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4 pages, 205 KiB

Open AccessEditorial

Advances in Lung Cancer Therapy

by Domenico Galetta

Cancers 2023, 15(10), 2671; https://doi.org/10.3390/cancers15102671 - 9 May 2023

Cited by 3 | Viewed by 1324

Abstract

Lung cancer, including both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), remains one of the most aggressive types of cancer, and the prognosis for individuals diagnosed with this neoplasm has, for the most part, been insufficient [...] Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

Research

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18 pages, 4056 KiB

Open AccessArticle

Fasudil Increased the Sensitivity to Gefitinib in NSCLC by Decreasing Intracellular Lipid Accumulation

by Tingting Liao, Jingjing Deng, Wenjuan Chen, Juanjuan Xu, Guanghai Yang, Mei Zhou, Zhilei Lv, Sufei Wang, Siwei Song, Xueyun Tan, Zhengrong Yin, Yumei Li and Yang Jin

Cancers 2022, 14(19), 4709; https://doi.org/10.3390/cancers14194709 - 27 Sep 2022

Cited by 4 | Viewed by 1971

Abstract

Tyrosine kinase inhibitors (TKIs) resistance is a challenge in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Here, we examined the effect of Fasudil in reversing TKIs resistance. The results of CCK8 assay, clone formation assay, cell cycle arrest analysis, [...] Read more.

Tyrosine kinase inhibitors (TKIs) resistance is a challenge in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Here, we examined the effect of Fasudil in reversing TKIs resistance. The results of CCK8 assay, clone formation assay, cell cycle arrest analysis, and apoptosis analysis show that Fasudil treatment effectively suppressed the growth and induced apoptosis of the EGFR-mutant NSCLC cells. Furthermore, Fasudil in combination with gefitinib showed a synergistic anti-tumor effect in gefitinib-resistant NSCLC cells. RNA-seq analysis and immunoblotting indicated that Fasudil treatment significantly inhibited intracellular lipid accumulation and EGFR/PI3K/AKT pathway activation. Mechanistic investigations showed that Fasudil regulated lipogenic gene expressions via AMPK signal pathway. In vivo, Fasudil and gefitinib co-administration significantly attenuated the growth of H1975 nude mouse xenograft models, suggesting that Fasudil treatment combined with gefitinib can be applied as a therapy for gefitinib-resistant NSCLC cells. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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19 pages, 4568 KiB

Open AccessArticle

NCAPG2 Maintains Cancer Stemness and Promotes Erlotinib Resistance in Lung Adenocarcinoma

by Shiyao Jiang, Jingjing Huang, Hua He, Yueying Liu, Lu Liang, Xiaoyan Sun, Yi Li, Li Cong, Bei Qing and Yiqun Jiang

Cancers 2022, 14(18), 4395; https://doi.org/10.3390/cancers14184395 - 9 Sep 2022

Cited by 6 | Viewed by 2494

Abstract

Erlotinib is a highly specific and reversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), but resistance inevitably develops as the disease progresses. Erlotinib resistance and cancer stem cells (CSCs) are poor factors hindering the prognosis of patients with lung adenocarcinoma (LUAD). Although [...] Read more.

Erlotinib is a highly specific and reversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), but resistance inevitably develops as the disease progresses. Erlotinib resistance and cancer stem cells (CSCs) are poor factors hindering the prognosis of patients with lung adenocarcinoma (LUAD). Although studies have shown that erlotinib resistance and CSCs can jointly promote cancer development, the mechanism is currently unclear. Here, we investigated the potential biomarker and molecular mechanism of erlotinib resistance and cancer stemness in LUAD. An erlotinib resistance model based on four genes was constructed from The Cancer Genome Atlas (TCGA), the GEO database, the Cancer Cell Line Encyclopedia (CCLE), and the Genomics of Drug Sensitivity in Cancer (GDSC). Through multiple bioinformatic analyses, NCAPG2 was identified as a key gene for erlotinib resistance and stemness in LUAD. Further in vitro experiments demonstrated that NCAPG2 maintains stemness and contributes to erlotinib resistance in LUAD. In summary, NCAPG2 plays a vital role in stemness and erlotinib resistance in LUAD. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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10 pages, 5292 KiB

