Advances in Prognosis and Theranostics of Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19054

Special Issue Editors

Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77005, USA
Interests: cancer theranostics; immunomodulatory biomaterials; angiogenesis; drug delivery; nanomedicine
Special Issues, Collections and Topics in MDPI journals
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, The University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Interests: stem cells; iPSC; ESC; premalignancy; disease modeling; drug discovery; nanotechnology; lung cancer; immuno-oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is one of the leading causes of cancer-related death worldwide. As per the recent cancer statistics data, lung cancer accounts for an estimated 2.1 million lung cancer cases and 1.8 million deaths in 2018. Lung cancer recurs following surgery in approximately 30% of patients and therefore has long been the number-one cause of death from cancer. Moreover, the prevalence of lung cancer is not only rising in men but also strikingly rising amongst women, thus making it an urgent priority to tackle this devastating disease. Non-small cell lung cancer (NSCLC) causes around 80% of all lung cancer-related deaths. Although advances have been made in the treatment of NSCLC, the 5-year survival rate has increased by only 5% in the past 30 years. Another form of lung cancer, small cell lung cancer (SCLC) is less common but is more aggressive than NSCLC. The lack of an early diagnosis and inefficiency in conventional therapies causes poor prognosis and overall survival of lung cancer patients.

Hence alternative prognostic, therapeutic, and diagnostic approaches are required to reduce overall mortality and improve patient quality of life. In this present issue, we will publish research, reviews, and short communications on the modern approaches to combat lung cancer. Contributions on biomarker discovery, diagnosis, therapeutic modalities including immunotherapy, cancer vaccines, biomaterials-based theranostics approaches, nanomedicine-based theranostics, small molecule-based targeting, immunomodulatory approaches and other emergent approaches in precision oncology are also encouraged.

Dr. Sudip Mukherjee
Dr. Manash Paul
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lung Cancer
  • Biomarker
  • Immunotherapy
  • Theranostics
  • Prognosis
  • Cell Therapy
  • Nanomedicine
  • Immunomodulation
  • Small molecule-based drugs
  • Biomaterials

Published Papers (7 papers)

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Research

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20 pages, 3799 KiB  
Article
Multiplex Droplet Digital PCR Assay for Detection of MET and HER2 Genes Amplification in Non-Small Cell Lung Cancer
by Igor P. Oscorbin, Maria A. Smertina, Ksenia A. Pronyaeva, Mikhail E. Voskoboev, Ulyana A. Boyarskikh, Andrey A. Kechin, Irina A. Demidova and Maxim L. Filipenko
Cancers 2022, 14(6), 1458; https://doi.org/10.3390/cancers14061458 - 11 Mar 2022
Cited by 4 | Viewed by 3050
Abstract
Non-small-cell lung cancer (NSCLC), a subtype of lung cancer, remains one of the most common tumors with a high mortality and morbidity rate. Numerous targeted drugs were implemented or are now developed for the treatment of NSCLC. Two genes, HER2 and MET, [...] Read more.
Non-small-cell lung cancer (NSCLC), a subtype of lung cancer, remains one of the most common tumors with a high mortality and morbidity rate. Numerous targeted drugs were implemented or are now developed for the treatment of NSCLC. Two genes, HER2 and MET, are among targets for these specific therapeutic agents. Alterations in HER2 and MET could lead to primary or acquired resistance to commonly used anti-EGFR drugs. Using current methods for detecting HER2 and MET amplifications is time and labor-consuming; alternative methods are required for HER2 and MET testing. We developed the first multiplex droplet digital PCR assay for the simultaneous detection of MET and HER2 amplification in NSCLC samples. The suitability of qPCR was assessed for the optimization of multiplex ddPCR. The optimal elongation temperature, reference genes for DNA quantification, and amplicon length were selected. The developed ddPCR was validated on control samples with various DNA concentrations and ratios of MET and HER2 genes. Using ddPCR, 436 EGFR-negative NSCLC samples were analyzed. Among the tested samples, five specimens (1.15%) showed a higher ratio of MET, and six samples (1.38%) showed a higher ratio of HER2. The reported multiplex ddPCR assay could be used for the routine screening of MET and HER2 amplification in NSCLC samples. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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14 pages, 1640 KiB  
Article
Methylation of DROSHA and DICER as a Biomarker for the Detection of Lung Cancer
by Michał Szczyrek, Anna Grenda, Barbara Kuźnar-Kamińska, Paweł Krawczyk, Marek Sawicki, Halina Batura-Gabryel, Radosław Mlak, Aneta Szudy-Szczyrek, Tomasz Krajka, Andrzej Krajka and Janusz Milanowski
Cancers 2021, 13(23), 6139; https://doi.org/10.3390/cancers13236139 - 06 Dec 2021
Cited by 6 | Viewed by 1796
Abstract
Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) [...] Read more.
Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) related to carcinogenesis, DICER and DROSHA, in 101 plasma samples (obtained prior to the treatment) of lung cancer patients and 45 healthy volunteers. Results: The relative level of methylation of DROSHA was significantly lower (p = 0.012 for first and p < 0.00001 for the second region) and DICER significantly higher (p = 0.029 for the first region) in cancer patients. The relative level of methylation of DROSHA was significantly (p = 0.037) higher in patients with early-stage NSCLC (IA-IIIA) and could discriminate them from healthy people with a sensitivity of 71% and specificity of 76% (AUC = 0.696, 95% CI: 0.545–0.847, p = 0.011) for the first region and with a sensitivity of 60% and specificity of 85% (AUC = 0.795, 95% CI: 0.689–0.901, p < 0.0001) for the second region. Methylation analysis of the first region of the DICER enabled the distinction of NSCLC patients from healthy individuals with a sensitivity of 96% and specificity of 60% (AUC = 0.651, 95% CI: 0.517–0.785, p = 0.027). The limitations of the study include its small sample size, preliminary nature, being an observational type of study, and the lack of functional experiments allowing for the explanation of the biologic backgrounds of the observed associations. Conclusion: The obtained results indicate that the assessment of DICER and DROSHA methylation status can potentially be used as a biomarker for the early detection of lung cancer. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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15 pages, 4036 KiB  
Article
First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes
by David Lang, Linda Ritzberger, Vanessa Rambousek, Andreas Horner, Romana Wass, Kaveh Akbari, Bernhard Kaiser, Jürgen Kronbichler, Bernd Lamprecht and Michael Gabriel
Cancers 2021, 13(23), 6096; https://doi.org/10.3390/cancers13236096 - 03 Dec 2021
Cited by 10 | Viewed by 2316
Abstract
Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy–ICI combinations are still scarce, we retrospectively evaluated baseline [...] Read more.
Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy–ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n = 70) or as monotherapy (n = 15). Maximum and mean standardized uptake value, total metabolic tumor volume (MTV), total lesion glycolysis, bone marrow-/and spleen to liver ratio (BLR/SLR) were calculated. Kaplan–Meier analyses and Cox regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Median follow-up was 12 months (M; 95% confidence interval 10–14). Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p < 0.001). Median PFS/OS were significantly longer in patients with MTV ≤ 70 mL vs. >70 mL (PFS: 10 M (4–16) vs. 4 M (3–5), p = 0.001; OS: not reached vs. 10 M (5–15), p = 0.004). Disease control rate was 81% vs. 53% for MTV ≤/> 70 mL (p = 0.007). BLR ≤ 1.06 vs. >1.06 was associated with better outcomes (PFS: 8 M (4–13) vs. 4 M (3–6), p = 0.034; OS: 19 M (12-/) vs. 6 M (4–12), p = 0.005). In patients with MTV > 70 mL, concomitant BLR ≤ 1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI-treated NSCLC, with BLR allowing additional risk stratification. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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15 pages, 960 KiB  
Article
Impact of Chronic Obstruction Pulmonary Disease on Survival in Patients with Advanced Stage Lung Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy
by Kuo-Chin Chiu, Wei-Chun Lin, Chia-Lun Chang and Szu-Yuan Wu
Cancers 2021, 13(13), 3231; https://doi.org/10.3390/cancers13133231 - 28 Jun 2021
Cited by 3 | Viewed by 1718
Abstract
Background: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). Patients and methods: We enrolled 3986 [...] Read more.
Background: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). Patients and methods: We enrolled 3986 patients with clinical stage IIIA–IIIB, unresectable lung SCC, who had received standard definitive CCRT, and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). Results: In the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval (CI)) of all-cause death for COPD was 1.04 (1.01, 1.16), compared no COPD in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. In the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥ 2 hospitalizations for COPDAE within 1 year before CCRT were 1.32 (1.19, 1.46) and 1.81 (1.49, 2.19) respectively, compared with no hospitalization for COPDAE. Conclusion: COPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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14 pages, 630 KiB  
Article
Durvalumab after Chemoradiotherapy for PD-L1 Expressing Inoperable Stage III NSCLC Leads to Significant Improvement of Local-Regional Control and Overall Survival in the Real-World Setting
by Julian Taugner, Lukas Käsmann, Chukwuka Eze, Amanda Tufman, Niels Reinmuth, Thomas Duell, Claus Belka and Farkhad Manapov
Cancers 2021, 13(7), 1613; https://doi.org/10.3390/cancers13071613 - 31 Mar 2021
Cited by 17 | Viewed by 2194
Abstract
Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) [...] Read more.
Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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14 pages, 1590 KiB  
Article
Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis
by Monika Karin, Julian Taugner, Lukas Käsmann, Chukwuka Eze, Olarn Roengvoraphoj, Amanda Tufman, Claus Belka and Farkhad Manapov
Cancers 2020, 12(10), 3035; https://doi.org/10.3390/cancers12103035 - 19 Oct 2020
Cited by 10 | Viewed by 2096
Abstract
Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and [...] Read more.
Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7–108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071–2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3–15.9) and 34.5 (95% CI: 25.6–43.4) months vs. 6.2 (95% CI: 3.1–9.3) (p = 0.057) and 12.7 (95% CI: 8.5–16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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20 pages, 825 KiB  
Review
Updated Prognostic Factors in Localized NSCLC
by Simon Garinet, Pascal Wang, Audrey Mansuet-Lupo, Ludovic Fournel, Marie Wislez and Hélène Blons
Cancers 2022, 14(6), 1400; https://doi.org/10.3390/cancers14061400 - 09 Mar 2022
Cited by 26 | Viewed by 4289
Abstract
Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate [...] Read more.
Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate is 59%. To improve survival, adjuvant chemotherapy (ACT) was largely explored and showed an overall benefit of survival at 5 years < 7%. The evaluation of recurrence risk and subsequent need for ACT is only based on tumor stage (TNM classification); however, more than 25% of patients with stage IA/B tumors will relapse. Recently, adjuvant targeted therapy has been approved for EGFR-mutated resected NSCLC and trials are evaluating other targeted therapies and immunotherapies in adjuvant settings. Costs, treatment duration, emergence of resistant clones and side effects stress the need for a better selection of patients. The identification and validation of prognostic and theranostic markers to better stratify patients who could benefit from adjuvant therapies are needed. In this review, we report current validated clinical, pathological and molecular prognosis biomarkers that influence outcome in resected NSCLC, and we also describe molecular biomarkers under evaluation that could be available in daily practice to drive ACT in resected NSCLC. Full article
(This article belongs to the Special Issue Advances in Prognosis and Theranostics of Lung Cancer)
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