Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Content
    • Current
    • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

Coexistence of Emphysema With Non-small-cell Lung Cancer Predicts the Therapeutic Efficacy of Immune Checkpoint Inhibitors

YUSUKE TAKAYAMA, TAKASHI NAKAMURA, YUKI FUKUSHIRO, SHOHEI MISHIMA, KEN MASUDA and HIROYASU SHODA
In Vivo January 2021, 35 (1) 467-474; DOI: https://doi.org/10.21873/invivo.12280
YUSUKE TAKAYAMA
1Department of Respiratory Medicine, Hiroshima Citizens Hospital, Hiroshima, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: highmt@city-hosp.naka.hiroshima.jp
TAKASHI NAKAMURA
2Department of Respiratory Medicine, Hiroshima General Hospital, Hatsukaichi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YUKI FUKUSHIRO
1Department of Respiratory Medicine, Hiroshima Citizens Hospital, Hiroshima, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHOHEI MISHIMA
1Department of Respiratory Medicine, Hiroshima Citizens Hospital, Hiroshima, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KEN MASUDA
1Department of Respiratory Medicine, Hiroshima Citizens Hospital, Hiroshima, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HIROYASU SHODA
1Department of Respiratory Medicine, Hiroshima Citizens Hospital, Hiroshima, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: Chronic obstructive pulmonary disease coexisting with non-small-cell lung cancer (NSCLC) was reported to be associated with a longer progression-free survival (PFS) in patients treated with immune checkpoint inhibitors (ICIs). In the present study, we investigated the impact of emphysematous change on the treatment response to ICIs in patients with NSCLC. Patients and Methods: A total of 153 patients with advanced NSCLC who received ICIs (nivolumab, pembrolizumab, or atezolizumab) at our hospital from January 2016 to May 2019 were retrospectively enrolled. Results: According to the Goddard scoring system, 71 (46.4%) patients were classified as having emphysema and 82 (53.6%) as having no emphysema. Multivariate analysis showed that a good performance status and coexisting emphysema (hazard ratio=0.49; 95% confidence intervaI=0.28-0.84; p=0.010) were independent predictors of a better PFS. Conclusion: Recognizing emphysema coexisting with NSCLC may help predict the therapeutic efficacy of ICIs in such patients.

  • non-small-cell lung cancer
  • immune checkpoint inhibitors
  • emphysema
  • Goddard scoring system

Lung cancer is a major cause of cancer-related death worldwide (1). Although immune checkpoint inhibitors (ICIs) are an approved treatment for advanced non-small-cell lung cancer (NSCLC), primary resistance to ICIs is common (2-4). Expression of programmed cell death ligand 1 (PD-L1) in tumor cells (5), tumor mutation burden (6), and the gene-expression signature of inflammation (7) have emerged as potential predictive biomarkers of the efficacy of inhibitors of the programmed cell death 1 (PD1) axis. However, these biomarkers are insufficient for evaluating a patient’s response to ICIs.

Cigarette smoking is the most common risk factor for lung cancer and chronic obstructive pulmonary disease (COPD) (8). COPD is considered an important risk factor for lung cancer (9) and has been shown to worsen the survival of patients with lung cancer (10). Previous studies revealed that current or former smokers with NSCLC are more likely to respond to ICI therapy (2, 3). Recently, it was reported that the presence of COPD was associated with longer progression-free survival (PFS) in patients with NSCLC treated with ICIs (11-13).

COPD is a heterogeneous syndrome consisting of emphysema, chronic bronchitis, and small airway disease. Emphysema is characterized by abnormal and permanent enlargement of airspaces distal from terminal bronchioles, which can be visualized by computed tomography (CT). To the best of our knowledge, no previous study has evaluated the prognostic significance of pulmonary emphysema in patients with NSCLC treated with ICIs. In the present study, we investigated the impact of emphysematous change on the treatment response to ICIs in patients with NSCLC.

Patients and Methods

Patient population. Patients with advanced NSCLC who received ICIs (nivolumab, pembrolizumab, or atezolizumab) at Hiroshima City Hiroshima Citizens Hospital from January 2016 to May 2019 were retrospectively enrolled in this study. The characteristics and clinical data of the patients before administration of single-agent anti-PD1/PD-L1 were obtained. This study was approved by the Ethical Review Board of Hiroshima City Hiroshima Citizens Hospital (approval number No. 2019-62, July 11, 2019). Patient approval or the requirement for informed consent was waived because this study was performed during routine clinical practice.

