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Cancers
Special Issues
Treatment-Related Predictive and Prognostic Factors in Lung Cancer
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Treatment-Related Predictive and Prognostic Factors in 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 January 2022) | Viewed by 16952

Special Issue Editors

Dr. Shinkichi Takamori

E-Mail Website
Guest Editor
Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan
Interests: lung cancer; immunotherapy; immune checkpoint inhibitor; surgery; sarcopenia; nutrition
Dr. Kazuki Takada

E-Mail Website
Guest Editor
Department of Thoracic Surgery, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-ku, Kitakyushu, Fukuoka, Japan
Interests: lung cancer; immunotherapy; PD-L1

Special Issue Information

Dear colleagues,

Lung cancer is a major cause of cancer death worldwide. Surgery is a standard therapy for patients with early-stage lung cancer. Prognostic factors for early-stage lung cancer patients are important for clinicians to determine the postoperative follow-up and to choose patients who should receive the adjuvant chemotherapy. In addition, there have been dramatic pharmacotherapy developments for non-small-cell lung cancer patients; in addition to chemotherapy, molecular-targeted drugs, such as epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors, have been adopted in the clinic. Recently, immunotherapy targeting programmed cell death 1 or programmed death-ligand 1 has gathered great attention as a novel pharmacological treatment. It is important to discover the factors that can be used to select patients who will benefit from such treatments. In this Special Issue, we welcome reports on the treatment-related predictive and prognostic factors in lung cancer.

Dr. Shinkichi Takamori
Dr. Kazuki Takada
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 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
  • predictive factor
  • prognostic factor
  • biomarker
  • immunotherapy
  • surgery

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Published Papers (5 papers)

