Author Interviews, Cancer Research, Lung Cancer, PNAS / 08.04.2018 Interview with: Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital Boston, MA 02115 What is the background for this study? Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target. KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial. (more…)
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018 Interview with: Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center What is the background for this study? Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  (more…)
Author Interviews, JAMA, Lung Cancer, Medical Imaging, Surgical Research, Vanderbilt / 10.11.2017 Interview with: Amelia W. Maiga, MD MPH Vanderbilt General Surgery Resident VA Quality Scholar, TVHS What is the background for this study? What are the main findings? Response: Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer. Our investigation adds to growing evidence that FDG-PET scans should be interpreted with caution in the diagnosis of lung cancer. Misdiagnosis of lung lesions driven by FDG-PET avidity can lead to unnecessary tests and surgeries for patients, along with potentially additional complications and mortality. To estimate FDG-PET diagnostic accuracy, we conducted a multi-center retrospective cohort study. The seven cohorts originating from Tennessee, Arizona, Massachusetts and Virginia together comprised 1188 nodules, 81 percent of which were malignant. Smaller nodules were missed by FDG-PET imaging. Surprisingly, negative PET scans were also not reliable indicators of the absence of disease, especially in patients with smaller nodules or who are known to have a high probability of lung cancer prior to the FDG-PET test. Our study supports a previous meta-analyses that found FDG-PET to be less reliable in regions of the country where fungal lung diseases are endemic. The most common fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and coccidioidomycosis is prevalent in the southwestern U.S. These infections generate inflamed nodules in the lungs (granulomas), which can be mistaken for cancerous lesions by imaging. (more…)
Author Interviews, Cancer Research, Eli Lilly, Lung Cancer / 20.10.2017 Interview with: Martin Reck, MD, PhD Head of the Department of Thoracic Oncology Head of the Clinical Trial Department Department of Thoracic Oncology at the Lung Clinic Grosshansdorf What is the background for this study? What are the main findings? Response: There is an urgent medical need to improve outcomes in pretreated patients with advanced non-small cell lung cancer (NSCLC), in particular those with fast progressing tumors. The Phase 3 REVEL study, which included patients with nonsquamous and squamous forms of NSCLC, demonstrated improved overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) – independent of histology. This analysis confirmed efficacy - with improvement of ORR, PFS and OS - in poor prognosis patients with fast progressing tumors (after 9, 12 or 18 weeks) without additional toxicity or impact on Quality of Life compared to the intent-to-treat (ITT) population results of REVEL. (more…)
Author Interviews, Cancer Research, Lung Cancer / 03.10.2017 Interview with: Dr. Sunitha Nagrath, PhD Associate Professor, Chemical Engineering University of Michigan What is the background for this study? What are the main findings? Response: Lung cancer is leading cause of cancer-related mortality, and detecting it in earlier stages is crucial to improving outcomes for patients. The motivation for this study lies in understanding the phenotypic and genetic make-up of lung cancer during its early stages, using a blood sample (blood biopsy). We have done this by employing a microfluidic device to capture cancer cells circulating in the blood that is obtained from the peripheral veins and the pulmonary vein (a vein next to the tumor itself) from patients with early stage lung cancers. The idea behind using blood from the pulmonary vein was to obtain a richer yield of these circulating tumor cells, which are rare in the blood. Through this study, we found that the pulmonary vein does yield a much higher quantity of circulating tumor cells, and also often harbors these cells in large clusters. We further went on to study the significance of these clusters, and found that these clusters indicated aggressive traits such as resistance to treatment, and could also potentially suggest poorer patient outcomes at long term. (more…)
Author Interviews, JAMA, Lung Cancer / 03.10.2017 Interview with: Raymond U. Osarogiagbon, MBBS, FACP Translational Lung Cancer Research Multidisciplinary Thoracic Oncology Program Baptist Centers for Cancer Care Memphis, TN What is the background for this study? What are the main findings? Response: Most long-term survivors of lung cancer are among the patients who were fortunate enough to be identified early enough to undergo curative-intent surgery. In the US, 60,000 individuals undergo curative-intent surgery for lung cancer every year. This number is likely to increase over the next few years as lung cancer screening becomes more widely adopted. Unfortunately, fewer than 50% of patients who undergo curative-intent surgery actually survive up to 5 years. We show that the quality of surgery, especially the quality of pathologic nodal staging is a powerful driver of survival differences between groups of patients. In general, pathologic nodal staging (important as it is stratifying patients into risk groups so those at high risk can be offered additional treatments to increase the chances of cure while those at truly low risk can be left alone without exposure to cost and side-effects of additional treatments) is very poorly done. We show how the percentage of patients whose pathologic staging met sequentially more stringently-define thoroughness of staging metrics falls off sharply, while the survival sequentially increases. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer, Radiation Therapy / 02.10.2017 Interview with: Florence K Keane MD Resident, Radiation Oncology Harvard Radiation Oncology Program Boston, Massachusetts What is the background for this study? Response: Checkpoint inhibitors (CPIs) have recently transformed the management of patients with metastatic lung cancer, demonstrating significant improvements in overall and progression-free survival in both the first-line setting in patients with increased expression of PD-L1 (≥50%) and in patients with previously treated NSCLC who have progressed on chemotherapy. CPIs are also moving into the treatment of patients with localized lung cancer, with the recently published PACIFIC trial demonstrating a significant improvement in progression-free survival in patients with inoperable stage III NSCLC treated with adjuvant durvalumab after definitive chemoradiotherapy. However, CPIs are associated with unique toxicities as compared to cytotoxic chemotherapy, including pulmonary, endocrine, neurologic, gastrointestinal, and dermatologic adverse events, which may be fatal in some cases. The risk of autoimmune pneumonitis with checkpoint inhibitors is estimated to be on the order of 5%. Many patients with lung cancer will require radiotherapy for palliation of symptoms. Thoracic radiotherapy (TRT) is also a risk factor for pneumonitis, with a dose- and volume-dependent impact on risk. However, it is unknown whether treatment with CPIs and TRT is associated with increased risk of toxicity. (more…)
Author Interviews, Journal Clinical Oncology, Lung Cancer / 23.08.2017 Interview with: Theodore M. Brasky, PhD Research Assistant Professor The Ohio State University – James Comprehensive Cancer Center Columbus, OH 43201 What is the background for this study? What are the main findings? Response: Prior literature has been suggestive of both a protective and harmful effect of certain B vitamins on lung cancer risk. We wanted to examine the association of intakes of vitamins B6, folic acid (B9), and B12 from supplements –which are typically taken at very high doses– and lung cancer risk in a large, prospective study of 77,000 men and women living in Washington State. The study is unique as it was designed specifically to examine associations of dietary supplements with cancer occurrence. We found that men who took high doses of vitamin B6 and B12 from individual supplements over a long period of time (meaning, doses much higher than the US RDA and much greater than what one would receive from taking a multivitamin over the long term) were at nearly 2-fold increased risk of lung cancer compared to men who did not have B6 or B12 intake from any supplemental source. This finding of increased risk appeared to be specific to men who were current smokers. Among them, long term high-dose supplementation was associated with 3-4 fold increases in lung cancer risk. We observed no increased risk for any of the supplements – B6, B12, or folic acid – with lung cancer risk in women or women who smoked. (more…)
Author Interviews, Chemotherapy, Lung Cancer, Science / 24.07.2017 Interview with: Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna What is the background for this study? What are the main findings? Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness. Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs - if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature. (more…)
Author Interviews, Dermatology, Immunotherapy, JAMA, Lung Cancer / 14.07.2017 Interview with: Dr. Noelia Rivera MD Dermatologist Hospital Universitari Germans Trias i Pujol, Badalona Universitat Autònoma de Barcelona What is the background for this study? Response: In the last few years some new therapies targeting immune checkpoints have been developed. The programmed death receptor-1 (PD-1) are immune checkpoints that prevent the immune system to act against own tissues. By blocking these mediators it is possible to prevent tumors to escape from the immune system. About half of the patients receiving these therapies will develop mild to moderate cutaneous adverse events. In the pre-authorization studies for malignant melanoma these include rash, vitiligo, and pruritus. "Rash" has commonly been reported as an adverse event in many oncologic trials evaluating the drugs, without providing further information about the clinical or histological details. Lately, lichenoid eruptions associated to these therapies have been reported and it suggests that an important percentage of these reactions present lichenoid histological features. (more…)
Author Interviews, JNCI, Lung Cancer, Smoking, Tobacco, Tobacco Research / 22.05.2017 Interview with: Peter G. Shields, M.D. Deputy Director, Comprehensive Cancer Center James Cancer Hospital Professor, College of Medicine Julius F. Stone Chair in Cancer Research The Ohio State University Columbus, OH What do we know about the health effects of cigarette filters?  Response:  The issue is that the design of the filters makes a cigarette even more dangerous, which can be regulated by the FDA. The issue is not about having a filter, but how they are made. And now we are changing the dialogue to the design of virtually all cigarettes. The holes on the filter are likely one reason the cigarettes of today are more dangerous. (more…)
Author Interviews, Biomarkers, Genetic Research, Lung Cancer / 25.04.2017 Interview with: Hestia Mellert, PhD Director, Molecular Product Development Biodesix: Making Medicine Personal Boulder, CO What is the background for this study? What are the main findings? Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies. This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians. (more…)