Assessments and data collection. We investigated the presence of emphysema on CT scans with a 1-5 mm slice thickness. The CT images at the time of diagnosis were independently evaluated by two pulmonologists who were blinded to the clinical data. The kappa coefficient was used to assess the degree of interrater agreement on specific comparisons. Final decisions were agreed upon by consensus between the two pulmonologists. The presence of emphysema was scored using the Goddard scoring system (14). Briefly, emphysema was scored visually in the bilateral upper, middle, and lower lung fields. The score for each of the six dimensions was calculated according to the percentage of low-attenuation area in each lung field as follows: score 0, <5%; score 1, ≥5%-<25%; score 2, ≥25%-<50%; score 3, ≥50%-<75%; and score 4, ≥75%. In the present study, we defined a total score of more than 8 points as the presence of emphysema. Demographic data, including age, sex, smoking history, and Eastern Cooperative Oncology Group (ECOG) performance status, were collected from electronic medical records.

Study design. PFS was measured from the date of starting ICIs to the date of initial disease progression, death from any cause, or the date last known to be alive without disease progression. Overall survival (OS) was measured from the date of starting ICIs to death from any cause or the date last known to be alive. The objective response rate and disease control rate were evaluated using the Response Evaluation Criteria for Solid Tumors, version 1.1 (15). Immune-related AEs (irAEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0 (16).

Statistical analysis. Data are presented as means±standard deviation or number (%) of patients. Differences between groups were assessed by Student’s t-test and Fisher’s exact test. The Kaplan-Meier method was used to estimate PFS and OS rates, and the log-rank test was used to determine the differences in survival rates. Cox proportional hazards models were used for univariate and multivariate analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). All statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria); EZR is a modified version of R commander designed to add frequently used statistical functions (17). p-Values of less than 0.05 were considered significant.

Results

Patient characteristics. Of 153 patients with advanced NSCLC, 72 underwent nivolumab monotherapy, 63 underwent pembrolizumab monotherapy, and 18 underwent atezolizumab monotherapy. This was the first exposure to ICIs for all patients. According to the Goddard scoring system, 71 (46.4%) patients were classified as having emphysema and 82 (53.6%) as having no emphysema (Table I). The kappa coefficient of diagnostic agreement was 0.81. No significant difference in age, body mass index, ECOG performance status, or lines of treatment was observed between the two groups. Patients with emphysema had a male predominance and a greater number of tobacco smoking pack-years (p<0.001) compared with patients without emphysema. In addition, they also had a higher prevalence of squamous-cell carcinoma. PD-L1 expression was evaluated in 94 patients, and there was no difference in the PD-L1 tumor proportion score (TPS) between patients with and those without emphysema. Among the patients without emphysema, 17 were positive for mutation of epidermal growth factor receptor (EGFR) gene, and one was positive for anaplastic lymphoma kinase (ALK) gene translocation.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Characteristics of the study patients (N=153).

ICI treatment outcomes of NSCLC in patients with and those without emphysema. The objective response rate was significantly higher in patients with than in those without emphysema (32.4% versus 15.9%; p=0.022), and the disease control rate was also higher in patients with emphysema (67.6% vs. 46.3%; p=0.012) (Table II). In addition, patients with emphysema had a better PFS (median 6.6 versus 2.7 months; HR=0.47, 95% CI=0.32-0.69; p<0.001) and OS (median 19.5 versus 11.6 months; HR=0.58, 95% CI=0.36-0.94; p=0.03) compared with patients without emphysema (Figure 1A). We next examined the impact of emphysema on PFS in the patients with a history of smoking. In the overall cohort, tobacco exposure of 30 pack-years or more was associated with a better PFS (median 4.9 versus 2.7 months, HR=0.58, 95% CI= 0.40-0.86; p=0.006). Notably, patients with emphysema had a better PFS compared with those without, even among those with ≥30 pack-years (median 9.3 versus 3.8 months, HR=0.49, 95% CI=0.30-0.80; p=0.004), although no significant difference in OS was observed (Figure 1B). Multivariate analyses showed that a good ECOG performance status and coexisting emphysema (HR=0.49, 95% CI=0.28-0.84; p=0.010) were independent predictors of better PFS (Table III); however, coexisting emphysema did not remain a statistically significant predictor of OS in the multivariate analysis (Table IV).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Response rates of patients with and without emphysema.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Kaplan-Meier curves of progression-free survival (PFS; left) and overall survival (OS; right) in patients with (+) and those without (−) emphysema in the overall cohort (N=152) (A) and in patients with ≥30 pack-years (N=95) (B).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Univariate and multivariate analyses for progression-free survival.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

Univariate and multivariate analyses for overall survival.

