Translational Lung Cancer Research Research Articles

Trends in women's representation as lead authors in high impact journals of lung cancer.

Women's participation in the clinical oncology practice has increased over the past decade. There is a need to investigate whether women's participation in academia, as reflected by publication activity, increased over the time. This study aimed to investigate trends in female authorship in top journals of lung cancer in the past ten years. In this cross-sectional study of all original research and review articles published in lung cancer journals including New England Journal of Medicine, Lancet journals, JAMA journals, Journal of Clinical Oncology, Annals of Oncology, Cancer Discovery, Journal of Thoracic Oncology, and Translational Lung Cancer Research (TLCR) between 2012 and 2021, the sex composition of lead authors were analyzed. The sex of the author was confirmed by internet searching for photographs, biographies, and gender-specific pronouns from journal or personal websites. The time-trend of female authorship was determined using Join-Point Regression (JPR) analysis. A total of 3,625 first authors and 3,612 corresponding authors were identified in the journals during the years studied. The sex of the author was revealed for 98.5%. Among 3,625 first authors with the sex being revealed, 1,224 (33.7%) were women. The proportion of female first authors increased remarkably from 29.4% in 2012 to 39.8% in 2021. The annual percentage change (APC) in female first authorship took place in 2019 [APC for 2019-2021, 37.03, 95% confidence interval (CI): 18.0-59.1, P=0.003]. The proportion of first authors in TLCR increased from 25.9% in 2012 to 42.8% in 2021 and showed the greatest rise in female first authorship. There were significant discrepancies in the female first authorship across the journals and regions. Among the 3,612 corresponding authors whose sex were determined, 884 (24.5%) were female. There is no significant increasing trend in female corresponding authorship. The sex gap in the first authorship of lung cancer research articles has improved markedly in the recent years, however, sex imparities persist especially in corresponding authorship. There is an urgent need to proactively support and promote women in taking the leadership roles, thereby increasing their contributions to and influence on the development or advancement for future healthcare policies and practices.

Lung Cancer Organoids: The Rough Path to Personalized Medicine.

Simple SummaryLung cancer is very difficult to cure, especially when it has spread to other parts of the body. One of the main reasons that delay the identification of effective therapies is the complexity of lung cancer cells, which can be very different among individual patients. Organoids are small aggregates of tumor cells that are generated from lung tumors and used in cancer research laboratories to study the features of tumor cells. Organoids have unique properties, as they reproduce many characteristics of the tumor derived from each specific patient. Due to their capacity to reproduce individual tumor features in the laboratory setting, organoids are an excellent system to study lung cancer and to identify functional therapies. This review summarizes the challenges encountered by researchers in the field of lung cancer organoids and describes how the advances in organoid technology may allow the future development of individualized therapies for lung cancer patients.Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients.

Characteristics of EGFR Mutations in Plasma Samples in Non-Small Cell Lung Cancer Patients after Treatment with 1st and 2nd Generation of TKI at Bach Mai Hospital

This study aims to describe EGFR mutation status detected in plasma samples and analyze some related factors in non-small cell lung cancer patients after treatment with the generation I and II Tyrosine Kinase inhibitors at Bach Mai Hospital. Patients and methods: A retrospective descriptive study on 75 patients with non-small cell lung cancer tested for EGFR mutations in plasma after treatment with 1st or 2nd EGFR-TKIs in 2019-2020. Results: EGFR mutations were detected in 97.3% plasma samples;  the T790M mutation accounted for  37.3% and is accompanied by a sensitive mutation TKI; The T790M mutations ratio after treatment was higher than before treatment with TKIs (p < 0.001); the median total duration of EGFR-TKI treatment was significantly longer in patients with T790M mutation than in those without (16.8 months vs 12.5 months, p = 0.005); the T790M mutation ratio was higher in patients with a deletion on exon 19 than in L858R mutation on exon 21 (p=0.028), in Erlotinib treatment group higher than in Gefitinib and Afatinib treatment group (51.4% vs. with 20.0% and 33.3%, p=0.039). Conclusions: EGFR mutation plasma test helps to monitor disease progression and detect resistance mutations T790M in NSCLC patients after TKI generation I and II.
 Keywords: non-small cell lung cancer, EGFR mutations, T790M mutations, TKIs..
 References
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ES16.01 Proton Therapy

