What is the optimal dose and fractionation schedule of prophylactic cranial irradiation in patients with limited stage SCLC?

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What is the optimal dose and fractionation schedule of prophylactic cranial irradiation in patients with limited stage SCLC?

The Prophylactic Cranial Irradiation Overview Collaborative Group meta-analysis of individual patient data from seven trials confirmed a reduction in the incidence of brain metastases with increasing doses of prophylactic cranial irradiation (PCI), but no effect on survival.[1]

A randomised intergroup trial directly compared standard dose to higher dose PCI in patients with limited stage small cell lung cancer and a CR to initial therapy.[2] The standard dose arm received 25Gy in 10 daily fractions. The higher dose arm received either 36Gy in 18 daily fractions, or 36Gy in twice daily fractions of 1.5Gy each as part of a RTOG sub study. Higher doses of PCI conferred neither an increase in survival nor a reduction in the incidence of subsequent brain metastases. Nor was there any advantage to hyperfractionation in terms of neurotoxicity or QOL in the RTOG sub study of 265 patients.[3] In that sub study, patients receiving 36Gy had a significantly higher incidence of neurological deterioration and toxicity (as per the study’s definition of these endpoints) than those receiving 25Gy. Quality of life and neurotoxicity were also reported for the entire patient cohort of 720 patients.[4] In this larger analysis, there were no differences in QOL or neurotoxicity observed between the different dose arms.

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Evidence summary and recommendations

Evidence summary Level References
In patients with limited stage small cell lung cancer achieving a CR to initial therapy, prophylactic cranial irradiation doses greater than 25Gy in 10 fractions confer no clinically significant advantage.

Last reviewed December 2015

I, II [1], [2]
Evidence-based recommendationQuestion mark transparent.png Grade
Patients with limited stage small cell lung cancer achieving a complete response to initial therapy should receive prophylactic cranial irradiation to a dose of 25Gy in 10 daily fractions.

Last reviewed December 2015

B


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References

  1. 1.0 1.1 Prophylactic Cranial Irradiation Overview Collaborative Group. Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission (review). Cochrane Database Syst Rev 2009 Jan Abstract available at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002805/pdf.
  2. 2.0 2.1 Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, 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 May;10(5):467-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19386548.
  3. Wolfson AH, Bae K, Komaki R, Meyers C, Movsas B, Le Pechoux C, 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 Sep 1;81(1):77-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20800380.
  4. Le Péchoux C, Laplanche A, Faivre-Finn C, Ciuleanu T, Wanders R, Lerouge D, 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 May;22(5):1154-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21139020.

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Appendices

Further resources

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