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RESPIRATORY DISEASES (102 journals)                     

Showing 1 - 102 of 102 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 253)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 20)
American Review of Respiratory Disease     Full-text available via subscription   (Followers: 4)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Annals of the American Thoracic Society     Full-text available via subscription   (Followers: 16)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
Archivos de Bronconeumología     Full-text available via subscription  
Archivos de Bronconeumología (English Edition)     Full-text available via subscription   (Followers: 1)
Asthma Research and Practice     Open Access   (Followers: 1)
BMC Pulmonary Medicine     Open Access   (Followers: 4)
BMJ Open Respiratory Research     Open Access   (Followers: 5)
Breathe     Open Access   (Followers: 4)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal  
Canadian Respiratory Journal     Open Access   (Followers: 2)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 100)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 3)
Clinical Pulmonary Medicine     Hybrid Journal   (Followers: 2)
COPD Research and Practice     Open Access   (Followers: 1)
COPD: Journal of Chronic Obstructive Pulmonary Disease     Hybrid Journal   (Followers: 15)
Current Opinion in Pulmonary Medicine     Hybrid Journal   (Followers: 10)
Current Pulmonology Reports     Hybrid Journal  
Current Research in Tuberculosis     Open Access   (Followers: 3)
Current Respiratory Care Reports     Hybrid Journal   (Followers: 1)
Current Respiratory Medicine Reviews     Hybrid Journal   (Followers: 5)
Der Pneumologe     Hybrid Journal   (Followers: 1)
Egyptian Journal of Chest Diseases and Tuberculosis     Open Access   (Followers: 3)
ERJ Open Research     Open Access   (Followers: 2)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 3)
European Respiratory Journal     Full-text available via subscription   (Followers: 38)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal  
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 11)
Heart, Lung and Circulation     Full-text available via subscription   (Followers: 9)
Indian Journal of Respiratory Care     Open Access   (Followers: 3)
Indian Journal of Tuberculosis     Full-text available via subscription  
Influenza and Other Respiratory Viruses     Open Access   (Followers: 2)
International Journal of Chronic Obstructive Pulmonary Disease     Open Access   (Followers: 3)
Journal of Association of Chest Physicians     Open Access   (Followers: 2)
Journal of Asthma     Hybrid Journal   (Followers: 4)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 3)
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases     Open Access  
Journal of Heart and Lung Transplantation     Hybrid Journal   (Followers: 12)
Journal of Respiratory Medicine     Open Access   (Followers: 4)
Journal of Respiratory Research     Open Access   (Followers: 1)
Journal of Tuberculosis Research     Open Access   (Followers: 1)
Jurnal Respirasi     Open Access  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Kindheit und Entwicklung     Hybrid Journal  
Lung     Hybrid Journal   (Followers: 2)
Lung Cancer     Hybrid Journal   (Followers: 15)
Lung Cancer International     Open Access   (Followers: 2)
Lung Cancer: Targets and Therapy     Open Access   (Followers: 3)
Lung India     Open Access   (Followers: 1)
Multidisciplinary Respiratory Medicine     Open Access   (Followers: 4)
npj Primary Care Respiratory Medicine     Open Access   (Followers: 2)
Open Journal of Respiratory Diseases     Open Access   (Followers: 1)
Open Respiratory Medicine Journal     Open Access   (Followers: 1)
Paediatric Respiratory Reviews     Hybrid Journal   (Followers: 11)
Pediatric Quality & Safety     Open Access  
Pediatric Respirology and Critical Care Medicine     Open Access   (Followers: 1)
Pulmonary Circulation     Open Access   (Followers: 4)
Pulmonary Medicine     Open Access   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 1)
Pulmonology and Respiratory Research     Open Access   (Followers: 1)
Respiratory Care     Full-text available via subscription   (Followers: 10)
Respiratory Investigation     Full-text available via subscription  
Respiratory Medicine     Hybrid Journal   (Followers: 17)
Respiratory Medicine : X     Open Access  
Respiratory Medicine Case Reports     Open Access  
Respiratory Medicine CME     Hybrid Journal  
Respiratory Medicine Extra     Full-text available via subscription   (Followers: 1)
Respiratory Physiology & Neurobiology     Hybrid Journal   (Followers: 4)
Respiratory Research     Open Access   (Followers: 1)
Respirology     Hybrid Journal   (Followers: 5)
Respirology Case Reports     Open Access  
Revista Americana de Medicina Respiratoria     Open Access  
Revista Chilena de Enfermedades Respiratorias     Open Access  
Revista Inspirar     Open Access  
Revista ORL     Open Access  
Revista Portuguesa de Pneumologia     Open Access  
Sarcoidosis Vasculitis and Diffuse Lung Disese     Full-text available via subscription   (Followers: 3)
Seminars in Respiratory and Critical Care Medicine     Hybrid Journal   (Followers: 14)
Sleep Medicine Reviews     Hybrid Journal   (Followers: 17)
The Clinical Respiratory Journal     Hybrid Journal   (Followers: 3)
The International Journal of Tuberculosis and Lung Disease     Full-text available via subscription   (Followers: 8)
The Lancet Respiratory Medicine     Full-text available via subscription   (Followers: 32)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 37)
Translational Respiratory Medicine     Open Access   (Followers: 1)
Tuberculosis     Hybrid Journal   (Followers: 12)
Tuberculosis Research and Treatment     Open Access   (Followers: 3)
Пульмонология     Full-text available via subscription  

           

Similar Journals
Journal Cover
Clinical Lung Cancer
Journal Prestige (SJR): 1.597
Citation Impact (citeScore): 4
Number of Followers: 5  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1525-7304 - ISSN (Online) 1938-0690
Published by Elsevier Homepage  [3161 journals]
  • Predictors of survival benefit from immune checkpoint inhibitors in
           patients with advanced non-small cell lung cancer: A systematic review and
           meta-analysis
    • Abstract: Publication date: Available online 3 January 2020Source: Clinical Lung CancerAuthor(s): Jacques. Raphael, Anupam. Batra, Gabriel. Boldt, Prakesh.S. Shah, Phillip. Blanchette, George. Rodrigues, Mark.D. VincentAbstractIntroductionRandomized trials showed inconsistent survival benefit with immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with low PD-L1 tumors (65 years old) and never-smokers. We conducted a systematic review and meta-analysis to assess the efficacy of single agent ICIs in these pre-defined subgroups.MethodsThe electronic databases PubMed and EMBASE, were searched for relevant randomized trials. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were meta-analyzed using the generic inverse variance method..ResultsNine studies were included. Compared to chemotherapy, the use of single agent ICIs in the second line setting reduced the risk of death independent of PD-L1 expression (HR 0.79, 95%CI 0.66-0.96 and HR 0.75, 95%CI 0.61-0.85 for patients with PD-L1 (-) and (+) tumors, respectively). Yet, a PFS benefit was only seen in patients with PD-L1 (+) tumors. Similarly, an OS benefit was seen in patients independent of age (HR 0.79, 95%CI 0.69-0.89 and HR 0.76, 95%CI 0.66-0.88 for elderly and non-elderly patients, respectively). Conversely, an OS benefit was only seen in ever-smokers (HR 0.78, 95%CI 0.68-0.89) and a detrimental effect on PFS in never-smokers (HR 1.68, 95%CI 1.07-2.63).ConclusionsAdvanced NSCLC patients derive a survival benefit from ICIs independent of tumor PD-L1 expression and age particularly in the second line while never-smokers do not. Caution should be exercised when offering single agent ICIs to elderly patients in the first line and other treatment options should be considered in never smokers.
       
