AACR, Author Interviews, Cancer Research, Lung Cancer, MD Anderson, Nutrition, Sugar / 05.03.2016

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.
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Lung Cancer, Radiology / 10.02.2016

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
Author Interviews, Lung Cancer, Pharmacology / 12.01.2016

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.
Author Interviews, CT Scanning, JAMA, Lung Cancer / 02.01.2016

  [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.
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, CT Scanning, Gender Differences, Lung Cancer / 04.12.2015

[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.
Author Interviews, JAMA, Lung Cancer, Radiation Therapy / 02.12.2015

[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.
Author Interviews, FDA, Immunotherapy, Lung Cancer / 24.10.2015

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.
Author Interviews, Chemotherapy, Lung Cancer, NEJM, UT Southwestern / 11.10.2015

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.
Author Interviews, Genetic Research, Lung Cancer, PLoS / 07.10.2015

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.
Author Interviews, Cancer Research, JAMA, Lung Cancer / 28.09.2015

[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.
Author Interviews, Lung Cancer, Outcomes & Safety, Surgical Research, University of Michigan / 15.08.2015

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.
Author Interviews, Biomarkers, Lung Cancer, Wistar / 11.06.2015

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.
Author Interviews, Cancer Research, UCSF / 03.04.2015

Trevor G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSFMedicalResearch.com Interview with: Trever G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSF Medical Research: What is the background for this study? What are the main findings? Dr. Bivona: Resistance to targeted cancer therapy remains a problem in the treatment of cancer patients.  These targeted drugs are often effective at shrinking the tumor, but do so incompletely.  This incomplete response results in residual disease that is drug resistant and eventually grows to cause relapse that is lethal in patients.  We investigated the mechanisms underlying this residual disease state in lung cancers treated with the EGFR targeted therapy Tarceva.  We discovered that the tumor cells survival initial EGFR targeted therapy treatment by activating a signaling pathway called NF-kappa B.  This NF-kappa B pathway then promotes tumor cell survival, residual disease, and eventual relapse in the lung cancer models we studied.
Author Interviews, Lung Cancer, Radiology / 19.03.2015

MedicalResearch.com Interview with: Prof. Dr. Nikolaus Becker Epidemiologisches Krebsregister Baden-Württemberg Deutsches Krebsforschungszentrum Heidelberg Germany Medical Research: What is the background for this study? What are the main findings? Prof. Becker: Lung cancer is the leading cause of cancer death in our Western countries as well as worldwide. One reason is that it is clinically diagnosed mostly in an advanced stage with a poor five-year survival of less than 10%. Diagnosed at an early stage, more than 70% would survive 5 years. For low dose-multislice CT (MSCT) indications exist that it is able to detect lung cancers early. As every newly upcoming screening tool, it has to be carefully analyzed whether it is really able to decrease the mortality from lung cancers and at which costs in terms of undesired side effects such as false-positive findings and overdiagnosis. Our results indicate that spontaneous MSCT screening with changing doctors might be ineffective due to many false-positive alarms; if screening then within an organizational framework.
Author Interviews, Lung Cancer, Pulmonary Disease / 10.03.2015

Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA MedicalResearch.com Interview with: Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation, and normal respiratory functions after birth. Alteration in the expression of this transcription factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer. MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets Nfib and Myb. These findings add new components to the gene regulatory network controlled by Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in development and disease particularly in this case lung cancer where the levels are seriously altered.
Author Interviews, JAMA, Lung Cancer, Mayo Clinic / 24.02.2015

MedicalResearch.com Interview with: David Mithun, M.D. Division of Pulmonary and Critical Care Medicine Mayo Clinic, Rochester, Minnesota Medical Research: What is the background for this study? Dr. Mithun: Lung cancer screening should be pursued for those people at highest risk who are otherwise in good enough health to be able to undergo curative intent treatment if cancer is found. The current criteria for screening recommended by the US Preventive Services Task Force of age 55-80 years, 30 pack-years of smoking, and if quit, have done so within 15 years and are based on the National Lung Screening Study (NLST). Medical Research: What are the main findings? Dr. Mithun: Our data was retrospective over a 28 year time period and showed that an increasing number of people who actually got cancer would not have been candidates for screening based on the current criteria.  This suggests there may be some degree of mismatch between risk as defined by the current criteria to screen and those who developed cancer.  An increasing number of those who would not have been candidates for screening yet got lung cancer were among those who quit smoking 15 years or longer.
Annals Internal Medicine, Author Interviews, Lung Cancer, NIH, Radiology / 13.02.2015