Open AccessArticle

No Impact of PolySia-NCAM Expression on Treatment Response in Neuroendocrine Neoplasms of the Lung

by Daniel Gagiannis, Anna Scheil, Sarah Gagiannis, Carsten Hackenbroch, Ruediger Horstkorte and Konrad Steinestel

Cancers 2022, 14(18), 4376; https://doi.org/10.3390/cancers14184376 - 8 Sep 2022

Cited by 2 | Viewed by 1539

Abstract

Background: Polysialic acids (abbr. polySia) are found on numerous tumors, including neuroendocrine lung tumors. They have previously been shown to impact metastatic potential, as they can influence the signaling and adhesion properties of neuronal cell adhesion molecules (abbr. NCAM) and other cell adhesion [...] Read more.

Background: Polysialic acids (abbr. polySia) are found on numerous tumors, including neuroendocrine lung tumors. They have previously been shown to impact metastatic potential, as they can influence the signaling and adhesion properties of neuronal cell adhesion molecules (abbr. NCAM) and other cell adhesion molecules. Therefore, the aim of this small pilot study was to analyze whether there was a correlation between polySia-NCAM expression and specific clinical or histopathologic characteristics, and if polySia-NCAM expression had an impact on treatment response, disease progression and prognosis of lung neuroendocrine neoplasms. Methods: This work was based on an analysis of 28 digitized patient records and corresponding patient samples. The response to therapy was radiologically determined at the time of diagnosis and at certain intervals during therapy following the current RECIST1.1 and volumetric sphere calculation. To analyze whether polySia-NCAM expression had prognostic relevance, polySia-NCAM-positive and -negative cases were compared in a Kaplan-Meier survival analysis. Findings: A majority of 78.6% lung neuroendocrine neoplasms showed a strong staining signal for polySia-NCAM. There was a significant correlation between expression and histopathological grade (p = 0.0140), since carcinoids were less likely polySia-NCAM-positive compared to small cell lung carcinoma (abbr. SCLC) and large cell neuroendocrine carcinomas of the lung (abbr. LCNEC). There was no significant association between polySia-NCAM expression and clinical characteristics (age: p = 0.3405; gender: p = 0.6730; smoking history: p = 0.1145; ECOG: p = 0.1756, UICC8 stage: p = 0.1182) or radiologically determined disease progression, regardless of the criteria used to categorize response (RECIST 1.1: p = 0.0759; sphere: p = 0.0580). Furthermore, polySia-NCAM expression did not affect progression-free survival (p = 0.4198) or overall survival (p = 0.6918). Interpretation: PolySia-NCAM expression was more common in high-grade compared to low-grade neuroendocrine neoplasms of the lung; however, this small pilot study failed to show an association between polySia-NCAM expression and response to therapy. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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15 pages, 2874 KiB

Open AccessArticle

The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study

by Mingying Xie, Na Li, Xiaoling Xu, Yanjun Xu, Hui Li, Liang Zhu, Jiamin Sheng, Zichao Zhou and Yun Fan

Cancers 2022, 14(17), 4333; https://doi.org/10.3390/cancers14174333 - 5 Sep 2022

Cited by 9 | Viewed by 3162

Abstract

Background: A controversy exists regarding the efficacy of programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors for patients with non-small cell lung cancer (NSCLC) and liver metastases. Our study retrospectively evaluated the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with liver metastases. Methods: [...] Read more.