Proton therapy is an attractive option for the treatment of lung cancer patients due to the physical properties of proton beams. Proton therapy allows a focused delivery of radiation at the Bragg peak, with very steep decline of the radiation dose beyond the target volume. These properties offer the possibility to 1) reduce toxicity by reducing the integral dose and the dose to adjacent normal tissues and 2) escalate the dose to the target in some patients. In this talk, I will summarise briefly the physics/radiobiology of protons and the need for adaptation. I will also discuss the rationale for the use of protons in patients with lung cancer, including reduction in integral dose, cardiac toxicity and reduction in haematological toxicity. The clinical trial evidence supporting the use of protons will be presented in early stage and locally advanced non-small cell lung cancer as well as in small-cell lung cancer. Finally I will discuss future research directions, including preclinical and drug-proton combination research, ongoing clinical trials, the model based-approach and the need for biomarkers. Liao Z, Lee JJ, Komaki R, eat l. Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018;36(18):1813-1822 Chang JY, Jabbour SK, De Ruysscher D, et al; International Particle Therapy Co-operative Group Thoracic Subcommittee.Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2016;95(1):505-16. Vyfhuis MAL, Onyeuku N, Diwanji T, Mossahebi S, Amin NP, Badiyan SN, Mohindra P, Simone CB 2nd. Advances in proton therapy in lung cancer. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618783878 C, Pawelke J, Seidlitz A, Peitzsch C, et al; “Radiobiology of Proton Therapy”: Results of an international expert workshop.Lühr A, von Neubeck Radiother Oncol. 2018; 128(1):56-67 Jin, J.Y., et al., Higher Radiation Dose to Immune System is Correlated With Poorer Survival in Patients With Stage III Non-small Cell Lung Cancer: A Secondary Study of a Phase 3 Cooperative Group Trial (NRG Oncology RTOG 0617). International Journal of Radiation Oncology Biology Physics, 2017. 99(2): p. S151-S152. Joseph, N., et al., Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy. Radiotherapy and Oncology, 2019. 135: p. 115-119. Durante, M., D.J. Brenner, and S.C. Formenti, Does Heavy Ion Therapy Work Through the Immune System? Int J Radiat Oncol Biol Phys, 2016. 96(5): p. 934-936. Lee, H.J., Jr., J. Zeng, and R. Rengan, Proton beam therapy and immunotherapy: an emerging partnership for immune activation in non-small cell lung cancer. Translational lung cancer research, 2018. 7(2): p. 180-188. Dess, R.T., et al., Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol, 2017. 35(13): p. 1395-1402. McWilliam, A., et al., Radiation dose to heart base linked with poorer survival in lung cancer patients. Eur J Cancer, 2017. 85: p. 106-113. Schulz-Ertner, D. and H. Tsujii, Particle radiation therapy using proton and heavier ion beams. J Clin Oncol, 2007. 25(8): p. 953-64. Gameiro, S.R., et al., Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing. Int J Radiat Oncol Biol Phys, 2016. 95(1): p. 120-30.