Outcome of ICI treatment of patients with NSCLC according to coexisting emphysema and PD-L1 expression. We examined the prognostic significance of coexisting pulmonary emphysema according to PD-L1 expression. The PD-L1 expression status was evaluated in 94 patients. As expected, PFS tended to be longer in patients with PD-L1 TPS≥50% compared with TPS<50% (median 6.0 versus 3.4 months, HR=0.68, 95% CI=0.42-1.12; p=0.128) (Figure 2A). Moreover, patients with both high PD-L1 expression and coexisting emphysema tended to have a longer PFS than that of patients with only one of these factors (Figure 2B).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Kaplan-Meier curves of progression-free survival (PFS) according to the level of programmed cell death ligand 1 (PD-L1) expression (N=94) (A) and PD-L1 expression with/without coexisting emphysema (B). The median PFS (95% confidence intervaI) was 7.1 (4.1–not reached) months in patients with a PD-L1 tumor proportion score (TPS) ≥50% with emphysema (N=29), 4.2 (1.9-9.3) months in patients with a PD-L1 TPS<50% with emphysema (N=25), 3.8 (1.6-6.6) months in patients with PD-L1 TPS≥50% without emphysema (N=21), and 4.1 (0.8-5.8) months in patients with PD-L1 TPS<50% without emphysema (N=19) (B).

Analysis of immune-related adverse events. The irAEs that developed are summarized in Table V. irAEs of any grade were observed in 56 patients (36.6%) and grade 3/4 irAEs in 16 patients (10.5%). However, no difference in the irAE rates was observed between patients with emphysema and those without.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table V.

Immune-related adverse events (irAEs) in patients with and without emphysema.

Discussion

The present study showed that emphysema coexisting with NSCLC was associated with a longer PFS and OS and a higher objective response rate in patients treated with ICIs. In addition, the survival benefit of coexisting emphysema in patients with NSCLC treated with ICIs persisted even after adjustment for all relevant covariates. Moreover, no difference in the rates of irAEs was observed between patients with and those without emphysema.

To our knowledge, this is the first study to show an association between coexisting emphysema and an improved response to ICIs. We used a visual CT scoring system to assess the presence of emphysema. Previous studies have reported that visual CT scores are correlated with pathological findings (18) and respiratory functions (14, 19). Notably, the Goddard semiquantitative scoring system can be performed easily and quickly (14). Moreover, almost all patients with lung cancer undergo chest CT scans for diagnosis and staging during the initial evaluation. Thus, it may be clinically useful to identify emphysema using visual CT scores, such as the Goddard scoring system, in predicting the efficacy of ICIs in patients with NSCLC.

The mechanism underlying the better outcome of emphysematous NSCLC patients treated with ICIs remains unclear. However, a few mechanisms underlying an improved outcome in patients with COPD treated with ICIs have been proposed. Firstly, CD4+ T-cell differentiation is skewed toward the interferon-γ-producing T-helper type 1 phenotype in the setting of COPD (20). Th1 immunity in a subset of patients with COPD may be responsible for a better ICI treatment outcome because the existence of an interferon-γ-related gene signature was recently shown to predict a favorable anti-PD1 treatment response (21). Secondly, it was reported that patients with NSCLC with COPD displayed tumor-infiltrating T-lymphocyte exhaustion, identified by enhanced immunostaining of PD1 and T-cell immunoglobulin mucin 3 in CD8+ cells (12, 20). Thus, immune activity was suggested to be enhanced in patients with NSCLC with COPD. We speculate that high ICI efficacy in NSCLC is obtained in patients with emphysema by the same mechanism as in patients with COPD.

Current or former smokers with NSCLC are more likely to respond to ICI therapy (2, 3), and similar results were found in the present study. Notably, PFS was better in patients with emphysema than in those without even among the patients with a smoking history of 30 or more pack-years. In addition, multivariate analysis showed that emphysema had a stronger association with PFS than did smoking status. A previous study reported that COPD and tobacco smoking have a synergistic impact on CD8+ tumor-infiltrating T-lymphocyte exhaustion and on the prognostic value of immune cells (12), supporting our results.

It has been reported that patients with high PD-L1 expression in tumor cells are more likely to respond to treatment with ICIs (2, 3), and similar results were found in the present study. The relationship between PD-L1 expression and emphysema remains unclear, even though some studies (22, 23) have evaluated this. In the present study, there was no difference in PD-L1 expression between patients with and those without emphysema. Therefore, we speculate that the PD-L1 expression status and emphysema are independent prognostic factors for PFS in patients with NSCLC treated with ICIs. In our study, patients with both high PD-L1 expression and emphysema tended to have a longer PFS compared with patients with only one of these factors. Treatment with ICIs may have a favorable antitumor effect in these patients.

