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Treatment and survival of patients with small cell lung cancer and brain metastasis

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Abstract

Purpose

To elucidate treatment patterns and their outcomes in patients with small cell lung cancer (SCLC) and brain metastasis (BM).

Methods

In this retrospective study, patients with SCLC and BM were stratified by treatment modality into three groups: those treated with systemic therapy only, those treated with stereotactic radiosurgery (SRS) and systemic therapy, and those treated with whole-brain radiotherapy (WBRT) and systemic therapy. The primary outcomes were overall survival (OS) and time to central nervous system progression (TTCP).

Results

The analysis included 149 patients. After BM diagnosis, 48 patients (32.2%) received systemic therapy alone, 33 received SRS with systemic therapy, and 68 received WBRT with systemic therapy. The median OS and TTCP were 7.2 months and 8.7 months, respectively. Patients receiving WBRT with systemic therapy exhibited better intracranial control, but not better OS, than did the other patients. Key prognostic factors affecting OS were age, BM lesion count, chemotherapy, and immunotherapy. Notably, the Eastern Cooperative Oncology Group performance status and BM lesion count significantly influenced intracranial control in patients treated with SRS and systemic therapy.

Conclusion

Although WBRT combined with systemic therapy offer better intracranial control in patients with SCLC and BM, this approach is not superior to the other approaches in terms of OS benefits. Emerging systemic therapies, such as immunotherapy, may be used as alternative or adjunctive treatments for specific patient populations. Further studies are warranted to refine treatment selection.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Goncalves PH, Peterson SL, Vigneau FD, Shore RD, Quarshie WO, Islam K, Schwartz AG, Wozniak AJ, Gadgeel SM (2016) Risk of brain metastases in patients with nonmetastatic Lung cancer: analysis of the Metropolitan Detroit Surveillance, Epidemiology, and end results (SEER) data. Cancer 122:1921–1927. https://doi.org/10.1002/cncr.30000

    Article  PubMed  Google Scholar 

  2. Hirsch FR, Paulson OB, Hansen HH, Larsen SO (1983) Intracranial metastases in small cell carcinoma of the lung. Prognostic aspects. Cancer 51:529–533. https://doi.org/10.1002/1097-0142(19830201)51:3<529::aid-cncr2820510327>3.0.co;2-0

    Article  CAS  PubMed  Google Scholar 

  3. Riihimäki M, Hemminki A, Fallah M, Thomsen H, Sundquist K, Sundquist J, Hemminki K (2014) Metastatic sites and survival in Lung cancer. Lung Cancer 86:78–84. https://doi.org/10.1016/j.lungcan.2014.07.020

    Article  PubMed  Google Scholar 

  4. Bernhardt D, Bozorgmehr F, Adeberg S, Opfermann N, von Eiff D, Rieber J, Kappes J, Foerster R, König L, Thomas M, Debus J, Steins M, Rieken S (2016) Outcome in patients with small cell Lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation. Lung Cancer 101:76–81. https://doi.org/10.1016/j.lungcan.2016.09.010

    Article  PubMed  Google Scholar 

  5. Videtic GM, Adelstein DJ, Mekhail TM, Rice TW, Stevens GH, Lee SY, Suh JH (2007) Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases. Int J Radiat Oncol Biol Phys 67:240–243. https://doi.org/10.1016/j.ijrobp.2006.08.019

    Article  PubMed  Google Scholar 

  6. Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D’Amico TA, D’Avella C, Dowlati A, Downey RJ, Edelman M, Florsheim C, Gold KA, Goldman JW, Grecula JC, Hann C, Iams W, Iyengar P, Kelly K, Khalil M, Koczywas M, Merritt RE, Mohindra N, Molina J, Moran C, Pokharel S, Puri S, Qin A, Rusthoven C, Sands J, Santana-Davila R, Shafique M, Waqar SN, Gregory KM, Hughes M (2021) Small cell Lung Cancer, Version 2.2022, NCCN Clinical Practice guidelines in Oncology. J Natl Compr Cancer Network: JNCCN 19:1441–1464. https://doi.org/10.6004/jnccn.2021.0058