MedicalResearch.com Interview with: Paul F. Pinsky, PhD MPH Acting Chief Early Detection Research Group National Cancer Institute Bethesda, MD, 20892 Medical Research: What is the background for this study? What are the main findings? Response: The National Lung Screening Trial (NLST) reported, in 2011, a 20% reduction in lung cancer mortality with low-dose CT screening. However, there was a high false positive rate, around 25% in the first two screening rounds, and somewhat lower in the final round. In order to reduce the high false positive rate, and also to standardize the reported system for low-dose CT screening, analogous to the use of BIRADS for mammography screening, the American College of Radiology (ACR) developed the Lung-RADS classification system. It was released in May, 2014. Although it was developed based on published summary data from several studies, including the NLST, it was never applied to a large group of screened subjects on an individual basis. Therefore, we retrospectively applied Lung-RADS to previously collected, detailed screening data from the National Lung Screening Trial . The major findings were that the false positive rate decreased very substantially using Lung-RADS instead of the original National Lung Screening Trial criteria. At the baseline screen, it decreased by 50% and at subsequent screens it decreased by 75%. There was also, however, a modest decrease in the sensitivity rate, from 93% to 85% at baseline and from 93% to 79% at subsequent screens.
Author Interviews, Biomarkers, Lung Cancer / 06.02.2015

MedicalResearch.com Interview with: Teresa W-M. Fan PhD and Andrew N Lane, PhD Markey Cancer Center, University of Kentucky Medical Research: What is the background for this study? What are the main findings? Response:  The study began about eight years ago at the University of Louisville as a collaboration between thoracic surgeon Michael Bousamra II, immunologist Jun Yan and our metabolomics team (T. Fan, R Higashi and A.N. Lane) now at the U. Kentucky. Lung cancer remains as the highest cancer mortality in North America, and is unfortunately often not diagnosed until the most successful treatment, surgery, is no longer an option.  Furthermore although there are numerous subtypes of the disease, the options for chemotherapy are quite limited. We wanted to know how the biochemistry of early stage (resectable) lung cancer differs from that of healthy or at least non-cancerous lung tissue from the point of view of basic tumor biology, and whether we might uncover better option for therapeutic intervention. To this end, we applied our stable isotope resolved metabolomics (SIRM) technique directly to patients who were diagnosed with resectable NSCLC. By this technique, the fate of individual atoms from a non-radioactive enriched precursor (C-13 glucose in this instance) are traced as they are taken up from the blood and metabolized in situ. This technique, along with model studies with mice, isolated cell cultures, and so-called “Warburg” slices provides tremendous detail about the functional biochemistry of a cancer within its natural microenvironments, compared with non-cancerous tissue. The major finding published in this article is that the anaplerotic enzyme pyruvate carboxylase is greatly upregulated in NSCLC compared with paired non-cancerous lung tissue, whereas the other commonly utilized anaplerotic enzyme glutaminase was not. Interestingly, only cancer cells showed strong staining for pyruvate carboxylase, whereas in the paired non-cancerous lung tissue, only resident macrophages stained for PC. Pyruvate carboxylase was further shown to be essential for tumor growth in both call culture and in mouse xenografts.
Author Interviews, Lung Cancer, Medical Imaging / 05.01.2015

Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ONMedicalResearch.com Interview with: Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ON Medical Research: What is the background for this study? What are the main findings? Dr. Inacio: Lung cancer is the most common and most lethal cancer worldwide. Its prognosis remains poor with a 5-year survival rate of 6–18%. Adenocarcinoma has surpassed squamous cell carcinoma as the leading histologic type. The presence of metastases carries the worst prognosis in lung cancer and is the most important in determining staging and management. Hematogenous spread (i.e., carried by blood) is the most common mechanism of intrapulmonary metastasis. Cumulative evidence suggests that intrapulmonary aerogenous spread may exist and is under recognized. Deriving from our clinical experience, we performed a literature review that supports the hypothesis that lung cancer, particularly adenocarcinoma, may spread through the airways. With aerogenous metastases, it has been postulated that cancer cells growing along the alveolar septa at the primary site detach from the basal membrane, spread through the airways and re-attach and grow along alveolar septa away from the primary focus. Radiology-pathology correlation studies, using Chest Computed Tomography (CT), have documented the radiological evolution from focal adenocarcinoma to multifocal airspace disease and demonstrated cytologic and histologic findings supportive of aerogenous spread.
Author Interviews, Journal Clinical Oncology, Lung Cancer, Radiation Therapy, UT Southwestern / 03.01.2015

