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Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

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Abstract

Background

This review was implemented to examine the impact of bone metastasis on the prognosis of non-small cell lung cancer patients (NSCLC) treated with immune checkpoint inhibitors (ICIs).

Methods

A literature search was conducted in the PubMed, CENTRAL, Web of Science, and Embase databases up to 4th September 2022. Multivariable adjusted data were pooled in a random-effects model.

Results

13 studies were included. On a combined analysis of 10 studies, it was noted that bony metastasis was associated with poor overall survival (OS) in NSCLC patients treated with ICIs (HR: 1.55 95% CI 1.24, 1.94 I2 = 69% p = 0.001). Meta-analysis of seven studies showed that bony metastasis was not associated with poor progression-free survival (PFS) in NSCLC patients treated with ICIs (HR: 1.31 95% CI 0.85, 2.01 I2 = 85% p = 0.22). Meta-regression analysis using the moderator's age, male gender, smoking history, squamous histology, and ICI as 1st line therapy for the outcome OS was not statistically significant.

Conclusion

The presence of bone metastasis is a predictor of poor OS in NSCLC treated with ICIs. However, PFS does not seem to be influenced by the presence of bone metastasis. Clinicians should prioritize the management of NSCLC patients with bone metastasis and explore the use of combination therapies to achieve optimal results. Further studies taking into account different combination therapies for such patients would strengthen the evidence.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2019;28:1563.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019;94:1623–40.

    Article  CAS  PubMed  Google Scholar 

  4. Van Meerbeeck JP, Fennell DA, De Ruysscher DKM. Small-cell lung cancer. Lancet (London, England). 2011;378:1741–55.

    Article  PubMed  Google Scholar 

  5. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363–85. https://doi.org/10.3322/caac.21565.

    Article  PubMed  Google Scholar 

  6. Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383:640–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Huang Y, Zhu L, Guo T, Chen W, Zhang Z, Li W, et al. Metastatic sites as predictors in advanced NSCLC treated with PD-1 inhibitors: a systematic review and meta-analysis. Hum Vaccin Immunother. 2021;17:1278–87.

    Article  CAS  PubMed  Google Scholar 

  8. Kitadai R, Okuma Y, Hakozaki T, Hosomi Y. The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases. J Cancer Res Clin Oncol. 2020;146:777–85.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang G, Cheng R, Wang H, Zhang Y, Yan X, Li P, et al. Comparable outcomes of nivolumab in patients with advanced NSCLC presenting with or without brain metastases: a retrospective cohort study. Cancer Immunol Immunother. 2020;69:399–405.

    Article  CAS  PubMed  Google Scholar 

  10. Kuchuk M, Addison CL, Clemons M, Kuchuk I, Wheatley-Price P. Incidence and consequences of bone metastases in lung cancer patients. J bone Oncol. 2013;2:22–9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sugiura H, Yamada K, Sugiura T, Hida T, Mitsudomi T. Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res. 2008;466:729–36.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7:1823–9.

    Article  CAS  PubMed  Google Scholar 

  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg. 2021;88: 105906.

    Article  PubMed  Google Scholar 

  14. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed 30 Oct2020).

  15. Juan ZY, Song CX, Zhou R, Dong CY, Chuan MH, Zhen XZ, et al. Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays ‘cold’ immune characteristics in Non-small cell lung cancer. Lung Cancer. 2022;166:189–96.

    Article  Google Scholar 

  16. Wu Y, Wu H, Lin M, Liu T, Li J. Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients. Transl Oncol. 2022. https://doi.org/10.1016/J.TRANON.2021.101268.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Qin A, Zhao S, Miah A, Wei L, Patel S, Johns A, et al. Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors. J Natl Compr Canc Netw. 2021;19:915–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Galland L, Lecuelle J, Favier L, Fraisse C, Lagrange A, Kaderbhai C, et al. Splenic volume as a surrogate marker of immune checkpoint inhibitor efficacy in metastatic non small cell lung cancer. Cancers (Basel). 2021. https://doi.org/10.3390/CANCERS13123020.

