Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer

Authors:
Nathan Y. Yu Department of Radiation Oncology, and

Search for other papers by Nathan Y. Yu in
Current site
Google Scholar
PubMed Close
 MD
,
Terence T. Sio Department of Radiation Oncology, and

Search for other papers by Terence T. Sio in
Current site
Google Scholar
PubMed Close
 MD, MS
,
Vinicius Ernani Division of Hematology and Medical Oncology, Mayo Clinic Hospital, Phoenix, Arizona.

Search for other papers by Vinicius Ernani in
Current site
Google Scholar
PubMed Close
 MD
,
Panayiotis Savvides Division of Hematology and Medical Oncology, Mayo Clinic Hospital, Phoenix, Arizona.

Search for other papers by Panayiotis Savvides in
Current site
Google Scholar
PubMed Close
 MD
, and
Steven E. Schild Department of Radiation Oncology, and

Search for other papers by Steven E. Schild in
Current site
Google Scholar
PubMed Close
 MD
Volume/Issue:
Volume 19: Issue 12
Online Publication Date:
Dec 2021
DOI:
https://doi.org/10.6004/jnccn.2021.7105
Restricted access

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.

Submitted July 20, 2021; final revision received October 5, 2021; accepted for publication October 21, 2021.

Disclosures: Dr. Schild has disclosed writing and editing for and receiving royalties from UpToDate. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Steven E. Schild, MD, Department of Radiation Oncology, Mayo Clinic Hospital, 5777 East Mayo Boulevard, Phoenix, AZ 85054. Email: sschild@mayo.edu
  • Collapse
  • Expand
Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
  • 1.

    Hirsch FR, Paulson OB, Hansen HH, et al. Intracranial metastases in small cell carcinoma of the lung. Prognostic aspects. Cancer 1983;51:529–533.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Nugent JL, Bunn PA Jr, Matthews MJ, et al. CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 1979;44:1885–1893.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Eagan RT, Frytak S, Lee RE, et al. A case for preplanned thoracic and prophylactic whole brain radiation therapy in limited small-cell lung cancer. Cancer Clin Trials 1981;4:261–266.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Lukas RV, Gondi V, Kamson DO, et al. State-of-the-art considerations in small cell lung cancer brain metastases. Oncotarget 2017;8:71223–71233.

  • 5.

    Komaki R, Cox JD, Whitson W. Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation. Cancer Treat Rep 1981;65:811–814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 1999;341:476–484.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Meert AP, Paesmans M, Berghmans T, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer 2001;1:5.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664–672.

  • 9.

    Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2017;18:663–671.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Rusthoven CG, Kavanagh BD. Prophylactic cranial irradiation in small-cell lung cancer. Lancet Oncol 2017;18:e365.

  • 11.

    Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002;346:85–91.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Hanna N, Bunn PA Jr, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006;24:2038–2043.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Lara PN Jr, Natale R, Crowley J, et al. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol 2009;27:2530–2535.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Schild SE, Foster NR, Meyers JP, et al. Prophylactic cranial irradiation in small-cell lung cancer: findings from a North Central Cancer Treatment Group pooled analysis. Ann Oncol 2012;23:2919–2924.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Maeng CH, Song JU, Shim SR, et al. The role of prophylactic cranial irradiation in patients with extensive stage small cell lung cancer: a systematic review and meta-analysis. J Thorac Oncol 2018;13:840–848.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Sharma S, McMillan M, Doucette A, et al. Impact of prophylactic cranial irradiation on overall survival in metastatic small cell lung cancer: a propensity score matched analysis of patients in the National Cancer Database. Int J Radiat Oncol Biol Phys 2017;98:224–225.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Sheikh S, Dey A, Datta S, et al. Role of radiation in extensive stage small cell lung cancer: a National Cancer Database registry analysis. Future Oncol 2021;17:2713–2724.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Rule WG, Foster NR, Meyers JP, et al. Prophylactic cranial irradiation in elderly patients with small cell lung cancer: findings from a North Central Cancer Treatment Group pooled analysis. J Geriatr Oncol 2015;6:119–126.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol 2009;10:467–474.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Wolfson AH, Bae K, Komaki R, et al. Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer. Int J Radiat Oncol Biol Phys 2011;81:77–84.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Péchoux CL, Sun A, Slotman BJ, et al. Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol 2016;17:e277–293.

  • 22.

    Le Péchoux C, Laplanche A, Faivre-Finn C, et al. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol 2011;22:1154–1163.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Gondi V, Paulus R, Bruner DW, et al. Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214. Int J Radiat Oncol Biol Phys 2013;86:656–664.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Gondi V, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole-brain radiotherapy: a “how-to” technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2010;78:1244–1252.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 2014;32:3810–3816.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Brown PD, Gondi V, Pugh S, et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: phase III trial NRG Oncology CC001. J Clin Oncol 2020;38:1019–1029.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Rodriguez de Dios N, Murcia M, Counago F, et al. Phase III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small-cell lung cancer. Int J Radiat Oncol Biol Phys 2019;105(Suppl):S35–36.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Belderbos JSA, De Ruysscher DKM, De Jaeger K, et al. Phase 3 randomized trial of prophylactic cranial irradiation with or without hippocampus avoidance in SCLC (NCT01780675). J Thorac Oncol 2021;16:840–849.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Gjyshi O, Ludmir EB, Pezzi TA, et al. Evolving practice patterns in the use of prophylactic cranial irradiation for extensive-stage small cell lung cancer. JAMA Netw Open 2019;2:e199135.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Keller A, Ghanta S, Rodríguez-López JL, et al. Utility of prophylactic cranial irradiation for extensive-stage small-cell lung cancer in the MRI screening era. Clin Lung Cancer 2021;S1525-7304(21)00063-2.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Kim H, Keller A, Beriwal S, et al. Cost-effectiveness of prophylactic cranial irradiation versus MRI surveillance for extensive-stage small cell lung cancer. Int J Radiat Oncol Biol Phys 2021;S0360-3016(21)00477-6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Rusthoven CG, Yamamoto M, Bernhardt D, et al. Evaluation of first-line radiosurgery vs whole-brain radiotherapy for small cell lung cancer brain metastases: the FIRE-SCLC cohort study. JAMA Oncol 2020;6:1028–1037.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 2017;318:2306–2316.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Paz-Ares L, Dvorkin M, Chen Y, et al. 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 2019;394:1929–1939.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 2018;379:2220–2229.

  • 36.

    Higgins KA, Curran WJ Jr, Liu SV, et al. Patterns of disease progression after carboplatin/etoposide + atezolizumab in extensive-stage small-cell lung cancer (ES-SCLC). Int J Radiat Oncol Biol Phys 2020;108:1398.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2021 by the National Comprehensive Cancer Network 2021
Page Numbers:
5
Article Category:
Review Article
Received:
20 Jul 2021
Accepted:
21 Oct 2021
Print Publication Date:
01 Dec 2021
Online Publication Date:
Dec 2021

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 4636 671 83
PDF Downloads 2660 341 27
EPUB Downloads 0 0 0