  • Extensive-Stage Small-Cell Lung Cancer With Sustained Complete Response to
           Single-Agent Nivolumab and Immune-Related Dermatitis
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Page Widick, Ritu R. Gill, Charlene Mantia, Daniel B. Costa, Deepa Rangachari
       
  • Four-Year Lasting Sustained Complete Response After Nivolumab in a Patient
           With Non–Small-Cell Lung Cancer and Confirmed Leptomeningeal
           Carcinomatosis: Changing the Paradigm
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Mateo Bover, Ramón Yarza, Lara Iglesias Docampo
       
  • Volumetric Modulated Arc Therapy After Lung Sparing Surgery for Malignant
           Pleural Mesothelioma: A Single Institution Experience
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Davide Franceschini, Fiorenza De Rose, Salvatore Cozzi, Ilaria Renna, Ciro Franzese, Lucia Di Brina, Pierina Navarria, Giuseppe R. D’Agostino, Pietro Mancosu, Stefano Tomatis, Marta ScorsettiAbstractIntroductionWe investigated the possible role of volumetric modulated arc therapy (VMAT) in the setting of adjuvant treatment of malignant pleural mesothelioma (MPM) after lung-sparing surgery with pleurectomy and decortication.Materials and MethodsPatients affected by MPM who had undergone pleurectomy and decortication and adjuvant radiotherapy with VMAT were included. The endpoints of the present analysis were local control, progression-free survival, and overall survival. Assessment of the variables affecting survival was performed using univariate and multivariate Cox proportional hazard models.ResultsA total of 49 patients were included in the present study. Of the 49 patients, 96% had been treated with a trimodality approach. Radiotherapy was delivered to a median dose of 44 Gy in 22 fractions (range, 22-59.4 Gy). The treatment was well tolerated, with just 2 grade 3 acute toxicities, 1 grade 5, and 2 grade 4 toxicities recorded during the follow-up period. The median follow-up period was 27.4 months. The local control rate at 12, 24, and 36 months was 75.2%, 67.4%, and 56.5%, respectively. The median progression-free survival was 14.9 months (95% confidence interval [CI], 7.5-25.2). The median overall survival was 21.5 months (95% CI, 15.3-37.1). On multivariate analysis, the administration of carboplatin- instead of cisplatin-based chemotherapy (hazard ratio, 2.97; 95% CI, 1.22-7.26; P = .017) and R2 resection (hazard ratio, 1.95; 95% CI, 1.27-2.99; P = .002) showed a negative correlation with overall survival. On univariate analysis, the percentage of the heart receiving>20 Gy and>30 was associated with the occurrence of late pneumonitis (P = .018 and P = .077).ConclusionVMAT is feasible in the setting of MPM after lung-sparing surgery. The toxicity rates were reduced with this technique compared with historical data of older techniques. Local and distant failure remain a major issue to be addressed in future trials.
       
  • Blood Predictive Biomarkers for Patients With Non–small-cell Lung Cancer
           Associated With Clinical Response to Nivolumab
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): M. Teresa Agulló-Ortuño, Óscar Gómez-Martín, Santiago Ponce, Lara Iglesias, Laura Ojeda, Irene Ferrer, Inmaculada García-Ruiz, Luis Paz-Ares, Virginia Pardo-MarquésAbstractBackgroundImmunotherapy is a promising cancer treatment, but surrogate biomarkers of clinical efficacy have not been fully validated. The aim of this work was to evaluate several biomarkers as predictors of response to nivolumab monotherapy in patients with non–small-cell lung cancer.Patients and MethodsBlood samples was collected at baseline, at 2 months after treatment start, and at disease progression. Lactate dehydrogenase level (LDH), neutrophils, and leukocyte values were obtained from medical record. Interleukin (IL)-8, IL-11, and kynurenine/tryptophan levels were determined by enzyme-linked immunosorbent assay. Total protein was extracted from circulating CD8+ T cells, and BCL-2 interacting mediator of cell death (BIM) protein expression tested by western blotting.ResultsBaseline LDH levels were significantly higher in non-responder patients than in those who responded (P = .045). The increase in indoleamine 2,3 dioxygenase activity was related to progression of disease, mainly in patients who did not respond to nivolumab treatment (P = .001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (hazard ratio, 7.49; P = .025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. The Student t test and Mann-Whitney U test were used to compare groups for continuous variables. Time to events was estimated using the Kaplan-Meier method, and compared by the log-rank test.ConclusionsChanges in plasma LDH and IL-8, indoleamine 2,3 dioxygenase activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from nivolumab treatment in these patients.
       
  • Development of a Novel Prognostic Risk Classification System for Malignant
           Pleural Mesothelioma
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Hiroshi Doi, Kozo Kuribayashi, Kazuhiro Kitajima, Koichiro Yamakado, Takashi KijimaAbstractIntroductionThis study aimed to assess prognostic factors to better understand malignant pleural mesothelioma (MPM) and to develop a new classification protocol beyond the standard tumor node metastasis (TNM) staging system.Materials and MethodsWe retrospectively reviewed the data of 188 patients with MPM who had not undergone surgical resection. For each patient, we calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis (TLG) on pretreatment 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography. Using the Cox proportional hazards model, we evaluated the relationships among potential MPM predictors, including age, gender, performance status, histologic type, stage, possible serum markers, and volume-based positron emission tomography parameters, as well as overall survival.ResultsThe median survival was 461 days, and the 1- and 2-year overall survival rates were 60.70% and 31.10%, respectively. Univariate and multivariate analyses revealed that the significant independent predictors of poor survival outcomes were the non-epithelioid histologic type, elevated serum lactate dehydrogenase levels, a neutrophil-to-lymphocyte ratio of ≥ 5.0, and a TLG of ≥ 525 g. We then used these results to develop a prognostic risk classification system. From the resulting survival curve, we found a significant difference among the 3 risk groups of independent variables. Moreover, there were significant differences between all pairs of 2 separated risk groups.ConclusionsPathologic subtypes, serum lactate dehydrogenase, neutrophil-to-lymphocyte ratio, and TLG in 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography were independent and significant prognostic factors of MPM. Using this model, we created a new risk classification system that supplants the standard TNM staging protocol.
       
  • Critical Assessment in Routine Clinical Practice of Liquid Biopsy for EGFR
           Status Testing in Non–Small-Cell Lung Cancer: A Single-Laboratory
           Experience (LPCE, Nice, France)
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Simon Heeke, Jonathan Benzaquen, Véronique Hofman, Marius Ilié, Maryline Allegra, Elodie Long-Mira, Sandra Lassalle, Virginie Tanga, Carole Salacroup, Christelle Bonnetaud, Julien Fayada, Loïc Gazoppi, Lydia Ribeyre, Olivier Castelnau, Georges Garnier, Florian Cattet, Isabelle Nanni, Florence de Fraipont, Charlotte Cohen, Jean-Philippe BerthetAbstractBackgroundThe introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France).Patients and MethodsA total of 345 samples were analyzed using the US Food and Drug Administration–approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients.ResultsCobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable.ConclusionPCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.
       
  • ROS1-rearranged Non–small-cell Lung Cancer is Associated With a High
           Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective,
           Multicenter, Two-arms Trial (METROS)
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Rita Chiari, Biagio Ricciuti, Lorenza Landi, Anna M. Morelli, Angelo Delmonte, Gianluca Spitaleri, Diego L. Cortinovis, Giuseppe Lamberti, Francesco Facchinetti, Sara Pilotto, Claudio Verusio, Antonio Chella, Laura Bonanno, Domenico Galetta, Federico CappuzzoAbstractBackgroundPatients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of patients with advanced non–small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC subgroups is still unclear. In this study, we investigated the incidence and the clinical correlates of VTE in patients with ROS1-rearranged NSCLC enrolled in the METROS trial (NCT02499614).Patients and MethodsThe METROS trial is a prospective phase II study designed to assess efficacy, safety, and tolerability of crizotinib in patients with pre-treated metastatic NSCLC ROS1 rearrangement (cohort A) or with MET amplification or MET exon 14 mutation (cohort B). Patients with ROS1-rearranged NSCLC enrolled within cohort A and the expansion cohort of the trial were included in the primary analysis.ResultsAmong 48 patients with ROS1-rearranged NSCLC enrolled in the METROS study, 20 (41.6%) of 48 had at least 1 VTE event. Among them, 7 (35%) of 20 patients had ≥ 2 VTE events. VTE events consisted of pulmonary embolism (46.4%), deep vein thrombosis (39.2%), renal vein thrombosis (7.1%), internal jugular thrombosis (3.5%), and peripheral inserted central catheter-related thrombosis (3.5%). VTE events occurred at disease progression in 35.7% of cases, at diagnosis in 32.1% of cases, and during chemotherapy or crizotinib in 17.8% and 14.2%, respectively.ConclusionThe incidence of VTE is 3- to 5-fold higher in patients harboring ROS1-rearrangment than previously observed for the general population with NSCLC. Larger studies are warranted to confirm our findings and determine whether the molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis and prophylaxis.
       
