Skip to main content
SpringerLink
Log in

Treatment of Small Cell Lung Cancer

  • Chapter
  • First Online:
Lung Cancer

Part of the book series: Respiratory Medicine ((RM))

  • 351 Accesses

Abstract

Small cell lung cancer (SCLC) is a neuroendocrine tumor strongly associated with tobacco use, encompasses ~12% of lung cancer diagnoses, and is systemic even at early stages. Local therapy alone, such as surgery or radiation, is insufficient in long-term control, even early-stage disease. Consequently, a backbone of systemic therapy with platinum- and etoposide-based chemotherapy has been a standard of care with modest advances until the last 5–10 years. In the chapter, we explore diagnosis, staging, and clinical presenting symptoms of SCLC. We also discuss optimization of local therapy with timing and radiation dose in limited-stage disease. Novel therapies are improving outcomes in extensive-stage disease, and we discuss these new treatment approaches as immunotherapy. We also explore systemic therapy options in relapsed SCLC. Further, we explore the risk of CNS metastases and the role of prophylactic cranial irradiation (PCI). Finally, we discuss novel therapies, including hippocampal avoidance PCI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ettinger DS, Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol. 2006;24(28):4526–7. https://doi.org/10.1200/JCO.2006.07.3841. PMID: 17008688.

    Article  PubMed  Google Scholar 

  2. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, Spitznagel EL, Piccirillo J. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24(28):4539–44. https://doi.org/10.1200/JCO.2005.04.4859. PMID: 17008692.

    Article  PubMed  Google Scholar 

  3. van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378(9804):1741–55. https://doi.org/10.1016/S0140-6736(11)60165-7. Epub 2011 May 10. PMID: 21565397.

    Article  PubMed  Google Scholar 

  4. Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017;17(12):725–37. https://doi.org/10.1038/nrc.2017.87. Epub 2017 Oct 27. Erratum in: Nat Rev Cancer. 2017; PMID: 29077690.

    Article  CAS  PubMed  Google Scholar 

  5. Marchioli CC, Graziano SL. Paraneoplastic syndromes associated with small cell lung cancer. Chest Surg Clin N Am. 1997;7(1):65–80. PMID: 9001756.

    CAS  PubMed  Google Scholar 

  6. Gandhi L, Johnson BE. Paraneoplastic syndromes associated with small cell lung cancer. J Natl Compr Cancer Netw. 2006;4(6):631–8. https://doi.org/10.6004/jnccn.2006.0052. PMID: 16813730.

    Article  Google Scholar 

  7. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Prim. 2021;7(1):3. https://doi.org/10.1038/s41572-020-00235-0. PMID: 33446664; PMCID: PMC8177722.

    Article  PubMed  Google Scholar 

  8. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to the 2015 World Health Organization Classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10(9):1240–2. https://doi.org/10.1097/JTO.0000000000000663. PMID: 26291007.

    Article  PubMed  Google Scholar 

  9. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838–54. https://doi.org/10.4065/mcp.2010.0099. Erratum in: Mayo Clin Proc. 2011;86(4):364. Dosage error in article text. PMID: 20810794; PMCID: PMC2931619.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hazell SZ, Mai N, Fu W, Hu C, Friedes C, Negron A, Voong KR, Feliciano JL, Han P, Myers S, McNutt TR, Hales RK. Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact. BMC Cancer. 2020;20(1):334. https://doi.org/10.1186/s12885-020-06843-z. PMID: 32306924; PMCID: PMC7169027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007;97(2):162–9. https://doi.org/10.1038/sj.bjc.6603810. Epub 2007 Jun 19. PMID: 17579629; PMCID: PMC2360311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shepherd FA, Crowley J, Van Houtte P, Postmus PE, Carney D, Chansky K, Shaikh Z, Goldstraw P. International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol. 2007;2(12):1067–77. https://doi.org/10.1097/JTO.0b013e31815bdc0d. PMID: 18090577.

    Article  PubMed  Google Scholar 

  13. Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG, Buhl R. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease? Lung Cancer. 2002;37(3):271–6. https://doi.org/10.1016/s0169-5002(02)00072-7. PMID: 12234695.

    Article  PubMed  Google Scholar 

  14. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 3. 1973;4(2):31–42. PMID: 4580860.

    CAS  PubMed  Google Scholar 

  15. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51. https://doi.org/10.1016/j.jtho.2015.09.009. PMID: 26762738.