In the present study, no difference in the rate of irAEs was observed between patients with emphysema and those without. Previous studies indicated that the presence of emphysema is not associated with the occurrence of ICI-induced interstitial lung disease (24, 25). Thus, the presence of emphysema is likely not a factor hindering treatment with ICIs.

The present study has several limitations. Firstly, this was a retrospective, single-center study with a small sample size. Secondly, ICIs have shown minimal therapeutic benefit in patients with EGFR mutations (2, 4, 26). In the present study, a higher proportion of the patients without emphysema had EGFR mutations. However, the driver mutation status, such as EGFR gene mutations and ALK gene translocation, was not associated with PFS in the multivariate analysis. Thirdly, we used the Goddard scoring system to assess the existence of emphysema. Although this method is simple and can be performed quickly, visual inspection is thought to be affected by interobserver and intraobserver variabilities. Therefore, additional detailed examinations using quantitative standardized assessments with computer algorithms are required to assess the existence of emphysema.

Conclusion

In this study, emphysema coexisting with NSCLC was associated with longer PFS and OS and a higher response rate to ICI treatment. In addition, emphysema had a stronger association with PFS than did smoking status. Therefore, recognizing coexisting emphysema may help predict the therapeutic efficacy of ICIs in patients with NSCLC.

Footnotes

  • Authors’ Contributions

    Y.T and H.S. devised the project and main conceptual ideas. Y.T and T.N. performed the retrospective chart review, carried out radiological measurements, and conducted the statistical analysis. Y.F, S.M, and K.M. supervised the project. All Authors gave final approval for publication.

  • This article is freely accessible online.

  • Conflict of Interest

    The Authors declare no conflicts of interest associated with this study.