  • Response to Letter to the Editor Titled “Surgery or Stereotactic Body
           Radiotherapy for Early Stage Lung Cancer: What is the Current
           Evidence'”
    • Abstract: Publication date: January 2020Source: Clinical Lung Cancer, Volume 21, Issue 1Author(s): Vieri Scotti, Alessio Bruni, Marco Perna, Polina Vasilyeva, Emanuela Olmetto, Frank Lohr, Luca Voltolini, Lorenzo Livi
       
  • Stereotactic body radiation therapy for extracranial oligometastatic
           non-small cell lung cancer: A systematic review
    • Abstract: Publication date: Available online 30 December 2019Source: Clinical Lung CancerAuthor(s): Lieke in ’t Ven, Patrick Cheung, Ian Poon, Yee Ung, Alexander V. Louie, May N. TsaoAbstractBackgroundStereotactic body radiation therapy (SBRT) has emerged as a treatment modality for selected patients with oligometastatic non-small cell lung cancer (NSCLC).ObjectivesThe objectives of this systematic review were to explore the benefits and risks of SBRT for extracranial oligometastatic NSCLC.Materials/MethodsMEDLINE, EMBASE, PUBMED, CENTRAL databases were searched for relevant articles from January 1, 2000 to July 23, 2019. Fully published phase III or phase II trials of any sample size were included. Retrospective series published in manuscript form with at least 50 patients were also included.ResultsFour prospective phase II randomized trials (total 188 participants), 4 prospective non-randomized studies (total 140 participants) and eleven retrospective studies (total 1 288 participants) were included in this systematic review. A variety of dose fractionation schemes were used. Median overall survival (OS) ranged from 13.5 to 55 months. Progression free survival (PFS) ranged from 4.4 to 14.7 months. Quality of life (QOL) outcomes were reported in 2 studies. None of the studies reported symptom control (SC) outcomes.ConclusionsThere are no fully completed phase III randomized trials that clarify the risks and benefits of SBRT for oligometastatic NSCLC. Higher PFS and overall survival with SBRT were reported in 4 phase II randomized studies. The results from mature phase III randomized data regarding whether SBRT for oligometastatic NSCLC benefits patients in terms of OS, PFS, QOL and SC are needed.
       
  • Patient-reported Outcomes After the Treatment of Early Stage
           Non-small-cell Lung Cancer With Stereotactic Body Radiotherapy Compared
           With Surgery
    • Abstract: Publication date: Available online 28 December 2019Source: Clinical Lung CancerAuthor(s): Leonie Alberts, Henri B. Wolff, Elisabeth A. Kastelijn, Franz M.N.H. Schramel, Veerle M.H. Coupe
       
  • Patient Reported Outcomes with Stereotactic Body Radiotherapy and Surgery
           for Lung Cancer
    • Abstract: Publication date: Available online 28 December 2019Source: Clinical Lung CancerAuthor(s): Jennifer Vogel, Charles B. Simone
       
  • Tyrosine Kinase Inhibitors for the Treatment of EGFR Mutation-Positive
           Non–Small-Cell Lung Cancer: a Clash of the Generations
    • Abstract: Publication date: Available online 20 December 2019Source: Clinical Lung CancerAuthor(s): Riyaz Shah, Jason F. LesterAbstractThe availability of three generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with different pharmacological characteristics and clinical profiles provides oncologists with a potentially confusing choice for the treatment of EGFR mutation-positive non–small-cell lung cancer. While recent head-to-head clinical trials have demonstrated improved efficacy with second- (afatinib, dacomitinib) and third-generation (osimertinib) TKIs versus the first-generation TKIs (erlotinib and gefitinib), acquired resistance is inevitable regardless of which agent is chosen as first-line therapy. Consequently, the potential availability of subsequent treatment options is an important consideration. Recent data have demonstrated that osimertinib confers overall survival (OS) benefit versus first-generation EGFR TKIs, while dacomitinib has shown OS benefit versus gefitinib in an exploratory analysis. However, the relative benefits of different sequential EGFR-TKI regimens, especially those involving second- and third-generation agents, remain uncertain and require prospective evaluation. Currently, few such data currently exist to inform treatment choice. In this review, we examine the pharmacological characteristics and current clinical data for EGFR TKIs, including emerging information on molecular mechanisms of resistance across the different generations of TKIs. Given uncertainties on optimal treatment choice, we focus on factors that may help drive treatment decisions, such as efficacy and safety in patient subgroups. We also discuss emerging real-world data, which provide some insights into the benefits of sequential regimens in everyday clinical practice.
       
  • Reply to “Prognostic Impact and Risk Factors of Immune-Related
           Pneumonitis in Patients With Non–Small-Cell Lung Cancer Who Received
           Programmed Death-1 Inhibitors”
    • Abstract: Publication date: Available online 2 December 2019Source: Clinical Lung CancerAuthor(s): Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa
       
  • High prevalence of EGFR mutations in lung adenocarcinomas from Brazilian
           patients harboring the TP53 p.R337H variant
    • Abstract: Publication date: Available online 28 November 2019Source: Clinical Lung CancerAuthor(s): Malu Viter R. Barbosa, Vladmir C. Cordeiro de Lima, Maria Nirvana Formiga, Cláudia A. Andrade de Paula, Giovana T. Torrezan, Dirce M. CarraroAbstractBackgroundLung cancer represents around 3.6% of all Li-Fraumeni Syndrome (LFS)-associated tumors. A high prevalence of p.R337H germline mutation in the TP53 gene has been observed in Brazil and family histories of cancer associated with this variant range from isolated cases to families fulfilling Li-Fraumeni-like or Li-Fraumeni criteria. We aimed to evaluate the frequency of EGFR mutations in lung adenocarcinoma (LA) diagnosed in Brazilian patients carrying the TP53 founder mutation p.R337H, as well as the frequency of TP53 p.R337H mutation among LA cases with EGFR mutation.MethodsPatients diagnosed with LA were selected from a total of 164 TP53 p.R337H mutation carriers followed at A.C. Camargo Cancer Center. Tumor samples were submitted to EGFR hotspot mutations sequencing. TP53 p.R337H was genotyped in a cohort of 257 LA tumor samples, 114 with and 143 without EGFR activating mutations. Sequencing was performed using Ion Torrent.ResultsThe frequency of LA among TP53 p.R337H carriers was 5.4% (9/164), and EGFR mutations were detected in 89% (8/9) of these patients. The prevalence of TP53 variants at codon 337 in patients with LA harboring EGFR activating mutations was 5.3% (6/114 – 5 p.R337H and 1 p.R337C) and 12.5% (4/32) in LA tumors diagnosed at any age and before the age of 50 years, respectively. This prevalence was significantly higher than that in the cohort of LA tumors with no EGFR activating mutation (1/143 in LA diagnosed at any age, 0/34 in LA diagnosed before the age of 50 years).ConclusionsThere is a higher than expected frequency of EGFR activating mutations in LA Brazilian patients with TP53 p.R337H mutation. The high frequency of p.R337H/C carriers among patients with EGFR-mutated LA indicates that TP53 genetic testing should be recommended to these patients, regardless of whether they fulfill LFS/LFL criteria or no defined cancer risk criteria.
       
  • Common Germline Mutations in a Patient with Multiple Primary Lung Cancers
    • Abstract: Publication date: Available online 21 November 2019Source: Clinical Lung CancerAuthor(s): Samuel Cytryn, Andre Moreira, Abraham Chachoua, Joshua SabariAbstractWe report a case of a patient with multiple primary lung cancers (MPLC) each with a unique somatic mutation, but also with underlying germline mutations of BRCA2 and TSC1. Given the improvements in screening modalities and advances in therapies leading to longer survival, the incidence of MPLC has increased. This case highlights the possibility that patients with multiple primary malignancies, each with distinct driver mutations, may have an underlying, identifiable predisposition. Next generation sequencing (NGS) and germline genetic testing has not been well studied in early stage cancers. However, given the findings in this patient, it may be reasonable to consider those with MPLC for additional testing as the implications of identifying such an underlying mutation will help guide treatment as well as inform screening for affected family members, though further investigation in this population is warranted.
       
  • Surveillance with PET/CT and liquid biopsies of stage I-III lung cancer
           patients after completion of definitive therapy; a Randomized controlled
           trial (SUPE_R)
    • Abstract: Publication date: Available online 21 November 2019Source: Clinical Lung CancerAuthor(s): Kristin Skougaard, Olga Østrup, Kasper Guldbrandsen, Boe Sørensen, Peter Meldgaard, Zaigham Saghir, Peter Gørtz, Markus Nowak Lonsdale, Malene Støchkel Frank, Oke Gerke, Beata Agnieszka Rychwicka-Kielek, Gitte Persson, Lotte Holm Land, Tine Schytte, Uffe Bødtger, Halla Skuladottir, Jes Søgaard, Søren Steen Nielsen, Torben Riis Rasmussen, Barbara Malene FischerAbstractDespite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intention have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with current as well as newer technologies, the impact on patient treatment, quality of life and survival, is urgently needed. Therefore, we have designed a randomized phase III trial. One arm with every other computed tomography (CT) replaced by positron emission tomography (PET)/CT, the other with standard follow-up scheme and modality; CT. The standard arm is identical to the current national Danish follow up programme. The primary endpoint is to compare the number of relapses treatable with curative intent in the two arms. We aim to include 750 patients over a two-year period. Additionally, we will test the feasibility of non-invasive lung cancer diagnostics and surveillance in the form of circulating tumour (ct)DNA analysis. Blood samples are, with this purpose, collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.
       