    Article  PubMed  Google Scholar 

  16. Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O’Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F, CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116–25. https://doi.org/10.1016/S1470-2045(17)30318-2. Epub 2017 Jun 20. PMID: 28642008; PMCID: PMC5555437.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Horn L, Mansfield AS, Szczęsna 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, IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220–9. https://doi.org/10.1056/NEJMoa1809064. Epub 2018 Sep 25. PMID: 30280641.

    Article  CAS  PubMed  Google Scholar 

  18. Haddadin S, Perry MC. History of small-cell lung cancer. Clin Lung Cancer. 2011;12(2):87–93. https://doi.org/10.1016/j.cllc.2011.03.002. Epub 2011 Apr 8. PMID: 21550554.

    Article  CAS  PubMed  Google Scholar 

  19. Sierocki JS, Hilaris BS, Hopfan S, Martini N, Barton D, Golbey RB, Wittes RE. cis-Dichlorodiammineplatinum(II) and VP-16-213: an active induction regimen for small cell carcinoma of the lung. Cancer Treat Rep. 1979;63(9–10):1593–7. PMID: 227598.

    CAS  PubMed  Google Scholar 

  20. Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992;10(2):282–91. https://doi.org/10.1200/JCO.1992.10.2.282. PMID: 1310103.

    Article  CAS  PubMed  Google Scholar 

  21. Turrisi AT III, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340(4):265–71. https://doi.org/10.1056/NEJM199901283400403. PMID: 9920950.

    Article  CAS  PubMed  Google Scholar 

  22. Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R, Weiss GR, Hicks WJ, Gandara DR, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995;13(7):1632–41. https://doi.org/10.1200/JCO.1995.13.7.1632. Erratum in: J Clin Oncol 1995;13(11):2860. PMID: 7602352.

    Article  PubMed  Google Scholar 

  23. Lad T, Piantadosi S, Thomas P, Payne D, Ruckdeschel J, Giaccone G. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest. 1994;106(6 Suppl):320S–3S. https://doi.org/10.1378/chest.106.6_supplement.320s. PMID: 7988254.

    Article  CAS  PubMed  Google Scholar 

  24. Lim E, Belcher E, Yap YK, Nicholson AG, Goldstraw P. The role of surgery in the treatment of limited disease small cell lung cancer: time to reevaluate. J Thorac Oncol. 2008;3(11):1267–71. https://doi.org/10.1097/JTO.0b013e318189a860. PMID: 18978561.

    Article  PubMed  Google Scholar 

  25. Ignatius Ou SH, Zell JA. The applicability of the proposed IASLC staging revisions to small cell lung cancer (SCLC) with comparison to the current UICC 6th TNM Edition. J Thorac Oncol. 2009;4(3):300–10. https://doi.org/10.1097/JTO.0b013e318194a355. PMID: 19156001.

    Article  PubMed  Google Scholar 

  26. NCCN. Guidelines for small cell lung cancer. n.d.. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.

  27. Mercier SL, Moore SM, Akurang D, Tiberi D, Wheatley-Price P. Stereotactic body radiotherapy (SBRT) in very limited-stage small cell lung cancer (VLS-SCLC). Curr Oncol. 2022;30(1):100–9. https://doi.org/10.3390/curroncol30010008. PMID: 36661657; PMCID: PMC9858162.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Verma V, Simone CB II, Allen PK, Gajjar SR, Shah C, Zhen W, Harkenrider MM, Hallemeier CL, Jabbour SK, Matthiesen CL, Braunstein SE, Lee P, Dilling TJ, Allen BG, Nichols EM, Attia A, Zeng J, Biswas T, Paximadis P, Wang F, Walker JM, Stahl JM, Daly ME, Decker RH, Hales RK, Willers H, Videtic GM, Mehta MP, Lin SH. Multi-institutional experience of stereotactic ablative radiation therapy for stage I small cell lung cancer. Int J Radiat Oncol Biol Phys. 2017;97(2):362–71. https://doi.org/10.1016/j.ijrobp.2016.10.041. Epub 2016 Nov 2. PMID: 28011047.

    Article  PubMed  Google Scholar 

  29. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol. 1992;10(6):890–5. https://doi.org/10.1200/JCO.1992.10.6.890. PMID: 1316951.

    Article  CAS  PubMed  Google Scholar 

  30. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, Brodin O, Joss RA, Kies MS, Lebeau B, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327(23):1618–24. https://doi.org/10.1056/NEJM199212033272302. PMID: 1331787.

