Treatments for Non-Small Cell Lung Cancer: The Multiple Options for Precision Medicine

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 25404

Special Issue Editors

Department of Medical Oncology, Hopital Foch, 92150 Suresnes, France
Interests: lung cancer; gastro-intestinal cancer; phase 1 trials; immunotherapy; targeted therapy
Medical Oncology Department, University Hospital of Nantes, Nantes, France
Interests: lung cancer; clinical trials; tumor biology; targeted therapy; antibody-drug conjugates; immunotherapy; blood biomarkers

Special Issue Information

Dear Colleagues,

Lung cancer is one of the most aggressive cancers, with 1,796,1442 estimated deaths in 2020 worldwide. During the same time, 2,206,771 lung cancers were diagnosed, the majority of them with advanced disease. A multidisciplinary approach, supported by a broad therapeutic armamentarium including surgery, radiotherapy, and systemic treatments contributed to the recent advances that we have seen the past few years. Progress will also come through new techniques for the early detection of lung cancer (e.g., low-dose CT-scan). 

Overall, the discovery of new anticancer drugs was prompted in part by the identification of predictive biomarkers, but has also been fostered by innovative designs (master protocols, umbrella and basket trials) for early-phase clinical trials. We can affirm that lung cancers are one of the best examples of what precision medicine can do.

In this Special Issue, we wish to collect original research and review articles addressing all innovations dedicated to lung cancers, screening to detect early stages, treatments for localized or oligometastatic disease, and certainly biomarkers, immune checkpoint inhibitors, targeted therapies, and antibody–drug conjugates.

Prof. Dr. Jaafar Bennouna
Dr. Elvire Pons-Tostivint
Guest Editors

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Keywords

  • lung cancer
  • immunotherapy
  • targeted therapies
  • antibody–drug conjugates
  • biomarkers
  • screening
  • neo-adjuvant treatment
  • loco-regional treatments

Published Papers (8 papers)

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Editorial

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3 pages, 166 KiB  
Editorial
Treatments for Non-Small-Cell Lung Cancer: The Multiple Options for Precision Medicine
by Elvire Pons-Tostivint and Jaafar Bennouna
Curr. Oncol. 2022, 29(10), 7106-7108; https://doi.org/10.3390/curroncol29100558 - 28 Sep 2022
Cited by 1 | Viewed by 1582
Abstract
In recent years, advances in molecular diagnostics have transformed the management of advanced non-small-cell lung cancer (NSCLC), allowing for increasingly personalized approaches [...] Full article

Research

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11 pages, 1147 KiB  
Article
Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience
by Gabrielle Drevet, Théo Broussolle, Yanis Belaroussi, Lucie Duponchelle, Jean Michel Maury, Renaud Grima, Gualter Vaz, Clément Silvestre and François Tronc
Curr. Oncol. 2022, 29(5), 3061-3071; https://doi.org/10.3390/curroncol29050248 - 26 Apr 2022
Cited by 1 | Viewed by 1656
Abstract
For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications [...] Read more.
For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the “one step” group tended to have more perioperative complications whereas patients in the “two step” group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers. Full article
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14 pages, 1486 KiB  
Article
Contribution of the IdyllaTM System to Improving the Therapeutic Care of Patients with NSCLC through Early Screening of EGFR Mutations
by Constance Petiteau, Gwladys Robinet-Zimmermann, Adèle Riot, Marine Dorbeau, Nicolas Richard, Cécile Blanc-Fournier, Frédéric Bibeau, Simon Deshayes, Emmanuel Bergot, Radj Gervais and Guénaëlle Levallet
Curr. Oncol. 2021, 28(6), 4432-4445; https://doi.org/10.3390/curroncol28060376 - 03 Nov 2021
Cited by 12 | Viewed by 4532
Abstract
Epidermal growth factor receptor (EGFR) genotyping, a critical examen for the treatment decisions of patients with non-small cell lung cancer (NSCLC), is commonly assayed by next-generation sequencing (NGS), but this global approach takes time. To determine whether rapid EGFR genotyping tests by the [...] Read more.
Epidermal growth factor receptor (EGFR) genotyping, a critical examen for the treatment decisions of patients with non-small cell lung cancer (NSCLC), is commonly assayed by next-generation sequencing (NGS), but this global approach takes time. To determine whether rapid EGFR genotyping tests by the IdyllaTM system guides earlier therapy decisions, EGFR mutations were assayed by both the IdyllaTM system and NGS in 223 patients with NSCLC in a bicentric prospective study. IdyllaTM demonstrated agreement with the NGS method in 187/194 cases (96.4%) and recovered 20 of the 26 (77%) EGFR mutations detected using NGS. Regarding the seven missed EGFR mutations, five were not detected by the IdyllaTM system, one was assayed in a sample with insufficient tumoral cells, and the last was in a sample not validated by the IdyllaTM system (a bone metastasis). IdyllaTM did not detect any false positives. The average time between EGFR genotyping results from IdyllaTM and the NGS method was 9.2 ± 2.2 working days (wd) (12.6 ± 4.0 calendar days (cd)). Subsequently, based on the IdyllaTM method, the timeframe from tumor sampling to the initiation of EGFR-TKI was 7.7 ± 1.2 wd (11.4 ± 3.1 cd), while it was 20.3 ± 6.7 wd (27.2 ± 8.3 cd) with the NGS method (p < 0.001). We thus demonstrated here that the IdyllaTM system contributes to improving the therapeutic care of patients with NSCLC by the early screening of EGFR mutations. Full article
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8 pages, 527 KiB  
Article
Feasibility of Stereotactic Body Radiation Therapy on Unresectable Stage III NSCLC with Peripheral Primary Tumor: A Prospective Study (GFPC 01-14)
by Isabelle Martel-Lafay, Isabelle Monnet, Audrey Lardy-Cleaud, Serge Danhier, Naji Salem, Olivier Gallocher, Pierre Fournel, Christos Chouaid, Olivier Bylicki and the GFPC 01-14 Investigators
Curr. Oncol. 2021, 28(5), 3804-3811; https://doi.org/10.3390/curroncol28050324 - 28 Sep 2021
Cited by 3 | Viewed by 1740
Abstract
Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase [...] Read more.
Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase II trial in unresectable stage III NSCLC with peripheral primary tumor evaluated the feasibility of stereotactic body radiation therapy (SBRT) in peripheral tumor after concomitant radio-chemotherapy (RT-CT). Nineteen patients were included and analyzed (median age, 60.9 years; male, 78%; adenocarcinoma, 74%; median size of peripheral primary tumor, 19 mm). At 6 months, the disease control rate was 79% (15/19). SBRT toxicity was generally mild with one (5%) patient having grade 3 lung toxicity. Recruitment for this study was stopped prior to completion, firstly due to the approval of adjuvant durvalumab after RT-CT, which was not anticipated in the design, and secondly due to the small number of stage III NSCLC patients with a peripheral tumor that was accessible to SBRT. Nevertheless, the combination of RT-CT and SBRT appeared to be feasible and safe. Full article
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7 pages, 1045 KiB  
Article
Clinical Implications of “Atypia” on Biopsy: Possible Precursor to Lung Cancer?
by Denise Albano, Lee Ann Santore, Thomas Bilfinger, Melissa Feraca, Samantha Novotny and Barbara Nemesure
Curr. Oncol. 2021, 28(4), 2516-2522; https://doi.org/10.3390/curroncol28040228 - 06 Jul 2021
Cited by 2 | Viewed by 1990
Abstract
Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of [...] Read more.
Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. Methods: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. Results: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. Conclusion: Given the high conversion rate to cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this time period for patients diagnosed with atypia. Full article
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Review

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18 pages, 394 KiB  
Review
ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date
by Sébastien Gendarme, Olivier Bylicki, Christos Chouaid and Florian Guisier
Curr. Oncol. 2022, 29(2), 641-658; https://doi.org/10.3390/curroncol29020057 - 28 Jan 2022
Cited by 32 | Viewed by 6682
Abstract
The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9–2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It [...] Read more.
The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9–2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It has been demonstrated that ROS-1 is a true oncogenic driver, and tyrosine kinase inhibitors (TKIs) targeting ROS-1 can block tumor growth and provide clinical benefit for the patient. Since 2016, crizotinib has been the first-line reference therapy, with two-thirds of the patients’ tumors responding and progression-free survival lasting ~20 months. More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration. This review summarizes current knowledge on ROS-1 rearrangement in NSCLCs, including the mechanisms responsible for ROS-1 oncogenicity, epidemiology of ROS-1-positive tumors, methods for detecting rearrangement, phenotypic, histological, and molecular characteristics, and their therapeutic management. Much of this work is devoted to resistance mechanisms and the development of promising new molecules. Full article
10 pages, 249 KiB  
Review
Neoadjuvant Therapy in Lung Cancer: What Is Most Important: Objective Response Rate or Major Pathological Response?
by Xi Chen and Kewei Ma
Curr. Oncol. 2021, 28(5), 4129-4138; https://doi.org/10.3390/curroncol28050350 - 13 Oct 2021
Cited by 13 | Viewed by 2692
Abstract
Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, [...] Read more.
Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS. Full article

Other

5 pages, 1489 KiB  
Case Report
Is Elevation of Alkaline Phosphatase a Predictive Factor of Response to Alectinib in NSCLC?
by Walid Shalata, Alexander Yakobson, Rachel Steckbeck, Ashraf Abu Jama, Omar Abu Saleh and Abed Agbarya
Curr. Oncol. 2022, 29(1), 173-177; https://doi.org/10.3390/curroncol29010016 - 31 Dec 2021
Cited by 2 | Viewed by 2568
Abstract
In the following report, we describe a case of alkaline phosphatase (ALP) elevation occurring during treatment with alectinib (Alecensa™), which was administered for anaplastic lymphoma kinase (ALK) mutated metastatic non-small cell lung cancer (mNSCLC). A 51 year-old female with widespread metastatic disease exhibited [...] Read more.
In the following report, we describe a case of alkaline phosphatase (ALP) elevation occurring during treatment with alectinib (Alecensa™), which was administered for anaplastic lymphoma kinase (ALK) mutated metastatic non-small cell lung cancer (mNSCLC). A 51 year-old female with widespread metastatic disease exhibited a rapid and significant response within a very short period to alectinib therapy, accompanied by a rapid increase of ALP to more than six times the upper limit of normal (grade 3) ALP, decreasing to within normal limits within 3 weeks after initiation of therapy without any dose modification. Full article
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