  • Clinicopathologic characteristics, treatment outcomes, and acquired
           resistance patterns of atypical EGFR mutations and HER2 alterations in
           stage IV non-small cell lung cancer
    • Abstract: Publication date: Available online 21 November 2019Source: Clinical Lung CancerAuthor(s): Tejas Patil, Rao Mushtaq, Sydney Marsh, Christine Azelby, Miheer Pujara, Kurt Davies, Dara L. Aisner, William T. Purcell, Erin L. Schenk, Jose M. Pacheco, Paul A. Bunn, D. Ross Camidge, Robert C. DoebeleAbstractBackgroundThe clinicopathologic characteristics, acquired resistance patterns, and outcomes among patients with atypical EGFR mutations and HER2 alterations remains underexplored.MethodsSingle-center retrospective review was conducted. Oncogenes assessed include typical EGFR, (t-EGFR; exon 19 del and L858R), atypical EGFR (a-EGFR; G719X, exon 20, L861Q), HER2 alterations (exon 19, exon 20, amplifications), gene fusions (ALK, ROS1, RET), and RAS/RAF mutations (KRAS, NRAS, BRAF V600E). PFS, OS, DCR, and ORR (RECIST 1.1) were collected.ResultsAmong 570 patients, we found 55 a-EGFR mutations (13 G719X, 38 Exon 20, 4 L861Q) and 31 HER2 alterations (2 exon 19 mutations, 27 exon 20 insertions, 2 amplifications). Patients with EGFR / HER2 alterations had increased lung and bone metastases relative to gene fusions, RAS/RAF mutations, and no identified driver oncogenes (p < 0.001). Patients with EGFR exon 20 insertions had a median PFS to EGFR TKIs of 5 months and an OS of 16 months, significantly worse than exon 19 del and L858R (Bonferroni correction; p < 0.001), but not G719X / L861Q. T790M and MET amplification occurred less frequently as acquired resistance among a-EGFR relative to t-EGFR mutations (p < 0.001). Ten patients with a-EGFR mutations and HER2 alterations received single agent ICI with no radiographic responses and a median PFS of 2 months.ConclusionsEGFR and HER2 alterations have a tropism for lung and bone metastases. Patients with a-EGFR mutations have inferior responses to targeted therapies and lower rates of acquired T790M. Responses to ICIs are uniformly poor. Novel therapeutic approaches are needed.
       
  • Nivolumab-Induced Guillain Barré Syndrome Coupled with Remarkable Disease
           Response in a Case of Heavily Pre-treated Lung Adenocarcinoma.
    • Abstract: Publication date: Available online 21 November 2019Source: Clinical Lung CancerAuthor(s): Giulia Mazzaschi, Paola Bordi, Rodanthi Fioretzaki, Letizia Gnetti, Gianluca Milanese, Chiara Tommasi, Melissa Bersanelli, Giovanni Roti, Umberto Scoditti, Francesco Leonardi, Federico Quaini, Marcello Tiseo
       
  • Acute Generalized Exanthematous Pustulosis Caused by the Combination of
           
    • Abstract: Publication date: Available online 20 November 2019Source: Clinical Lung CancerAuthor(s): Taichi Matsubara, Hiroshi Uchi, Naoki Haratake, Shinkichi Takamori, Ryo Toyozawa, Naoko Miura, Masafumi Yamaguchi, Takashi Seto, Mitsuhiro Takenoyama
       
  • Rapid clinical and radiological responses with larotrectinib in a patient
           with TRK-fusion–positive metastatic lung cancer
    • Abstract: Publication date: Available online 20 November 2019Source: Clinical Lung CancerAuthor(s): Maximilian Johannes Hochmair, Ulrike Setinek, Dagmar Krenbek, Andreas Fazekas, Oliver Illini, Christoph Weinlinger, Hermann Draxler, Markus Macher, Arschang Valipour, Leonhard Müllauer, Lucian Beer
       
  • Overcoming primary resistance to PD-1 inhibitor with anti-PD-L1 agent in
           squamous NSCLC: a case report
    • Abstract: Publication date: Available online 20 November 2019Source: Clinical Lung CancerAuthor(s): Francesco Gelsomino, Alessandro Di Federico, Daria M. Filippini, Filippo G. Dall’Olio, Giuseppe Lamberti, Francesca Sperandi, Caterina Balacchi, Stefano Brocchi, Andrea Ardizzoni
       
  • Predictors of Respiratory Decline Following Stereotactic Ablative
           Radiotherapy to Multiple Lung Tumors
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Everett J. Moding, Rachel Liang, Frederick M. Lartey, Peter G. Maxim, Arthur Sung, Maximilian Diehn, Billy W. Loo, Michael F. GensheimerAbstractIntroductionStereotactic ablative radiotherapy (SABR) is highly effective at controlling early stage primary lung cancer and lung metastases. Although previous studies have suggested that treating multiple lung tumors with SABR is safe, post-treatment changes in respiratory function have not been analyzed in detail.Patients and MethodsWe retrospectively identified patients with 2 or more primary lung cancers or lung metastases treated with SABR and analyzed clinical outcomes and predictors of toxicity. We defined a composite respiratory decline endpoint to include increased oxygen requirement, increased dyspnea scale, or death from respiratory failure not owing to disease progression.ResultsA total of 86 patients treated with SABR to 203 lung tumors were analyzed. A total of 21.8% and 41.8% of patients developed composite respiratory decline at 2 and 4 years, respectively. When accounting for intrathoracic disease progression, 12.7% of patients developed composite respiratory decline at 2 years. Of the patients, 7.9% experienced grade 2 or greater radiation pneumonitis. No patient- or treatment-related factor predicted development of respiratory decline. The median overall survival was 46.9 months, and the median progression-free survival was 14.8 months. The cumulative incidence of local failure was 9.7% at 2 years.ConclusionAlthough our results confirm that SABR is an effective treatment modality for patients with multiple lung tumors, we observed a high rate of respiratory decline after treatment, which may be owing to a combination of treatment and disease effects. Future studies may help to determine ways to avoid pulmonary toxicity from SABR.
       
  • Effectiveness of Treatments for Advanced Non–Small-Cell Lung Cancer With
           Exon 20 Insertion Epidermal Growth Factor Receptor Mutations
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Jenn-Yu Wu, Chong-Jen Yu, Jin-Yuan ShihAbstractBackgroundTwo main categories of epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC) patients are deletions in exon 19 and L858R in exon 21. Treatments of advanced NSCLC patients with these mutations are well documented, and clinical responses to tyrosine kinase inhibitors (TKIs) are favorable. However, effective treatments for patients with exon 20 insertion mutations are not well verified. We investigated the clinical response to various treatments (chemotherapy and TKIs) of advanced NSCLC patients with EGFR exon 20 insertions.Patients and MethodsIn this study, specimens from 3805 NSCLC patients were examined for EGFR mutations. Different first-line treatments and their effectiveness in NSCLC patients with exon 20 insertion EGFR mutations were investigated.ResultsIn the cohort of the 3805 patients, 2112 (55.5%) had EGFR mutations, including 84 patients (4.0%) with exon 20 insertion mutations. Efficacy of different first-line chemotherapy or TKIs were evaluated. Pemetrexed-containing therapies were related to better progression-free survival (6.2 vs. 2.7 months; P < .001) and overall survival (28.0 vs. 15.4 months; P = .009) than regimens without pemetrexed. Patients with exon 20 insertions had a poor response to TKIs. However, the mutation Ala763_Tyr764insPheGlnGluAla (A763_Y764 insFQEA) was related to a favorable response to TKIs.ConclusionExon 20 insertion EGFR mutations comprised a considerable group of the entire population of patients with EGFR mutations. Different first-line treatments and variants of the exon 20 insertions might be related to different outcomes in advanced NSCLC patients.
       
