Advances in the Diagnosis and Treatment of Lung Adenocarcinoma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (24 May 2023) | Viewed by 8140

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Guest Editor
Department of Thoracic Surgery, Hammersmith Hospital, London, UK
Interests: lung cancer; minimally invasive thoracic surgery; translational medicine; health policy
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E-Mail Website
Guest Editor
1. Imperial College Healthcare NHS Trust, London, UK
2. 424 General Military Hospital, Thessaloniki, Greece
Interests: cardiothoracic surgery; thoracic surgical oncology; lung cancer; tracheal disease; coronary artery disease; cardiac valve disease; thoracic trauma; military medicine; translational cardiovascular medicine; surgical education and simulation; health policy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related death worldwide, with an estimated 2.2 million new cases and 1.8 million deaths in 2020. The histological pattern of lung cancer changed significantly over a period of only a few decades, with a decrease in squamous cell carcinoma and a sharp rise in adenocarcinoma. Currently, adenocarcinoma represents the most common histologic type of pulmonary tumors, accounting for more than 65% of all lung cancers. Of interest, it is also the most common form of lung cancer in never smokers. With the recent introduction of lung cancer screening programs and the increasing detection of adenocarcinoma spectrum lesions (e.g., adenocarcinoma in situ, minimally invasive adenocarcinoma), the number of newly diagnosed cases is expected to further rise.

Apart from changes in the epidemiology and biology of lung cancer, significant advances have recently occurred in the diagnosis and treatment of the disease. The discovery of treatable oncogenic alterations has led to the routine implementation of molecular testing in the diagnostic evaluation of patients with lung adenocarcinoma. Indeed, an increasing number of targetable gene alterations has been recently identified, allowing individualized therapies that have demonstrated remarkable responses in selected patients. Targeted therapies were initially used for the management of advanced lung adenocarcinoma, but they have also recently shown promising results in early disease as part of multimodality treatments. The success of targeted therapies has resulted in ongoing efforts to identify and therapeutically target other driver mutations. Furthermore, important progress has been achieved in the development of immunotherapies, which now constitute the first-line treatment of advanced wild-type lung adenocarcinomas. Moreover, a paradigm shift in the surgical management of small, peripheral adenocarcinomas, which may radiologically manifest as subsolid lung nodules, has been recently observed. Sublobar resections in the form of segmentectomy or even wedge resection have been increasingly adopted by thoracic surgeons as a valid alternative to the traditional lobectomy. Such lesions may also be successfully treated with stereotactic ablative radiotherapy, which is currently being investigated as an alternative to surgical resection.

It is evident that the landscape of lung adenocarcinoma is transforming rapidly. This has created great opportunities for research in diagnosis and treatment; however, it has also provided challenges for clinicians, who are often presented with an excessive amount of new information. This Special Issue on the “Advances in the Diagnosis and Treatment of Lung Adenocarcinoma” aims to provide the readers of the Journal of Clinical Medicine with concise, high-quality, and up-to-date knowledge, as well as to present unpublished evidence on this topic. It therefore welcomes both reviews and original articles. By discussing the advances in the diagnosis and treatment of lung adenocarcinoma and identifying avenues for future research, this Special Issue will be a valuable resource for researchers, clinicians, and patients alike.

Dr. Marco Scarci
Dr. Savvas Lampridis
Guest Editors

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Keywords

  • biomarkers
  • chemotherapy
  • immunotherapy
  • lung adenocarcinoma
  • lung surgery
  • molecular targeted therapy
  • non-small cell lung cancer
  • radiotherapy
  • screening

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Published Papers (4 papers)

