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Prophylactic cranial irradiation in lung cancer

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Opinion statement

Patients with locally advanced lung cancer (non-small cell lung cancer or small cell lung cancer [SCLC]) are threatened by concurrent risks of local, regional, and distant failure. By improving locoregional and systemic control within multimodality protocols, the brain emerges as one of the major relapse sites; therefore, prevention of brain relapse has become a primary focus of attention. Prophylactic cranial irradiation (PCI) has a high potential to reduce the risk of brain metastases. Clear evidence exists from meta-analysis that PCI improves overall and disease-free survival rates for patients with SCLC in complete remission. Long-term toxicities, predominantly neurocognitive impairments, represent potential risks, but within large prospective trials, including adequate control groups, late complications of clinical significance rarely have been observed. PCI is the recommended standard of care for the patients with limited disease SCLC in complete remission. As long as the optimal dose and fractionation remain to be defined in this setting, conventional fractionation with moderate total doses of approximately 30 Gy is preferred. In patients with locally advanced stage III non-small cell lung cancer treated within multimodality protocols, comparable relative risks for cumulative brain relapse have been demonstrated in long-term survivors. Although not the standard of care in this situation, the scientific community should be encouraged to further investigate PCI in these patient subgroups within carefully designed clinical trials, including untreated control arms.

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References and Recommended Reading

  1. 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, 50:2433–2437.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Arriagada R, Le Chevalier T, Borie F: Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. J Natl Cancer Inst 1995, 87:183–190. The study provides evidence of baseline abnormalities independent of PCI delivery in patients with lung cancer.

    Article  PubMed  CAS  Google Scholar 

  4. Laplanche A, Monnet I, Santos-Miranda JA, et al.: Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Lung Cancer 1998, 21:193–201.

    Article  PubMed  CAS  Google Scholar 

  5. Gregor A, Cull A, Stephens RJ, et al.: Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomized trial. Eur J Cancer 1997, 16:1752–1758. The trial supports the hypothesis of a dose-response relationship in patients with SCLC.

    Article  Google Scholar 

  6. Auperin 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. The meta-analysis has given impact to a change in treatment policy.

    Article  PubMed  CAS  Google Scholar 

  7. Cox JD, Yesner R, Mietlowski W, Petrovich Z: Influence of cell type on failure pattern after irradiation for locally advanced carcinoma of the lung. Cancer 1979, 44:94–98.

    Article  PubMed  CAS  Google Scholar 

  8. Feld R, Rubinstein LV, Weisenberger TH: Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies. J Clin Oncol 1984, 2:1352–1358.

    PubMed  CAS  Google Scholar 

  9. Martini N, Beattie EJ: Results of surgical treatment in stage I lung cancer. J Thorac Cardiovasc Surg 1977, 74:499–505.

    PubMed  CAS  Google Scholar 

  10. Perez CA, Pajak TF, Rubin P, et al.: Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer 1987, 59:1874–1881.

    Article  PubMed  CAS  Google Scholar 

  11. Andre F, Grunenwald D, Pujol JL, et al.: Patterns of relapse of N2 non-small cell lung carcinoma patients treated with preoperative chemotherapy: should prophylactic cranial irradiation be reconsidered? Cancer 2001, 91:2394–2400.

    Article  PubMed  CAS  Google Scholar 

  12. Kumar P, Herndon J, Langer M, et al.: Patterns of disease failure after trimodality therapy of non-small cell lung carcinoma pathologic stage IIIA (N2): analysis of CALGB protocol 8935. Cancer 1996, 77:2393–2399.

    Article  Google Scholar 

  13. Albain KS, Rusch VW, Crowley JJ, et al.: Concurrent cisplatin/ etoposide plus chest radiotherapy followed by surgery for stages IIIA(N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol 1995, 13:1880–1892.

    PubMed  CAS  Google Scholar 

  14. Eberhardt W, Wilke H, Stamatis G, et al.: Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol 1998, 16:622–634.

    PubMed  CAS  Google Scholar 

  15. Law A, Karp DD, Dipetrillo T, Daly BT: Emergence of increased cerebral metastasis after high-dose preoperative radiotherapy with chemotherapy in patients with locally advanced non-small cell lung carcinoma. Cancer 2001, 92:160–164.

