that C/EBPα suppressed lung tumor formation by inhibiting the expression of BMI1. Dr Levantini then demonstrated that reducing the levels of BMI1 in her mouse model by genetic means, or by using a drug reducing expression of BMI1, led to inhibition of tumor formation. This study has established an important link between C/EBPα and BMI1 for the first time.

05 Aug

Posted at 11:54h in Author Interviews, BMJ, Environmental Risks, Lung Cancer
[caption id="attachment_26722" align="alignleft" width="150"]Sandrah P. Eckel PhD Assistant Professor of Preventive Medicine USC Division of Biostatistics Dr. Sandrah Eckel[/caption] MedicalResearch.com Interview with: Sandrah P. Eckel PhD Assistant Professor of Preventive Medicine USC Division of Biostatistics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lung cancer is the most common cancer and it is responsible for 1 in 5 cancer deaths. There is a growing body of evidence that ambient air pollution exposures are linked to lung cancer incidence and mortality, but the effect on survival of exposures after diagnosis are unclear. The International Agency for Research on Cancer recently classified ambient air pollution as carcinogenic. We reasoned that if air pollution drives lung cancer development, it could impact lung cancer progression—and shorten survival—through the same biological pathways. We used 20 years of data on more than 300,000 newly diagnosed lung cancer cases from the California Cancer Registry and calculated average air pollution exposures at each patient’s residence from the date of diagnosis through the end of follow-up. We found that patients living in areas with higher pollution levels had shorter survival, particularly for patients who were diagnosed at an early stage and for those diagnosed at an early stage with adenocarcinoma histology. Interestingly, adenocarcinoma is the most common histological subtype of lung cancer in non-smokers.

15 Jul

Posted at 23:36h in Author Interviews, Cancer, Cancer Research, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_26169" align="alignleft" width="170"]Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 Dr. Jan Marie Eberth[/caption] Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Large, randomized clinical trials have shown that chest x-rays do not reduce mortality from lung cancer. Low-dose computed tomography (LDCT) screening, however, was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. The most significant risk of LDCT screening is the high rate of false-positives (about 25%), which subsequent studies have shown can be reduced by using new nodule management criteria such as Lung-RADS. Less than half of the physicians surveyed in our study reported reduced lung cancer mortality as a benefit of LDCT screening. Many also reported concerns about radiation exposure (50%) and unnecessary follow-up procedures (88%) as risks. Since the majority of family physicians surveyed did not know that organizations such as the US Preventive Services Task Force or National Comprehensive Cancer Network recommend high-risk individuals receive annual LDCT screening, it is not surprising that some family physicians would continue to order a chest x-ray for screening, despite the lack of scientific evidence. Similarly, only 36% of physicians reported that high-risk patients should be screened annually (vs. every 6 months, 2 years, or 3 years).

22 Jun

Posted at 20:00h in ASCO, Author Interviews, Cancer Research, Chemotherapy, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_25414" align="alignleft" width="133"]Dr. Lan Huang PhD Co-founder and Chief Executive Officer BeyondSpring Pharmaceuticals, Inc Dr. Lan Huang[/caption] Dr. Lan Huang PhD Co-founder, Chairman and CEO BeyondSpring Pharmaceuticals, Inc MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study is the toxicity of Docetaxel chemotherapy causes inadequate dosing with Docetaxel due to dose delay, reduction or discontinuation, thus leaving the patient with inadequate chemotherapy treatment. A main finding is a statistically significant p value of 0.002 in lower rates of grade 3 and 4 Neutropenia for patients dosed with a combination of BeyondSpring’s Plinabulin and Docetaxel compared to those patients dosed with Docetaxel alone. As a result, approximately 14 percent more patients stayed on the adequate (dense) dose of Docetaxel in the Docetaxel + Plinabulin arm as compared to Docetaxel alone.