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Research

14 pages, 3155 KiB  
Article
Spectral Dual-Layer Computed Tomography Can Predict the Invasiveness of Ground-Glass Nodules: A Diagnostic Model Combined with Thymidine Kinase-1
by Tong Wang, Yong Yue, Zheng Fan, Zheng Jia, Xiuze Yu, Chen Liu and Yang Hou
J. Clin. Med. 2023, 12(3), 1107; https://doi.org/10.3390/jcm12031107 - 31 Jan 2023
Cited by 2 | Viewed by 1232
Abstract
Objectives: Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aimed to evaluate the quantitative and qualitative parameters generated from SDCT [...] Read more.
Objectives: Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aimed to evaluate the quantitative and qualitative parameters generated from SDCT for predicting the pathological subtypes of GGN-featured lung adenocarcinoma combined with TK1 and TAP. Material and Methods: Between July 2021 and September 2022, 238 patients with GGNs were retrospectively enrolled in this study. SDCT and tests for TK1 and TAP were performed preoperatively, and the lesions were divided into glandular precursor lesions (PGL), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC), according to the pathological results. A receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of these parameters. Multivariate logistic regression analysis was performed to construct a joint diagnostic model and create a nomogram. Results: This study included 238 GGNs, including 41 atypical adenomatous hyperplasias (AAH), 62 adenocarcinomas in situ (AIS), 49 MIA, and 86 IAC, with a high proportion of women, non-smokers, and pure ground-glass nodule (pGGN). CT100 keV (a/v), electronic density (EDW) (a/v), Daverage, Dsolid, TK1, and TAP of MIA and IAC were higher than those of PGL. The effective atomic number (Zeff (a/v)) was lower in MIA and IAC than in PGL (all p < 0.05). Logistic regression analysis showed that Zeff (a), EDW (a), TK1, Daverage, and internal bronchial morphology were crucial factors in predicting the aggressiveness of GGN. Zeff (a) had the highest diagnostic performance with an area under the ROC curve (AUC) = 0.896, followed by EDW (a) (AUC = 0.838) and CT100 keVa (AUC = 0.819). The diagnostic model and nomogram constructed using these five parameters (Zeff (a) + EDW (a) + CT100 keVa + Daverage + TK1) had an AUC = 0.933, which was higher than the individual parameters (p < 0.05). Conclusions: Multiple quantitative and functional parameters can be selected based on SDCT, especially Zeff (a) and EDW (a), which have high sensitivity and specificity for predicting GGNs’ invasiveness. Additionally, the combination of TK1 can further improve diagnostic performance, and using a nomogram is helpful for individualized predictions. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Lung Adenocarcinoma)
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13 pages, 844 KiB  
Article
Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer
by Akira Nakao, Hiroyuki Inoue, Nobumitsu Ikeuchi, Fumiyasu Igata, Takashi Aoyama, Makoto Hamasaki, Hisatomi Arima and Masaki Fujita
J. Clin. Med. 2023, 12(1), 137; https://doi.org/10.3390/jcm12010137 - 24 Dec 2022
Cited by 1 | Viewed by 2311
Abstract
Background: Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people. Objective: We aimed to examine the [...] Read more.
Background: Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people. Objective: We aimed to examine the impact of the results of the TTF-1 immunostaining of tumor cells on the therapeutic effect of chemotherapy in Japanese patients with nonsq NSCLC. Methods: We examined the results of TTF-1 immunostaining and the clinical background of Japanese patients with nonsq NSCLC who received platinum-doublet chemotherapy at our hospital, from April 2009 to April 2021, and the correlation between regimens with or without pemetrexed in progression-free survival (PFS) and overall survival (OS). The efficacy of each regimen was then compared between TTF-1-positive and TTF-1-negative tumors. Results: TTF-1 immunostaining was performed in 145 patients during the study period: 92 were positive, and 53 were negative. A total of 24 patients presented with EGFR/ALK gene abnormality (16.6%). The PFS and OS of patients who were TTF-1-positive tended to be longer than those of the patients who were TTF-1-negative under either regimen. In other words, patients who were TTF-1-negative were frequently resistant to numerous chemotherapy drugs and experienced a poor prognosis under both regimens. The OS of patients who were TTF-1-positive and treated with the pemetrexed regimen was significantly longer than those on regimens without pemetrexed (963 vs. 412 days, HR = 0.73; 95% CI 0.55–0.96, p = 0.022), whereas there was no difference in PFS. Conclusions: The positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who have advanced nonsq NSCLC. Our analysis examined the possibility of a pemetrexed regimen leading to a longer prognosis in Asian patients who were TTF-1-positive for nonsq NSCLC, as shown in previous studies. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Lung Adenocarcinoma)
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13 pages, 3839 KiB  
Article