S02.04 Dr. Gazdar as a Mentor

It was September in 1989 when I joined the NCI-Navy Medical Oncology Branch as a postdoctoral fellow. At that time, I was in my 10th year as a surgeon. The reason why I wanted to join the NCI-Navy was that I was greatly fascinated by the book entitled “The Biology of Lung Cancer” published by Marcel Dekker authored by many of the NCI-Navy MOB investigators. Especially, I was attracted by experimental works that used many lung cancer cell lines established by Adi’s group. When I first met Adi, my impression was that he was a calm and quiet person. My first project was to characterize peripheral airway cell phenotype in the adenocarcinoma cell lines by examining the expression of surfactant proteins as well as class II MHC. But I did not like this project and after 2 months or so, he agreed to change my theme to KRAS or TP53 mutations in lung cancer cell lines. He never pushed me to do or not to do something and never became emotional. I was deeply immersed in the research to look for the clinical and pathologic significance of those genetic abnormalities in lung cancer. This was what is called “translational research” today. I thought I could find what I should pursue throughout my life as a lung cancer doctor. It is obvious that without this experience and Adi, my life would have been so different. In addition, human network owing to Adi has been a precious treasure for me. One day in 1990, he gave me a paraffin block of bronchial biopsy sample and told me to search for TP53 mutation. It is currently a routine diagnostic workup to examine genetic alterations in the biopsy samples when you see lung cancer patients. It was as if he had known what would be the future diagnostic workup before 30 years. During this fruitful time of my life, I am so proud that I was able to co-authored 18 papers with Adi. After coming back to Japan, I saw Adi occasionally but periodically at various meetings such as the AACR, ASCO, ELCC and especially WCLC. Every time, he encouraged me to pursue my goal and gave some suggestions on my experiments. When Adi was to edit a special issue on Lung Cancer in Never Smokers in Translational Lung Cancer Research in 2018, he invited me to write about GGO lesions in never smokers. It was the last homework that he assigned to me. I am going to organize the Annual meeting of the Japanese Lung Cancer Society in December 2019. When I talked to him and his wife Celia at the Toronto WCLC meeting in 2018, Adi promised me to come to Japan to give a lecture. That was our last conversation. The promise has been broken and I really miss him. Adi. Please rest in peace. There are many of your children all over the world who have inherited your spirit as a lung cancer researcher. Translational research, mentor

In memoriam: Professor Adi F. Gazdar, a pre-eminent pathologist and devoted man

On the last day of December 2018, we were grieved to hear the sad news that Professor Adi F. Gazdar had passed away on Dec 29, 2018. We will never forget his generous support as a distinguished editorial board member of our journal Translational Lung Cancer Research ( TLCR ).

Lung cavitation in lung metastases of gastric and non-small-cell lung cancer patients treated with apatinib

In one of the latest issues of Translational Lung Cancer Research ( TLCR ), Jiang et al. have reported on the frequent cavitation of lung metastases in metastatic lung and gastric cancer patients following treatment with apatinib. It has been recognized that anti-angiogenic compounds surface among the anti-cancer therapies, inducing lung cavitation. Although lung cavitation was not found to influence PFS and OS in previous studies (1), the study of Man Jiang, directed by Xiaochun Zhang, has shown that apatinib induces cavitation of lung metastases in a significant number of patients treated with apatinib. Detection of cavitation of lung metastases was associated with longer PFS and OS.