  • Comment on the data of the article titled “Second Primary
           Non–Small-Cell Lung Cancer After Head and Neck Cancer: A
           Population-Based Study of Clinical and Pathologic Characteristics and
           Survival Outcomes in 3597 Patients”
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Junmiao Wen
       
  • Clinical Outcomes of Up-front Surgery Versus Surgery After Induction
           Chemotherapy for Thymoma and Thymic Carcinoma: A Retrospective Study
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Wei-Li Ma, Chia-Chi Lin, Feng-Ming Hsu, Jang-Ming Lee, Jin-Shing Chen, Min-Shu Hsieh, Yih-Leong Chang, Ying-Ting Chao, Chin-Hao Chang, James Chih-Hsin YangAbstractIntroductionAlthough induction chemotherapy improves the resectability of thymic neoplasms, it is unclear whether surgery after induction chemotherapy can improve outcomes. We compared long-term outcomes of surgery with and without induction chemotherapy in patients with thymic neoplasms.Patients and MethodsWe retrospectively investigated the clinical information of patients with thymic neoplasms at the National Taiwan University Hospital between 2005 and 2013.ResultsOf 204 patients, 119 underwent direct surgery (group 1), 45 underwent surgery after induction chemotherapy (group 2), and 40 underwent no surgery (group 3). The 5-year overall survival rates of groups 1, 2, and 3 were as follows: for 204 patients, 96.3%, 76.4%, and 35.5% (P < .001); for 119 thymoma patients, 96.6%, 88.9%, and 100.0% (P = .835); for 85 thymic carcinoma patients, 94.7%, 69.7%, and 17.7% (P < .001); for 36 American Joint Committee on Cancer (AJCC) stage III-IVA thymoma patients, 92.9%, 83.3%, and 100% (P = .833); and for 28 stage III-IVA thymic carcinoma patients, 75.0%, 76.2%, and 62.5%, (P = .160). Univariate analysis showed that for group 2 (P = .0208) and group 3 (P < .0001), thymic carcinoma pathology type (P = .0010) and stage IVB disease (P < .0001) were poor prognostic factors. Multivariate analysis found thymic carcinoma (P = .0026) and stage IVB disease (P = .0449) to be poor prognostic factors.ConclusionUp-front surgery leads to best overall survival, and induction chemotherapy followed by surgery may improve resectability and outcomes. Only thymic carcinoma and stage IVB disease were poor prognostic factors in multivariate analysis.
       
  • Prognostic Significance of Liver Metastasis in Durvalumab-Treated Lung
           Cancer Patients
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Sriram Sridhar, Luis Paz-Ares, Hao Liu, Kui Shen, Chris Morehouse, Naiyer Rizvi, Neil H. Segal, Xiaoping Jin, Yanan Zheng, Rajesh Narwal, Ashok Gupta, Phillip A. Dennis, Jiabu Ye, Pralay Mukhopadhyay, Brandon W. Higgs, Koustubh RanadeAbstractIntroductionTwo clinical studies (Study 1108 and ATLANTIC) were analyzed to evaluate the prognostic value of baseline liver metastases (LMs) in advanced/metastatic non–small-cell lung cancer patients treated with durvalumab 10 mg/kg every 2 weeks.Patients and MethodsA multivariate Cox proportional hazards analysis was conducted; covariates included performance status, tumor stage, histology, sex, age, smoking status, and programmed cell death ligand 1 (PD-L1) status.ResultsIn all, 569 patients were included. LMs were present in 31.6% (96/304) of Study 1108 patients and 17.9% (47/263) of ATLANTIC patients. Median overall survival (OS) was shorter in patients with LMs than in those without in both studies. In both studies, LMs were an independent negative prognostic factor for OS and progression-free survival. Objective response rates were also significantly lower. PD-L1 independently predicted benefit across all patients.ConclusionLiver metastases were associated with worse outcomes irrespective of PD-L1 status, but PD-L1 status predicted benefit from durvalumab irrespective of LMs.
       
  • Identifying Resistance Mechanisms to Osimertinib via Blood Biopsy
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Michael J. Jelinek, Samantha A. Armstrong, Jyoti D. Patel, Deepa S. Subramaniam
       
  • ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and
           Current Perspectives
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Florian Guisier, Nicolas Piton, Mathieu Salaun, Luc ThibervilleAbstractROS1 rearranged non-small cell lung cancer represents approximately 1% of non squamous NSCLC. Crizotinib was the first tyrosine kinase inhibitor to demonstrate a clinical benefit in this group of patients. Several ROS1 mutations have been described as resistance mechanisms in the setting of crizotinib treatment, including the G2032R mutation, which is the most frequently identified. It was described in two preclinical reports as potentially sensitive to cabozantinib. Nevertheless, no clinical observation in this setting has been reported. Here we report the case of a Crizotinib resistant ROS1 rearranged NSCLC patient with G2032R mutation for which cabozantinib treatment failed, and review the current knowledge about ROS1 TKI resistance mutations and their management.
       
  • Survival Outcomes With Thoracic Radiotherapy in Extensive-Stage Small-Cell
           Lung Cancer: A Propensity Score-Matched Analysis of the National Cancer
           Database
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Sibo Tian, Xinyan Zhang, Renjian Jiang, Rathi N. Pillai, Taofeek K. Owonikoko, Conor E. Steuer, Nabil F. Saba, Suchita Pakkala, Pretesh R. Patel, Chandra P. Belani, Fadlo R. Khuri, Walter J. Curran, Suresh S. Ramalingam, Madhusmita Behera, Kristin A. HigginsAbstractBackgroundThe prognosis of patients with extensive-stage small-cell lung carcinoma (ES-SCLC) is poor. The benefit of consolidative thoracic radiation therapy (TRT) in ES-SCLC has been inconclusive, and its use inconsistent. The objective of this study was to evaluate overall survival (OS) of ES-SCLC patients treated with chemotherapy (CT) with or without TRT using an administrative database approach.Patients and MethodsThe National Cancer Database was queried to identify patients with ES-SCLC diagnosed between 2010 and 2014. Those with brain metastases, those who received radiotherapy before CT, or radiotherapy outside the thorax, were excluded. Propensity score-matching (PSM) was used to compare OS of patients treated with CT and TRT with those who received CT alone. Patients who received>10 radiotherapy fractions were also compared with those who received 10 or fewer.ResultsWe included 14,367 patients in the primary analysis; 12,019 received CT alone, and 2348 received CT with TRT. In multivariate analysis, CT was associated with an increased risk of death relative to CT with TRT (hazard ratio [HR], 1.74 [95% confidence interval (CI), 1.64-1.84]; log-rank P < .001), which remained significant with PSM. Median OS was 12.1 versus 8.2 months (CT with TRT vs. CT); 12-month OS was 50.5% versus 28.5%, and 5-year OS 7.6% versus 2.0% (HR, 1.80 [95% CI, 1.67-1.95], HR P < .001). Of 3099 patients who received TRT,>10 radiotherapy fractions was associated with superior OS (HR, 1.70 [95% CI, 1.49-1.95], log-rank P < .001); this finding remained significant with PSM.ConclusionUse of TRT after CT in ES-SCLC patients was associated with long-term survival; its use should be considered in addition to standard of care CT.
       
  • Subgroup Analysis of Japanese Patients in a Phase III Study of
           Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133)
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Makoto Nishio, Shunichi Sugawara, Shinji Atagi, Hiroaki Akamatsu, Hiroshi Sakai, Isamu Okamoto, Koichi Takayama, Hidetoshi Hayashi, Yuki Nakagawa, Tomohisa KawakamiAbstractBackgroundAtezolizumab is effective and well-tolerated in patients with extensive-stage small-cell lung cancer (ES-SCLC), but differences in response to systemic therapy exist between Asian and Caucasian patients. Here, we assess the efficacy and tolerability of atezolizumab in Japanese patients from the IMpower133 trial (NCT02763579).Patients and MethodsKey eligibility criteria for this multicenter, double-blind, placebo-controlled, randomized study included age ≥ 18 years; histologically or cytologically confirmed ES-SCLC, measurable per Response Evaluation Criteria in Solid Tumors version 1.1; an Eastern Cooperative Oncology Group performance status of 0/1; and no prior systemic treatment for ES-SCLC. Patients were treated with either atezolizumab 1200 mg or placebo with carboplatin (area under the curve of 5 mg/mL/min) and etoposide (100 mg/m2). Primary endpoints were overall survival and investigator-assessed progression-free survival in the intention-to-treat population. Of the 403 patients randomized in the IMpower133 trial, 42 were enrolled at Japanese centers.ResultsIn Japanese patients in the intention-to-treat population, the median overall survival in the atezolizumab group (n = 20) was longer than that in the placebo group (n = 22; 14.6 months; 95% confidence interval [CI], 11.8-17.8 months vs. 11.9 months; 95% CI, 8.4-15.8, respectively; hazard ratio, 0.72; 95% CI, 0.31-1.67). The median progression-free survival was 4.5 months (95% CI, 4.2-8.1 months) versus 4.0 months (95% CI, 2.9-5.6 months; hazard ratio, 0.47; 95% CI, 0.23-0.96), respectively. Atezolizumab was generally well-tolerated, with no treatment-related deaths.ConclusionThe addition of atezolizumab to carboplatin and etoposide was effective and well-tolerated in Japanese patients with ES-SCLC. Results are consistent with the primary analysis of the IMpower133 trial.
       