[caption id="attachment_10398" align="alignleft" width="200"]Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman[/caption] MedicalResearch.com Interview with: Dr. Puneeth Iyengar, MD, PhD. Assistant Professor Director of Clinical Research Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center UT Southwestern Medical Center  Dallas, TX Medical Research: What is the background for this study? What are the main findings? Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure. To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious – only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes. These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial.
Author Interviews, Lung Cancer, PLoS / 03.12.2014

dr_Martin_C_TammemägiMedicalResearch.com Interview with: Dr. Martin C. Tammemägi Professor (Epidemiology), Brock University Department of Health Sciences St. Catharines, Ontario, Canada L2S 3A1 Medical Research: What is the background for this study? What are the main findings? Dr. Tammemägi: Lung cancer is the leading cause of cancer death in North America and the world. Lung cancer survival following diagnosis is generally poor, in the range of 10% to 15%, and has improved little over the last four decades. The biggest recent breakthrough for reducing lung cancer mortality came with the findings of the National Lung Screening Trial (NLST), a large, well-conducted randomized screening trial, which demonstrated that low dose computed tomography (LDCT) screening versus chest X-ray (CXR) screening can reduce lung cancer mortality by 20%. Currently, most guidelines for selecting screenees for lung screening use the NLST enrolment criteria of 30 or more pack-years smoked, former smokers must have quit smoking within 15 years and ages between 55 and 74, or use a variant of the NLST criteria. The US Preventive Services Task Force (USPSTF) essentially recommends using the NLST criteria but extended the inclusion age to 80 years. The current study applied the PLCOm2012 lung cancer risk prediction model1 to NLST data and identified that the risk above which lung cancer mortality is consistently lower in the LDCT arm compared to the CXR arm, is ≥1.51% 6-year risk (65th percentile). The USPSTF and the PLCOm2012 risk ≥0.0151 criteria were then applied to the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) intervention arm smokers (the PLCOm2012 was developed in PLCO controls) to determine who would be selected for lung cancer screening. Compared to USPSTF criteria, the PLCOm2012 risk ≥0.0151 threshold selected 8.8% fewer individuals, but identified 12.4% more lung cancers (sensitivity 80.1% vs. 71.2%), and had fewer false positives (specificity 66.2% vs. 62.7%). 26% of smokers who were USPSTF criteria positive had risks below the PLCOm2012 risk ≥0.0151 threshold. Of PLCO former smokers who quit more than 15 years ago, 8.5% had PLCOm2012 risk ≥0.0151, suggesting that they might benefit from screening (2.9% of them developed lung cancer in 6 year). None of 65,711 never-smokers in the PLCO had PLCOm2012 risk ≥0.0151, indicating that never-smokers should not be screened. Individuals age ≥65–80 years had significantly higher risks and more lung cancers than those 55-64 years.
Author Interviews, Biomarkers, Lung Cancer / 20.11.2014

