FDG-PET Scans of Lung Nodules Should Be Interpreted With Caution

MedicalResearch.com Interview with:

PET Scan Vanderbilt Health

PET Scan Vanderbilt Health

Amelia W. Maiga, MD MPH
Vanderbilt General Surgery Resident
VA Quality Scholar, TVHS

MedicalResearch.com: 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.

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REVEL Trial of Ramucirumab Plus Docetaxel For Fast Progressing NSC Lung Cancer Demonstrates Promise

MedicalResearch.com 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

Dr. Reck

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 


MedicalResearch.com: 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.

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Circulating Tumor Cells Linked To Poor Prognosis in Early Stage Lung Cancers

MedicalResearch.com Interview with:

Dr. Sunitha Nagrath, PhD Associate Professor, Chemical Engineering University of Michigan

Dr. Nagrath

Dr. Sunitha Nagrath, PhD
Associate Professor, Chemical Engineering
University of Michigan 

MedicalResearch.com: 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.

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Lymph Node Staging of Potentially Curable Lung Cancer Needs Improvement

MedicalResearch.com Interview with:

Raymond U. Osarogiagbon, MBBS, FACP Translational Lung Cancer Research Multidisciplinary Thoracic Oncology Program Baptist Centers for Cancer Care Memphis, TN

Dr. Osarogiagbon

Raymond U. Osarogiagbon, MBBS, FACP
Translational Lung Cancer Research
Multidisciplinary Thoracic Oncology Program
Baptist Centers for Cancer Care
Memphis, TN 

MedicalResearch.com: 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.

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Radiation Therapy Plus Checkpoint Inhibitors Did Not Increase Adverse Events in Metastatic Lung Cancer

MedicalResearch.com Interview with:

Florence K Keane MD Resident, Radiation Oncology Harvard Radiation Oncology Program Boston, Massachusetts

Dr. Keane

Florence K Keane MD
Resident, Radiation Oncology
Harvard Radiation Oncology Program
Boston, Massachusetts

MedicalResearch.com: 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.

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High Doses of B Vitamins Linked to INCREASED Lung Cancer in Male Smokers

MedicalResearch.com Interview with:

Theodore M. Brasky, PhD Research Assistant Professor The Ohio State University – James Comprehensive Cancer Center Columbus, OH 43201

Dr. Brasky

Theodore M. Brasky, PhD
Research Assistant Professor
The Ohio State University – James Comprehensive Cancer Center
Columbus, OH 43201

MedicalResearch.com: 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.

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Small Cell Lung Cancers Form Chemotherapy-Resistant Circulating Tumor Spheres

MedicalResearch.com Interview with:

Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna 

Prof. Hamilton

Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna

MedicalResearch.com: 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.

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Study Reports Hair Repigmentation During Immunotherapy For Lung Cancer

MedicalResearch.com Interview with:
Dr. Noelia Rivera MD

Dermatologist
Hospital Universitari Germans Trias i Pujol, Badalona
Universitat Autònoma de Barcelona

MedicalResearch.com: 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.

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Holes in Cigarette Filters Linked To Increase in Lung Adenocarcinomas

MedicalResearch.com 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

MedicalResearch.com: 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.

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GeneStrat Test Provides Quick Analysis of Genetic Lung Cancer Mutations

MedicalResearch.com Interview with:
Hestia Mellert, PhD

Director, Molecular Product Development
Biodesix: Making Medicine Personal
Boulder, CO

MedicalResearch.com: 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.

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Cost Effectiveness of Lung Cancer Screening Requires Careful Patient Selection

MedicalResearch.com Interview with:
Kevin ten Haaf MSc

Scientific researcher, Public Health
Erasmus Medical Center
Rotterdam

MedicalResearch.com: 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.

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Annual CT Lung Cancer Screening Among Former Smokers Remains Underutilized

MedicalResearch.com Interview with:

Ahmedin Jemal, DVM, PHD Vice President, Surveillance and Health Services Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303

Dr. Ahmedin Jemal

Ahmedin Jemal, DVM, PHD
Vice President, Surveillance and Health Services Research
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

MedicalResearch.com: 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.

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Comprehensive Lung Cancer Screening Is Complex Task With Many False Positives

MedicalResearch.com Interview with:

Dr-Linda-Kinsinger.jpg

Dr. Linda Kinsinger

Linda Kinsinger, MD, MPH
National Center for Health Promotion and Disease Prevention
U.S. Department of Veterans Affairs
NW Washington DC 20420

MedicalResearch.com: 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.