    Article  CAS  PubMed  Google Scholar 

  31. Carney DN, Mitchell JB, Kinsella TJ. In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants. Cancer Res. 1983;43(6):2806–11. PMID: 6303568.

    CAS  PubMed  Google Scholar 

  32. Abadir R, Orton C. Radiotherapy for small-cell lung cancer. N Engl J Med. 1999;340(25):2002–3; author reply 2003-4. PMID: 10383278.

    Article  CAS  PubMed  Google Scholar 

  33. Bogart J, Wang X, Masters G, Gao J, Komaki R, Gaspar LE, Heymach J, Bonner J, Kuzma C, Waqar S, Petty W, Stinchcombe TE, Bradley JD, Vokes E. High-dose once-daily thoracic radiotherapy in limited-stage small-cell lung cancer: CALGB 30610 (Alliance)/RTOG 0538. J Clin Oncol. 2023;41:2394. https://doi.org/10.1200/JCO.22.01359. PMID: 36623230.

    Article  CAS  PubMed  Google Scholar 

  34. Grønberg BH, Killingberg KT, Fløtten Ø, Brustugun OT, Hornslien K, Madebo T, Langer SW, Schytte T, Nyman J, Risum S, Tsakonas G, Engleson J, Halvorsen TO. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet Oncol. 2021;22(3):321–31. https://doi.org/10.1016/S1470-2045(20)30742-7. PMID: 33662285.

    Article  PubMed  Google Scholar 

  35. De Ruysscher D, Bremer RH, Koppe F, Wanders S, van Haren E, Hochstenbag M, Geeraedts W, Pitz C, Simons J, ten Velde G, Dohmen J, Snoep G, Boersma L, Verschueren T, van Baardwijk A, Dehing C, Pijls M, Minken A, Lambin P. Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial. Radiother Oncol. 2006;80(3):307–12. https://doi.org/10.1016/j.radonc.2006.07.029. Epub 2006 Sep 1. PMID: 16949169.

    Article  PubMed  Google Scholar 

  36. van Loon J, De Ruysscher D, Wanders R, Boersma L, Simons J, Oellers M, Dingemans AM, Hochstenbag M, Bootsma G, Geraedts W, Pitz C, Teule J, Rhami A, Thimister W, Snoep G, Dehing-Oberije C, Lambin P. Selective nodal irradiation on basis of (18)FDG-PET scans in limited-disease small-cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys. 2010;77(2):329–36. https://doi.org/10.1016/j.ijrobp.2009.04.075. Epub 2009 Sep 24. PMID: 19782478.

    Article  PubMed  Google Scholar 

  37. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002;20(14):3054–60. https://doi.org/10.1200/JCO.2002.12.071. PMID: 12118018.

    Article  CAS  PubMed  Google Scholar 

  38. Fried DB, Morris DE, Poole C, Rosenman JG, Halle JS, Detterbeck FC, Hensing TA, Socinski MA. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol. 2004;22(23):4837–45. https://doi.org/10.1200/JCO.2004.01.178. Erratum in: J Clin Oncol. 2005;23(1):248. PMID: 15570087.

    Article  PubMed  Google Scholar 

  39. De Ruysscher D, Pijls-Johannesma M, Bentzen SM, Minken A, Wanders R, Lutgens L, Hochstenbag M, Boersma L, Wouters B, Lammering G, Vansteenkiste J, Lambin P. Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol. 2006;24(7):1057–63. https://doi.org/10.1200/JCO.2005.02.9793. PMID: 16505424.

    Article  PubMed  Google Scholar 

  40. Liao Z, Lee JJ, Komaki R, Gomez DR, O’Reilly MS, Fossella FV, Blumenschein GR Jr, Heymach JV, Vaporciyan AA, Swisher SG, Allen PK, Choi NC, DeLaney TF, Hahn SM, Cox JD, Lu CS, Mohan R. Bayesian adaptive randomization trial of passive scattering proton therapy and intensity-modulated photon radiotherapy for locally advanced non-small-cell lung cancer. J Clin Oncol. 2018;36(18):1813–22. https://doi.org/10.1200/JCO.2017.74.0720. Epub 2018. Erratum in: J Clin Oncol. 2018;36(24):2570. PMID: 29293386; PMCID: PMC6008104.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rwigema JM, Verma V, Lin L, Berman AT, Levin WP, Evans TL, Aggarwal C, Rengan R, Langer C, Cohen RB, Simone CB II. Prospective study of proton-beam radiation therapy for limited-stage small cell lung cancer. Cancer. 2017;123(21):4244–51. https://doi.org/10.1002/cncr.30870. Epub 2017 Jul 5. PMID: 28678434.