16 May

Posted at 20:55h in Author Interviews, CT Scanning, JAMA, Lung Cancer, NIH
MedicalResearch.com Interview with: [caption id="attachment_24418" align="alignleft" width="152"]Hormuzd A. Katki, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Department of Health and Human Services, Bethesda, Maryland Dr. Hormuzd Katki[/caption] Hormuzd A. Katki, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Department of Health and Human Services, Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Katki: The National Lung Screening Trial (NLST) showed that 3 annual CT screens reduced lung cancer death by 20% in a subgroup of high-risk smokers.  However, selecting smokers for screening based on their individual lung cancer risk might improve the effectiveness and efficiency of screening.  We developed and validated new lung cancer risk tools, and used them to project the potential impact of different selection strategies for CT lung cancer screening. We found that risk-based selection might substantially increase the number of prevented lung cancer deaths versus current subgroup-based guidelines.  Risk-based screening might also improve the effectiveness of screening, as measured by reducing the number needed to screening to prevent 1 death.  Risk-based screening might also improve the efficiency of screening, as measured by reducing the number of false-positive CT screens per prevented death.

02 May

Posted at 14:04h in AACR, Author Interviews, Cancer Research, Lung Cancer, Race/Ethnic Diversity, Surgical Research
MedicalResearch.com Interview with: [caption id="attachment_23958" align="alignleft" width="150"]Asal Mohamadi Johnson, PhD, MPH Assistant Professor of Epidemiology, Integrative Health Science Stetson University DeLand, FL 32723 Dr. Asal Mohamadi Johnson[/caption] Asal Mohamadi Johnson, PhD, MPH Assistant Professor of Epidemiology, Integrative Health Science Stetson University DeLand, FL 32723 MedicalResearch.com: What is the background for this study? Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.

08 Apr

Posted at 21:39h in Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_23298" align="alignleft" width="191"]Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital Dr. Adrian Sacher[/caption] Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Dr. Sacher: The aim of this prospective study was to determine the accuracy, turnaround time and robustness of ddPCR-based liquid biopsy for the detection of EGFR and KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC). The detection of these mutations is key to selecting optimal therapy for patients with this disease. Currently, the standard of care is to perform tissue biopsies on patients in order to obtain material to detect these mutations and make decisions about treatment. Frequently, patients undergo multiple tissue biopsies during the course of their treatment. We sought to determine if liquid biopsy could quickly and accurately detect these mutations with the ultimate goal of understanding how to use these tests to select treatment for patients.

05 Mar

Posted at 14:58h in AACR, Author Interviews, Cancer Research, Lung Cancer, MD Anderson, Nutrition, Sugar
MedicalResearch.com Interview with: [caption id="attachment_22379" align="alignleft" width="98"]Xifeng Wu, M.D., Ph.D Professor of Epidemiology Dr. Xifeng Wu[/caption] Xifeng Wu, M.D., Ph.D Professor of Epidemiology and [caption id="attachment_22380" align="alignleft" width="150"]Dr. Stephanie Claire Melkonian PhD Epidemiologist, Postdoctoral Research Fellow Dr. Melkonian[/caption] Dr. Stephanie Claire Melkonian  PhD Epidemiologist, Postdoctoral Research Fellow The University of Texas MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glycemic index (GI) assigns foods an indexed value to show how quickly and how much carbohydrates in the food cause blood glucose levels to rise after eating and is a measure of overall carbohydrate quality. Glycemic load (GL) is a related measure that is calculated by multiplying Glycemic index by the amount of carbohydrates in grams in that specific food and by the amount consume, then dividing by 100. Previous studies have investigated the association of GI and GL with certain types of cancer, including colorectal, stomach, and pancreatic cancer, but there has been limited research into the association with lung cancer. We conducted a study using patients and control subjects from an ongoing case-control study of lung cancer conducted at MD Anderson. The patients were newly diagnosed and had not received treatment other than surgery. The healthy control subjects were selected from patient lists at Kelsey-Seybold Clinics, a large physician group in the Houston area. The study results encompass 1,905 cases and 2,413 controls. Using data collected from in-person interviews regarding health histories and dietary behaviors, we were able to categorize the study subjects according to their dietary Glycemic index and GL. What we found was that individuals in the highest category of GI were at an almost 50% increased risk for developing lung cancer as compared to those in the lowest group. This association was different based on different subtypes of cancer. Most interestingly, however, among those individuals that never smoked, high Glycemic index was associated with an almost 2 fold increased risk of lung cancer. In other words, we found a more profound association between GI and lung cancer in never smokers in this study.

