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Current Oncology
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Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance...
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Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Thoracic Oncology".

Deadline for manuscript submissions: closed (20 June 2023) | Viewed by 32400

Special Issue Editor

Dr. Antonio Passaro

E-Mail Website
Guest Editor
Division of Thoracic Oncology, Istituto Europeo di Oncologia, Milan, Italy
Interests: lung cancer; NSCLC; EGFR; tyrosine kinase inhibitors; targeted therapy; immunotherapy; oncogene addiction; co-mutation patterns; resistance mechanisms

Special Issue Information

Dear Colleagues,

Molecular advancements in the field of lung cancer have rapidly led to increased knowledge of tumor biology and a subsequent expansion of the horizons for the treatment of the biggest cancer-related killer worldwide.

In particular, the portfolio of actionable gene alterations that may function as potential therapeutic targets (so-called targetable gene alterations) is rapidly growing. In parallel, the emerging data regarding immunotherapy applicability in oncogene-addicted lung cancer make it mandatory to have complete molecular profiles together with PD-L1 statuses to better tailor treatment options. Of note, the impact of targeted and immune-based treatments is also being investigated in early-stage disease, with positive results. This knowledge requires the prompt improvement of testing, from early diagnosis to advanced disease, to allow patients to receive the best therapeutic option at any stage of their disease.

This Special Issue will highlight the current knowledge and future opportunities to tailor the treatment of lung cancer through clinical and translational research as a key to improve survival.

Dr. Antonio Passaro
Guest Editor

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. Current Oncology is an international peer-reviewed open access monthly 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 2200 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

  • EGFR
  • ALK
  • ROS1
  • RET
  • KRAS
  • MET
  • BRAF
  • HER2
  • NTRK
  • PD-L1
  • NSCLC
  • lung cancer
  • immunotherapy
  • immune checkpoint inhibitors
  • targeted therapy
  • tyrosine kinase inhibitors (TKI)
  • resistance mechanisms
  • resectable
  • next-generation sequencing
  • molecular oncology
  • liquid biopsy
  • adjuvant treatment

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Published Papers (6 papers)

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Research

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13 pages, 1685 KiB  
Article
Real-World Clinical Outcomes for Patients with EGFR and HER2 Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer
by Kelly Li, Ian Bosdet, Stephen Yip, Cheryl Ho, Janessa Laskin, Barbara Melosky, Ying Wang and Sophie Sun
Curr. Oncol. 2023, 30(8), 7099-7111; https://doi.org/10.3390/curroncol30080515 - 25 Jul 2023
Cited by 1 | Viewed by 3283
Abstract
(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes [...] Read more.
(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in EGFR or HER2 were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan–Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the EGFR cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not (p < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; p = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST (p = 0.744). For the HER2 cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not (p = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not (p = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST (p = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among HER2 ex20ins patients who received ex20ins-specific TKIs. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
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14 pages, 1122 KiB  
Article
Association between COPD and Stage of Lung Cancer Diagnosis: A Population-Based Study
by Stacey J. Butler, Alexander V. Louie, Rinku Sutradhar, Lawrence Paszat, Dina Brooks and Andrea S. Gershon
Curr. Oncol. 2023, 30(7), 6397-6410; https://doi.org/10.3390/curroncol30070471 - 5 Jul 2023
Cited by 9 | Viewed by 3191
Abstract
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer; however, the association between COPD and stage of lung cancer diagnosis is unclear. We conducted a population-based cross-sectional analysis of lung cancer patients (2008–2020) in Ontario, Canada. Using estimated [...] Read more.
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer; however, the association between COPD and stage of lung cancer diagnosis is unclear. We conducted a population-based cross-sectional analysis of lung cancer patients (2008–2020) in Ontario, Canada. Using estimated propensity scores and inverse probability weighting, logistic regression models were developed to assess the association between COPD and lung cancer stage at diagnosis (early: I/II, advanced: III/IV), accounting for prior chest imaging. We further examined associations in subgroups with previously diagnosed and undiagnosed COPD. Over half (55%) of all lung cancer patients in Ontario had coexisting COPD (previously diagnosed: 45%, undiagnosed at time of cancer diagnosis: 10%). Compared to people without COPD, people with COPD had 30% lower odds of being diagnosed with lung cancer in the advanced stages (OR = 0.70, 95% CI: 0.68 to 0.72). Prior chest imaging only slightly attenuated this association (OR = 0.77, 95% CI: 0.75 to 0.80). The association with lower odds of advanced-stage diagnosis remained, regardless of whether COPD was previously diagnosed (OR = 0.68, 95% CI: 0.66 to 0.70) or undiagnosed (OR = 0.77, 95% CI: 0.73 to 0.82). Although most lung cancers are detected in the advanced stages, underlying COPD was associated with early-stage detection. Lung cancer diagnostics may benefit from enhanced partnership with COPD healthcare providers. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
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31 pages, 6867 KiB  
Article
Advanced Lung Cancer Patients’ Use of EGFR Tyrosine Kinase Inhibitors and Overall Survival: Real-World Evidence from Quebec, Canada
by Samia Qureshi, Gino Boily, Jim Boulanger, Kossi Thomas Golo, Aude-Christine Guédon, Camille Lehuédé, Ferdaous Roussafi, Catherine Truchon and Erin Strumpf
Curr. Oncol. 2022, 29(11), 8043-8073; https://doi.org/10.3390/curroncol29110636 - 26 Oct 2022
Cited by 2 | Viewed by 2848
Abstract
EGFR tyrosine kinase inhibitors (EGFR-TKIs) are breakthrough palliative treatments for advanced lung cancer patients with tumors harboring mutations in the EGFR gene. Using healthcare administrative data, three cohorts were created to describe the use of three EGFR-TKIs that are publicly funded in Quebec [...] Read more.
EGFR tyrosine kinase inhibitors (EGFR-TKIs) are breakthrough palliative treatments for advanced lung cancer patients with tumors harboring mutations in the EGFR gene. Using healthcare administrative data, three cohorts were created to describe the use of three EGFR-TKIs that are publicly funded in Quebec for specific indications (i.e., 1st-line gefitinib, 1st-line afatinib, and post-EGFR-TKI osimertinib). The main objective was to compare overall survival (OS) among patients receiving these treatments to those in previous experimental and real-world studies. The patients who received EGFR-TKIs for indications of interest between 1 April 2001, and 31 March 2019 (or 31 March 2020, for post-EGFR-TKI osimertinib) were included to estimate the Kaplan-Meier-based median OS for each cohort. An extensive literature search was conducted to include comparable studies. For the gefitinib 1st-line (n = 457), the afatinib 1st-line (n = 80), and the post-EGFR-TKI osimertinib (n = 119) cohorts, we found a median OS (in months) of 18.9 (95%CI: 16.3–21.9), 26.6 (95%CI: 13.7-NE) and 19.9 (95%CI: 17.4-NE), respectively. Out of the 20 studies that we retained from the literature review and where comparisons were feasible, 17 (85%) had similar OS results, which further confirms the value of these breakthrough therapies in real-world clinical practice. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
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Review

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10 pages, 266 KiB  
Review
Prospective Clinical Trials to Advance the Study of Immune Checkpoint Inhibitor Toxicity
by Christopher Cluxton and Jarushka Naidoo
Curr. Oncol. 2023, 30(7), 6862-6871; https://doi.org/10.3390/curroncol30070502 - 20 Jul 2023
Cited by 7 | Viewed by 3341
Abstract
Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (IrAEs). Knowledge of such toxicities, [...] Read more.
Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (IrAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the IrAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of IrAEs with an aim to develop standardised, randomised controlled trial-based management algorithms for ICI-related toxicities. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
21 pages, 3439 KiB  
Review
Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?
by Gianluca Spitaleri, Pamela Trillo Aliaga, Ilaria Attili, Ester Del Signore, Carla Corvaja, Chiara Corti, Edoardo Crimini, Antonio Passaro and Filippo de Marinis
Curr. Oncol. 2023, 30(5), 5072-5092; https://doi.org/10.3390/curroncol30050384 - 16 May 2023
Cited by 8 | Viewed by 4713
Abstract
ALK translocation amounts to around 3–7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven [...] Read more.
ALK translocation amounts to around 3–7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
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16 pages, 1024 KiB  
Review
Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems
by George Doumat, Darine Daher, Morgan Bou Zerdan, Nasri Nasra, Hisham F. Bahmad, Monica Recine and Robert Poppiti
Curr. Oncol. 2023, 30(1), 704-719; https://doi.org/10.3390/curroncol30010055 - 5 Jan 2023
Cited by 20 | Viewed by 14064
Abstract
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of [...] Read more.
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of metastatic NSCLC remains low at approximately 3%. Common treatment approaches for NSCLC include surgery, multimodal chemotherapy, and concurrent radio and chemotherapy. NSCLC exhibits high rates of resistance to treatment, driven by its heterogeneity and the plasticity of cancer stem cells (CSCs). Drug repurposing offers a faster and cheaper way to develop new antineoplastic purposes for existing drugs, to help overcome therapy resistance. The decrease in time and funds needed stems from the availability of the pharmacokinetic and pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved drugs to be repurposed. This review provides a synopsis of the drug-repurposing approaches and mechanisms of action of potential candidate drugs used in treating NSCLC, including but not limited to antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials. Full article
(This article belongs to the Special Issue Tailored Treatments for Lung Cancer: From Early Diagnosis to Resistance Approaches in Advanced Stages)
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