  • Received September 30, 2020.
  • Revision received October 13, 2020.
  • Accepted October 14, 2020.
  • Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Torre LA,
    2. Bray F,
    3. Siegel RL,
    4. Ferlay J,
    5. Lortet-Tieulent J and
    6. Jemal A
    : Global cancer statistics. CA Cancer J Clin 65(2): 87-108, 2015. PMID: 25651787. DOI: 10.3322/caac.21262
    OpenUrlCrossRefPubMed
  2. ↵
    1. Borghaei H,
    2. Paz-Ares L,
    3. Horn L,
    4. Spigel DR,
    5. Steins M,
    6. Ready NE,
    7. Chow LQ,
    8. Vokes EE,
    9. Felip E,
    10. Holgado E,
    11. Barlesi F,
    12. Kohlhäufl M,
    13. Arrieta O,
    14. Burgio MA,
    15. Fayette J,
    16. Lena H,
    17. Poddubskaya E,
    18. Gerber DE,
    19. Gettinger SN,
    20. Rudin CM,
    21. Rizvi N,
    22. Crinò L,
    23. Blumenschein GR Jr.,
    24. Antonia SJ,
    25. Dorange C,
    26. Harbison CT,
    27. Graf Finckenstein F and
    28. Brahmer JR
    : Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17): 1627-39, 2015. PMID: 26412456. DOI: 10.1056/NEJMoa1507643
    OpenUrlCrossRefPubMed
  3. ↵
    1. Reck M,
    2. Rodríguez-Abreu D,
    3. Robinson AG,
    4. Hui R,
    5. Csőszi T,
    6. Fülöp A,
    7. Gottfried M,
    8. Peled N,
    9. Tafreshi A,
    10. Cuffe S,
    11. O’Brien M,
    12. Rao S,
    13. Hotta K,
    14. Leiby MA,
    15. Lubiniecki GM,
    16. Shentu Y,
    17. Rangwala R and
    18. Brahmer JR
    : Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19): 1823-1833, 2016. PMID: 27718847. DOI: 10.1056/NEJMoa1606774
    OpenUrlCrossRefPubMed
  4. ↵
    1. Rittmeyer A,
    2. Barlesi F,
    3. Waterkamp D,
    4. Park K,
    5. Ciardiello F,
    6. von Pawel J,
    7. Gadgeel SM,
    8. Hida T,
    9. Kowalski DM,
    10. Dols MC,
    11. Cortinovis DL,
    12. Leach J,
    13. Polikoff J,
    14. Barrios C,
    15. Kabbinavar F,
    16. Frontera OA,
    17. De Marinis F,
    18. Turna H,
    19. Lee JS,
    20. Ballinger M,
    21. Kowanetz M,
    22. He P,
    23. Chen DS,
    24. Sandler A and
    25. Gandara DR
    : Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomized controlled trial. Lancet 389(10066): 255-265, 2017. PMID: 27979383. DOI: 10.1016/S0140-6736(16)32517-X
    OpenUrlCrossRefPubMed
  5. ↵
    1. Patel SP and
    2. Kurzrock R
    : PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 14(4): 847-856, 2015. PMID: 25695955. DOI: 10.1158/1535-7163.MCT-14-0983
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Rizvi NA,
    2. Hellmann MD,
    3. Snyder A,
    4. Kvistborg P,
    5. Makarov V,
    6. Havel JJ,
    7. Lee W,
    8. Yuan J,
    9. Wong P,
    10. Ho TS,
    11. Miller ML,
    12. Rekhtman N,
    13. Moreira AL,
    14. Ibrahim F,
    15. Bruggeman C,
    16. Gasmi B,
    17. Zappasodi R,
    18. Maeda Y,
    19. Sander C,
    20. Garon EB,
    21. Merghoub T,
    22. Wolchok JD,
    23. Schumacher TN and
    24. Chan TA
    : Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348(6230): 124-128, 2015. PMID: 25765070. DOI: 10.1126/science.aaa1348
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Prat A,
    2. Navarro A,
    3. Paré L,
    4. Reguart N,
    5. Galván P,
    6. Pascual T,
    7. Martínez A,
    8. Nuciforo P,
    9. Comerma L,
    10. Alos L,
    11. Pardo N,
    12. Cedrés S,
    13. Fan C,
    14. Parker JS,
    15. Gaba L,
    16. Victoria I,
    17. Viñolas N,
    18. Vivancos A,
    19. Arance A and
    20. Felip E
    : Immune-related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma, head and neck squamous cell carcinoma, and melanoma. Cancer Res 77(13): 3540-3550, 2017. PMID: 28487385. DOI: 10.1158/0008-5472.CAN-16-3556
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Lim SS,
    2. Vos T,
    3. Flaxman AD,
    4. Danaei G,
    5. Shibuya K,
    6. Adair-Rohani H,
    7. Amann M,
    8. Anderson HR,
    9. Andrews KG,
    10. Aryee M,
    11. Atkinson C,
    12. Bacchus LJ,
    13. Bahalim AN,
    14. Balakrishnan K,
    15. Balmes J,
    16. Barker-Collo S,
    17. Baxter A,
    18. Bell ML,
    19. Blore JD,
    20. Blyth F,
    21. Bonner C,
    22. Borges G,
    23. Bourne R,
    24. Boussinesq M,
    25. Brauer M,
    26. Brooks P,
    27. Bruce NG,
    28. Brunekreef B,
    29. Bryan-Hancock C,
    30. Bucello C,
    31. Buchbinder R,
    32. Bull F,
    33. Burnett RT,
    34. Byers TE,
    35. Calabria B,
    36. Carapetis J,
    37. Carnahan E,
    38. Chafe Z,
    39. Charlson F,
    40. Chen H,
    41. Chen JS,
    42. Cheng AT,
    43. Child JC,
    44. Cohen A,
    45. Colson KE,
    46. Cowie BC,
    47. Darby S,
    48. Darling S,
    49. Davis A,
    50. Degenhardt L,
    51. Dentener F,
    52. Des Jarlais DC,
    53. Devries K,
    54. Dherani M,
    55. Ding EL,
    56. Dorsey ER,
    57. Driscoll T,
    58. Edmond K,
    59. Ali SE,
    60. Engell RE,
    61. Erwin PJ,
    62. Fahimi S,
    63. Falder G,
    64. Farzadfar F,
    65. Ferrari A,
    66. Finucane MM,
    67. Flaxman S,
    68. Fowkes FG,