Marie-Christine Aubry, M.D. Professor of Laboratory Medicine and Pathology Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic in Rochester, Minn.MedicalResearch.com Interview with: Marie-Christine Aubry, M.D. Professor of Laboratory Medicine and Pathology Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic in Rochester, Minn.   Medical Research: What is the background for this study? What are the main findings? Dr. Aubry: Up to 20% of patients will present with multifocal lung cancer or will develop a second lung cancer.  The main clinical issue is distinguishing between independent primaries from true intrapulmonary metastases since this distinction will drive the therapy of the patient.  Currently no ancillary studies allows for this distinction and the distinction is provider specific based on a combination of clinical, radiologic and pathologic assumptions. Based on our prior research using a method called mate pair sequencing , we observed that the probability of detecting identical chromosomal breakpoints in two unrelated tumors, from 2 different patients was basically zero. Similarly, when assessing different components within a single tumor, we always found identical chromosomal breakpoints between these components.  We thus hypothesized that if two tumors within a patient were related, i.e. true metastasis, we should always find a number of identical chromosomal breakpoints between the tumors. And in contrast, if 2 tumors were truly independent primaries, we should not observe any chromosomal breakpoints in common. We first studied a control group of patients that had 1- a primary lung cancer with a known distant metastasis (usually brain metastasis), 2- two lung cancers of different histologic subtype, adenocarcinoma and squamous cell carcinoma which are accepted as true independent primaries and 3- 1 tumor with different portions of the tumor being analyzed individually and compared as true relatedness. There were thus a total of 11 pairs of tumors with predetermined status of independent primaries versus relatedness (ie metastasis or same tumor).  The mate pair generated data showed a perfect concordance with this status.  We then studied 11 pairs of lung tumors of similar histology (2 adenocarcinomas or 2 squamous cell carcinomas).  The current gold standard for the distinction between independent primaries and intrapulmonary metastasis relies on a pathologist’s comparative morphologic assessment. In order to strengthen this gold standard, 2 pulmonary pathologists independently made this assessment. Interestingly, the pathologists agreed on the status of independent primaries and intrapulmonary metastasis in 9 (of 11) cases demonstrating the shortcomings of this gold standard.  Furthermore, there were discordance between the pathologists’ prediction and the clinicians’ assessment in 3 of the 11 patients and the clinician could not come to a final assessment in 1 patient.  The MP data was concordant with the pathology assessment in 8 of these 9 cases, and supported the pathologists’ prediction in 2 (of the 3) discordance with the clinical assumptions.
Author Interviews, Dartmouth, Lung Cancer, NEJM / 07.11.2014

William C. Black, MD Professor of Radiology Department of Radiology Dartmouth-Hitchcock Medical Center Lebanon, NH 03756MedicalResearch.com Interview with: William C. Black, MD Professor of Radiology Department of Radiology Dartmouth-Hitchcock Medical Center Lebanon, NH 03756 Medical Research: What is the background for this study? What are the main findings? Dr. Black: Lung cancer is the leading cause of cancer related death in the U.S., killing more people than cancers of the colon, breast, and prostate combined. In 2011, the National Lung Screening Trial (NLST) demonstrated that screening for lung cancer with low-dose CT could reduce lung cancer mortality by 20% in adults at high risk for the disease. Since then, several medical organizations have recommended that eligible adults be offered screening. The U.S. Preventive Services Task Force (USPSTF) released a grade B recommendation for low-dose CT screening in December 2012, which means that private insurers must cover the cost of screening by January 1, 2015. The Centers for Medicare and Medicaid (CMS) is expected to issue a final decision on national coverage for CT screening in February 2015 and a preliminary decision for public comment on November 10, 2014.
CHEST, Lung Cancer / 21.10.2014

Peter J. Mazzone, MD, FCCP MPH Director of the Lung Cancer Program for the Respiratory Institute Cleveland ClinicMedicalResearch.com Interview with: Peter J. Mazzone, MD, FCCP MPH Director of the Lung Cancer Program for the Respiratory Institute Cleveland Clinic Medical Research: What are the main findings of this study? Dr. Mazzone:   There were 2 parts to this study. In the first part we looked at how the breath collection instrument and sensor were performing and made adjustments to both in order to optimize its performance. In the second part we used the improved device and sensor to see if we could accurately separate a sensor signal of our patients with lung cancer from those without lung cancer. We found good separation of lung cancer from non-cancer breath signals, and very good separation of signals of one type of lung cancer from another. We have concluded that a colorimetric sensor array based breath test is capable of separating those with lung cancer from those without.
Author Interviews, Cancer Research, JNCI, Lung Cancer, UT Southwestern / 02.10.2014

Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical CenterMedicalResearch.com Interview with: Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical Center Medical Research: What are the main findings of the study? Dr. Gerber: Fewer than 3% of adult cancer patients in the United States are enrolled in clinical trials.  Increasingly numerous and stringent eligibility criteria are a major factor limiting participation in clinical trials.  We examined the longstanding and widespread practice of excluding patients with prior cancer from oncology clinical trials.  This policy presumably reflects concerns that a prior cancer would interfere with the conduct, outcomes, or interpretation of a clinical trial, although there is no clear evidence supporting that assumption. We examined more than 50 National Cancer Institute (NCI)-sponsored lung cancer clinical trials.  We found that 80% excluded patients with prior cancers.  This exclusion criterion was applied broadly, including to more than two-thirds of trials with non-survival endpoints.  We then examined national Surveillance Epidemiology and End Results (SEER)-Medicare linked data to estimate the proportion of patients who would be excluded from these trials due to prior cancer.  We found that up to 18% of potential patients are excluded for this reason alone.  In large phase 3 clinical trials, that corresponds to more than 200 patients.
Author Interviews, Lancet, Lung Cancer, Radiation Therapy / 15.09.2014

