Which patients with SCLC benefit from prophylactic cranial irradiation?

From Cancer Guidelines Wiki

The addition of prophylactic cranial irradiation (PCI) to patients who achieve a complete response to initial therapy reduces the incidence of brain metastases and improves disease free- and overall survival.[1][2][3][4] For patients with Extensive Stage (ES) SCLC who achieve either complete or partial response to initial therapy, PCI reduces the incidence of symptomatic brain metastases and improves disease free- and overall survival.[4] The survival benefit from PCI is achieved at the cost of modest detriment in some Quality of Life (QOL) domains.[5]

Two meta analyses of individual patient data from randomised trials,[1][2] as well as a third meta analysis[3] confirm an absolute survival benefit from PCI of about 5% at three years. A minority of patients in these studies had extensive stage disease at presentation. The EORTC performed a randomised trial of PCI in patients with ES and WHO performance status ≤2 who had “any response” to systemic chemotherapy.[4] The median survival was 6.7 versus 5.4 months in favour of PCI (p=0.003). The effect of PCI on health-related quality of life (HRQOL) was prospectively studied.[4][5] Clinically significant deterioration was observed in the domains of hair loss and fatigue at six weeks and three months in the PCI arm. The impact of PCI was limited for role, emotional, and cognitive functioning with no clinically significant differences reported. In contrast, a pooled secondary analysis of two randomised RTOG trials did reveal a decline both in patient-reported, as well as tested cognitive functioning at six and twelve months.[6] This resulted in a consequent reduction in QOL, and was the only domain in which self-reported QOL declined.

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Evidence summary and recommendations

Evidence summary Level References
For patients with limited stage SCLC and a CR to initial therapy, prophylactic cranial irradiation improves survival and reduces the incidence of brain metastases.

Last reviewed December 2015

I [1], [2], [3]
For good performance status patients with extensive stage SCLC and any response to initial therapy, prophylactic cranial irradiation improves survival and reduces the incidence of brain metastases.

Last reviewed December 2015

II [4]
Prophylactic cranial irradiation produces clinically significant hair loss and fatigue, but effects on other quality of life domains are more limited.

Last reviewed December 2015

II [5]
Evidence-based recommendationQuestion mark transparent.png Grade
Patients with limited stage and a complete response to initial therapy, and patients with extensive stage and any response to initial therapy should be offered prophylactic cranial irradiation.

Last reviewed December 2015

A


Practice pointQuestion mark transparent.png

Although there is no high level data to directly support the practice of prophylactic cranial irradiation in SCLC limited stage patients who achieve a partial response to initial therapy, the benefits of such practice may be inferred from randomised data in SCLC extensive stage patients. Prophylactic cranial irradiation may, therefore, be considered for patients with limited stage SCLC who are partial responders to initial therapy.
Last reviewed December 2015


Practice pointQuestion mark transparent.png

It is appropriate to obtain a brain CT scan before embarking on prophylactic cranial irradiation, to exclude pre-existing brain metastases. If brain metastases are detected then a palliative rather than prophylactic dose of whole brain radiotherapy may be delivered.
Last reviewed December 2015

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References

  1. 1.0 1.1 1.2 Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999 Aug 12;341(7):476-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10441603.
  2. 2.0 2.1 2.2 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.
  3. 3.0 3.1 3.2 Meert AP, Paesmans M, Berghmans T, Martin B, Mascaux C, Vallot F, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer 2001;1:5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11432756.
  4. 4.0 4.1 4.2 4.3 4.4 Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007 Aug 16;357(7):664-72 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17699816.
  5. 5.0 5.1 5.2 Slotman BJ, Mauer ME, Bottomley A, Faivre-Finn C, Kramer GW, Rankin EM, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol 2009 Jan 1;27(1):78-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19047288.
  6. Gondi V, Paulus R, Bruner DW, Meyers CA, Gore EM, Wolfson A, 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 Apr 15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23597420.

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Appendices

Further resources

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