Background: A controversy exists regarding the efficacy of programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors for patients with non-small cell lung cancer (NSCLC) and liver metastases. Our study retrospectively evaluated the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with liver metastases. Methods: This retrospective study included 1627 lung cancer patients who received immunotherapy. Among 648 patients who had advanced NSCLC and received PD-1/PD-L1 inhibitors, 61 had liver metastases and 587 did not have. We analyzed patient characteristics, progression-free survival (PFS) and overall survival (OS). An exploratory analysis of biomarkers including CD4, CD8 and CD68 for efficacy in patients with liver metastases was also performed. Results: In liver metastasis patients receiving PD-1/PD-L1 inhibitors, the objective response rate (ORR) was 29.5%, the disease control rate (DCR) was 72.1%, PFS was 6.4 months and OS was 15.2 months, which were all worse than those of patients without liver metastases (ORR: 35.8%; DCR: 81.8%; PFS: 7.9 months, p = 0.001; OS: 20.6 months, p = 0.008). When compared to non-liver lesions, the ORR (26.2 vs. 39.3%) and DCR (75.4 vs. 88.5%) of liver lesions were lower. During the analysis of PD-L1 expression, 27 PD-L1-positive patients had a longer PFS than 21 patients in the negative group (p = 0.012). Being PD-L1 positive was the independent prognostic indicators for PFS (p = 0.006). Additionally, the PD-L1 and CD8 dual-positive group responded favorably to PD-1/PD-L1 inhibitors. Conclusions: PD-1/PD-L1 inhibitors are effective in liver metastasis–NSCLC patients. However, the efficacy is inferior when compared to those of patients without liver metastases. In NSCLC patients with liver metastases, PD-L1 expression and CD8+ T cell infiltration can predict the response of PD-1/PD-L1-directed immunotherapy. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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11 pages, 1111 KiB

Open AccessArticle

Completion Pneumonectomy for Non-Small-Cell Lung Cancer: Does Induction Treatment Influence Postoperative Outcomes?

by Domenico Galetta and Lorenzo Spaggiari

Cancers 2022, 14(14), 3408; https://doi.org/10.3390/cancers14143408 - 13 Jul 2022

Cited by 3 | Viewed by 1783

Abstract

Background: Completion pneumonectomy (CP) is associated with high morbidity and mortality. We reviewed our experience to evaluate whether induction treatment (IT) may affect postoperative outcomes and analyzed factors influencing long-term results. Methods: Between 1998 and 2020, 69 patients with lung cancer underwent CP [...] Read more.

Background: Completion pneumonectomy (CP) is associated with high morbidity and mortality. We reviewed our experience to evaluate whether induction treatment (IT) may affect postoperative outcomes and analyzed factors influencing long-term results. Methods: Between 1998 and 2020, 69 patients with lung cancer underwent CP (50 males, median age 63 years, right CP in 47 patients). A total of 23 patients (33.3%) received IT (chemotherapy in 15, chemoradiotherapy in 7, and radiation in 1). Surgery included 25 (36.2%) extended resections and five (7.2%) tracheal sleeve CP. Results: The 30-day mortality rate was 7.2% (5/69), and overall morbidity was 37.6%. Major complications occurred in five patients (7.2%): one cardiac dislocation, one diaphragmatic hernia, one transient ischemic attack (TIA), and two bronchopleural fistulas. Minor complications occurred in 21 cases (30.4%): pulmonary in 12, cardiac in 7, and neurological in 2. The median hospital stay was 8 days (range, 5–56 days). IT did not influence postoperative morbidity and mortality. Pathological staging included 19 (27.5%) stage I, 36 (52.2%) stage II, and 14 (20.3%) stage III. Overall 5-year survival was 51.7%. Factors influencing survival were IT (p = 0.01), extension of resection (p = 0.04), histology (p = 0.01), pathological stage (p = 0.03), and T and N factors (p = 0.2, respectively). Factors affecting survival in multivariate analysis included IT (p = 0.02) and histology (p = 0.03). Conclusions: In our experience, CP had a low mortality, acceptable morbidity, and good long-term survival, which justifies this surgical procedure. Postoperative complications were not influenced by IT. Long-term survival was adversely influenced by the absence of IT, the presence of extended resection, the presence of squamous cell carcinoma, and cancers at advanced stages. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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13 pages, 4978 KiB

Open AccessFeature PaperArticle

Rescue Surgery after Immunotherapy/Tyrosine Kinase Inhibitors for Initially Unresectable Lung Cancer

by Domenico Galetta, Filippo De Marinis and Lorenzo Spaggiari

Cancers 2022, 14(11), 2661; https://doi.org/10.3390/cancers14112661 - 27 May 2022

Cited by 8 | Viewed by 2294

Abstract

Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability. Methods: We retrospectively reviewed the clinical, surgical, [...] Read more.

Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability. Methods: We retrospectively reviewed the clinical, surgical, and pathological data of 42 patients with histologically proven, inoperable NSCLC who received rescue surgery after a good response to TKI or immunotherapy between March 2014 and December 2021. Results: Of 42 patients, 39 underwent pulmonary resection with therapeutic intent (three explorative thoracotomies). There were 26 males, with a median age of 64 years (range, 41–78 years). Twenty-three patients received TKIs and 19 immunotherapies. Anatomic resection was performed in 97.4% of resected patients (38/39) including 30 lobectomies, one right upper sleeve lobectomy, five pneumonectomies, one tracheal sleeve pneumonectomy, and one bilobectomy; a patient underwent wedge resection. Of 10 procedures attempted via a robotic approach, two required conversion to thoracotomy. No intraoperative morbidity/mortality occurred. The median operative time was 190 (range, 80–426) minutes; estimated blood loss was 200 mL (range, 35–780 mL). Morbidity occurred in 13/39 (33.3%). The median length of hospital stay was 6.5 days (range, 4–23 days). Pathologic downstaging was 74.4% (29/39). With a median follow-up of 28.7 months, the 5-year disease-free interval was 46.5%, and the 5-year overall survival was 66.0%; 32/39 patients (82.1%) are alive, 10 with the disease. Conclusions: Lung resection for suspected residual disease after immunotherapy or TKIs is feasible, with encouraging pathological downstaging. Surgical operation may be technically challenging due to the presence of fibrosis, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survival during the short-interval follow-up. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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15 pages, 851 KiB

Open AccessArticle

Association of Diabetes Severity and Mortality with Lung Squamous Cell Carcinoma

by Chih-Hsiung Su, Wan-Ming Chen, Mingchih Chen, Ben-Chang Shia and Szu-Yuan Wu

Cancers 2022, 14(10), 2553; https://doi.org/10.3390/cancers14102553 - 22 May 2022

Cited by 9 | Viewed by 2306

Abstract

Purpose: The survival impact of diabetes severity on lung cancer remains unclear. We performed head-to-head propensity score matching to estimate the survival impact of various adapted diabetes complications severity index (aDCSI) scores in patients with both diabetes and lung squamous cell carcinoma (SqCLC). [...] Read more.

Purpose: The survival impact of diabetes severity on lung cancer remains unclear. We performed head-to-head propensity score matching to estimate the survival impact of various adapted diabetes complications severity index (aDCSI) scores in patients with both diabetes and lung squamous cell carcinoma (SqCLC). Patients and Methods: We enrolled patients with both diabetes and lung SqCLC and categorized them into the mild (aDCSI = 0–1) and moderate-to-severe (aDCSI ≥ 2) diabetes groups. The patients in both groups were matched at a 1:1 ratio. Results: the matching process yielded a final cohort of 5742 patients with both diabetes and lung SqCLC (2871 patients in the mild diabetes group and 2871 patients in the moderate-to-severe diabetes groups) who were eligible for further analysis. A multivariate Cox regression analysis revealed that the adjusted hazard ratio (aHR; 95% confidence interval) of all-cause death for the mild diabetes group relative to the moderate-to-severe diabetes group was 1.17 (1.08–1.28; p = 0.0005). Conclusion: severe diabetes (aDCSI ≥ 2) is an independent prognostic factor for OS among patients with both diabetes and lung SqCLC who receive standard treatments. Preventing diabetes progression is necessary for patients with diabetes because it not only supports diabetes control but also improves survival for patients with lung SqCLC. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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15 pages, 5789 KiB