25 Feb

Posted at 18:21h in Author Interviews, Cancer Research, Esophageal, Lung Cancer, Radiology, Surgical Research, University of Michigan
MedicalResearch.com Interview with: [caption id="attachment_22050" align="alignleft" width="133"]Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI Dr. Mark Healy[/caption] Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Healy: In our study, we found high overall use of PET as a primary study for recurrence detection in lung and esophageal cancers, with substantial hospital-based variation in the use of PET. Despite this, there was not a significant difference in survival for patients across high and low PET use hospitals.

12 Feb

Posted at 19:32h in Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature
MedicalResearch.com Interview with: [caption id="attachment_21559" align="alignleft" width="180"]Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain Dr. Chiara Ambrogio[/caption] Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies.

10 Feb

Posted at 16:28h in Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Lung Cancer, Radiology
MedicalResearch.com Interview with: [caption id="attachment_21454" align="alignleft" width="172"]Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Dr. Phillip Boiselle[/caption] Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Medical Research: What is the background for this study? Dr. Boiselle: We surveyed leading academic medical centers in 2013 and found considerable variability in their practice patterns as well as a relatively small number of patients being screened for lung cancer at these sites. Considering landmark developments since that time, including favorable policy and payment decisions by USPSTF  and CMS  and development of radiology-specific nodule guidelines by the American College of Radiology, we were curious to see whether there would be greater conformity of practice patterns and increased patient volumes in response to these developments. Medical Research: What are the main findings? Dr. Boiselle: First, our finding of greater conformity of lung cancer screening practices at present compared to 2013 confirmed our hypothesis that the development of radiology-specific guidelines by ACR would contribute to greater uniformity. Second, we were surprised by the very modest level of increase in patient volumes for CT screening over time despite the favorable USPSTF and CMS decisions. We emphasize, however, that the timing of our survey occurred too early to determine the full impact of CMS coverage on patient volumes

12 Jan

Posted at 23:33h in Author Interviews, Lung Cancer, Pharmacology
MedicalResearch.com Interview with: Glen Weiss, MD, MBA Director of Clinical Research & Medical Oncologist and Dr. Zoltan Lohinai MD National Koranyi Institute of Pulmonology Budapest, Hungary Western Regional Medical Center Cancer Treatment Centers of America Goodyear, Arizona MedicalResearch: What is the background for this study? What are the main findings? Response: With nearly 1.4 million deaths each year, lung cancer is the world’s leading cause of cancer-related mortality. In the U.S., more than 162,000 die annually of this disease. One subtype of this cancer, small cell lung cancer (SCLC), is one of the most progressive tumor types. No new class of systemic treatment has been adopted as a new benchmark for standard therapy against SCLC for nearly three decades. Lung cancer researchers focus on SCLC not only because of its scientific challenge, but also because of their great desire to help patients suffering from this aggressive tumor. Drug repurposing bioinformatical analysis, a new research direction, has found that FDA-approved drugs in non-malignant diseases may have antitumor effects. Our study attempted to evaluate the recent laboratory findings in a clinical setting. Statins are a class of drugs primarily used to lower cholesterol in patients at risk for heart disease. They have been hypothesized by preclinical data to affect tumor cells through the extracellular signal-regulated kinase (ERK) pathway, which regulates many cellular functions. Our study of 876 metastatic-stage  small cell lung cancer patients, published Jan. 6, 2015, in the peer-reviewed scientific journal PLOS ONE, showed that statins appeared to provide an increase in overall survival for those cancer patients who were prescribed those medications. Patients prescribed other classes of drugs, including aspirin, antidepressants, and blood pressure-lowering agents, have reportedly shown anti-SCLC activity in previous preclinical studies. However, our study found no such survival benefits. All in all, our study is a good example of how to evaluate drug repurposing in oncology, and that statins might have clinical relevance in the treatment of SCLC.