DECEIVED: INVASIVE MUCINOUS ADENOCARCINOMA MASQUERADING AS MULTI-LOBAR CONSOLIDATIONS

SESSION TITLE: Lung Cancer SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung accounts for 5% of lung adenocarcinomas. It commonly presents as a mass or lobar consolidation. We describe a rare presentation of advanced IMA. CASE PRESENTATION: A 36-year-old healthy woman presented with dyspnea for 3 weeks. Admission vitals were Temp 97.9 F, BP 103/79, HR 77, RR 18, SpO2 97% on 2L nasal cannula. Exam was notable for a cachectic, non-toxic appearing woman with diffuse expiratory wheezing and decreased breath sounds at the right lung base. Laboratory studies were unremarkable (Table 1). CXR and CT showed extensive multi-lobar consolidations (Fig 1a,b). She disclosed having eight parakeets and two turtles at home. The working diagnosis was hypersensitivity pneumonitis from bird exposure. Bronchoscopy with trans-bronchial biopsies showed alveolar pneumocyte hyperplasia without atypia. She was prescribed prednisone 1mg/kg PO daily. She returned multiple times with persistent symptoms and worsening radiographic findings (Fig 2). She required bilevel ventilation with 100% FiO2 and was deemed too unstable for open lung biopsy. A transthoracic CT guided core needle lung biopsy was done; pathological findings were identical to the trans-bronchial biopsy (Fig 3). Samples were sent for a second opinion to a local expert; IMA was diagnosed. Her hypoxemia worsened requiring intubation. Despite mechanical ventilatory support, she had refractory hypoxemia and was started on V-V ECMO with the goal of receiving palliative chemotherapy. She received one cycle of platinum-based chemotherapy and subsequently developed multi-organ system failure; ECMO was stopped and she was palliatively extubated. DISCUSSION: Multi-lobar consolidations are typically seen in the setting of pneumonia; however, they are present in other disease processes. The case patient had an indolent presentation, was non-toxic appearing, and lacked fever and leukocytosis, making an infectious pneumonia unlikely. In the case patient, imaging revealed extensive multi-lobar consolidations which progressed over weeks. Little is known about IMA progression; treatment outcomes are guided by small retrospective studies. Platinum based chemotherapy is used as first line treatment, however, it has not been shown to significantly improve survival in stage IV disease. In stage I disease, resection and adjuvant chemotherapy has improved 5-year survival with rates of 93%. CONCLUSIONS: Clinicians should build a broad differential for multi-lobar consolidations especially when patient's presentation is inconsistent with a pulmonary infection. Tissue is crucial to arriving at the correct diagnosis. In this case, the initial presentation was consistent with hypersensitivity pneumonitis. However, the patient's lack of improvement with therapy prompted the search for an alternative diagnosis. Further investigation is needed to elucidate IMA disease prognostication and treatment regimens. Reference #1: Cha, YJ, and Hyo Sup Shim. Biology of Invasive Mucinous Adenocarcinoma of the Lung. Translational Lung Cancer Research 6.5 (2017): 508-512. Reference #2: Lee, HY, Cha, MJ, Lee, KS et al Prognosis in Resected Invasive Mucinous Adenocarcinomas of the Lung: Related Factors and Comparison with Resected Non-mucinous Adenocarcinomas Journal of Thoracic Oncology 6 (2017): 1064-1073. Reference #3: Koo H, Kim M, Kim H, et al. Computerized margin and texture analyses for differentiating bacterial pneumonia and invasive mucinous adenocarcinoma presenting as consolidation. Plos ONE 2017;12(5):1-14 DISCLOSURES: No relevant relationships by Bisma Alam, source=Web Response No relevant relationships by Yonatan Greenstein, source=Web Response

Malignant pleural and peritoneal mesothelioma: clinical update 2018.

With great pleasure we present this focused issue of Translational Lung Cancer Research ( TLCR ) on pleural and peritoneal mesothelioma which anno 2018 remain challenging health problems with a grim prognosis. In this special issue of TLCR we cover many of the current topics related to epidemiology, screening, diagnosis and especially, the different treatment modalities of pleural and peritoneal mesothelioma. Dedicated authors from renowned centers contributed to this issue.

Lung cancer screening: the path forward.

Although the primary results of the National Lung Screening Trial (NLST) were published only 7 years ago, lung cancer screening today is rapidly advancing (1). In this issue of Translational Lung Cancer Research ( TLCR ) dedicated to CT screening for lung cancer, we include reviews of many of those advances—some already in clinical use, and some still in development.

Erratum to current state of immunotherapy for non-small cell lung cancer.

[This corrects the article on p. 196 in vol. 6, PMID: 28529902.].

Spotlight on circulating tumour cells.

This focused issue of Translational Lung Cancer Research aims to capture the progress that has been made in the past decade to understand the biology and clinical significance of circulating tumour cells (CTCs) in patients with lung cancer. Crucially, understanding cancer evolution in lung cancer and its associated resistance to therapy can only be achieved with repeated sampling and analysis of the cancer. CTCs provide a readily obtained liquid biopsy and offer unprecedented potential to inform on new treatment strategies. Several platforms now exist for CTC isolation, enumeration and analysis. CTC enumeration is of proven prognostic utility in patients with lung cancer and the demonstration that CTC derived tumour explant models (CDX models) can be established that recapitulate response to treatment in the donor patient provides a new foundation for discovery of biology, preclinical drug development and even co-clinical trials. CTC subpopulations exist for which their significance for prognostication, prediction of treatment response and contribution to disease biology is an emerging focus of research. Similarly, the CTC microenvironment, interactions with macrophages and other cells of the immune and haemopoetic systems now warrants increased attention. The reader will be orientated to the challenges and unanswered questions that remain for the next decade of CTC research in lung cancer. While there is still plenty of work to do the future looks bright for CTCs to inform better understanding of lung cancer biology and as biomarkers that can be exploited for improved therapeutic control throughout the disease trajectory.