    Article  CAS  PubMed  Google Scholar 

  7. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S (2007) Prophylactic cranial irradiation in extensive small-cell Lung cancer. N Engl J Med 357:664–672. https://doi.org/10.1056/NEJMoa071780

    Article  CAS  PubMed  Google Scholar 

  8. Gjyshi O, Ludmir EB, Pezzi TA, Boyce-Fappiano D, Dursteler AE, Mitin T, Lin SH (2019) Evolving practice patterns in the use of prophylactic cranial irradiation for extensive-stage small cell Lung Cancer. JAMA Netw open 2:e199135–e199135. https://doi.org/10.1001/jamanetworkopen.2019.9135

    Article  PubMed  PubMed Central  Google Scholar 

  9. Takahashi T, Yamanaka T, Seto T, Harada H, Nokihara H, Saka H, Nishio M, Kaneda H, Takayama K, Ishimoto O, Takeda K, Yoshioka H, Tachihara M, Sakai H, Goto K, Yamamoto N (2017) Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell Lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 18:663–671. https://doi.org/10.1016/s1470-2045(17)30230-9

    Article  PubMed  Google Scholar 

  10. Lim YJ, Song C, Kim HJ (2022) Survival impact of prophylactic cranial irradiation in small-cell Lung cancer in the modern era of magnetic resonance imaging staging. Radiation Oncol (London England) 17:26. https://doi.org/10.1186/s13014-022-01994-8

    Article  CAS  Google Scholar 

  11. Lee CC, Hsu SPC, Lin CJ, Wu HM, Chen YW, Luo YH, Chiang CL, Hu YS, Chung WY, Shiau CY, Guo WY, Hung-Chi Pan D, Yang HC (2019) Epidermal growth factor receptor mutations: association with favorable local Tumor control following Gamma Knife Radiosurgery in patients with non-small cell Lung cancer and brain metastases. J Neurosurg 1–8. https://doi.org/10.3171/2019.4.jns19446

  12. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483–2491. https://doi.org/10.1001/jama.295.21.2483

    Article  CAS  PubMed  Google Scholar 

  13. Gaebe K, Li AY, Park A, Parmar A, Lok BH, Sahgal A, Chan KKW, Erickson AW, Das S (2022) Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic Disease and small-cell Lung cancer: a systematic review and meta-analysis. Lancet Oncol 23:931–939. https://doi.org/10.1016/s1470-2045(22)00271-6

    Article  PubMed  Google Scholar 

  14. Cifarelli CP, Vargo JA, Fang W, Liscak R, Guseynova K, Warnick RE, Lee CC, Yang HC, Borghei-Razavi H, Maiti T, Siddiqui ZA, Yuan JC, Grills IS, Mathieu D, Touchette CJ, Cordeiro D, Chiang V, Hess J, Tien CJ, Faramand A, Kano H, Barnett GH, Sheehan JP, Lunsford LD (2020) Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: a multi-institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF). Neurosurgery 87:664–671. https://doi.org/10.1093/neuros/nyz428

    Article  PubMed  Google Scholar 

  15. Jiang W, Haque W, Verma V, Butler B, Teh BS (2019) Stereotactic radiosurgery for brain metastases from newly diagnosed small cell Lung cancer: practice patterns and outcomes. Acta Oncol (Stockholm Sweden) 58:491–498. https://doi.org/10.1080/0284186x.2018.1562207

    Article  Google Scholar 

  16. Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA (2019) Current diagnosis and management of small-cell Lung Cancer. Mayo Clin Proc 94:1599–1622. https://doi.org/10.1016/j.mayocp.2019.01.034

    Article  PubMed  Google Scholar 

  17. Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM (2017) Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol 14:549–561. https://doi.org/10.1038/nrclinonc.2017.71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV (2018) First-line atezolizumab plus chemotherapy in extensive-stage small-cell Lung Cancer. N Engl J Med 379:2220–2229. https://doi.org/10.1056/NEJMoa1809064

    Article  CAS  PubMed  Google Scholar 

  19. Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW (2019) Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell Lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet (London England) 394:1929–1939. https://doi.org/10.1016/s0140-6736(19)32222-6