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Research

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18 pages, 4764 KiB  
Article
Identification of Potential Prognostic and Predictive Immunological Biomarkers in Patients with Stage I and Stage III Non-Small Cell Lung Cancer (NSCLC): A Prospective Exploratory Study
by Rianne D. W. Vaes, Kobe Reynders, Jenny Sprooten, Kathleen T. Nevola, Kasper M. A. Rouschop, Marc Vooijs, Abhishek D. Garg, Maarten Lambrecht, Lizza E. L. Hendriks, Marijana Rucevic and Dirk De Ruysscher
Cancers 2021, 13(24), 6259; https://doi.org/10.3390/cancers13246259 - 13 Dec 2021
Cited by 23 | Viewed by 4738
Abstract
Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer [...] Read more.
Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy (n = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy (n = 18) were included. Blood samples were collected before (v1), during (v2), and after RT (v3). In patients with stage I NSCLC, CD244 (HR: 10.2, 95% CI: 1.8–57.4) was identified as a negative prognostic biomarker. In patients with stage III NSCLC, CR2 and IFNGR2 were identified as positive prognostic biomarkers (CR2, HR: 0.00, 95% CI: 0.00–0.12; IFNGR2, HR: 0.04, 95% CI: 0.00–0.46). In addition, analysis of the treatment-induced changes of circulating protein levels over time (Δv2/v3−v1) also identified CXCL10 and IL-10 as negative predictive biomarkers (CXCL10, HR: 3.86, 95% CI: 1.0–14.7; IL-10, HR: 16.92 (2.74–104.36)), although serum-induced interferon (IFN) response was a positive prognostic. In conclusion, we identified several circulating immunogenic proteins that are correlated with PFS in patients with stage I and stage III NSCLC before and during treatment. Full article
(This article belongs to the Special Issue Treatment-Related Predictive and Prognostic Factors in Lung Cancer)
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11 pages, 413 KiB  
Article
A Principal Component of Quality-of-Life Measures Is Associated with Survival: Validation in a Prospective Cohort of Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy
by Mark K. Farrugia, Han Yu, Gregory M. Videtic, Kevin L. Stephans, Sung Jun Ma, Adrienne Groman, Jeffrey A. Bogart, Jorge A. Gomez-Suescun and Anurag K. Singh
Cancers 2021, 13(18), 4542; https://doi.org/10.3390/cancers13184542 - 10 Sep 2021
Cited by 5 | Viewed by 1897
Abstract
The association between HRQOL metrics and survival has not been studied in early stage non-small-cell lung cancer (NSCLC) patients undergoing SBRT. The cohort was derived via a post-hoc analysis of a prospective randomized clinical trial examining definitive SBRT for peripheral, early-stage NSCLC with [...] Read more.
The association between HRQOL metrics and survival has not been studied in early stage non-small-cell lung cancer (NSCLC) patients undergoing SBRT. The cohort was derived via a post-hoc analysis of a prospective randomized clinical trial examining definitive SBRT for peripheral, early-stage NSCLC with a single or multi-fraction regimen. Patients completed HRQOL questionnaires prior to and 3 months after treatment. Using principal component analysis (PCA), changes in each HRQOL scale following treatment were reduced to two eigenvectors, PC1 and PC2. Cox regression was employed to analyze associations with survival-based endpoints. A total of 70 patients (median age 75.6 years; median follow-up 41.1 months) were studied. HRQOL and symptom comparisons at baseline and 3 months were vastly unchanged except for improved coughing (p = 0.02) and pain in the chest at 3 months (p = 0.033). PC1 and PC2 explained 21% and 9% of variance, respectively. When adjusting for covariates, PC1 was significantly correlated with progression-free (PFS) (HR = 0.78, 95% CI 0.67–0.92, p = 0.003) and overall survival (OS) (HR = 0.76, 95% CI 0.46, p = 0.041). Changes in global health status, functional HRQOL performance, and/or symptom burden as described by PC1 values are significantly associated with PFS and OS. The PC1 quartile may facilitate the identification of at-risk patients for additional interventions. Full article
(This article belongs to the Special Issue Treatment-Related Predictive and Prognostic Factors in Lung Cancer)
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20 pages, 1427 KiB  
Article
Elderly Patients with Locally Advanced and Unresectable Non-Small-Cell Lung Cancer May Benefit from Sequential Chemoradiotherapy
by Magdalena Zaborowska-Szmit, Marta Olszyna-Serementa, Dariusz M. Kowalski, Sebastian Szmit and Maciej Krzakowski
Cancers 2021, 13(18), 4534; https://doi.org/10.3390/cancers13184534 - 9 Sep 2021
Cited by 6 | Viewed by 2257
Abstract
Concurrent chemoradiotherapy is recommended for locally advanced and unresectable non-small-cell lung cancer (NSCLC), but radiotherapy alone may be used in patients that are ineligible for combined-modality therapy due to poor performance status or comorbidities, which may concern elderly patients in particular. The best [...] Read more.
Concurrent chemoradiotherapy is recommended for locally advanced and unresectable non-small-cell lung cancer (NSCLC), but radiotherapy alone may be used in patients that are ineligible for combined-modality therapy due to poor performance status or comorbidities, which may concern elderly patients in particular. The best candidates for sequential chemoradiotherapy remain undefined. The purpose of the study was to determine the importance of a patients’ age during qualification for sequential chemoradiotherapy. The study enrolled 196 patients. Older patients (age > 65years) more often had above the median Charlson Comorbidity Index CCI > 4 (p < 0.01) and Simplified Charlson Comorbidity Index SCCI > 8 (p = 0.03), and less frequently the optimal Karnofsky Performance Score KPS = 100 (p < 0.01). There were no significant differences in histological diagnoses, frequency of stage IIIA/IIIB, weight loss, or severity of smoking between older and younger patients. Older patients experienced complete response more often (p = 0.01) and distant metastases less frequently (p = 0.03). Univariable analysis revealed as significant for overall survival: age > 65years (HR = 0.66; p = 0.02), stage IIIA (HR = 0.68; p = 0.01), weight loss > 10% (HR = 1.61; p = 0.04). Multivariable analysis confirmed age > 65years as a uniquely favorable prognostic factor (HR = 0.54; p < 0.01) independent of lung cancer disease characteristics, KPS = 100, CCI > 4, SCCI > 8. Sequential chemoradiotherapy may be considered as favorable in elderly populations. Full article
(This article belongs to the Special Issue Treatment-Related Predictive and Prognostic Factors in Lung Cancer)
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14 pages, 424 KiB  
Article
Exceeding Radiation Dose to Volume Parameters for the Proximal Airways with Stereotactic Body Radiation Therapy Is More Likely for Ultracentral Lung Tumors and Associated with Worse Outcome
by Mark Farrugia, Sung Jun Ma, Mark Hennon, Chukwumere Nwogu, Elisabeth Dexter, Anthony Picone, Todd Demmy, Sai Yendamuri, Han Yu, Simon Fung-Kee-Fung, Jorge Gomez-Suescun, Anurag Singh and Harish Malhotra
Cancers 2021, 13(14), 3463; https://doi.org/10.3390/cancers13143463 - 10 Jul 2021
Cited by 16 | Viewed by 1968
Abstract
The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either [...] Read more.
The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010–April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways. Full article
(This article belongs to the Special Issue Treatment-Related Predictive and Prognostic Factors in Lung Cancer)
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Review

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13 pages, 296 KiB  
Review
Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review
by Alice Indini, Erika Rijavec and Francesco Grossi
Cancers 2021, 13(8), 1794; https://doi.org/10.3390/cancers13081794 - 9 Apr 2021
Cited by 38 | Viewed by 5170
Abstract
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to [...] Read more.
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care. Full article
(This article belongs to the Special Issue Treatment-Related Predictive and Prognostic Factors in Lung Cancer)
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