    Article  PubMed  CAS  Google Scholar 

  16. Stuschke M, Eberhardt W, Pöttgen C, et al.: Prophylactic cranial irradiation in locally advanced non-small cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuropsychologic effects. J Clin Oncol 1999, 17:2700–2709.

    PubMed  CAS  Google Scholar 

  17. Figlin RA, Piantadosi S, Feld R: Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small cell lung cancer. N Engl J Med 1988, 318:1300–1305.

    Article  PubMed  CAS  Google Scholar 

  18. Robnett TJ, Machtay M, Stevenson JP, et al.: Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced non-small-cell lung carcinoma. J Clin Oncol 2001, 19:1344–1349.

    PubMed  CAS  Google Scholar 

  19. Russell AH, Pajak TE, Selim HM, et al.: Prophylactic cranial irradiation for lung cancer patients at high risk for development of cerebral metastasis: results of a prospective randomized trial conducted by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1991, 21:637–643.

    PubMed  CAS  Google Scholar 

  20. Jacobs RH, Awan A, Bitran JC, et al.: Prophylactic cranial irradiation in adenocarcinoma of the lung: a possible role. Cancer 1987, 59:2016–2019.

    Article  PubMed  CAS  Google Scholar 

  21. Nussbaum ES, Djalilian HR, Cho KH, Hall WA: Brain metastases: histology, multiplicity, surgery, and survival. Cancer 1996, 78:1781–1788.

    Article  Google Scholar 

  22. Postmus PE, Smit EF: Chemotherapy for brain metastases of lung cancer: a review. Ann Oncol 1999, 10:753–759.

    Article  PubMed  CAS  Google Scholar 

  23. Grossi F, Scolaro T, Tixi L, et al.: The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer. Crit Rev Oncol Hematol 2001, 37:61–67.

    PubMed  CAS  Google Scholar 

  24. Korfel A, Oehm C, von Pawel J, et al.: Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation: a multicentre phase-II study. Eur J Cancer 2002, 38:1724.

    Article  PubMed  CAS  Google Scholar 

  25. Cox JD, Scott CB, Emami B, et al.: Addition of chemotherapy to radiation therapy alters failure pattern by cell type within non-small cell carcinoma of lung: analysis of Radiation Therapy Oncology Group trials. Int J Radiat Oncol Biol Phys 1999, 43:505–509.

    Article  PubMed  CAS  Google Scholar 

  26. Suwinski R, See SP, Withers R: Dose-response relationship for prophylactic cranial irradiation in small cell lung cancer. Int J Radiat Oncol Biol Phys 1998, 40:797–806.

    Article  PubMed  CAS  Google Scholar 

  27. Yang GY, Matthews RH: Prophylactic cranial irradiation in small-cell lung cancer. Oncologist 2000, 5:293–298.

    Article  PubMed  CAS  Google Scholar 

  28. Turrisi AT, Sherman CA: The treatment of limited small cell lung cancer: a report of the progress made and future prospects. Eur J Cancer 2002, 38:279–291. The report provides an excellent overview of recent developments.

    Article  PubMed  CAS  Google Scholar 

  29. Cox JD, Stanley K, Petrovich Z, et al.: Cranial irradiation in cancer of the lung of all cell types. JAMA 1981, 245:469–472.

    Article  PubMed  CAS  Google Scholar 

  30. Umsawasdi T, Valdivieso M, Chen TT, et al.: Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer. J Neurooncol 1984, 2:253–259.

    Article  PubMed  CAS  Google Scholar 

  31. Miller TP, Crowley JJ, Mira J, et al.: A randomized trial of chemotherapy and radiotherapy for stage III nonsmall cell lung cancer. Cancer Ther 1998, 1:229–236.

    CAS  Google Scholar 

  32. Rusch VW, Griffin BR, Livingston RB: The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer: a Southwest Oncology Group study. J Thorac Cardiovasc Surg 1989, 98:535–539.

    PubMed  CAS  Google Scholar 

  33. Mira JG, Taylor SL, Stephens RL, et al.: Simultaneous chemotherapy-radiotherapy with prophylactic cranial irradiation for inoperable adeno and large cell lung carcinoma: a Southwest Oncology Group study. Int J Radiat Oncol Biol Phys 1988, 15:757–761.