    Article  CAS  PubMed  Google Scholar 

  42. Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999;17(11):3540–5. https://doi.org/10.1200/JCO.1999.17.11.3540. PMID: 10550152.

    Article  CAS  PubMed  Google Scholar 

  43. Schmittel A, von Weikersthal LF, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006;17(4):663–7. https://doi.org/10.1093/annonc/mdj137. Epub 2006 Jan 19. PMID: 16423848.

    Article  CAS  PubMed  Google Scholar 

  44. Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L, CASPIAN Investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51–65. https://doi.org/10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4. PMID: 33285097.

    Article  CAS  PubMed  Google Scholar 

  45. O’Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006;24(34):5441–7. https://doi.org/10.1200/JCO.2006.06.5821. PMID: 17135646.

    Article  CAS  PubMed  Google Scholar 

  46. Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D’Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645–54. https://doi.org/10.1016/S1470-2045(20)30068-1. Epub 2020 Mar 27. Erratum in: Lancet Oncol. 2020;21(12): e553. PMID: 32224306.

    Article  CAS  PubMed  Google Scholar 

  47. FDA. n.d.. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer.

  48. Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T, JCOG0605 Investigators. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016;17(8):1147–57. https://doi.org/10.1016/S1470-2045(16)30104-8. Epub 2016 Jun 14. PMID: 27312053.

    Article  CAS  PubMed  Google Scholar 

  49. von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999;17(2):658–67. https://doi.org/10.1200/JCO.1999.17.2.658. PMID: 10080612.

    Article  Google Scholar 

  50. Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012;18(4):1138–45. https://doi.org/10.1158/1078-0432.CCR-11-2059. Epub 2012 Jan 6. PMID: 22228633.

    Article  CAS  PubMed  Google Scholar 

  51. 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. 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. 2020;15(4):618–27. https://doi.org/10.1016/j.jtho.2019.12.109. Epub 2019 Dec 20. PMID: 31870883.

    Article  CAS  PubMed  Google Scholar 

  52. Jeremic B, Shibamoto Y, Nikolic N, Milicic B, Milisavljevic S, Dagovic A, Aleksandrovic J, Radosavljevic-Asic G. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol. 1999;17(7):2092–9. https://doi.org/10.1200/JCO.1999.17.7.2092. PMID: 10561263.

    Article  CAS  PubMed  Google Scholar 

  53. Gore EM, Hu C, Sun AY, Grimm DF, Ramalingam SS, Dunlap NE, Higgins KA, Werner-Wasik M, Allen AM, Iyengar P, Videtic GMM, Hales RK, McGarry RC, Urbanic JJ, Pu AT, Johnstone CA, Stieber VW, Paulus R, Bradley JD. Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive-disease small cell lung cancer (ED SCLC): NRG oncology RTOG 0937. J Thorac Oncol. 2017;12(10):1561–70. https://doi.org/10.1016/j.jtho.2017.06.015. Epub 2017 Jun 23. PMID: 28648948; PMCID: PMC5610652.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S, EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664–72. https://doi.org/10.1056/NEJMoa071780. PMID: 17699816.

    Article  CAS  PubMed  Google Scholar 

  55. Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, Keijser A, Faivre-Finn C, Senan S. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015;385(9962):36–42. https://doi.org/10.1016/S0140-6736(14)61085-0. Epub 2014 Sep 14. Erratum in: Lancet. 2015;385(9962):28. PMID: 25230595.

    Article  PubMed  Google Scholar 

  56. Komaki R. Prophylactic cranial irradiation for small cell carcinoma of the lung. Cancer Treat Symp. 1985;2:1.

    Google Scholar 

  57. Arriagada R, Le Chevalier T, Borie F, Rivière A, Chomy P, Monnet I, Tardivon A, Viader F, Tarayre M, Benhamou S. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst. 1995;87(3):183–90. https://doi.org/10.1093/jnci/87.3.183. PMID: 7707405.

    Article  CAS  PubMed  Google Scholar 

  58. Hirsch FR, Paulson OB, Hansen HH, Vraa-Jensen J. Intracranial metastases in small cell carcinoma of the lung: correlation of clinical and autopsy findings. Cancer. 1982;50(11):2433–7. https://doi.org/10.1002/1097-0142(19821201)50:11<2433::aid-cncr2820501131>3.0.co;2-e. PMID: 6182974.

