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Kepka. J Cancer Metastasis Treat 2019;5:53 I http://dx.doi.org/10.20517/2394-4722.2018.114 Page 7 of 11

Table 1. Characteristics and outcome of patients undergoing radiosurgery (RS) for brain metastases (BM) from small-cell
lung cancer (SCLC)
Number of patients
Number of Number of BM Median overall Distant
Author, year included treated/doses of undergoing prior WBRT survival from Local control control in the
patients SRS (details on previous RS (months) brain
treatment)
Bernhardt et al. [35] , 2016 13 Maximum: 4 / 18- 13 (PCI: 30 Gy in 15 fractions) 5 (range: Not Not provided
24 Gy 0-12) provided
Rava et al. [37] , 2015 40 Single: 15 37 (27: WBRT, 10: PCI) 6.5 (range: Actuarial Actuarial
2-3: 15 4.1-8.9) 1-year: 69% 1-year: 22%
≥ 4: 10/
No details
Harris et al. [36] , 2012 51 Single: 22 51 (35: WBRT, 16: PCI) 5.9 Actuarial Actuarial
2-3: 18 1-year: 57% 1-year: 42%
≥ 4: 11/10-24 Gy
(median: 18 Gy)
Wegner et al. [40] , 2011 44 Median: 1 (range: 36 (18: WBRT at median dose: 9 Actuarial Crude rate of
1-14)/14-20 Gy 30 Gy in 10 fractions; 6 WBRT 1-year: 86% failure: 61%
(median: 18 Gy) combined with SRS; 9: PCI, 3:
PCI + WBRT for relapse)
Olson et al. [39] , 2012 27 Median: 2 27 (19: WBRT, 8: PCI) 3 Actuarial Actuarial
(range:1-6)/15-24 1-year: 75% 1-year: 31%
Gy (median: 20.5
Gy)
Yomo et al. [41] , 2015 70 Median: 2 23 (16: WBRT, 7: PCI) + 1 7.8 (range: Actuarial Actuarial
(range:1-21)/12-22 Hypofractionated partial 0.6-56) 1-year: 77% 1-year: 53%
Gy (median: 20 Gy) brain irradiation
Nakazaki et al. [38] , 2012 44 Median: 5 44 (34: WBRT with median 5.8 (range: 33 out of 44 33 out of 44
(range:1-98)/10-21 dose of 30 Gy, 10: PCI) 0.5-24) evaluated: evaluated: in
Gy (median: 20 Gy) in 10 out of 24 out of 33
33 failure: failure: 28%
70% crude crude distant
local control control
Abbreviations: PCI: Prophylactic Cranial Irradiation; WBRT: Whole-Brain Radiotherapy

patients who are not candidates for radiosurgery and the short survival of such patients prevents them from
the development of serious late neurotoxicity.

In the case of a limited number of BM < 3 cm in diameter, the minimal invasiveness and ease of use of
radiosurgery make it the preferred salvage method after prior PCI for patients with life expectancy > 3 months.
Retrospective data indicate that for patients with good performance status, radiosurgery for BM in SCLC gave
results that were at least comparable with WBRT in terms of survival, with the median range of 3-9 months [30-36] .
However, some reports reported lower local control after radiosurgery for BM from SCLC than for BM from
other solid tumors. One-year local control rates were < 70% in evaluated patients [36-41] , whilst in prospective trials
on radiosurgery with the exclusion of SCLC histology, these rates were 70%-90% [42,43] . Distant brain control
was also at the lower limit or < 60% as reported in prospective trials on radiosurgery alone [36-41] . This may be
related to the known aggressiveness of SCLC, but also to the inclusion of patients with multiple (> 4) BM, which
may affect these results. Recently, it was demonstrated that radiosurgery without WBRT in patients with 5-10
BM was not inferior to that in patients with 2-4 BM in terms of survival . Table 1 summarizes the results of
[44]
radiosurgery for BM from SCLC used as a salvage method after WBRT, as well as a first-line irradiation. To
conclude, radiosurgery is an attractive treatment option after prior PCI and should be used if the technical
possibilities for its use exist; however, WBRT at moderate doses is also feasible. WBRT is the treatment of first
choice in patients who are unsuitable for radiosurgery or symptomatic patients with limited life expectancy (<
3 months).

REDUCTION OF NEUROTOXICITY IN BRAIN RADIOTHERAPY FOR SCLC
WBRT in SCLC plays a role in prevention in the form of PCI and remains the standard in the treatment of
BM. However, we have evidence that WBRT has a detrimental effect on neurocognitive functioning. In a