    Article  CAS  PubMed  Google Scholar 

  20. Chung HC, Piha-Paul SA, Lopez-Martin J, Schellens JHM, Kao S, Miller WH Jr., Delord JP, Gao B, Planchard D, Gottfried M, Zer A, Jalal SI, Penel N, Mehnert JM, Matos I, Bennouna J, Kim DW, Xu L, Krishnan S, Norwood K, Ott PA (2020) Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol 15:618–627. https://doi.org/10.1016/j.jtho.2019.12.109

    Article  CAS  PubMed  Google Scholar 

  21. Schapira E, Hubbeling H, Yeap BY, Mehan WA Jr., Shaw AT, Oh K, Gainor JF, Shih HA (2018) Improved overall survival and Locoregional Disease Control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for Lung Cancer patients with brain metastases. Int J Radiat Oncol Biol Phys 101:624–629. https://doi.org/10.1016/j.ijrobp.2018.02.175

    Article  PubMed  Google Scholar 

  22. Chiou GY, Chiang CL, Yang HC, Shen CI, Wu HM, Chen YW, Chen CJ, Luo YH, Hu YS, Lin CJ, Chung WY, Shiau CY, Guo WY, Pan DH, Lee CC (2021) Combined stereotactic radiosurgery and tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone for the treatment of non-small cell Lung cancer patients with brain metastases. J Neurosurg 1–8. https://doi.org/10.3171/2021.9.jns211373

  23. Lee CC, Chou CL, Chen CJ, Yang HC, Wu HM, Shiau CY, Pan DH, Chung WY (2018) Stereotactic radiosurgery for hypervascular intracranial tumors. J Neurooncol 140:547–558. https://doi.org/10.1007/s11060-018-2980-8

    Article  PubMed  Google Scholar 

  24. Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90 – 05. Int J Radiat Oncol Biol Phys 47:291–298. https://doi.org/10.1016/s0360-3016(99)00507-6

    Article  CAS  PubMed  Google Scholar 

  25. Rittberg R, Banerji S, Kim JO, Rathod S, Dawe DE (2021) Treatment and Prevention of Brain metastases in Small Cell Lung Cancer. Am J Clin Oncol 44:629–638. https://doi.org/10.1097/coc.0000000000000867

    Article  CAS  PubMed  Google Scholar 

  26. Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW (2019) Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell Lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet (London England) 394:1929–1939. https://doi.org/10.1016/s0140-6736(19)32222-6

    Article  CAS  PubMed  Google Scholar 

  27. Rusthoven CG, Yamamoto M, Bernhardt D, Smith DE, Gao D, Serizawa T, Yomo S, Aiyama H, Higuchi Y, Shuto T, Akabane A, Sato Y, Niranjan A, Faramand AM, Lunsford LD, McInerney J, Tuanquin LC, Zacharia BE, Chiang V, Singh C, Yu JB, Braunstein S, Mathieu D, Touchette CJ, Lee CC, Yang HC, Aizer AA, Cagney DN, Chan MD, Kondziolka D, Bernstein K, Silverman JS, Grills IS, Siddiqui ZA, Yuan JC, Sheehan JP, Cordeiro D, Nosaki K, Seto T, Deibert CP, Verma V, Day S, Halasz LM, Warnick RE, Trifiletti DM, Palmer JD, Attia A, Li B, Cifarelli CP, Brown PD, Vargo JA, Combs SE, Kessel KA, Rieken S, Patel S, Guckenberger M, Andratschke N, Kavanagh BD, Robin TP (2020) Evaluation of first-line Radiosurgery vs whole-brain radiotherapy for small cell Lung Cancer Brain metastases: the FIRE-SCLC Cohort Study. JAMA Oncol 6:1028–1037. https://doi.org/10.1001/jamaoncol.2020.1271