  • Assessment of a Radiomic Signature Developed in a General NSCLC Cohort for
           Predicting Overall Survival of ALK-Positive Patients With Different
           Treatment Types
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Lyu Huang, Jiayan Chen, Weigang Hu, Xinyan Xu, Di Liu, Junmiao Wen, Jiayu Lu, Jianzhao Cao, Junhua Zhang, Yu Gu, Jiazhou Wang, Min FanAbstractBackgroundThe purpose of the study was to investigate the potential of a radiomic signature developed in a general non–small-cell lung cancer (NSCLC) cohort for predicting the overall survival of anaplastic lymphoma kinase (ALK)-positive (ALK+) patients with different treatment types.Materials and MethodsAfter test-retest in the Reference Image Database to Evaluate Therapy Response data set, 132 features (intraclass correlation coefficient> 0.9) were selected in the least absolute shrinkage and selection operator Cox regression model with a leave-one-out cross-validation. The NSCLC radiomics collection from The Cancer Imaging Archive was randomly divided into a training set (n = 254) and a validation set (n = 63) to develop a general radiomic signature for NSCLC. In our ALK+ set, 35 patients received targeted therapy and 19 patients received nontargeted therapy. The developed signature was tested later in this ALK+ set. Performance of the signature was evaluated with the concordance index (C-index) and stratification analysis.ResultsThe general signature had good performance (C-index> 0.6; log rank P < .05) in the NSCLC radiomics collection. It includes 5 features: Geom_va_ratio, W_GLCM_Std, W_GLCM_DV, W_GLCM_IM2, and W_his_mean. Its accuracy of predicting overall survival in the ALK+ set achieved 0.649 (95% confidence interval [CI], 0.640-0.658). Nonetheless, impaired performance was observed in the targeted therapy group (C-index = 0.573; 95% CI, 0.556-0.589) whereas significantly improved performance was observed in the nontargeted therapy group (C-index = 0.832; 95% CI, 0.832-0.852). Stratification analysis also showed that the general signature could only identify high- and low-risk patients in the nontargeted therapy group (log rank P = .00028).ConclusionThis preliminary study suggests that the applicability of a general signature to ALK+ patients is limited. The general radiomic signature seems to be only applicable to ALK+ patients who had received nontargeted therapy, which indicates that developing special radiomics signatures for patients treated with tyrosine kinase inhibitors might be necessary.
       
  • Comparative Efficacy of Second- and Subsequent-line Treatments for
           Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer
           Immunotherapies
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Christian Schulz, David Gandara, Carmen G. Berardo, Rachel Rosenthal, Jason Foo, Chaienna Morel, Marcus Ballinger, Claire Watkins, Paula ChuAbstractBackgroundExtended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources.Materials and MethodsStudies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival.ResultsPD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%).ConclusionThis NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.
       
  • Increased Incidence of Lung Cancer Among Patients With Superficial
           Transitional Cell Carcinoma: A Potential Risk Cohort for Lung Cancer
           Screening
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Yaakov Tolwin, Roni Gillis, Inbar Nardi Agmon, Noa Shani Shrem, Eli Rosenbaum, Nir PeledAbstractBackgroundSmoking is a major risk factor for lung cancer (LC) and transitional cell carcinoma of the bladder (TCC). Current recommendations for LC screening do not include TCC as a risk factor for determining screening eligibility. In this study we aimed to evaluate whether TCC patients constitute a population who might benefit from LC screening.Patients and MethodsThe Surveillance, Epidemiology, and End Results 18 database was used to determine the incidence, standardized incidence ratio (SIR), and the average time to diagnosis of LC in patients with localized TCC of the bladder (American Joint Committee on Cancer, sixth edition, stages 0-1).ResultsOn the basis of 91,606 patients with localized TCC, The SIR for LC in men was 1.89 (95% confidence interval [CI], 1.8-1.97), significantly different from the risk for all solid tumors. The SIR for LC in women was 2.43 (95% CI, 2.22-2.65), significantly higher than for men. The 5-year incidence of LC was 3.2%, and the 10-year incidence was 5.94%. The average time to diagnosis of LC was 3.4 years, with>80% of LC cases occurring within 5 years of TCC diagnosis.ConclusionPatients with localized TCC have a higher incidence of LC than the general population. The risk is significantly increased among women compared with men. Considering this increased risk, patients with early stage TCC might stand to benefit from LC screening. Additional differences were noted between male and female TCC patients, which bear further study.
       
  • Prognostic Significance of 18F-FDG PET/CT Metabolic Parameters and Tumor
           Galectin-1 Expression in Patients With Surgically Resected Lung
           Adenocarcinoma
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Hongna Zheng, Yan Cui, Xuena Li, Bulin Du, Yaming LiAbstractPurposeTo study the prognostic significance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) metabolic parameters and tumor galectin-1 (Gal-1) expression in patients surgically treated for lung adenocarcinoma.Patients and MethodsThe medical records of 96 patients with primary lung adenocarcinoma who underwent surgery after 18F-FDG PET/CT were retrospectively reviewed. The maximal standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis of the primary tumor were measured through PET/CT imaging. The expression of tumor Gal-1, glucose transporter 1 (GLUT-1), and hexokinase II (HK-II) were examined through immunohistochemistry.ResultsThere were significant positive correlations between tumor Gal-1 and SUVmax, tumor Gal-1 and metabolic tumor volume, tumor Gal-1 and total lesion glycolysis, tumor Gal-1 and GLUT-1 expression, tumor Gal-1 and HK-II expression, and SUVmax and tumor GLUT-1 and HK-II expression (P < .0001 in all cases). SUVmax was the only independent predictor of tumor Gal-1 expression. On receiver operating characteristic analysis, the optimal cutoff value of SUVmax for predicting tumor Gal-1 expression was 5.1. Progression-free and overall survival were significantly shorter in patients with Gal-1–positive tumors than in those with Gal-1–negative tumors (P ≤ .001). On multivariate analysis, advanced tumor stage (P = .001) and tumor Gal-1 expression (P < .0001) were independent prognostic indicators of poor progression-free survival, while advanced tumor stage (P < .0001) and SUVmax (P = .024) were independent prognostic indicators of poor overall survival.Conclusion18F-FDG PET/CT has the potential to be used as a noninvasive imaging modality to assess tumor Gal-1 status and prognosis in lung adenocarcinoma.
       
  • Clinical Characteristics, Molecular Phenotyping, and Management of
           Isolated Adrenal Metastases From Lung Cancer
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Antonio Mazzella, Mauro Loi, Audrey Mansuet-Lupo, Antonio Bobbio, Helene Blons, Diane Damotte, Marco AlifanoAbstractIntroductionAdrenal gland metastases occur in up to 20% of patients with non–small-lung cancer. In selected cases with limited burden of disease, surgery may be offered to improve patient outcome; furthermore, tissue analysis would provide useful information on genotype of primary and secondary neoplasms.Materials and MethodsWe report our experience in the management of adrenal metastasis by retrospectively reviewing data of 21 consecutive patients treated with curative intent to the primary tumor followed by adrenalectomy in a 15-year time span. Targeted next generation sequencing was performed to compare molecular profile of primary lung cancers and adrenal metastases. Patient overall survival was assessed by Kaplan-Meier method, using adrenalectomy as time zero. Survival rates were compared by log rank test.ResultsNo surgery-related mortality or morbidity was observed. Median survival was 50 months; 5-year overall survival was 34.5% (95% confidence interval, 12%-66%). No significant survival difference was observed with respect to timing of onset (synchronous vs. metachronous) or side (homolateral vs. contralateral) of adrenal metastasis, T or N status of primary lung cancer, mutational asset, and histologic type. Mutations in TP53 genes were found in 61% and 85% of primary and metastatic tumors, respectively. In 3 of 15 cases, we found differences between molecular mutation patterns in primary lung cancer and corresponding adrenal metastasis.ConclusionsAdrenalectomy is a safe and effective approach in selected cases. Discordance between primary and secondary tumor mutational profile was found in 20% of assessable patients.
       
  • Spirituality and Emotional Distress Among Lung Cancer Survivors
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Lisa M. Gudenkauf, Matthew M. Clark, Paul J. Novotny, Katherine M. Piderman, Shawna L. Ehlers, Christi A. Patten, Lise Solberg Nes, Kathryn J. Ruddy, Jeff A. Sloan, Ping YangAbstractBackgroundEmerging research is highlighting the importance of spirituality in cancer survivorship as well as the importance of early distress screening. The purpose of this study was to prospectively examine the relationships among spirituality, emotional distress, and sociodemographic variables during the early period of lung cancer survivorship.Patients and MethodsEight hundred sixty-four lung cancer survivors completed the Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being, and the Short-Form-8 for emotional distress within the first year after lung cancer diagnosis, and 474 of these survivors completed the survey again 1 year later.ResultsAt baseline, spirituality was associated with lower prevalence of emotional distress, being married, fewer years of cigarette smoking, and better Eastern Cooperative Oncology Group performance status. Additionally, high baseline spirituality was associated with lower rates of high emotional distress at 1-year follow-up.ConclusionThese findings suggest that spirituality might serve as a protective factor for emotional distress among lung cancer survivors. Further research is warranted to explore the role of spirituality in promoting distress management among lung cancer survivors.
       