Open AccessEditor’s ChoiceArticle

Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2

by Swati Misri, Kirti Kaul, Sanjay Mishra, Manish Charan, Ajeet Kumar Verma, Martin P. Barr, Dinesh K. Ahirwar and Ramesh K. Ganju

Cancers 2022, 14(5), 1181; https://doi.org/10.3390/cancers14051181 - 24 Feb 2022

Cited by 27 | Viewed by 4315

Abstract

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy [...] Read more.

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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14 pages, 1670 KiB

Open AccessArticle

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

by Andrea Spini, Rosa Gini, Pietro Rosellini, Allison Singier, Cristiana Bellan, Alessandra Pascucci, Lorenzo Leoncini, Clément Mathieu, Ignazio Martellucci, Folco Furiesi, Silvano Giorgi, Sandra Donnini, Giuseppe Roberto, Marina Ziche and Francesco Salvo

Cancers 2021, 13(23), 6129; https://doi.org/10.3390/cancers13236129 - 5 Dec 2021

Cited by 11 | Viewed by 2124

Abstract

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of [...] Read more.

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009–2011) and 30.6% (2018–2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018–2019 vs. 2009–2011 was found (non-squamous: HR: 0.95 CI95%: 0.92–0.98; squamous: HR: 0.94 CI95%: 0.90–0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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10 pages, 1244 KiB

Open AccessArticle

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

by Valéry Refeno, Michele Lamuraglia, Safae Terrisse, Clément Bonnet, Clément Dumont, Ludovic Doucet, Damien Pouessel and Stephane Culine

Cancers 2021, 13(15), 3887; https://doi.org/10.3390/cancers13153887 - 2 Aug 2021

Cited by 3 | Viewed by 2472

Abstract

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated [...] Read more.

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53–37.6) and the median follow-up duration was 40.83 months (range 11.33–88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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9 pages, 1113 KiB

Open AccessFeature PaperArticle

Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study

by Beung-Chul Ahn, Jee Hung Kim, Kyoung-Ho Pyo, Sun Min Lim, Min Hee Hong, Hye Ryun Kim and Byoung Chul Cho

Cancers 2021, 13(15), 3681; https://doi.org/10.3390/cancers13153681 - 22 Jul 2021

Cited by 6 | Viewed by 3311

Abstract

Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor blood–brain barrier [...] Read more.

Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor blood–brain barrier permeability. Therefore, we conducted preplanned analyses of ASTRIS, a clinical study of the third-generation EGFR-TKI osimertinib to demonstrate its potential role in intracranial response efficacies. We retrospectively examined 89 NSCLC patients with brain evaluation who were not amenable to curative surgery or radiotherapy and received osimertinib upon confirmation of the presence of the T790M mutation. We collected the information regarding patients’ baseline characteristics, baseline intracranial status, including leptomeningeal metastases (LM), and intracranial responses measured by Response Evaluation Criteria in Solid Tumors version 1.1, using independent central review. The median age was 60 years, and 69.7% of the patients were female. Sixty-five patients (73.0%) had brain metastases (BM) at baseline and nineteen patients (23.5%) had additional LM. Among patients with brain metastases, 24 (36.9%) had ≥1 measurable brain metastases and 16 were evaluated for the objective response. In the CNS evaluable for response set, the intracranial objective response rate (cORR) and disease control rate (cDCR) were 62.5% (95% confidence interval (CI), 38.3–82.6%) and 93.8% (95% CI, 74.3–99.3%), respectively. The median intracranial progression-free survival (cPFS) was 11.8 (95% CI, 8.7–14.8 months), including patients with measurable and non-measurable BM or LM. Our cORR, cDCR, and cPFS were comparable to those observed in previous clinical trials. The outcome of this study helps to demonstrate the potential role of intracranial efficacies of osimertinib 80 mg administration in T790M-positive advanced NSCLC with/without BM or LM. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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10 pages, 493 KiB