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Cancer Deaths Drop 25% in Less Than 25 Years

MedicalResearch.com Interview with:

Rebecca Siegel, MPH Strategic Director, Surveillance Information Services American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303

Rebecca Siegel

Rebecca Siegel, MPH
Strategic Director, Surveillance Information Services
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

MedicalResearch.com: 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.

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Vandetanib Had Antitumor Activity In RET-rearranged NSC Lung Cancer

MedicalResearch.com Interview with:
Dr Kiyotaka Yoh

Department of Thoracic Oncology
National Cancer Center Hospital East
Kashiwa, Japan

MedicalResearch.com: 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.

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Mesothelioma: Nintedanib Plus Chemotherapy Demonstrated Improved Progression-Free Survival

Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy

Prof. Scagliotti

MedicalResearch.com Interview with:
Professor Giorgio V. Scagliotti

Chair of the Department of Oncology
University of Torino,Italy


MedicalResearch.com: 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.

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.

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Estimating Survival in Patients With Lung Cancer and Brain Metastases

MedicalResearch.com Interview with:

Paul W. Sperduto, MD, MPP, FASTRO

Dr. Paul W. Sperduto

Paul W. Sperduto, MD, MPP, FASTRO
Minneapolis Radiation Oncology
University of Minnesota Gamma Knife Center, Minneapolis, Minnesota

MedicalResearch.com: 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.

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Overall survival data from LUX-Lung 7 head-to-head trial of Afatinib versus Gefitinib

MedicalResearch.com Interview with:

Shirish Gadgeel, MD Leader of the Thoracic Oncology Multidisciplinary team Professor at Karmanos Cancer Institute Detroit

Dr. Shirish Gadgeel

Shirish Gadgeel, MD
Leader of the Thoracic Oncology Multidisciplinary team
Professor at Karmanos Cancer Institute
Detroit

MedicalResearch.com: 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.

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Depression Common in Lung Cancer and Linked To Mortality

MedicalResearch.com 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

Dr. Donald Sullivan

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

MedicalResearch.com: 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.
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Penn Reports Successful Pilot Study of Liquid Biopsy To Monitor Advanced Lung Cancer

MedicalResearch.com 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

Dr. Erica Carpenter

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.

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Lung Cancer: Adjusting Afatinib Dose Reduced Side Effects With No Impact on Efficacy

MedicalResearch.com Interview with:

Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital

Dr. Chih-Hsin Yang

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).

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Liquid Biopsies Hold Promise of Diagnosing Response to Chemotherapy

MedicalResearch.com Interview with:

Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010

Dr. Karen Reckamp

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.

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Lung Cancers Detected On Screening CT Scans Have Better Survival

MedicalResearch.com Interview with:

Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida

Dr. Matthew Schabath

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.

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BMI1 Gene Expression May Predict Response To Lung Cancer Treatment

MedicalResearch.com 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

Dr. Elena Levantini

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.

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Air Pollution May Shorten Lung Cancer Survival

Sandrah P. Eckel PhD Assistant Professor of Preventive Medicine USC Division of Biostatistics

Dr. Sandrah Eckel

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.

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Recommended Low-dose CT Scanning For Lung Cancer Often Not Understood or Implemented

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

Dr. Jan Marie Eberth

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).

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Lung Cancer Risk Calculator Improves CT Screening Efficiency and May Save Lives

MedicalResearch.com 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

Dr. Hormuzd Katki

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.

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Carefully Chosen Liquid Biopsy Can Detect and Monitor Lung Cancer Mutations

MedicalResearch.com Interview with:

Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital

Dr. Adrian Sacher

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.

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High Glycemic Index May Raise Lung Cancer Risk Especially in Never Smokers

MedicalResearch.com Interview with:

Xifeng Wu, M.D., Ph.D Professor of Epidemiology

Dr. Xifeng Wu

Xifeng Wu, M.D., Ph.D
Professor of Epidemiology and

Dr. Stephanie Claire Melkonian PhD Epidemiologist, Postdoctoral Research Fellow

Dr. Melkonian

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.

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Only Small Increase in CT Screening for Lung Cancer Despite New Guidelines

MedicalResearch.com Interview with:

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

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

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Drug Repurposing Trial Suggests Statins May Improve Survival in Small Cell Lung Cancer

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.

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Lung Cancer: New Screening Guidelines and Reimbursement Protocols

 

Jan Marie Eberth

Dr. Eberth

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.