Author Interviews, Lung Cancer, PLoS / 09.02.2017 Interview with: Kevin ten Haaf MSc Scientific researcher, Public Health Erasmus Medical Center Rotterdam What is the background for this study? Response: Lung cancer screening is currently recommended in the United States, for persons aged 55 through 80 who smoked at least 30 pack-years (the average number of cigarettes smoked per day multiplied by the number of years the person has smoked) and who currently smoke or have quit within the last 15 years. Other countries, such as Canada, are investigating the feasibility of implementing lung cancer screening policies. However, the cost-effectiveness of lung cancer screening in a population-based setting is uncertain. Concerns have been raised on the feasibility of implementing lung cancer screening policies, especially with regards to the potential costs. In this study, the benefits, harms and costs of implementing lung cancer screening in the province of Ontario, Canada were assessed. (more…)
Author Interviews, Cancer Research, CT Scanning, JAMA, Lung Cancer / 02.02.2017 Interview with: Ahmedin Jemal, DVM, PHD Vice President, Surveillance and Health Services Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the background for this study? Response: In December 2013, the United States Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low dose computed tomography (LDCT) for current or former heavy smokers who quit within the past 15 years. A previous study estimated that only 2-4% of heavy smokers received LDCT for lung cancer screening in 2010 in the United States. We sought to determine whether lung cancer screening among high risk smokers increased in 2015, following the USPSTF recommendation in 2013. (more…)
Author Interviews, Cancer Research, CT Scanning, JAMA, Lung Cancer / 30.01.2017 Interview with: Linda Kinsinger, MD, MPH National Center for Health Promotion and Disease Prevention U.S. Department of Veterans Affairs NW Washington DC 20420 What is the background for this study?  Response: The U.S. Preventive Services Task Force recommends annual lung cancer screening with low-dose computed tomography (LDCT) for current and former heavy smokers ages 55 to 80. However, clinicians have questioned the practical aspects of implementing lung cancer screening. VA provides care for 6.7 million Veterans each year, mostly older men – many of whom are current or former smokers – thus the implementation of a lung cancer screening program for VA patients would require substantial resources. In order to understand the feasibility and implications of this for patients and clinical staff, VA implemented a three-year Lung Cancer Screening Demonstration Project (LCSDP) in eight geographically-diverse VA hospitals. Investigators identified 93,033 primary care patients at eight sites who were assessed on screening criteria, of whom 2,106 patients were screened between July 2013 and June 2015. (more…)
Author Interviews, Cancer Research / 06.01.2017 Interview with: Rebecca Siegel, MPH Strategic Director, Surveillance Information Services American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the bottom line for incidence and mortality trends? Response: The bottom line for cancer mortality is that in contrast to many other major causes of death, cancer death rates continue to decline, dropping by 25% from 1991 to 2014. This translates to about 2 million fewer cancer deaths over this time period than would be expected if cancer death rates had remained at their peak. Death rates are the best measure of progress against disease. Cancer incidence rates also dropped in men over the past decade of data, whereas in women they are flat. The drop in men is because of large declines for the top 3 cancers (prostate, lung, and colorectum), which account for more than 40% of cancers diagnosed in men. The stable trend in women is largely because declines in lung and colorectal cancers are offset by a flat trend for both breast and uterine corpus (i.e., endometrial) cancers, which combined account for almost 40% of cases in women, as well as rapid increases for thyroid cancer over the past decade -- increasing by almost 5% annually. Importantly, thyroid incidence rates have stabilized in the past few data years because of modifications in diagnostic criteria. (more…)
Author Interviews, Immunotherapy, Lancet, Lung Cancer / 23.12.2016 Interview with: Dr Kiyotaka Yoh Department of Thoracic Oncology National Cancer Center Hospital East Kashiwa, Japan What is the background for this study? What are the main findings? Response: LURET is multicenter, single-arm, phase II study to evaluate the efficacy and safety of vandetanib as RET inhibitor in patients with advanced RET-rearranged non-small-cell lung cancer (NSCLC). In 2012, RET rearrangements were identified as rare oncogenic alterations for NSCLC. Among 17 eligible patients included in primary analysis, the objective response rate was 53% (95% CI 28–77), which met the primary endpoint. At the data cutoff, median progression-free survival was 4.7 months (95% CI 2.8–8.5). Overall, vandetanib was tolerated, with an adverse event profile similar to those seen in previous large population studies of vandetanib in patients with unselected NSCLC. (more…)