    Article  CAS  PubMed  Google Scholar 

  59. Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476–84. https://doi.org/10.1056/NEJM199908123410703. PMID: 10441603.

    Article  PubMed  Google Scholar 

  60. Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A, Prophylactic Cranial Irradiation (PCI) Collaborative Group. 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(5):467–74. https://doi.org/10.1016/S1470-2045(09)70101-9. Epub 2009 Apr 20. PMID: 19386548.

    Article  PubMed  Google Scholar 

  61. Hochstenbag MM, Twijnstra A, Wilmink JT, Wouters EF, ten Velde GP. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neuro-Oncol. 2000;48(3):243–8. https://doi.org/10.1023/a:1006427407281. PMID: 11100822.

    Article  CAS  Google Scholar 

  62. Seute T, Leffers P, Wilmink JT, ten Velde GP, Twijnstra A. Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy. J Clin Oncol. 2006;24(13):2079–83. https://doi.org/10.1200/JCO.2005.03.2946. PMID: 16648509.

    Article  CAS  PubMed  Google Scholar 

  63. 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. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomized, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663–71. https://doi.org/10.1016/S1470-2045(17)30230-9. Epub 2017 Mar 23. PMID: 28343976.

    Article  PubMed  Google Scholar 

  64. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. 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(34):3810–6. https://doi.org/10.1200/JCO.2014.57.2909. Epub 2014 Oct 27. PMID: 25349290; PMCID: PMC4239303.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Redmond KJ, Hales RK, Anderson-Keightly H, Zhou XC, Kummerlowe M, Sair HI, Duhon M, Kleinberg L, Rosner GL, Vannorsdall T. Prospective study of hippocampal-sparing prophylactic cranial irradiation in limited-stage small cell lung cancer. Int J Radiat Oncol Biol Phys. 2017;98(3):603–11. https://doi.org/10.1016/j.ijrobp.2017.03.009. Epub 2017 Mar 14. PMID: 28581401.

    Article  PubMed  Google Scholar 

  66. Rodríguez de Dios N, Couñago F, Murcia-Mejía M, Rico-Oses M, Calvo-Crespo P, Samper P, Vallejo C, Luna J, Trueba I, Sotoca A, Cigarral C, Farré N, Manero RM, Durán X, Gispert JD, Sánchez-Benavides G, Rognoni T, Torrente M, Capellades J, Jiménez M, Cabada T, Blanco M, Alonso A, Martínez-San Millán J, Escribano J, González B, López-Guerra JL. Randomized phase III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small-cell lung cancer (PREMER): a GICOR-GOECP-SEOR study. J Clin Oncol. 2021;39(28):3118–27. https://doi.org/10.1200/JCO.21.00639. Epub 2021 Aug 11. PMID: 34379442.

    Article  CAS  PubMed  Google Scholar 

  67. Belderbos JSA, De Ruysscher DKM, De Jaeger K, Koppe F, Lambrecht MLF, Lievens YN, Dieleman EMT, Jaspers JPM, Van Meerbeeck JP, Ubbels F, Kwint MH, Kuenen MA, Deprez S, De Ruiter MB, Boogerd W, Sikorska K, Van Tinteren H, Schagen SB. Phase 3 randomized trial of prophylactic cranial irradiation with or without hippocampus avoidance in SCLC (NCT01780675). J Thorac Oncol. 2021;16(5):840–9. https://doi.org/10.1016/j.jtho.2020.12.024. Epub 2021 Feb 2. PMID: 33545387.

    Article  PubMed  Google Scholar 

  68. NRG Oncology. n.d.. https://www.nrgoncology.org/Home/News/Post/nrg-oncology-ncorp-trial-of-hippocampal-avoidance-for-small-cell-lung-cancer-patients-receiving-prophylactic-cranial-irradiation-reaches-accrual-goal.

Download references

Author information

Authors and Affiliations

  1. Johns Hopkins School of Medicine, Baltimore, MD, USA

    Russell Hales & Khinh Ranh Voong

Authors
  1. Russell Hales
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Khinh Ranh Voong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Russell Hales .

Editor information

Editors and Affiliations

  1. Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA

    Christina R. MacRosty

  2. Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA

    M. Patricia Rivera

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hales, R., Voong, K.R. (2023). Treatment of Small Cell Lung Cancer. In: MacRosty, C.R., Rivera, M.P. (eds) Lung Cancer. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-031-38412-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-38412-7_9

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-031-38411-0

  • Online ISBN: 978-3-031-38412-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation