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Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy

Erfolgreiche Behandlung einer leptomeningealen Metastasierung bei großzelligem neurodokrinen Lungenkarzinom mit stereotaktischer Radiotherapie

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Abstract

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

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References

  1. Asamura H, Kameya T, Matsuno Y et al (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24(1):70–76

    Article  PubMed  Google Scholar 

  2. Aupérin A, Arriagada R, Pignon JP et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 341(7):476–484

    Article  PubMed  Google Scholar 

  3. Bene GD, Prelaj A, Berrios JRG, Filippis LD, Emiliani A, Galletti A, Ferrara C, Longo F (2016) 94P: first-line treatment with cisplatin plus etoposide for small cell lung cancer and large cell neuroendocrine carcinoma: our center experience. J Thorac Oncol 11(4):S97

    Article  Google Scholar 

  4. Brown PD, Ballman KV, Cerhan JH et al (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18(8):1049–1060

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401–409

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10(11):1037–1044

    Article  PubMed  Google Scholar 

  7. Fasano M, Della Corte CM, Papaccio F, Ciardiello F, Morgillo F (2015) Pulmonary large-cell neuroendocrine carcinoma: from epidemiology to therapy. J Thorac Oncol 10(8):1133–1141

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fournel L, Falcoz PE, Alifano M, Charpentier MC, Boudaya MS, Magdeleinat P, Damotte D, Régnard JF (2013) Surgical management of pulmonary large cell neuroendocrine carcinomas: a 10-year experience. Eur J Cardiothorac Surg 43(1):111–114

    Article  PubMed  Google Scholar 

  9. Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gleissner B, Chamberlain MC (2006) Neoplastic meningitis. Lancet Neurol 5(5):443–452

    Article  PubMed  Google Scholar 

  11. Glisson BS, Moran CA (2011) Large-cell neuroendocrine carcinoma: controversies in diagnosis and treatment. J Natl Compr Canc Netw 9(10):1122–1129

    Article  PubMed  Google Scholar 

  12. Gore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H (2010) Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non–small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol 29(3):272–278

    Article  PubMed  PubMed Central  Google Scholar 

  13. Huang AJ, Huang KE, Page BR, Ayala-Peacock DN, Lucas JT, Lesser GJ, Laxton AW, Tatter SB, Chan MD (2014) Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery. J Neurooncol 120(1):163–169

    Article  PubMed  Google Scholar 

  14. Igawa S, Watanabe R, Ito I et al (2010) Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer 68(3):438–445

    Article  PubMed  Google Scholar 

  15. Iyoda A, Makino T, Koezuka S, Otsuka H, Hata Y (2014) Treatment options for patients with large cell neuroendocrine carcinoma of the lung. Gen Thorac Cardiovasc Surg 62(6):351–356

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kawabe T, Yamamoto M, Sato Y et al (2016) Gamma knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401). J Neurosurg 125(Suppl 1):11–17

    Article  PubMed  Google Scholar 

  17. Lehrer EJ, Peterson JL, Zaorsky NG, Brown PD, Sahgal A, Chiang VL et al (2019) Single versus multifraction stereotactic radiosurgery for large brain metastases: an international meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 103(3):618–630

    Article  Google Scholar 

  18. Li J, Brown PD (2017) The diminishing role of whole-brain radiation therapy in the treatment of brain metastases. JAMA Oncol 3(8):1023–1024

    Article  PubMed  Google Scholar 

  19. Lo Russo G, Pusceddu S, Proto C et al (2016) Treatment of lung large cell neuroendocrine carcinoma. Tumor Biol 37(6):7047–7057

    Article  Google Scholar 

  20. Ma R, Levy M, Gui B et al (2018) Risk of leptomeningeal carcinomatosis in patients with brain metastases treated with stereotactic radiosurgery. J Neurooncol 136(2):395–401

    Article  PubMed  Google Scholar 

  21. McPherson CM, Suki D, Feiz-Erfan I, Mahajan A, Chang E, Sawaya R, Lang FF (2010) Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases. Neuro Oncol 12(7):711–719

    Article  PubMed  PubMed Central  Google Scholar 

  22. Naidoo J, Santos-Zabala ML, Iyriboz T et al (2016) Large cell neuroendocrine carcinoma of the lung: clinico-pathologic features, treatment, and outcomes. Clin Lung Cancer 17(5):e121–e129

    Article  PubMed  PubMed Central  Google Scholar 

  23. Owonikoko TK, Arbiser J, Zelnak A et al (2014) Current approaches to the treatment of metastatic brain tumours. Nat Rev Clin Oncol 11(4):203–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B (1998) Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280(17):1485–1489