Expression Profiles of AQP3 and AQP4 in Lung Adenocarcinoma Samples Generated via Bronchoscopic Biopsies
by Lukasz Jaskiewicz, Karolina Hejne, Blazej Szostak, Karolina Osowiecka, Mariusz T. Skowronski, Ewa Lepiarczyk, Anna Doboszynska, Marta Majewska, Pawel Kordowitzki and Agnieszka Skowronska
J. Clin. Med. 2022, 11(19), 5954; https://doi.org/10.3390/jcm11195954 - 9 Oct 2022
Cited by 6 | Viewed by 1677
Abstract
Aquaporins (AQPs) are highly conserved channel proteins which are mainly responsible for the exchange of water and small molecules and have shown to play a pivotal role in the development and progression of cancer. Lung adenocarcinoma is the most common primary lung cancer [...] Read more.
Aquaporins (AQPs) are highly conserved channel proteins which are mainly responsible for the exchange of water and small molecules and have shown to play a pivotal role in the development and progression of cancer. Lung adenocarcinoma is the most common primary lung cancer seen in patients in Europe and the United States. However, in patients it is often not diagnosed until the advanced tumor stage is present. Previous studies provided strong evidence that some members of the AQP family could serve as clinical biomarkers for different diseases. Therefore, we aimed to investigate how AQP3 and AQP4 protein expression in lung adenocarcinoma (ADC) biopsy samples correlate with clinical and pathological parameters. The protein expression of AQP3 and AQP4 was analyzed based on immunohistochemical staining. AQP3 protein was observed in the cytoplasmic membrane of cancer tissue in 82% of lung samples. Significant differences in relative protein expression of AQP3 were noted between advanced age patients compared to younger counterparts (p = 0.017). A high expression of AQP3 was significant in cancer tissue when compared to the control group (p < 0.001), whereas a low AQP4 membrane expression was noted as significantly common in cancer tissue compared to non-neoplastic lung tissue (p < 0.001). Moreover, a low AQP4 membrane expression was positively correlated with a more advanced disease status, e.g., lymph node metastases (p = 0.046). Based on our findings, AQP3 and AQP4 could be used as biomarkers in ADC patients. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Lung Adenocarcinoma)
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12 pages, 965 KiB  
Article
Survival Analysis in Patients with Lung Cancer and Subsequent Primary Cancer: A Nationwide Cancer Registry Study
by Wen-Ru Chou, Ben-Chang Shia, Yen-Chun Huang, Chieh-Wen Ho and Mingchih Chen
J. Clin. Med. 2022, 11(19), 5944; https://doi.org/10.3390/jcm11195944 - 8 Oct 2022
Cited by 2 | Viewed by 2110
Abstract
With improved survival in patients with cancer, the risk of developing multiple primary malignancies (MPMs) has increased. We aimed to characterize MPMs involving lung cancer and compare these characteristics between patients with single lung cancer and those with lung cancer and subsequent primary [...] Read more.
With improved survival in patients with cancer, the risk of developing multiple primary malignancies (MPMs) has increased. We aimed to characterize MPMs involving lung cancer and compare these characteristics between patients with single lung cancer and those with lung cancer and subsequent primary cancer (known as lung cancer first [LCF]). Methods: This retrospective study was conducted based on Taiwan Cancer Database from Taiwan’s National Health Insurance Registry Database. Patients with lung cancer (n = 72,219) from 1 January 2011 to 31 December 2015, were included in this study, and their medical records were traced back to 1 January 2002, and followed until 31 December 2019. Results: MPMs occurred in 10,577 (14.65%) patients with lung cancer, and LCF and other cancer first (OCF) accounted for 35.55% and 64.45% of these patients, with a mean age at lung cancer diagnosis of 65.18 and 68.92 years, respectively. The median interval between primary malignancies in the OCF group was significantly longer than that in the LCF group (3.26 vs. 0.11 years, p < 0.001). Patients in the single lung cancer group were significantly older than those in the LCF group (67.12 vs. 65.18 years, p < 0.001). The mean survival time of patients with LCF was longer than that of patients with single lung cancer. Following initial lung cancer, the three most common second primary malignancies were lung, colon, and breast cancers. For patients with advanced lung cancer, survival in patients with mutant epidermal growth factor receptor (EGFR) was longer than that in patients with undetected EGFR. In stage 3 and 4 patients with EGFR mutations, the LCF group showed better survival than the single lung cancer group. Conversely, in stage 1 patients with mutant EGFR, the LCF group exhibited worse survival than the single lung cancer group. Conclusions: Survival in patients with MPMs depends on baseline characteristics and treatments. Our findings may contribute to the development of precision medicine for improving personalized treatment and survival as well as the reduction of medical costs. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Lung Adenocarcinoma)
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