Prof. dr. B.J. Slotman VU University Medical Center Cancer Center Amsterdam NetherlandsMedicalResearch.com Interview wth: Prof. dr. B.J. Slotman VU University Medical Center Cancer Center Amsterdam Netherlands Medical Research: What are the main findings of this study? Prof. Slotman: This randomized trial showed that the use of thoracic radiotherapy in patients with extensive stage small cell lung cancer reduces the risk of intrathoracic progression by about 50% and improves 2 years survival from 3 to 13%.
Biomarkers, Lung Cancer / 10.09.2014

MedicalResearch.com Interview with: Dr. Giulia Scioscia Coauthor of this study with the Prof. Carpagnano University of Foggia. Medical Research: What are the main findings of this study? Dr. Scioscia: The principal and newest findings of our study are:
  • Airways inflammation and neoangionesis are critical component of the lung cancer pathogenesis and they contribute to the regulation of airways temperature. They cause a regional hyperthermia in the lung lesion.
  • The exhaled Breath temperature has been proven to be the expression of the airways temperature and for this reason of their inflammation and neoangionesis.
  • For the first time we have measured this hyperthermia in lung cancer patients with the xhalo. The patient with diagnosis of tumor shows an higher temperature than in healthy ones and this values correlate with cigarette smoking and tumor progression.
Author Interviews, Cancer Research, CHEST, Critical Care - Intensive Care - ICUs, University of Michigan / 22.06.2014

Colin R. Cooke, MD, MSc, MS; Assistant Professor of Medicine, Division of Pulmonary & Critical Care Medicine Faculty, Center for Healthcare Outcomes & Policy University of MichiganMedicalResearch.com Interview with: Colin R. Cooke, MD, MSc, MS; Assistant Professor of Medicine, Division of Pulmonary & Critical Care Medicine Faculty, Center for Healthcare Outcomes & Policy University of Michigan MedicalResearch: What are the main findings of the study? Dr. Cooke: There were three primary findings from our study. First, we determined that between 1992 and 2005 there was almost a 40% increase in the number of admissions to an intensive care unit (ICU) among patients with lung cancer who were hospitalized for reasons other than surgical removal of their cancer. Second, most of this increase was because doctors were admitting these patients to intermediate intensive care units. These are units that provide greater monitoring and nurse staffing than typically available in general hospital wards, but usually also have less ability to provide life support measures than full service ICUs. Third, over the same period the reasons for ICU admission have changed. Although the most common reason for admission continues to be for problems related to the patients’ lung cancer, problems such as breathing difficulties requiring a ventilator and severe infections are increasingly common. These findings suggest that although overall use of the ICU for patients with lung cancer is increasing over time, providers may be shifting some of the intensive care for lung cancer patients toward less aggressive settings such as the intermediate care unit.
Author Interviews, Biomarkers, CHEST, Cleveland Clinic, Lung Cancer / 20.04.2014

Daniel I. Sessler, M.D. Michael Cudahy Professor and Chair, Department of Outcomes Research Cleveland Clinic, Cleveland,MedicalResearch.com Interview with: Daniel I. Sessler, M.D. Michael Cudahy Professor and Chair, Department of Outcomes Research Cleveland Clinic, Cleveland, OH MedicalResearch.com: What are the main findings of the study? Dr. Sessler: Free fatty acids, arachidonic acid and linoleic acid, and their metabolites hydroxyeicosatetraenoic acids (5-HETE, 11-HETE, 12-HETE, and 15-HETE) were 1.8 to 5.7-fold greater in 37 patients with adenocarcinoma versus 111 patients without cancer (all P<0.001). Areas under the receiver operating characteristics (ROC) curve were significantly greater than 0.50 discriminating lung cancer patients and controls for all biomarkers and phospholipids, and ranged between 0.69 and 0.82 (all P<0.001) for lung cancer patients versus controls. Arachidonic acid, linoleic acid, and 15-HETE showed sensitivity and specificity >0.70 at the best cutpoint. Concentrations of free fatty acids and their metabolites were similar in 18 squamous-cell carcinoma patients and 54 non-cancer controls.