Author Interviews, Boehringer Ingelheim, Cancer Research / 12.12.2016 Interview with: Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy What is the background for this study? What are the main findings? Response: LUME-Meso II is an international study designed to evaluate the safety and efficacy of nintedanib plus pemetrexed/cisplatin, followed by nintedanib versus placebo plus pemetrexed/cisplatin, followed by placebo, for the treatment of patients with unresectable malignant pleural mesothelioma (MPM). MPM is a rare cancer that affects the cells that make up the mesothelium of the pleura – the lining or membrane that covers and protects the lungs. It represents less than 1% of all cancers and is often related to long-term asbestos exposure with some suffering from malignant mesothelioma. A significant improvement in progression-free survival (PFS), the study’s primary endpoint, was observed for patients receiving nintedanib plus chemotherapy compared to patients receiving placebo plus chemotherapy. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer / 27.11.2016 Interview with: Paul W. Sperduto, MD, MPP, FASTRO Minneapolis Radiation Oncology University of Minnesota Gamma Knife Center, Minneapolis, Minnesota What is the background for this study? What are the main findings? Response: Analysis of past randomized clinical trials involving patients with brain metastases, an extremely heterogeneous population, suggested that the stratification tools of the past were inadequate to ensure those trials were comparing similar patients which made the results of those trials difficult to interpret or misleading. So, in 2008, a new prognostic index, the Graded Prognostic Assessment (GPA) was designed and published to more accurately predict survival. In 2010, the GPA was refined when we learned survival and the factors that predict survival varied by diagnosis (i.e. lung, breast, melanoma, kidney cancer patients with brain metastases had different survival). Now we have learned survival also varies by gene mutations and the diagnosis-specific GPA for lung cancer is further refined in this article with this new information, specifically EGFR and ALK gene alterations. 27 co-authors from 12 academic medical centers contributed patients to this database which represents the largest study of lung cancer patients with brain metastases ever reported. (more…)
Author Interviews, ESMO, Immunotherapy, Lung Cancer / 21.10.2016 Interview with: Shirish Gadgeel, MD Leader of the Thoracic Oncology Multidisciplinary team Professor at Karmanos Cancer Institute Detroit What is the background for this study? What are the main findings? Response: LUX-Lung 7 is the first global, head-to-head trial comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib respectively) for patients with EGFR mutation-positiveNon-Small Cell Lung Cancer NSCLC who received no prior treatment. The Phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R). The trial's co-primary endpoints were progression-free survival (PFS) by independent review, time to treatment failure and overall survival (OS); and the secondary endpoints included ORR, disease control rate, tumor shrinkage, patient-reported outcomes and safety. (more…)
Author Interviews, Depression, Journal Clinical Oncology, Lung Cancer / 05.10.2016 Interview with: Donald R. Sullivan, M.D., M.A. Assistant Professor, Division of Pulmonary & Critical Care Medicine Oregon Health & Science University Investigator, VA Portland Health Care System What is the background for this study? Response: There is an inextricably link between physical and mental health, and all too often clinicians focus solely on the physical components of disease. A life-threatening diagnosis such as cancer often evokes significant psychological distress and lung cancer patients are at significantly risk. Up to 44% of lung cancer patients experience depression symptoms and 5-13% major depressive disorder, higher than most other cancers. Previous studies have demonstrated the development of depression or depression symptoms at lung cancer diagnosis can increase patient mortality, but there is a paucity of research exploring how longitudinal changes in depression symptoms impact patient outcomes. (more…)
Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania / 13.09.2016 Interview with: 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 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. (more…)
Author Interviews, Chemotherapy, Immunotherapy, Lung Cancer / 13.09.2016 Interview with: Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital 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). (more…)
Author Interviews, Biomarkers, Cancer Research, Lung Cancer / 11.09.2016 Interview with: Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 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. (more…)
Author Interviews, CT Scanning, Lung Cancer, PLoS, Radiology / 19.08.2016 Interview with: Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida 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. (more…)
Author Interviews, Beth Israel Deaconess, Biomarkers, Lung Cancer, Science / 05.08.2016 Interview with: Dr. Elena Levantini, PhD Beth Israel Deaconess Medical Center Instructor, Medicine, Harvard Medical School Research Associate, Hematology-Oncology Beth Israel Deaconess Medical Center 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. (more…)
Author Interviews, BMJ, Environmental Risks, Lung Cancer / 05.08.2016 Interview with: Sandrah P. Eckel PhD Assistant Professor of Preventive Medicine USC Division of Biostatistics 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. (more…)
Author Interviews, Cancer, Cancer Research, Lung Cancer / 15.07.2016 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 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). (more…)
Author Interviews, CT Scanning, JAMA, Lung Cancer, NIH / 16.05.2016 Interview with: 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 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. (more…)
Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016 Interview with: Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital 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. (more…)