  • Long-term Follow-up and Patterns of Recurrence of Patients With
           Oligometastatic NSCLC Treated With Pulmonary SBRT
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Juliane Hörner-Rieber, Denise Bernhardt, Oliver Blanck, Marciana Duma, Hans Th. Eich, Sabine Gerum, Eleni Gkika, Peter Hass, Christoph Henkenberens, Hans-Ulrich Herold, Guido Hildebrandt, Detlef Imhoff, Henning Kahl, Stefan Janssen, Katrin Jurianz, Robert Krempien, Stefan Friedrich Lautenschläger, Fabian Lohaus, Arndt-Christian Mueller, Cordula PetersenAbstractIntroductionThis multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non–small-cell lung cancer (NSCLC).Materials and MethodsThis analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.ResultsThe median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.ConclusionSBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.
       
  • The Prognostic Role of TNM Staging Compared With Tumor Volume and Number
           of Pleural Sites in Malignant Pleural Mesothelioma
    • Abstract: Publication date: November 2019Source: Clinical Lung Cancer, Volume 20, Issue 6Author(s): Claudia Proto, Diego Signorelli, Sandra Mallone, Arsela Prelaj, Giuseppe Lo Russo, Martina Imbimbo, Giulia Galli, Roberto Ferrara, Monica Ganzinelli, Giovanni Leuzzi, Francesca Gabriella Greco, Giuseppina Calareso, Laura Botta, Gemma Gatta, Marina Garassino, Annalisa TramaAbstractBackgroundAge, sex, stage, histotype, and surgery are the most recognized prognostic factors for malignant pleural mesothelioma (MPM). Tumor volume (TV) was suggested as an alternative prognostic evaluation. We aimed to assess the prognostic role of Tumor, Node, Metastases (TNM) versus TV and number of pleural sites (NPS).Patients and MethodsInformation on stage, TV, and NPS was collected for 52 MPM patients (pts) at our institution from 2009 to 2012. Baseline computed tomography imaging was performed to define TNM, TV, and NPS. Pts were divided in 3 stage groups: early (I-II), III, and IV. A dedicated computer system calculated TV. Pts were divided in 2 groups according to mean baseline TV (483 cm3). NPS was defined on the basis of the NPS macroscopically involved by disease (1-3). The association between TNM, tumor size (T), TV, NPS, TV and NPS, and overall survival was assessed using Cox models adjusted for age, sex, histology, and treatment.ResultsMost pts were male; mean age was 62 years. We showed an association between TV, TNM, and T. Stage III (hazard ratio [HR], 4.71; P = .02) and IV (HR, 7.40; P < .01), T3 (HR, 5.07; P < .01) and T4 (HR, 5.09; P < .01), TV> 483 cm3 (HR, 3.47; P < .01) and NPS 2 (HR, 3.00; P = .08) and 3 (HR, 6.05; P < .01) were predictive of worse survival. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as a prognostic classifier.ConclusionWe showed that TV is related to TNM staging and T, in particular. Improved prognostic performance might be achievable using quantitative clinical staging combining TV and NPS.
       
  • Lower survival in patients who develop pneumonitis following immunotherapy
           for lung cancer
    • Abstract: Publication date: Available online 6 November 2019Source: Clinical Lung CancerAuthor(s): Karthik Suresh, Jarushka Naidoo
       
  • Lung cancer screening by low-dose CT scan: Baseline results of a French
           prospective study
    • Abstract: Publication date: Available online 31 October 2019Source: Clinical Lung CancerAuthor(s): Olivier Leleu, Damien Basille, Marianne Auquier, Caroline Clarot, Estelle Hoguet, Valérie Pétigny, Amale Aït Addi, Bernard Milleron, Bruno Chauffert, Pascal Berna, Vincent Jounieaux
       
  • Evidence that Established Lung Cancer Mortality Disparities in American
           Indians are Not Due to Lung Cancer Genetic Testing and Targeted Therapy
           Disparities
    • Abstract: Publication date: Available online 30 October 2019Source: Clinical Lung CancerAuthor(s): Abbie Begnaud, Ping Yang, Camille Robichaux, Nathan Rubin, Robert Kratzke, Anne Melzer, Constantin Aliferis, Pamala JacobsonAbstract:American Indians and Alaska Natives (AI/AN) continue to experience extreme lung cancer health disparities. The state of Minnesota is home to over 70,000 AI/AN, and they have a three-fold increase in lung cancer mortality compared with other races within Minnesota. Genetic mutation testing in lung cancer is now a standard of highquality lung cancer care and epidermal growth factor receptor (EGFR) mutation testing has been recommended for all adenocarcinoma lung cases, regardless of smoking status. However, genetic testing is a controversial topic for some AI/AN.This is a multi-site retrospective chart review funded by the Minnesota Precision Medicine Grand Challenge as a demonstration project to examine lung cancer health disparities in AI/AN. We sought to measure epidemiology of lung cancer among AI receiving diagnosis or treatment in Minnesota cancer referral centers as well as rate of EGFR testing. The primary outcome is the rate of EGFR mutational analysis testing among cases and controls with non-squamous, nonsmall cell lung cancer.We secured collaborations with five health care systems covering a diverse geographic and demographic population. We identified 200 cases and 164 matched controls from these sites. Controls were matched on histology, smoking status, sex and age. In both groups, about one-third of subjects with adenocarcinoma received genetic mutation testing.There was no significant difference in mutation testing in AI compared to non-AI controls at large health care systems in Minnesota. These data indicate that other factors are likely contributing to the higher mortality in this group.
       
  • Elevated circulating activin A levels in malignant pleural mesothelioma
           patients are related to cancer cachexia and reduced response to
           platinum-based chemotherapy
    • Abstract: Publication date: Available online 25 October 2019Source: Clinical Lung CancerAuthor(s): Juuso Paajanen, Ilkka Ilonen, Helena Lauri, Tommi Järvinen, Eva Sutinen, Hely Ollila, Eeva Rouvinen, Karl Lemström, Jari Räsänen, Olli Ritvos, Katri Koli, Marjukka MyllärniemiAbstractBackroundPrevious preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists’ follistatin/FSTL3 in intrathoracic tumors.Materials and MethodsPatients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 MPM, 59 non-small-cell lung cancer (NSCLC), 22 benign lung lesion patients. Circulating activin/follistatin levels were measured using ELISA and compared to clinicopathological parameters.ResultsCirculating activin A levels were elevated in MPM patients when compared with NSCLC or benign lung lesion samples (P < 0.0001). Also, follistatin and FSTL3 levels were the highest in MPM, although with less difference compared to activin A. Receiver operating characteristic analysis for activin A for separating NSCLC from benign lung lesion showed an AUC of 0.856 (95% confidence interval 0.77 – 0.94). Activin A levels were higher in patients with cachexia (P < 0.001). In MPM patients, activin A levels correlated positively with CT-based baseline tumor size (R = 0.549; P = 0.010) and the change in tumor size after chemotherapy (R = 0.743; P = 0.0006). Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease (P = 0.028).ConclusionActivin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors. Circulating activin A levels were elevated in MPM and associates with cancer cachexia and reduced chemotherapy response.
       
  • Integrating Imaging, Histologic, and Genetic Features to Predict Tumor
           Mutation Burden of Non-Small Cell Lung Cancer
    • Abstract: Publication date: Available online 25 October 2019Source: Clinical Lung CancerAuthor(s): Nasha Zhang, Jia Wu, Jinming Yu, Hui Zhu, Ming Yang, Ruijiang LiAbstractBackgroundImmune checkpoint inhibitors have dramatically changed the landscape of therapeutic management of non-small cell lung cancer (NSCLC). Tumor mutation burden (TMB) is an important biomarker of response to cancer immunotherapy. This study aims to investigate the relation between TMB and imaging, histologic, genetic features in NSCLC.Materials and methodsWe evaluated associations between semantic image features (7 quantitative or semiquantitative image features and 13 qualitative features that reflect the tumor characteristics) and TMB, and built an imaging signature for TMB by using logistic regression. Finally, we integrated the imaging signature, histological type, and TP53 genotype into a composite model.ResultsAmong 89 patients, 37 (41.6%) patients had low TMB and 52 (58.4%) patients had high TMB. Tumors with high TMB were more prevalent in squamous cell carcinoma (P=0.017) and those harboring TP53 mutation (P
       
  • Surgery or stereotactic body radiotherapy for early-stage lung cancer:
           what is the current evidence'
    • Abstract: Publication date: Available online 22 October 2019Source: Clinical Lung CancerAuthor(s): Han-Yu Deng, Lei Peng
       