    69. Freedman G,
    70. Freeman MK,
    71. Gakidou E,
    72. Ghosh S,
    73. Giovannucci E,
    74. Gmel G,
    75. Graham K,
    76. Grainger R,
    77. Grant B,
    78. Gunnell D,
    79. Gutierrez HR,
    80. Hall W,
    81. Hoek HW,
    82. Hogan A,
    83. Hosgood HD 3rd.,
    84. Hoy D,
    85. Hu H,
    86. Hubbell BJ,
    87. Hutchings SJ,
    88. Ibeanusi SE,
    89. Jacklyn GL,
    90. Jasrasaria R,
    91. Jonas JB,
    92. Kan H,
    93. Kanis JA,
    94. Kassebaum N,
    95. Kawakami N,
    96. Khang YH,
    97. Khatibzadeh S,
    98. Khoo JP,
    99. Kok C,
    100. Laden F,
    101. Lalloo R,
    102. Lan Q,
    103. Lathlean T,
    104. Leasher JL,
    105. Leigh J,
    106. Li Y,
    107. Lin JK,
    108. Lipshultz SE,
    109. London S,
    110. Lozano R,
    111. Lu Y,
    112. Mak J,
    113. Malekzadeh R,
    114. Mallinger L,
    115. Marcenes W,
    116. March L,
    117. Marks R,
    118. Martin R,
    119. McGale P,
    120. McGrath J,
    121. Mehta S,
    122. Mensah GA,
    123. Merriman TR,
    124. Micha R,
    125. Michaud C,
    126. Mishra V,
    127. Mohd Hanafiah K,
    128. Mokdad AA,
    129. Morawska L,
    130. Mozaffarian D,
    131. Murphy T,
    132. Naghavi M,
    133. Neal B,
    134. Nelson PK,
    135. Nolla JM,
    136. Norman R,
    137. Olives C,
    138. Omer SB,
    139. Orchard J,
    140. Osborne R,
    141. Ostro B,
    142. Page A,
    143. Pandey KD,
    144. Parry CD,
    145. Passmore E,
    146. Patra J,
    147. Pearce N,
    148. Pelizzari PM,
    149. Petzold M,
    150. Phillips MR,
    151. Pope D,
    152. Pope CA 3rd.,
    153. Powles J,
    154. Rao M,
    155. Razavi H,
    156. Rehfuess EA,
    157. Rehm JT,
    158. Ritz B,
    159. Rivara FP,
    160. Roberts T,
    161. Robinson C,
    162. Rodriguez-Portales JA,
    163. Romieu I,
    164. Room R,
    165. Rosenfeld LC,
    166. Roy A,
    167. Rushton L,
    168. Salomon JA,
    169. Sampson U,
    170. Sanchez-Riera L,
    171. Sanman E,
    172. Sapkota A,
    173. Seedat S,
    174. Shi P,
    175. Shield K,
    176. Shivakoti R,
    177. Singh GM,
    178. Sleet DA,
    179. Smith E,
    180. Smith KR,
    181. Stapelberg NJ,
    182. Steenland K,
    183. Stöckl H,
    184. Stovner LJ,
    185. Straif K,
    186. Straney L,
    187. Thurston GD,
    188. Tran JH,
    189. Van Dingenen R,
    190. van Donkelaar A,
    191. Veerman JL,
    192. Vijayakumar L,
    193. Weintraub R,
    194. Weissman MM,
    195. White RA,
    196. Whiteford H,
    197. Wiersma ST,
    198. Wilkinson JD,
    199. Williams HC,
    200. Williams W,
    201. Wilson N,
    202. Woolf AD,
    203. Yip P,
    204. Zielinski JM,
    205. Lopez AD,
    206. Murray CJ,
    207. Ezzati M,
    208. AlMazroa MA and
    209. Memish ZA
    : A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study. Lancet 380(9859): 2224-2260, 2012. PMID: 23245609. DOI: 10.1016/S0140-6736(12)61766-8
    OpenUrlCrossRefPubMed
  9. ↵
    1. de Torres JP,
    2. Marín JM,
    3. Casanova C,
    4. Cote C,
    5. Carrizo S,
    6. Cordoba-Lanus E,
    7. Baz-Dávila R,
    8. Zulueta JJ,
    9. Aguirre-Jaime A,
    10. Saetta M,
    11. Cosio MG and
    12. Celli BR
    : Lung cancer in patients with chronic obstructive pulmonary disease– incidence and predicting factors. Am J Respir Crit Care Med 184(8): 913-919, 2011. PMID: 21799072. DOI: 10.1164/rccm.201103-0430OC
    OpenUrlCrossRefPubMed
  10. ↵
    1. Gao YH,
    2. Guan WJ,
    3. Liu Q,
    4. Wang HQ,
    5. Zhu YN,
    6. Chen RC and
    7. Zhang GJ
    : Impact of COPD and emphysema on survival of patients with lung cancer: A meta-analysis of observational studies. Respirology 21(2): 269-279, 2016. PMID: 26567533. DOI: 10.1111/resp.12661
    OpenUrlCrossRef
  11. ↵
    1. Mark NM,
    2. Kargl J,
    3. Busch SE,
    4. Yang GHY,
    5. Metz HE,
    6. Zhang H,
    7. Hubbard JJ,
    8. Pipavath SNJ,
    9. Madtes DK and
    10. Houghton AM
    : Chronic obstructive pulmonary disease alters immune cell composition and immune checkpoint inhibitor efficacy in non-small cell lung cancer. Am J Respir Crit Care Med 197(3): 325-336, 2018. PMID: 28934595. DOI: 10.1164/rccm.201704-0795OC
    OpenUrlCrossRef
  12. ↵
    1. Biton J,
    2. Ouakrim H,
    3. Dechartres A,
    4. Alifano M,
    5. Mansuet-Lupo A,
    6. Si H,
    7. Halpin R,
    8. Creasy T,
    9. Bantsimba-Malanda C,
    10. Arrondeau J,
    11. Goldwasser F,
    12. Boudou-Rouquette P,
    13. Fournel L,
    14. Roche N,
    15. Burgel PR,
    16. Goc J,
    17. Devi-Marulkar P,
    18. Germain C,
    19. Dieu-Nosjean MC,
    20. Cremer I,
    21. Herbst R and
    22. Damotte D
    : Impaired tumor-infiltrating T-cells in patients with chronic obstructive pulmonary disease impact lung cancer response to PD-1 blockade. Am J Respir Crit Care Med 198(7): 928-940, 2018. PMID: 29518341. DOI: 10.1164/rccm.201706-1110OC
    OpenUrlCrossRefPubMed
  13. ↵
    1. Shin SH,
    2. Park HY,
    3. Im Y,
    4. Jung HA,