    Article  PubMed  Google Scholar 

  19. Gu X, Shi Z, Shao L, Zhang Y, Zhang Y, Song Z, et al. Efficacy and safety of maintenance immune checkpoint inhibitors with or without pemetrexed in advanced non-squamous non-small cell lung cancer: a retrospective study. BMC Cancer. 2022. https://doi.org/10.1186/S12885-022-09674-2.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ruiz-Patiño A, Arrieta O, Cardona AF, Martín C, Raez LE, Zatarain-Barrón ZL, et al. Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non-small cell lung cancer (NSCLC) compared with chemotherapy (Quijote-CLICaP). Thorac cancer. 2020;11:353–61.

    Article  PubMed  Google Scholar 

  21. Li X, Wang L, Chen S, Zhou F, Zhao J, Zhao W, et al. Adverse impact of bone metastases on clinical outcomes of patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Thorac cancer. 2020;11:2812–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kawachi H, Tamiya M, Tamiya A, Ishii S, Hirano K, Matsumoto H, et al. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study. Invest New Drugs. 2020;38:211–8.

    Article  CAS  PubMed  Google Scholar 

  23. Dallolio FG, Gelsomino F, Conci N, Marcolin L, De Giglio A, Grilli G, et al. PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non-small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors. Clin Lung Cancer. 2021;22:423–31.

    Article  CAS  PubMed  Google Scholar 

  24. Prelaj A, Ferrara R, Rebuzzi SE, Proto C, Signorelli D, Galli G, et al. EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort. Cancers (Basel). 2019. https://doi.org/10.3390/CANCERS11121954.

    Article  PubMed  Google Scholar 

  25. Landi L, Dincà F, Gelibter A, Chiari R, Grossi F, Delmonte A, et al. Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer. J Immunother Cancer. 2019. https://doi.org/10.1186/S40425-019-0793-8.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Garde-Noguera J, Martin-Martorell P, De Julián M, Perez-Altozano J, Salvador-Coloma C, García-Sanchez J, et al. Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients. Clin Transl Oncol. 2018;20:1072–9.

    Article  CAS  PubMed  Google Scholar 

  27. Fukui T, Okuma Y, Nakahara Y, Otani S, Igawa S, Katagiri M, et al. Activity of Nivolumab and Utility of Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study. Clin Lung Cancer. 2019;20:208-214.e2.

    Article  CAS  PubMed  Google Scholar 

  28. Zheng XQ, Huang JF, Lin JL, Chen L, Zhou TT, Chen D, et al. Incidence, prognostic factors, and a nomogram of lung cancer with bone metastasis at initial diagnosis: a population-based study. Transl lung cancer Res. 2019;8:367–79.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Knapp BJ, Devarakonda S, Govindan R. Bone metastases in non-small cell lung cancer: a narrative review. J Thorac Dis. 2022;14:1696–712.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lecouvet FE, Talbot JN, Messiou C, Bourguet P, Liu Y, De Souza NM. Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer. 2014;50:2519–31.

    Article  CAS  PubMed  Google Scholar 

  31. Xiang L, Gilkes DM. The Contribution of the Immune System in Bone Metastasis Pathogenesis. Int J Mol Sci. 2019. https://doi.org/10.3390/IJMS20040999.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–51.

    Article  CAS  PubMed  Google Scholar 

  33. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:2078–92.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Wenzhou Hospital of Traditional Chinese Medicine, Wenzhou City, Zhejiang Province, China

    Lina Liu

  2. Department of Surgical Oncology, Wenzhou Hospital of Traditional Chinese Medicine, Wenzhou City, Zhejiang Province, China

    Zhongyi Shi

  3. Department of Orthopedics and Traumatology, Wenzhou Hospital of Traditional Chinese Medicine, No. 27, Dashimen, Xinhe Street, Lucheng District, Wenzhou City, Zhejiang Province, China

    Xingdong Qiu

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Liu, L., Shi, Z. & Qiu, X. Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Clin Transl Oncol 26, 747–755 (2024). https://doi.org/10.1007/s12094-023-03300-8

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  • DOI: https://doi.org/10.1007/s12094-023-03300-8

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