  • Impact of Radiation Doses to the Heart on Survival for Stereotactic
           Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: An
           Artificial Neural Network Approach
    • Abstract: Publication date: Available online 21 October 2019Source: Clinical Lung CancerAuthor(s): Shawna T. Chan, Dan Ruan, Narek Shaverdian, Govind Raghavan, Minsong Cao, Percy LeeAbstractIntroduction/BackgroundCardiac radiation dose is an important predictor of cardiac toxicity and overall survival (OS) for locally advanced non-small cell lung cancer (NSCLC). However, radiation-induced cardiac toxicity among early-stage NSCLC patients treated with Stereotactic ABlative Radiotherapy (SABR) is less well-characterized. Our objective was to assess associations between cardiac radiation dosimetry and OS in early-stage NSCLC patients receiving SABR.Materials and MethodsFrom 2009 to 2014, 153 early-stage NSCLC patients were treated with SABR at a single institution. Maximum dose, mean dose, V10Gy, V25Gy, and V50Gy to 15 cardiac substructures and the whole heart were analyzed for association with OS using the Kaplan-Meier method. Artificial neural network (ANN) analysis was performed to modulate out confounding behaviors of dosimetric variables to predict for OS.Results112 patients were included in this analysis. Right ventricle V10Gy most negatively predicted for survival, where patients who received right ventricle V10Gy < 4% had significantly longer OS than patients who received right ventricle V10Gy> 4% (5.3 years vs. 2.4 years). Upon ANN analysis, 74 input features including cardiac dosimetry parameters predicted for survival with a test accuracy of 64.7%; repeat ANN analysis using dosimetry to dose neutral structure confirmed predictive power of cardiac dosimetry.ConclusionCardiac dosimetry to subvolumes of the heart was associated with decreased OS in early-stage NSCLC patients treated with SABR. These data support the importance of minimizing radiation dose to cardiac substructures, and further prioritizing the heart as an organ at risk may be warranted; additionally, cardiac follow-up should be considered.
       
  • Fatal Simultaneous Multi-organ Failure Following Pembrolizumab Treatment
           for Refractory Thymoma
    • Abstract: Publication date: Available online 19 October 2019Source: Clinical Lung CancerAuthor(s): Jae-Won Hyun, Geun Soo Kim, Su-Hyun Kim, Joong-Yang Cho, Ho Jin Kim, Geon Kook Lee, Hak Jin Kim, Sung Uk Kwon
       
  • Validation of an independent prognostic value of the asphericity of
           F18-fluorodeoxyglucose (FDG) uptake in non-small cell lung cancer (NSCLC)
           patients undergoing treatment in curative intent
    • Abstract: Publication date: Available online 15 October 2019Source: Clinical Lung CancerAuthor(s): Julian M.M. Rogasch, Christian Furth, Christoph Chibolela, Frank Hofheinz, Sebastian Ochsenreither, Jens-Carsten Rückert, Jens Neudecker, Dirk Böhmer, Maximilian von Laffert, Holger Amthauer, Nikolaj FrostAbstractBackgroundIn patients with non-small cell lung cancer (NSCLC), asphericity (ASP) of the primary tumor’s metabolic tumor volume (MTV) has shown prognostic significance. This study aimed at validation in an independent, sufficiently large cohort.Patients and MethodsRetrospective study in 311 NSCLC patients undergoing FDG-PET/CT before curatively intended treatment (always including surgery). 140 patients had UICC stage I, 78 stage II, and 93 stage III (adenocarcinoma [ADC]:153; squamous cell carcinoma [SCC]:141). Primary tumor MTV was delineated with semiautomated background-adapted threshold relative to SUVmax. Cox regression (PFS/OS) for PET (MTV, ASP, SUVmax), clinical (T/N descriptor, UICC stages), histological and treatment variables (Rx/1 vs. R0 resection, chemotherapy/radiotherapy yes/no).ResultsEvents (progression/relapse) occurred in 167/311 patients, 137 died (median survivor follow-up, 37 months). In multivariable Cox regression for OS, ASP>33.3% (HR, 1.58 [1.04-2.39]), male sex (1.84), age (1.04 per year), EGOG≥2 vs. 0/1 (2.68), stage II vs. I (1.96), and Rx/1 vs. R0 resection (2.1) were significant. Among separate UICC stages, ASP only predicted OS in stage II (optimal,>19.5%; median OS, 33 vs. 59 months). Regarding PFS, ASP>21.2%, male sex, EGOG≥2, stage II vs. I, and Rx/1 resection were prognostic. ASP remained prognostic in stage II (optimal,>19.5%; PFS, 12 vs. 47 months). Log-rank test for ASP was significant at any cut-off ≥18% (OS) or from 9-59% (PFS).ConclusionASP was validated as prognostic factor for PFS and OS in patients with NSCLC and curative treatment intent, especially stage II. High ASP in stage II could imply intensified treatment or intensified follow-up.
       
  • Successful Retreatment using Pembrolizumab for Non-small Cell Lung Cancer
           after Severe Immune-related Hepatitis: A Case Report
    • Abstract: Publication date: Available online 13 October 2019Source: Clinical Lung CancerAuthor(s): Keigo Kobayashi, Ichiro Nakachi, Akifumi Mitsuishi, Daisuke Arai, Kaori Sakurai, Katsunori Masaki, Atsushi Chiyotani, Hidenori Takahashi, Toshiyuki Tahara, Kenzo Soejima
       
  • Complete Pathological Response to Crizotinib in a Patient with
           ALK-rearranged Lung Adenocarcinoma
    • Abstract: Publication date: Available online 13 October 2019Source: Clinical Lung CancerAuthor(s): Marissa S. Mattar, Jason Chang, Ryma Benayed, Darragh Halpenny, Astin Powers, David Kleiner, Alexander Drilon, Mark G. Kris
       
  • Phase 2 study evaluating the MEchanisms of resistance on tumor tissue and
           Liquid biopsy in patients with EGFR mutated nonpretreated advanced Lung
           cancer Receiving OSimErtinib until and beyond radiological progression:
           the MELROSE trial
    • Abstract: Publication date: Available online 1 October 2019Source: Clinical Lung CancerAuthor(s): Bennouna J, Girard N, C. Audigier-Valette, le Thuaut A, Gervais R, Masson P, Marcq M, Molinier O, Cortot A, Debieuvre D, Cadranel J, Lena H, D. Moro-Sibilot, Chouaid C, Mennecier B, Urban T, Sagan C, Perrier L, Barlesi F, Denis MGAbstractBackgroundOsimertinib, a third generation tyrosine kinase inhibitor (TKI), is a new therapeutic option in EGFR mutated non pretreated advanced Non Small Cell Lung Cancer (NSCLC). The tumor escape mechanisms after first-line treatment with osimertinib are partially known, most of the data being obtained by analysis of circulating tumor DNA (ctDNA) from the FLAURA phase III trial. Study design: The MELROSE study, a French multicentric, open label, phase 2 trial (ClinicalTrials.gov NCT03865511) plans to enroll 150 patients with a treatement naive advanced EGFR mutated (L858R or exon 19 deletion) NSCLC, age ≥ 18 years with an Eastern Cooperative Oncology Group performance status 0 or 1. All patients will receive osimertinib at the dose of 80 mg/d. Tumor assessment according to RECIST 1.1 criteria will be performed every 3 months, with brain and thoracoabdominal computed tomographic scan. The continuation of osimertinib is at the discretion of the referring physician, particularly if clinical benefit is observed. The primary objective is the genetic tumor profile, both on tissue biopsy and ctDNA analyses, at the time of disease progression. Other endpoints include kinetic studies of ctDNA, biological Progression Free Survival (bPFS) (time from first study dose to first biological event on ctDNA), median PFS according to RECIST criteria 1.1 [called radiological (r) PFS], and median clinical (c) PFS (time from the first study dose to off-osimertinib). This study started in April 2019 and 18 centers in France are participants.
       
  • Multiclonality and Radiosensitivity of Granulocyte Colony-Stimulating
           Factor–Producing Lung Adenocarcinoma Positive for an Activating EGFR
           Mutation
    • Abstract: Publication date: Available online 26 September 2019Source: Clinical Lung CancerAuthor(s): Hirono Tsutsumi, Yasuto Yoneshima, Keiichi Ota, Kohei Otsubo, Eiji Iwama, Hiroyuki Inoue, Kentaro Tanaka, Yoichi Nakanishi, Isamu Okamoto
       
  • Durable Responses to Afatinib as First Line Therapy for HER2-Mutated
           Metastatic Non-Small Cell Lung Cancer
    • Abstract: Publication date: Available online 26 September 2019Source: Clinical Lung CancerAuthor(s): Ebaa Al-Obeidi, Tianhong Li, Karen Kelly
       
 
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