Abstract 4801: Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies

Abstract Background: Translational cancer research needs appropriated preclinical models to discover predictive biomarkers and evaluate precision therapeutic strategies. Conventional available preclinical models have proven not been optimal to this end, since cell lines based xenografts do not reconstitute the complexity of human cancer and carry acquired mutations not found in the original tumor. For these reasons our aim was generate and completely characterize a collection of non-small cell lung cancer (NSCLC) PDX models useful for translational lung cancer research. Materials and methods: Resected primary tumors from NSCLC patients were subcutaneous xenografted in athymic nude mice and expanded in successive groups of mice to get a perpetual live bank of each tumor. Every tumor, which successfully grew in mice, was analyzed by histologic and molecular techniques (NGS gene panel, exome and RNA Seq). Furthermore, a bank of frozen pieces of tumor was expanded and stored in order to generate later cohorts of tumor-bearing mice suitable for preclinical drug evaluation. Results: Our collection consists on 42 PDX models (26 SCC, 12ADC, 3LCC). We have characterized all of them histologically and molecularly with a 22 genes NGS panel. Furthermore, we have analyzed the exome and transcriptome of 33 models (20 SCC, 10 ADC and 3 LCC). All PDX models mostly retain the principal histologic and molecular characteristics of their donors and recapitulate the heterogeneity of human lung tumors. In our PDX collection we have sufficiently represented all the NSCLC histology and the most relevant molecular alterations in lung cancer in order to perform precision medicine evaluation studies. Conclusions: We have generated a collection of 42 PDX models of NSCLC characterized at the histological, genomic and transcriptomic level, which represents the most frequent histological and molecular subtypes of this type of lung cancer. This collection will be really useful to integrate drug screening with biomarker discovery and to evaluate precision therapeutic strategies. Our future aim will be to use this collection for biomarkers identification and preclinical evaluation of new therapeutic strategies targeted to bad prognostic lung tumors with suboptimal therapeutic approaches. Citation Format: Sonia Molina-Pinelo, Ricardo Melendez, Rocío Suarez, Laura García, Laura Ojeda, Nicolas Moreno, María V Guijarro, Luis Paz-Ares, Irene Ferrer. Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4801. doi:10.1158/1538-7445.AM2017-4801

Liquid biopsy in lung cancer: present and future.

In lung cancer, as well as in other malignancies, the so-called “liquid biopsy” is quickly moving from research into clinical practice. Although it has not yet reached its full potential, the “liquid biopsy” is no longer a promise but a reality that is allowing a better monitoring and treatment selection of cancer patients in many hospitals and oncology departments. We can already envision a day when “liquid biopsy” tests will be as common and useful as imaging techniques and “standard” biopsies, offering invaluable prognostic and predictive information. The objective of this special issue of Translational Lung Cancer Research ( TLCR ) is to offer an overview of this exciting area, with a particular emphasis on the clinical utility of the so-called “liquid biopsy” and the diversity of applications, methodologies and information that can be derived from it.

1524P - Generation and characterization of a collection of patient-derived xenografts (PDX) models for translational lung cancer research

1524P - Generation and characterization of a collection of patient-derived xenografts (PDX) models for translational lung cancer research

Hypothesis Nature has provided the two Subsets required for Translational Lung Cancer Research

Hypothesis Nature has provided the two Subsets required for Translational Lung Cancer Research

Hypothesis Nature has provided the two Subsets required for Translational Lung Cancer Research

Hypothesis Nature has provided the two Subsets required for Translational Lung Cancer Research

From the bench to the bedside-promoting the roles of nurses and allied health professionals in the management of lung cancer and mesothelioma.

It is my great pleasure to introduce this special issue of Translational Lung Cancer Research ( TLCR ) which showcases the diversity of lung cancer and mesothelioma multi-disciplinary (MDT) working with invited articles from nurses and allied health professionals (AHP) working in these specialities.

Anticoagulation, ferrotoxicity and the future of translational lung cancer research.

Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms.

Translational Lung Cancer Research is endorsed by the Brazilian Society of Thoracic Surgery

Translational Lung Cancer Research is endorsed by the Brazilian Society of Thoracic Surgery