Open AccessArticle

Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features

by Antonio Passaro, Silvia Novello, Diana Giannarelli, Emilio Bria, Domenico Galetta, Alain Gelibter, Maria Lucia Reale, Simona Carnio, Emanuele Vita, Alessio Stefani, Pamela Pizzutilo, Valeria Stati, Ilaria Attili and Filippo de Marinis

Cancers 2021, 13(12), 2935; https://doi.org/10.3390/cancers13122935 - 11 Jun 2021

Cited by 15 | Viewed by 3864

Abstract

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. [...] Read more.

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored. Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model. Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9–4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0–13, with three-risk group stratification: 0–2 (good prognosis), 3–6 (intermediate prognosis), and 7–13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70–0.81). Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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Review

Jump to: Editorial, Research, Other

24 pages, 1204 KiB

Open AccessReview

Non-Invasive Biomarkers for Early Lung Cancer Detection

by Harman Saman, Afsheen Raza, Kalyani Patil, Shahab Uddin and Tatjana Crnogorac-Jurcevic

Cancers 2022, 14(23), 5782; https://doi.org/10.3390/cancers14235782 - 24 Nov 2022

Cited by 13 | Viewed by 6359

Abstract

Worldwide, lung cancer (LC) is the most common cause of cancer death, and any delay in the detection of new and relapsed disease serves as a major factor for a significant proportion of LC morbidity and mortality. Though invasive methods such as tissue [...] Read more.

Worldwide, lung cancer (LC) is the most common cause of cancer death, and any delay in the detection of new and relapsed disease serves as a major factor for a significant proportion of LC morbidity and mortality. Though invasive methods such as tissue biopsy are considered the gold standard for diagnosis and disease monitoring, they have several limitations. Therefore, there is an urgent need to identify and validate non-invasive biomarkers for the early diagnosis, prognosis, and treatment of lung cancer for improved patient management. Despite recent progress in the identification of non-invasive biomarkers, currently, there is a shortage of reliable and accessible biomarkers demonstrating high sensitivity and specificity for LC detection. In this review, we aim to cover the latest developments in the field, including the utility of biomarkers that are currently used in LC screening and diagnosis. We comment on their limitations and summarise the findings and developmental stages of potential molecular contenders such as microRNAs, circulating tumour DNA, and methylation markers. Furthermore, we summarise research challenges in the development of biomarkers used for screening purposes and the potential clinical applications of newly discovered biomarkers. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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16 pages, 5311 KiB

Open AccessReview

Parenchymal Sparing Surgery for Lung Cancer: Focus on Pulmonary Artery Reconstruction

by Cecilia Menna, Erino Angelo Rendina and Antonio D’Andrilli

Cancers 2022, 14(19), 4782; https://doi.org/10.3390/cancers14194782 - 30 Sep 2022

Cited by 5 | Viewed by 1915

Abstract

Reconstruction of the pulmonary artery (PA) associated with lobectomy for the radical resection of lung cancer has been progressively gaining diffusion in lung cancer surgery as a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, [...] Read more.

Reconstruction of the pulmonary artery (PA) associated with lobectomy for the radical resection of lung cancer has been progressively gaining diffusion in lung cancer surgery as a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, avoiding pneumonectomy. There are some controversial aspects concerning the intraoperative and perioperative management of a sleeve resection with PA reconstruction that may influence the outcome. In the present article, the authors have analyzed some of the main technical and oncological aspects to take stock of what they have learned from their lung-sparing operations experience over time. PA reconstruction may require prosthetic materials including different options with variable cost. A main concern in vascular reconstructive procedures is avoiding tension on the anastomosis. When PA reconstruction is required, appropriate anticoagulation management is crucial. Results from the main literature data confirm the reliability of lobectomy associated with PA reconstruction in terms of perioperative morbidity and long-term survival. Sleeve lobectomy and PA reconstruction can be performed safely and effectively even after induction therapy. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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19 pages, 693 KiB

Open AccessReview

Impact of Cancer Stem Cells and Cancer Stem Cell-Driven Drug Resiliency in Lung Tumor: Options in Sight

by Lourdes Cortes-Dericks and Domenico Galetta

Cancers 2022, 14(2), 267; https://doi.org/10.3390/cancers14020267 - 6 Jan 2022

Cited by 14 | Viewed by 2935

Abstract

Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of [...] Read more.

Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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33 pages, 1692 KiB

Open AccessEditor’s ChoiceReview

Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy

by Olga Rodak, Manuel David Peris-Díaz, Mateusz Olbromski, Marzenna Podhorska-Okołów and Piotr Dzięgiel

Cancers 2021, 13(18), 4705; https://doi.org/10.3390/cancers13184705 - 20 Sep 2021

Cited by 111 | Viewed by 14494

Abstract

Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer in the world. Its epidemiology depends not only on tobacco exposition but also air quality. While the global trends in NSCLC incidence have started to decline, we can observe [...] Read more.

Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer in the world. Its epidemiology depends not only on tobacco exposition but also air quality. While the global trends in NSCLC incidence have started to decline, we can observe region-dependent differences related to the education and the economic level of the patients. Due to an increasing understanding of NSCLC biology, new diagnostic and therapeutic strategies have been developed, such as the reorganization of histopathological classification or tumor genotyping. Precision medicine is focused on the recognition of a genetic mutation in lung cancer cells called “driver mutation” to provide a variety of specific inhibitors of improperly functioning proteins. A rapidly growing group of approved drugs for targeted therapy in NSCLC currently allows the following mutated proteins to be treated: EGFR family (ERBB-1, ERBB-2), ALK, ROS1, MET, RET, NTRK, and RAF. Nevertheless, one of the most frequent NSCLC molecular sub-types remains without successful treatment: the K-Ras protein. In this review, we discuss the current NSCLC landscape treatment focusing on targeted therapy and immunotherapy, including first- and second-line monotherapies, immune checkpoint inhibitors with chemotherapy treatment, and approved predictive biomarkers. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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9 pages, 997 KiB

Open AccessSystematic Review

Are Routine Chest X-rays Necessary following Thoracic Surgery? A Systematic Literature Review and Meta-Analysis

by Christian Galata, Lorena Cascant Ortolano, Saeed Shafiei, Svetlana Hetjens, Lukas Müller, Roland H. Stauber, Davor Stamenovic, Eric D. Roessner and Ioannis Karampinis

Cancers 2022, 14(18), 4361; https://doi.org/10.3390/cancers14184361 - 7 Sep 2022

Cited by 7 | Viewed by 1847

Abstract

(1) Background: The number of chest X-rays that are performed in the perioperative window of thoracic surgery varies. Many clinics X-ray patients daily, while others only perform X-rays if there are clinical concerns. The purpose of this study was to assess the evidence [...] Read more.

(1) Background: The number of chest X-rays that are performed in the perioperative window of thoracic surgery varies. Many clinics X-ray patients daily, while others only perform X-rays if there are clinical concerns. The purpose of this study was to assess the evidence of perioperative X-rays following thoracic surgery and estimate the clinical value with regard to changes in patient care. (2) Methods: A systematic literature research was conducted up until November 2021. Studies reporting X-ray outcomes in adult patients undergoing general thoracic surgery were included. (3) Results: In total, 11 studies (3841 patients/4784 X-rays) were included. The X-ray resulted in changes in patient care in 488 cases (10.74%). In patients undergoing mediastinoscopic lymphadenectomy or thoracoscopic sympathectomy, postoperative X-ray never led to changes in patient care. (4) Conclusions: There are no data to recommend an X-ray before surgery or to recommend daily X-rays. X-rays immediately after surgery seem to rarely have any consequences. It is probably reasonable to keep requesting X-rays after drain removal since they serve multiple purposes and alter patient care in 7.30% of the cases. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Therapy)

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