    Article  CAS  Google Scholar 

  25. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322(8):494–500

    Article  CAS  PubMed  Google Scholar 

  26. Patel KR, Burri SH, Boselli D et al (2017) Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis. J Neurooncol 131(3):611–618

    Article  CAS  Google Scholar 

  27. Patel KR, Prabhu RS, Kandula S et al (2014) Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone. J Neurooncol 120(3):657–663

    Article  CAS  PubMed  Google Scholar 

  28. Prabhu RS, Turner BE, Asher AL et al (2019) A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases. Neuro Oncol 21(8):1049–1059

    Article  PubMed  PubMed Central  Google Scholar 

  29. Prayongrat A, Tao R, Allen PK et al (2018) Outcomes of stereotactic radiosurgery of brain metastases from neuroendocrine tumors. Neurooncol Pract 5(1):37–45

    PubMed  Google Scholar 

  30. Rekhtman N, Pietanza MC, Hellmann MD et al (2016) Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma–like and non–small cell carcinoma–like subsets. Clin Cancer Res 22(14):3618–3629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rhun EL, Preusser M, van den Bent M, Andratschke N, Weller M (2019) How we treat patients with leptomeningeal metastases. ESMO Open 4(Suppl 2):e507

    Article  PubMed  PubMed Central  Google Scholar 

  32. Roesel C, Terjung S, Weinreich G, Gauler T, Theegarten D, Stamatis G, Welter S (2016) A single-institution analysis of the surgical management of pulmonary large cell neuroendocrine carcinomas. Ann Thorac Surg 101(5):1909–1914

    Article  PubMed  Google Scholar 

  33. Sarkaria IS, Iyoda A, Roh MS, Sica G, Kuk D, Sima CS, Pietanza MC, Park BJ, Travis WD, Rusch VW (2011) Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg 92(4):1180–1187

    Article  PubMed  Google Scholar 

  34. 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(7):664–672

    Article  CAS  PubMed  Google Scholar 

  35. Suki D, Hatiboglu MA, Patel AJ, Weinberg JS, Groves MD, Mahajan A, Sawaya R (2009) Comparative risk of leptomeningeal dissemination of cancer after surgery or stereotactic radiosurgery for a single supratentorial solid tumor metastasis. Neurosurgery 64(4):664–676

    Article  Google Scholar 

  36. Sun JM, Ahn MJ, Ahn JS et al (2012) Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer? Cancer Treat Res 77(2):365–370

    Google Scholar 

  37. Sun A, Bae K, Gore EM et al (2010) Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non–small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol 29(3):279–286

    Article  PubMed  PubMed Central  Google Scholar 

  38. Trifiletti DM, Brown PD (2020) Leptomeningeal disease following local brain irradiation: a new frontier. Neuro Oncol 22(1):5–6

    Article  PubMed  Google Scholar 

  39. Veronesi G, Morandi U, Alloisio M et al (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Cancer Treat Res 53(1):111–115

    Google Scholar 

  40. Wang N, Bertalan MS, Brastianos PK (2018) Leptomeningeal metastasis from systemic cancer: review and update on management. Cancer 124(1):21–35

    Article  PubMed  Google Scholar 

  41. Wegner RE, Hasan S, Williamson RW et al (2019) Management of brain metastases from large cell neuroendocrine carcinoma of the lung: improved outcomes with radiosurgery. Acta Oncol 58:499–504

    Article  PubMed  Google Scholar 

  42. Zhao Y, Castonguay M, Wilke D, Xu Z, Plourde M, Mulroy L, MacNeil M, Bowes D (2019) Treatment outcomes and incidence of brain metastases in pulmonary large cell neuroendocrine carcinoma. Curr Probl Cancer 43(1):54–65

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Radio-Onkologie-Zentrum KSA-KSB, Kantonsspital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland

    Seok-Yun Lee, Nicoletta Lomax, Oliver Riesterer, Stephan Bodis & Susanne Rogers

  2. Klinik für Neurochirurgie, Kantonsspital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland

    Sven Berkmann

  3. Klinik für Onkologie, Kantonsspital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland

    Kathrin Vollmer

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  1. Seok-Yun Lee
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  2. Nicoletta Lomax
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Correspondence to Seok-Yun Lee.

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S. Rogers has received speakers honoraria from Brainlab. S.‑Y. Lee, N. Lomax, S. Berkmann, K. Vollmer, O. Riesterer and S. Bodis declare that they have no competing interests.

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Lee, SY., Lomax, N., Berkmann, S. et al. Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy. Strahlenther Onkol 197, 1143–1147 (2021). https://doi.org/10.1007/s00066-021-01814-0

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  • DOI: https://doi.org/10.1007/s00066-021-01814-0

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