    5. Sun JM,
    6. Ahn JS,
    7. Ahn MJ,
    8. Park K,
    9. Lee HY and
    10. Lee SH
    : Improved treatment outcome of pembrolizumab in patients with non-small cell lung cancer and chronic obstructive pulmonary disease. Int J Cancer 145(9): 2433-2439, 2019. PMID: 30807641. DOI: 10.1002/ijc.32235
    OpenUrlCrossRef
  14. ↵
    1. Goddard PR,
    2. Nicholson EM,
    3. Laszlo G and
    4. Watt I
    : Computed tomography in pulmonary emphysema. Clin Radiol 33(4): 379-87, 1982. PMID: 7083738. DOI: 10.1016/s0009-9260(82)80301-2
    OpenUrlCrossRefPubMed
  15. ↵
    1. Eisenhauer EA,
    2. Therasse P,
    3. Bogaerts J,
    4. Schwartz LH,
    5. Sargent D,
    6. Ford R,
    7. Dancey J,
    8. Arbuck S,
    9. Gwyther S,
    10. Mooney M,
    11. Rubinstein L,
    12. Shankar L,
    13. Dodd L,
    14. Kaplan R,
    15. Lacombe D and
    16. Verweij J
    : New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228-247, 2009. PMID: 19097774. DOI: 10.1016/j.ejca.2008.10.026
    OpenUrlCrossRefPubMed
  16. ↵
    1. Chen AP,
    2. Setser A,
    3. Anadkat MJ,
    4. Cotliar J,
    5. Olsen EA,
    6. Garden BC and
    7. Lacouture ME
    : Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0. J Am Acad Dermatol 67(5): 1025-1039, 2012. PMID: 22502948. DOI: 10.1016/j.jaad.2012.02.010
    OpenUrlCrossRefPubMed
  17. ↵
    1. Kanda Y
    : Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3): 452-458, 2013. PMID: 23208313. DOI: 10.1038/bmt.2012.244
    OpenUrlCrossRefPubMed
  18. ↵
    1. Müller NL,
    2. Staples CA,
    3. Miller RR and
    4. Abboud RT
    : “Density mask”. An objective method to quantitate emphysema using computed tomography. Chest 94(4): 782-787, 1988. PMID: 3168574. DOI: 10.1378/chest.94.4.782
    OpenUrlCrossRefPubMed
  19. ↵
    1. Park KJ,
    2. Bergin CJ and
    3. Clausen JL
    : Quantitation of emphysema with three-dimensional CT densitometry: Comparison with two-dimensional analysis, visual emphysema scores, and pulmonary function test results. Radiology 211(2): 541-547, 1999. PMID: 10228540. DOI: 10.1148/radiology.211.2.r99ma52541
    OpenUrlCrossRefPubMed
  20. ↵
    1. Houghton AM
    : Common mechanisms linking chronic obstructive pulmonary disease and lung cancer. Ann Am Thorac Soc 15(Suppl 4): S273-S277, 2018. PMID: 30759018. DOI: 10.1513/AnnalsATS.201808-537MG
    OpenUrlCrossRef
  21. ↵
    1. Ayers M,
    2. Lunceford J,
    3. Nebozhyn M,
    4. Murphy E,
    5. Loboda A,
    6. Kaufman DR,
    7. Albright A,
    8. Cheng JD,
    9. Kang SP,
    10. Shankaran V,
    11. Piha-Paul SA,
    12. Yearley J,
    13. Seiwert TY,
    14. Ribas A and
    15. McClanahan TK
    : IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest 127(8): 2930-2940, 2017. PMID: 28650338. DOI: 10.1172/JCI91190
    OpenUrlCrossRefPubMed
  22. ↵
    1. Toyokawa G,
    2. Takada K,
    3. Okamoto T,
    4. Kozuma Y,
    5. Matsubara T,
    6. Haratake N,
    7. Takamori S,
    8. Akamine T,
    9. Katsura M,
    10. Shoji F,
    11. Oda Y and
    12. Maehara Y
    : High frequency of programmed death-ligand 1 expression in emphysematous bullae-associated lung adenocarcinomas. Clin Lung Cancer 18(5): 504-511.e1, 2017. PMID: 28038981. DOI: 10.1016/j.cllc.2016.11.011
    OpenUrlCrossRef
  23. ↵
    1. Arimura K,
    2. Sekine Y,
    3. Hiroshima K,
    4. Shimizu S,
    5. Shibata N,
    6. Kondo M,
    7. Takeyama K and
    8. Tagaya E
    : PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression in pulmonary emphysema and chronic obstructive pulmonary disease with resected lung squamous cell carcinoma. BMC Pulm Med 19(1): 169, 2019. PMID: 31481045. DOI: 10.1186/s12890-019-0913-8
    OpenUrlCrossRef
  24. ↵
    1. Yamaguchi T,
    2. Shimizu J,
    3. Hasegawa T,
    4. Horio Y,
    5. Inaba Y,
    6. Yatabe Y and
    7. Hida T
    : Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis. Lung Cancer 125: 212-217, 2018. PMID: 30429022. DOI: 10.1016/j.lungcan
    OpenUrlCrossRefPubMed
  25. ↵
    1. Nakanishi Y,
    2. Masuda T,
    3. Yamaguchi K,
    4. Sakamoto S,
    5. Horimasu Y,
    6. Nakashima T,
    7. Miyamoto S,
    8. Tsutani Y,
    9. Iwamoto H,
    10. Fujitaka K,
    11. Miyata Y,
    12. Hamada H,
    13. Okada M and
    14. Hattori N
    : Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer. Respir Investig 57(5): 451-459, 2019. PMID: 31248832. DOI: 10.1016/j.resinv.2019.05.002
    OpenUrlCrossRef
  26. ↵
    1. Herbst RS,
    2. Baas P,
    3. Kim DW,
    4. Felip E,
    5. Pérez-Gracia JL,
    6. Han JY,
    7. Molina J,
    8. Kim JH,
    9. Arvis CD,
    10. Ahn MJ,
    11. Majem M,
    12. Fidler MJ,
    13. de Castro G Jr.,
    14. Garrido M,
    15. Lubiniecki GM,
    16. Shentu Y,
    17. Im E,
    18. Dolled-Filhart M and
    19. Garon EB
    : Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomized controlled trial. Lancet 387(10027): 1540-1550, 2016. PMID: 26712084. DOI: 10.1016/S0140-6736(15)01281-7
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top