02 Jan

Posted at 00:30h in Author Interviews, CT Scanning, JAMA, Lung Cancer
  [caption id="attachment_20279" align="alignleft" width="170"]Jan Marie Eberth Dr. Eberth[/caption] MedicalResearch.com Interview with: Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 Medical Research: What is the background for this study? Dr. Eberth: With the breakthrough findings of the National Lung Screening Trial released in 2011, professional organizations have largely embraced population-based screening guidelines for patients at high risk for lung cancer. The diffusion of screening into broad clinical practice has been slow to be adopted, given concerns about the efficacy of screening in community settings, lack of insurance reimbursement and unclear billing logistics, and difficulty weighing the pros of screening against the known cons (e.g., high rate of false positives). Medical Research: What are the main findings? Dr. Eberth: Provisions of the Patient Protection and Affordable Care Act mandate that US Preventive Services Task Force-recommended screening tests with an A or B rating receive full insurance coverage by private payers. The Centers for Medicare and Medicaid (CMS) soon thereafter approved full coverage for lung cancer screening in high-risk patients (i.e., those aged 55-77 years, asymptomatic for lung cancer, tobacco smoking history of 30+ pack-years, is a current smoker or has quit smoking within the past 15 years). Coding is rapidly evolving; as of November 2015, CMS released HCPCS codes G0296 (pre-screening counseling visit) and G0297 (screening visit). These codes will be accepted retroactively starting January 4, 2016 to the date of the final coverage determination (back to February 5, 2015). No coinsurance or deductibles shall be charged to the patient for either the pre-screening counseling visit, or the screening visit itself. Quality of screening  is an important, but understudied, area of research. Several publications have focused on aspects of quality programs, and how to achieve quality benchmarks, but data is still being collected to assess variation across programs. In the future, data from screening registries, such as the American College of Radiology Lung Cancer Screening Registry (LCSR), can be leveraged to examine these quality metrics and improve risk-prediction models for lung cancer.

23 Dec

Posted at 15:17h in Author Interviews, Cancer Research, JAMA, Lung Cancer, Surgical Research
[caption id="attachment_20177" align="alignleft" width="129"]Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Dr. Najib Rahman[/caption] MedicalResearch.com Interview with: Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Medical Research: What is the background for this study? Dr. Rahman : Up to TIME1, the evidence base behind optimal pleurodesis for malignant pleural effusion in terms of tube size and analgesia was poor. Optimal pleurodesis in this context is one which is successful (i.e. the patient needs no further pleural interventions for that malignant effusion), but occurs with the minimum discomfort. This is particularly important as the treatment intent in malignant effusion pleurodesis is palliative. This is the first adequately powered randomized trial to address two important issues in pleurodesis for malignant pleural effusion - that of whether NSAIDs reduce pleurodesis efficacy, and if smaller chest tubes (12F) are "as good as" larger chest tubes (24F) for pleurodesis success and in terms of pain. Medical Research: What are the main findings? Dr. Rahman : The main and somewhat surprising findings are that:
  1. NSAIDs given short term but at high dose do not impair pleurodesis - they are no better than morphine for pain control (in fact, they needed modestly more rescue medication), but can be freely used during malignant effusion pleurodesis with no fear of reducing pleurodesis success.
  1. Smaller tubes were marginally less painful than larger tubes - but this difference was not clinically very relevant
  1. Smaller tubes cannot now be said to be "as good as" larger tubes for malignant effusion pleurodesis. Our data shows that they failed in non-inferiority to larger tubes for pleurodesis success at 3 months. 
  1. Smaller tubes resulted in higher fall our rates, a higher incidence of not being able to administer talc and were associated with more complications during insertion .