    PubMed  CAS  Google Scholar 

  34. Strauss GM, Herndon JE, Sherman DD, et al.: Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study. J Clin Oncol 1992, 10:1237–1244.

    PubMed  CAS  Google Scholar 

  35. Cull A, Gregor A, Hopwood P, et al.: Neurological and cognitive impairment in long-term survivors of small cell lung cancer. Eur J Cancer 1994, 30A:1067–1074.

    Article  PubMed  CAS  Google Scholar 

  36. van Oosterhout AG, van de Pol M, ten Velde GP, Twijnstra A: Neurologic disorders in 203 consecutive patients with small cell lung cancer. Cancer 1996, 77:1434–1441.

    Article  Google Scholar 

  37. Fleck JF, Einhorn LH, Lauer RC, et al.: Is prophylactic cranial irradiation indicated in small-cell lung cancer? J Clin Oncol 1990, 8:209–214.

    PubMed  CAS  Google Scholar 

  38. Johnson BE, Patronas N, Hayes W, et al.: Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with smallcell lung cancer: further follow-up of 6-to 13-year survivors. J Clin Oncol 1990, 8:48–56.

    PubMed  CAS  Google Scholar 

  39. HarrisJR, Levene MB: Visual complications following irradiation for pituitary adenomas and craniopharyngiomas. Radiology 1976, 120:167–171.

    PubMed  CAS  Google Scholar 

  40. Penitzka S, Steinvorth S, Sehlleier S, et al.: Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing. Strahlenther Onkol 2002, 178:252–258.

    Article  PubMed  Google Scholar 

  41. Lilja AM, Portin RI, Hämäläinen PI, Salminen EK: Shortterm effects of radiotherapy on attention and memory performances in patients with brain tumors. Cancer 2001, 91:2361–2368.

    Article  PubMed  CAS  Google Scholar 

  42. Kurtz JM, Gelber R, Brady LW, et al.: The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1981, 7:891–895.

    PubMed  CAS  Google Scholar 

  43. Sause WT, Crowley JJ, Morantz R, et al.: Solitary brain metastasis: results of RTOG/SWOG protocol evaluation surgery + RT versus RT alone. Am J Clin Oncol 1990, 13:427–432.

    Article  PubMed  CAS  Google Scholar 

  44. Williams J, Enger C, Wharam M, et al.: Stereotactic radiosurgery for brain metastases: comparison of lung carcinoma vs non-lung tumors. J Neurooncol 1998, 37:79–85.

    Article  PubMed  CAS  Google Scholar 

  45. Li B, Yu J, Suntharalingam M, et al.: Comparison of three treatment options for single brain metastasis from lung cancer. Int J Cancer 2000, 90:37–45.

    Article  PubMed  CAS  Google Scholar 

  46. Adler JR, Cox RS, Kaplan I, Martin DP: Stereotactic radiosurgical treatment of brain metastases. J Neurosurg 1992, 76:444–449.

    Article  PubMed  CAS  Google Scholar 

  47. Alexander E, Moriarty TM, Davis RB: Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases. J Natl Cancer Inst 1995, 87:34–40.

    Article  PubMed  Google Scholar 

  48. Burt M, Wronski M, Arbit E, Galicich JH: Resection of brain metastases from non-small cell lung carcinoma: results of therapy. J Thorac Cardiovasc Surg 1992, 103:399–410.

    PubMed  CAS  Google Scholar 

  49. Patchell RA, Tibbs PA, Regine WF, et al.: Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998, 280:1485–1489.

    Article  PubMed  CAS  Google Scholar 

  50. Schellinger PD, Meinck HM, Thron A: Diagnostic accuracy of MRI compared to CCT in patients with brain metastases. J Neurooncol 1999, 44:275–281.

    Article  PubMed  CAS  Google Scholar 

  51. Schiff D: Single brain metastasis. Curr Treat Options Neurol 2001, 3:89–99.

    Article  PubMed  Google Scholar 

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Pöttgen, C., Eberhardt, W. & Stuschke, M. Prophylactic cranial irradiation in lung cancer. Curr. Treat. Options in Oncol. 5, 43–50 (2004). https://doi.org/10.1007/s11864-004-0005-7

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