In this issue

In Vivo: 35 (1)
In Vivo
Vol. 35, Issue 1
January-February 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Coexistence of Emphysema With Non-small-cell Lung Cancer Predicts the Therapeutic Efficacy of Immune Checkpoint Inhibitors
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
6 + 2 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Coexistence of Emphysema With Non-small-cell Lung Cancer Predicts the Therapeutic Efficacy of Immune Checkpoint Inhibitors
YUSUKE TAKAYAMA, TAKASHI NAKAMURA, YUKI FUKUSHIRO, SHOHEI MISHIMA, KEN MASUDA, HIROYASU SHODA
In Vivo Jan 2021, 35 (1) 467-474; DOI: 10.21873/invivo.12280

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Coexistence of Emphysema With Non-small-cell Lung Cancer Predicts the Therapeutic Efficacy of Immune Checkpoint Inhibitors
YUSUKE TAKAYAMA, TAKASHI NAKAMURA, YUKI FUKUSHIRO, SHOHEI MISHIMA, KEN MASUDA, HIROYASU SHODA
In Vivo Jan 2021, 35 (1) 467-474; DOI: 10.21873/invivo.12280
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Patients and Methods
    • Results
    • Discussion
    • Conclusion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Three-month Prostate-specific Antigen Level After Androgen Deprivation Therapy Predicts Survival in Patients With Metastatic Castration-sensitive Prostate Cancer
  • A Finnish Version of RAND-36-Item Health Survey Versus Structured Interview 8 Years Postoperatively
  • Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) Gene Polymorphism (rs3087243) Is Related to Risk and Survival in Patients With Colorectal Cancer
Show more Clinical Studies

Similar Articles

Keywords

  • non-small-cell lung cancer
  • immune checkpoint inhibitors
  • emphysema
  • Goddard scoring system
In Vivo

© 2021 In Vivo

Powered by HighWire