04 Dec

Posted at 19:24h in Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, CT Scanning, Gender Differences, Lung Cancer
[caption id="attachment_19804" align="alignleft" width="172"]Phillip Boiselle, M.D. Staff, Cardiothoracic Imaging Beth Israel Deaconess Medical Center Associate Dean for Academic and Clinical Affairs Professor of Radiology, Harvard Medical School Boston, Mass Dr. Boiselle[/caption] MedicalResearch.com Interview with: Phillip Boiselle, M.D. Staff, Cardiothoracic Imaging Beth Israel Deaconess Medical Center Associate Dean for Academic and Clinical Affairs Professor of Radiology, Harvard Medical School Boston, Mass Medical Research: What is the background for this study? What are the main findings? Dr. Boiselle: Previous studies have shown that women have a greater mortality benefit from lung cancer screening then men, and that this test (CT screening) is more cost-effective for women than men. Our purpose was to determine whether the relative risk of lung cancer for women and men differed depending on the specific type of lung nodule that was discovered at screening. Such differences could potentially help to influence a more personalized approach to patient management in lung cancer screening.

02 Dec

Posted at 17:36h in Author Interviews, JAMA, Lung Cancer, Radiation Therapy
[caption id="attachment_19752" align="alignleft" width="125"]Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan Dr. Movsas[/caption] MedicalResearch.com Interview with: Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan  Medical Research: What is the background for this study? What are the main findings? Dr. Movsas: The background is that a recent randomized lung cancer trial (RTOG 0617) showed a lower (rather than a higher) survival among the patients who received a higher dose of radiation (RT).  This unexpected finding was puzzling as there were few differences in toxicity between the radiation dose arms noted by health care providers. The main finding of the quality of life (QOL) analysis was that there was indeed a large difference in QOL as reported by the patients themselves (with lower QOL on the high RT dose arm at 3 months).  Moreover, while this study was not randomized for RT technique, about half of the patients received intensity modulated RT (IMRT), a more sophisticated approach than the alternative (3D conformal RT), which can better protect normal tissues.  Despite the fact that patients with larger tumors received IMRT, their self reported QOL one year later was significantly better (ie, much less decline in QOL) relative to patients who received 3D conformal RT.  Finally, higher QOL at baseline significantly predicated for better survival.

05 Nov

Posted at 14:40h in Annals Thoracic Surgery, Author Interviews, Brigham & Women's - Harvard, Lung Cancer, Outcomes & Safety, Surgical Research

[caption id="attachment_19119" align="alignleft" width="129"] Dr. Bravo[/caption] MedicalResearch.com Interview with: Carlos E. Bravo Iñiguez, M.D. Clinical Research Fellow in Thoracic Oncology Brigham and Women´s Hospital (BWH)/Harvard Medical School (HMS) Department of Surgery, Division of Thoracic Surgery Center for Surgery and Public Health Boston, MA, 02115 Medical Research: What is the background for this study? What are the main findings? Dr....

24 Oct

Posted at 11:44h in Author Interviews, FDA, Immunotherapy, Lung Cancer
MedicalResearch.com Interview with: Dickran Kazandjian, MD Office of Hematology and Oncology Products Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kazandjian: Nivolumab is the first approved immunotherapy, for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) after platinum-based chemotherapy.  FDA initiated an expedited review after obtaining the data monitoring committee report of a planned interim analysis of a second-line squamous NSCLC trial demonstrating a large overall survival benefit (CheckMate 017). Nivolumab efficacy in metastatic Squamous (SQ) NSCLC has been previously reported in two studies.  CheckMate 063 was a single-arm trial in 117 patients with metastatic SQ NSCLC who had progressed after previous treatment with 2 systemic regimens including platinum-based doublet chemotherapy (Rizvi et al)  CheckMate 017 was a randomized study of nivolumab compared to docetaxel in 272 patients with metastatic SQ NSCLC who had progressed after prior platinum-based doublet chemotherapy (Brahmer et al).  The median survival of patients randomized to nivolumab was 9.2 months vs 6.0 months for docetaxel (hazard ratio, 0.59; 95%CI, 0.44-0.79; P < .001) a 41% improvement in the risk of death. Approval was supported by the single-arm study which demonstrated an objective response rate of 15% and at the time of analysis, 10 of the 17 responding patients (59%) had response  durations of 6 months or longer. The FDA approved nivolumab on March 4, 2015, saving 6 months by not waiting for formal preparation of data by the sponsor and 2.5 months by expediting review.

12 Oct

Posted at 17:09h in Author Interviews, Lung Cancer, Melanoma
[caption id="attachment_18318" align="alignleft" width="207"]Prof. Martin O. Bergo Sahlgrenska Cancer Center Department of Molecular and Clinical Medicine Institute of Medicine University of Gothenburg Gothenburg, Sweden Prof. Martin O. Bergo[/caption] MedicalResearch.com Interview with: Prof. Martin O. Bergo Sahlgrenska Cancer Center Department of Molecular and Clinical Medicine Institute of Medicine University of Gothenburg Gothenburg, Sweden Medical Research: What is the background for this study? What are the main findings? Prof. Bergo: Dietary antioxidants and antioxidant supplements can protect cells and people from harmful effects of free radicals. The free radicals have the potential, over time, to cause cancer. But why is this research field so enormously fraught with controversy, and why have clinical trials with antioxidants not established this potential anti-cancer effects? We believe it is because the question of “whether antioxidants protect against cancer” should be divided into two separate questions: 1. Do antioxidants protect a healthy cell or a tumor-free person from cancer in the future.?and 2. What is the impact of antioxidant supplementation on an already established tumor? Focusing specifically on the second question, we showed previously that the antioxidants N-acetylcysteine and vitamin E markedly increase lung cancer progression in mice and cause human lung cancer cells to proliferate faster. The mechanism for this effect was directly linked to the ability of the antioxidants to scavenge free-radicals, which is why it is likely that other antioxidants, synthetic or natural, could have a similar effect. In the current study, we argued that it would be important to test this in malignant melanoma for three reasons. First, melanoma cancer cells are known to be sensitive to changes in free radicals. Second, melanoma is the cancer that increases most in incidence and lethality in the western world. And third, primary melanomas may be exposed to antioxidants from both the diet and from skin lotions and sun creams. We found that supplementing the diet of mice with acetylcysteine has no impact on the primary tumors on the skin but doubles the rate of metastasis – i.e. the ability of the tumor cells to spread in the body. We found similar results with human malignant melanoma cells in culture: antioxidants (acetylcysteine and vitamin E) increased their ability to migrate and invade surrounding tissue. Thus, all in all, we have found that antioxidants can worsen cancer in two different ways, one in the lung, and another in the skin.    

11 Oct

Posted at 01:47h in Author Interviews, Chemotherapy, Lung Cancer, NEJM, UT Southwestern
David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with: David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited. Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer. The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs. In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has. Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.

07 Oct

Posted at 11:29h in Author Interviews, Genetic Research, Lung Cancer, PLoS
MedicalResearch.com Interview with: Keiji Tanimoto, D.D.S., Ph.D Assistant Professor Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan Medical Research: What is the background for this study? Dr. Tanimoto: Hypoxia-inducible factor-2α (HIF-2αor EPAS1) is important for cancer progression, and its overexpression is considered a putative biomarker for poor prognosis in patients with lung cancer. However, molecular mechanisms underlying EPAS1 overexpression are not fully understood. Recently, several SNPs of EPAS1 have been reported to be associated with the development of various diseases including cancer. Therefore, we focused on SNPs within EPAS1, and examined the roles of these SNPs in regulation of EPAS1 gene expression and the association of these SNPs with prognosis of non-small cell lung cancer (NSCLC) patients by bioinformatics analyses. Medical Research: What are the main findings? Dr. Tanimoto:
  • The SNP within the EPAS1 intron 1 region (rs13419896) may affect EPAS1 gene and protein expression;
  • The fragment with A allele of the SNP showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun;
  • The median survival time of NSCLC patients with at least one A allele of rs13419896 was significantly shorter than that with the G/G homozygote (28.0 vs. 52.5 months, P = 0.047, log-rank test);
  • The possession of A allele of rs13419896, along with clinical stage, was an independent variable for risk estimation of overall survival for NSCLC patients [hazard ratio (HR) = 2.31, 95% CI = 1.14-4.81, P = 0.021], after adjustment for age, gender, stage, histology, tumor size, and differentiation.

28 Sep

Posted at 20:05h in Author Interviews, Cancer Research, JAMA, Lung Cancer
[caption id="attachment_17881" align="alignleft" width="107"]Dr. Rebecca Prince Clinical Research Fellow and first author Dr. Rebecca Prince[/caption] MedicalResearch.com Interview with: Dr. Rebecca Prince MBBS Clinical Research Fellow and first author and [caption id="attachment_17883" align="alignleft" width="119"]Monika K. Krzyzanowska, MD MPH FRCPC Medical Oncologist, Princess Margaret Cancer Centre Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences Clinical Lead, Quality Care & Access, Systemic Treatment Program, Dr Monika Krzyzanowska[/caption] Monika K. Krzyzanowska, MD MPH FRCPC Medical Oncologist, Princess Margaret Cancer Centre, Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences Clinical Lead, Quality Care & Access, Systemic Treatment Program, Cancer Care Ontario Toronto, ON  Medical Research: What is the background for this study? What are the main findings? Response: This study was inspired by our previous work using administrative data in which we found that a large proportion of patients receiving chemotherapy in routine practice were visiting the emergency department and being admitted to hospital. Our perception was that the frequency of these events was higher than expected but when we went to look what was expected, ie. how often were people ending up in hospital during treatment in clinic trials, this data was not readily available. This led us to perform a systematic review of the literature including a comparison of hospitalization rates between patients treated in clinical trials and patients in similar clinical scenarios treated in routine practice. We ended up focusing on metastatic lung cancer as that was one of the clinical scenarios where we were able to identify published data from both clinical trials and routine practice. The main finding of our study is that hospitalizations are very common during chemotherapy. We compared patients with metastatic lung cancer being treated in routine practice and clinical trials and found that that approximately half (51%) of patients treated in routine practice were hospitalized during chemotherapy, compared to 16% of trial patients. We also found that very few clinical trials reported this information which is routinely collected during the trial.

15 Aug

Posted at 01:10h in Author Interviews, Lung Cancer, Outcomes & Safety, Surgical Research, University of Michigan
Tyler Grenda, MD House Officer VI Section of General Surgery Department of Surgery University of Michigan MedicalResearch.com Interview with: Tyler Grenda, MD House Officer VI Section of General Surgery Department of Surgery University of Michigan   Medical Research: What is the background for this study? What are the main findings? Dr. Grenda: The main purpose for this study was to better understand the factors underlying differences in mortality rates for hospitals performing lung cancer resection.  The methodology we used included only the highest and lowest mortality hospitals (Commission on Cancer accredited cancer programs) so the sampling frame was specific. There are wide variations in mortality rates across hospitals performing lung cancer resection (overall unadjusted mortality rates were 10.8% vs. 1.6%, respectively.

11 Aug

Posted at 20:48h in Annals Thoracic Surgery, Author Interviews, Cancer Research, Lung Cancer, Outcomes & Safety

MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP Thoracic Oncology Research Group Baptist Cancer Center Memphis, Tennessee MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP Thoracic Oncology Research Group Baptist Cancer Center Memphis, Tennessee

Medical Research: What is the background for this study? What are the main findings? Dr. Osarogiagbon: Lung cancer care is complicated, but can be broken down into 5 steps: x-ray detection, biopsy, x-ray tests of cancer spread (the ‘stage’), biopsy of suspicious areas where cancer may have spread, and treatment. Looking only at patients who had surgery for a suspected lung cancer, we worked backwards to see how their care went through the key steps and how long it took. We found that patients often skip some of the crucial steps. For example, 22% did not have a staging PET/CT scan, 88% did not have an invasive staging test. Only 10% had the recommended combination of 3 staging tests leading up to surgery: a CT scan, PET/CT scan, and invasive staging test. It took a month and a half to more than 6 months for the middle half of patients to go from first abnormal x-ray sign of possible lung cancer to surgery.

11 Jun

Posted at 20:31h in Author Interviews, Biomarkers, Lung Cancer, Wistar
MedicalResearch.com Interview with: Qihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar InstituteQihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease.  Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available. When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules.  However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer.  In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need. In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules.   When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules.