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Cancers
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Recent Advances in Non-Small Cell Lung Cancer
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Recent Advances in Non-Small Cell Lung Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 May 2018) | Viewed by 43897

Special Issue Editor

Prof. Dr. Siow Ming Lee

E-Mail Website
Guest Editor
Department of Oncology, University College Hospital, 250 Euston Road, London NW1 2PG, UK
Interests: lung cancer; HIV-related cancers; lymphoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Significant progress has been made in the field of targeted treatment, immunotherapy and cancer biology since our last Special Issue in 2015 on “Non-Small Cell Lung Cancer Therapies”. After decades of disappointment, cancer immunotherapy treatment has finally come of age, especially with the ability of anti-PD-1 and anti-PD-L1 agents to significantly improve treatment outcome as first- and second-line agents over standard chemotherapy treatment in advanced Non-Small Cell Lung Cancer (NSCLC). In addition, durvalumab, an anti-PD-L1 agent, when used as adjuvant treatment after chemo radiotherapy treatment in stage III NSCLC, was also found to improve outcomes. There were also significant developments seen in the field of targeted treatment. Newer generation targeted TKI agents, osimertinib and alectinib were significantly found to be superior compared to the first-generation agents, with a doubling of PFS outcome. They also have substantial clinical activity against brain metastases. In the field of cancer biology, the TRACERx consortium based in the UK published the first results of their 100 recruited patients which have provided new insights how lung cancer evolves with implications for possible new targeted and immunotherapy for the future.

This Special Issue aims to summarize and update researchers and clinicians as to the remarkable progress made in the field of targeted therapy, immunotherapy and cancer biology made recently for lung cancer.

Prof. Dr. Siow Ming Lee
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. 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

  • NSCLC
  • immunotherapy
  • EGFR TKIs
  • ALK inhibitors
  • tumor heterogeneity
  • circulating tumor DNA

Published Papers (8 papers)

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Research

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11 pages, 2222 KiB  
Article
Stereotactic Body Radiation Therapy for Patients with Pulmonary Interstitial Change: High Incidence of Fatal Radiation Pneumonitis in a Retrospective Multi-Institutional Study
by Hiroshi Onishi, Hideomi Yamashita, Yoshiyuki Shioyama, Yasuo Matsumoto, Kenji Takayama, Yukinori Matsuo, Akifumi Miyakawa, Haruo Matsushita, Masahiko Aoki, Keiji Nihei, Tomoki Kimura, Hiromichi Ishiyama, Naoya Murakami, Kensei Nakata, Atsuya Takeda, Takashi Uno, Takuma Nomiya, Tuyoshi Takanaka, Yuji Seo, Takafumi Komiyama, Kan Marino, Shinichi Aoki, Ryo Saito, Masayuki Araya, Yoshiyasu Maehata, Licht Tominaga and Kengo Kuriyamaadd Show full author list remove Hide full author list
Cancers 2018, 10(8), 257; https://doi.org/10.3390/cancers10080257 - 02 Aug 2018
Cited by 29 | Viewed by 3690
Abstract
Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of [...] Read more.
Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of SBRT for stage I non-small cell lung cancer in patients with PIC. A total of 242 patients are included in this study (88% male). The median age is 77 years (range, 55–92 years). A total dose of 40–70 Gy is administered in 4 to 10 fractions during a 4-to-25 day period. One, two, and three-year overall survival (OS) rates are 82.1%, 57.1%, and 42.6%, respectively. Fatal RP is identified in 6.9% of all patients. The percent vital capacity <70%, mean percentage normal lung volume receiving more than 20 Gy (>10%), performance status of 2–4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (<70%) are associated with worse prognoses for OS. Our results indicate that fatal RP frequently occurs after SBRT for stage I lung cancer in patients with PIC. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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Review

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17 pages, 255 KiB  
Review
Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer
by Yosuke Miura and Noriaki Sunaga
Cancers 2018, 10(8), 245; https://doi.org/10.3390/cancers10080245 - 27 Jul 2018
Cited by 32 | Viewed by 3938
Abstract
The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly [...] Read more.
The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
22 pages, 279 KiB  
Review
A Review of Recent Advances in the Treatment of Elderly and Poor Performance NSCLC
by Juliet A. Carmichael, Daisy Wing-san Mak and Mary O’Brien
Cancers 2018, 10(7), 236; https://doi.org/10.3390/cancers10070236 - 18 Jul 2018
Cited by 35 | Viewed by 4602
Abstract
Until recently, chemotherapy has remained the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC). Excellent responses have been observed with immune-checkpoint inhibitors, and targeted treatments for those tumours with actionable mutations, resulting in a paradigm shift [...] Read more.
Until recently, chemotherapy has remained the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC). Excellent responses have been observed with immune-checkpoint inhibitors, and targeted treatments for those tumours with actionable mutations, resulting in a paradigm shift in the treatment approach for these patients. Elderly patients and those with poor performance status (PS), such as Eastern Cooperative Oncology Group (ECOG) 2, have historically been excluded from clinical trials due to poor outcomes. There is therefore a lack of data to define the optimal treatment strategy for these patients. Due to improved tolerability of novel therapies, inclusion of these patients in clinical trials has increased, and sub-group analyses have identified many treatments demonstrating potential activity. Here, we summarise key recent advances in the treatment of NSCLC, specifically evaluating their efficacy and tolerability in these patient cohorts. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
17 pages, 1665 KiB  
Review
Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance
by Zachary Schrank, Gagan Chhabra, Leo Lin, Tsatsral Iderzorig, Chike Osude, Nabiha Khan, Adijan Kuckovic, Sanjana Singh, Rachel J. Miller and Neelu Puri
Cancers 2018, 10(7), 224; https://doi.org/10.3390/cancers10070224 - 04 Jul 2018
Cited by 88 | Viewed by 11300
Abstract
Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted [...] Read more.
Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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11 pages, 1264 KiB  
Review
Measuring Surgery Outcomes of Lung Cancer Patients with Concomitant Pulmonary Fibrosis: A Review of the Literature
by Taichiro Goto
Cancers 2018, 10(7), 223; https://doi.org/10.3390/cancers10070223 - 04 Jul 2018
Cited by 23 | Viewed by 3308
Abstract
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonias, often progresses to restrictive respiratory disturbance and mortality, typically within 10 years. IPF frequently coexists with lung cancer, and the combination of these two disease entities is far more difficult to [...] Read more.
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonias, often progresses to restrictive respiratory disturbance and mortality, typically within 10 years. IPF frequently coexists with lung cancer, and the combination of these two disease entities is far more difficult to treat than either lung cancer or IPF alone. In particular, surgery for lung cancer with IPF in the background increases postoperative morbidity and mortality by exacerbating pre-existing IPF, i.e., acute exacerbation of IPF (AEIPF). Furthermore, the long-term outcome after lung cancer surgery is considerably worsened by the presence of IPF. We present here a comprehensive review of AEIPF and the long-term outcomes after surgery. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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16 pages, 584 KiB  
Review
Radiation Pneumonitis: Old Problem, New Tricks
by Varsha Jain and Abigail T. Berman
Cancers 2018, 10(7), 222; https://doi.org/10.3390/cancers10070222 - 03 Jul 2018
Cited by 102 | Viewed by 8381
Abstract
Radiation therapy is a major treatment modality for management of non-small cell lung cancer. Radiation pneumonitis is a dose limiting toxicity of radiotherapy, affecting its therapeutic ratio. This review presents patient and treatment related factors associated with the development of radiation pneumonitis. Research [...] Read more.
Radiation therapy is a major treatment modality for management of non-small cell lung cancer. Radiation pneumonitis is a dose limiting toxicity of radiotherapy, affecting its therapeutic ratio. This review presents patient and treatment related factors associated with the development of radiation pneumonitis. Research focusing on reducing the incidence of radiation pneumonitis by using information about lung ventilation, imaging-based biomarkers as well as normal tissue complication models is discussed. Recent advances in our understanding of molecular mechanisms underlying lung injury has led to the development of several targeted interventions, which are also explored in this review. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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16 pages, 1509 KiB  
Review
Understanding Intratumor Heterogeneity and Evolution in NSCLC and Potential New Therapeutic Approach
by Taichiro Goto, Yosuke Hirotsu, Kenji Amemiya, Hitoshi Mochizuki and Masao Omata
Cancers 2018, 10(7), 212; https://doi.org/10.3390/cancers10070212 - 22 Jun 2018
Cited by 16 | Viewed by 4987
Abstract
Advances in innovative technology, including next-generation sequencing, have allowed comprehensive genomic analysis and the elucidation of the genomic aspect of intratumor heterogeneity (ITH). Moreover, models of the evolution of the cancer genome have been proposed by integrating these analyses. Cancer has been considered [...] Read more.
Advances in innovative technology, including next-generation sequencing, have allowed comprehensive genomic analysis and the elucidation of the genomic aspect of intratumor heterogeneity (ITH). Moreover, models of the evolution of the cancer genome have been proposed by integrating these analyses. Cancer has been considered to accumulate genetic abnormalities for clonal evolution in time and space, and these evolutionary patterns vary depending on the organs of primary sites. Selection pressure is an important determinant of such evolutionary patterns. With weak selection pressure, more diverse clones coexist, and heterogeneity increases. Heterogeneity is maximized when there is no selection pressure; in other words, neutral evolution occurs. Some types of cancer such as lung cancer evolve in conditions that have maintained close to neutral evolution and produce diverse variants. This ITH is a key factor contributing to the lethal outcome of cancer, therapeutic failure, and drug resistance. This factor reaffirms the complexity and subtle adaptability of cancer. It is expected that further understanding of ITH and cancer genome evolution will facilitate the development of new therapeutic strategies to overcome ITH. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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Other

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8 pages, 202 KiB  
Perspective
Surgical Resection Versus Stereotactic Body Radiation Therapy for Stage I NSCLC: Can Randomized Trials Provide the Solution?
by Melanie P. Subramanian and Bryan F. Meyers
Cancers 2018, 10(9), 310; https://doi.org/10.3390/cancers10090310 - 04 Sep 2018
Cited by 18 | Viewed by 2635
Abstract
Surgical resection has traditionally been considered the standard of care for patients with stage I non-small cell lung cancer (NSCLC). With the introduction of stereotactic radiation body therapy (SBRT), there is now a viable option for medically inoperable patients with stage I NSCLC. [...] Read more.
Surgical resection has traditionally been considered the standard of care for patients with stage I non-small cell lung cancer (NSCLC). With the introduction of stereotactic radiation body therapy (SBRT), there is now a viable option for medically inoperable patients with stage I NSCLC. The effectiveness of SBRT in patients with stage I disease but at elevated surgical risk is unknown. Multiple randomized controlled trials (RCTs) have been attempted to compare surgical resection and SBRT in this population, but have been aborted due to poor patient enrollment. Despite these failures, there still remains a push for more RCTs. In this commentary, we review the challenges that RCTs face in their ability to appropriately compare these two therapies. Full article
(This article belongs to the Special Issue Recent Advances in Non-Small Cell Lung Cancer)
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