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kowalchuk RO, Niranjan A, Lee CC, Yang HC, Liscak R, Guseynova K, Tripathi M, Kumar N, Peker S, Samanci Y, Hess J, Chiang V, Iorio-Morin C, Mathieu D, Pikis S, Wei Z, Lunsford LD, Trifiletti DM, Sheehan JP (2022) Reirradiation with Stereotactic Radiosurgery after local or marginal recurrence of Brain metastases from previous Radiosurgery. Int J Radiat Oncol Biol Phys 112:726–734. https://doi.org/10.1016/j.ijrobp.2021.10.008

    Article  PubMed  Google Scholar 

  29. Iorio-Morin C, Mercure-Cyr R, Figueiredo G, Touchette CJ, Masson-Côté L, Mathieu D (2019) Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases. J Neurooncol 145:551–559. https://doi.org/10.1007/s11060-019-03323-8

    Article  PubMed  Google Scholar 

  30. Chang J, Jing X, Hua Y, Geng K, Li R, Lu S, Zhu H, Zhang Y (2023) Programmed cell death 1 pathway inhibitors improve the overall survival of small cell Lung cancer patients with brain metastases. J Cancer Res Clin Oncol 149:1825–1833. https://doi.org/10.1007/s00432-022-04121-y

    Article  CAS  PubMed  Google Scholar 

  31. Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, Hummel HD, Borghaei H, Johnson ML, Steeghs N, Blackhall F, Dowlati A, Reguart N, Yoshida T, He K, Gadgeel SM, Felip E, Zhang Y, Pati A, Minocha M, Mukherjee S, Goldrick A, Nagorsen D, Hashemi Sadraei N, Owonikoko TK (2023) Tarlatamab, a first-in-class DLL3-Targeted bispecific T-Cell engager, in recurrent small-cell Lung Cancer: an Open-Label, phase I study. J Clin Oncology: Official J Am Soc Clin Oncol 41:2893–2903. https://doi.org/10.1200/jco.22.02823

    Article  CAS  Google Scholar 

  32. Manzo A, Sforza V, Carillio G, Palumbo G, Montanino A, Sandomenico C, Costanzo R, Esposito G, Laudato F, Mercadante E, La Manna C, Muto P, Totaro G, De Cecio R, Picone C, Piccirillo MC, Pascarella G, Normanno N, Morabito A (2022) Lurbinectedin in small cell Lung cancer. Front Oncol 12:932105. https://doi.org/10.3389/fonc.2022.932105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by National Science and Technology Council, Taiwan [grant number 111-2926-I-075-501-G].

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Authors and Affiliations

  1. Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Chi-Lu Chiang, Ying-Ting Liao, Yung-Hung Luo & Yuh-Min Chen

  2. School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Chi-Lu Chiang, Huai-Che Yang, Ying-Ting Liao, Yung-Hung Luo, Yuan-Hung Wu, Hsiu-Mei Wu & Yuh-Min Chen

  3. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Chi-Lu Chiang

  4. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

    Huai-Che Yang

  5. Department of Heavy Particles and Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

    Yuan-Hung Wu

  6. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

    Hsiu-Mei Wu

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Contributions

Material preparation, data collection and analysis were performed by CLC, HCY and YTL. The first draft of the manuscript was written by CLC and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chi-Lu Chiang.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Taipei Veterans General Hospital, Taiwan (approval number: 2023-06-016CC).

Consent to participate

Written informed consent was waived due to retrospective design.

Consent to publish

Not appliable.

Competing interests

CLC has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, and Roche. YHL has received honoraria from AstraZeneca, Boehringer Ingelheim, and Pfizer.YMC has received honoraria from Boehringer Ingelheim, Eli Lilly, Roche/Genentech/Chugai, MSD, Pfizer, Novartis, BMS, Ono Pharmaceutical, AstraZeneca, and Takeda Oncology and provided advisory services to Boehringer Ingelheim, Eli Lilly, Roche/Chugai, MSD, AstraZeneca, and Takeda Oncology.The other authors declare no conflicts of interest relevant to the content of this manuscript.

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Chiang, CL., Yang, HC., Liao, YT. et al. Treatment and survival of patients with small cell lung cancer and brain metastasis. J Neurooncol 165, 343–351 (2023). https://doi.org/10.1007/s11060-023-04512-2

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