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Some Nodules on CT Scans More Likely to Be Lung Cancer In Women

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

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.

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Lung Cancer: Intensity Modulated Radiation Therapy Linked to Improved Quality of Life

Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan

Dr. Movsas

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.

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Mortality After Lung Cancer Resection Steadily Decreasing

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

Dr. Bravo

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. Bravo: The National Lung Screening Trial (NLST) determined the ability of low-dose computed tomography (LDCT) scans to reduce Lung Cancer specific mortality by 20% in high-risk patients. This reduction was partly dependent on the low surgical mortality experienced at the major academic centers, centers that were pioneers in minimally invasive lobectomy techniques.

In December 2013, The United States Preventive services task force (USPTF) endorsed annual low-dose computed tomography screening for Americans between ages 55 to 80 years who have 30 pack-years of smoking history and have smoked within 15 years.

On April 30th, 2014 the Centers for Medicare and Medicaid Services expressed concerns and raised skepticism as to whether the benefit of implementing a Lung Cancer Screening Program for the Medicare population could be maintained nationwide.  Specifically, they doubted low mortality and morbidity rates achieved by the NLST in the elderly patients could be maintained throughout the United States and across a broad range of hospital settings.

Medical Research: What are the main findings? 

Dr. Bravo: Mortality after lung resection has been decreasing over the past five decades. We analyzed a nationally validated database intended to measure and improve quality of surgical care – The American College of Surgeons National Surgical Quality improvement Program (ACS-NSQIP)- in order to find this answer.

The Overall Mortality rate was 2.34%. This included academic and community hospitals. Further analysis showed a significant difference on this rate depending on surgical technique: 3.13% for those undergoing Open thoracotomy lobectomy and 1.19% for those who underwent minimally invasive video-assisted Thoracoscopic lobectomy. Morbidity rate was 19.9% consistent with other recent prospective clinical trials. 

Medical Research: What should clinicians and patients take away from your report?

Dr. Bravo: These results showed that current operative mortality is not limited to pioneering centers in minimally invasive surgery or large academic centers but has now pervaded centers participating in the ACS-NSQIP database. Briefly, 8% of US hospitals providing adult care participate in the database. They include a mixture of academic centers and community hospitals with 29% of participants defined as non teaching hospitals and 31% having fewer than 500 licensed beds.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Bravo: Prospective data collection in the context of the recently implemented lung cancer screening program will be necessary to further refine screening criteria and implementation strategies. Also, results of ongoing randomized trials on sublobar resections for Lung cancer can favorably impact the results of the screening program reducing even more the morbidity and mortality.

Citation:

Thirty-Day Mortality After Lobectomy in Elderly Patients Eligible for Lung Cancer Screening

Bravo Iñiguez, Carlos E. et al.
The Annals of Thoracic Surgery Published Online:October 22, 2015

Carlos E. Bravo Iñiguez, M.D. (2015). Mortality After Lung Cancer Resection Steadily Decreasing 

New Immunotherapy May Extend Lives Of Some Lung Cancer Patients

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.

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PD-1 Blocker Extends Lives in Lung Cancer Patients

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.

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Genotyping May Lead To Personalized Lung Cancer Therapy

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.

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Many Patients Require Hospitalization During Chemotherapy

Dr. Rebecca Prince Clinical Research Fellow and first author

Dr. Rebecca Prince

MedicalResearch.com Interview with:
Dr. Rebecca Prince MBBS
Clinical Research Fellow and first author and

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

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.

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Hospital Mortality Outcomes Differ After Lung Cancer Surgery Complications

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.

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AKAP4 Is a Promising Blood Biomarker For Early Detection of Lung Cancer

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. Continue reading

Signal Pathway Allows Lung Cancer Cells To Resist Chemotherapy

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.

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German Study Suggests CT Screening For Lung Cancer Has Unresolved Questions

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.

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New Mechanism Driving Lung Cancer Elucidated

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.

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CT Lung Cancer Screening Guidelines May Miss Some At Risk

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.
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New Classification System For Low-dose CT Screening For Lung Cancer

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.

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Enzyme Critical to Non-Small Cell Lung Cancer Growth Identified

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.

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Adenocarcinoma of Lung May Spread Through Airways

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.

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Non-Small Cell Lung Cancer: Stereotactic Radiation Plus Chemo Improved Survival

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman

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.

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Lung Cancer: More Efficient CT Screening Model Proposed

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.

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