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Page 2 of 11 Kepka. J Cancer Metastasis Treat 2019;5:53 I http://dx.doi.org/10.20517/2394-4722.2018.114

other cancers whole brain radiotherapy (WBRT) remains a standard treatment even if BM are suitable for
radiosurgery. The well recognized radio- and chemo-sensitivity of SCLC are also present in the case of BM.
Despite their radio- and chemo-responsiveness, the prognosis of BM from SCLC remains very poor with
median survival after WBRT of 3.0-4.7 months in both retrospective and prospective studies . The high
[2-5]
risk of developing BM with a dismal disease course once BM have occurred and their high radiosensitivity
have led to many trials assessing the value of prophylactic cranial irradiation (PCI). To date, SCLC is the only
solid tumor in which the prolongation of survival with the use of PCI has been demonstrated for localized
stage (LS) SCLC in a meta-analysis . A total dose of 25 Gy in 10 fractions was established in a randomized
[6]
trial as a standard dose of PCI for responders to initial therapy of LS SCLC . In addition, for extensive stage
[7]
(ES) SCLC, there were some indications that the use of PCI is of value for prolongation of survival and this
[6]
was demonstrated in one randomized trial .
[8]
The present review summarizes the problems related to radiotherapy of BM from SCLC with an emphasis
on the distinctiveness of this approach in relation to management of BM from solid tumors. Different
approaches in specific indications for treatment of BM from SCLC are discussed.

PROGNOSTIC FACTORS
Patients with BM from SCLC are usually excluded from trials on management of BM due to the different
biological behavior of the primary tumor. The question arises if existing prognostic scores for overall survival
in patients with BM are also relevant for BM from SCLC. The pivotal RTOG prognostic score was published
after carrying out a recursive partitioning analysis (RPA) of pretreatment characteristics of patients in the
randomized trials on BM. The prognosis of BM patients was related to the presence of three prognostic factors:
performance status, presence of extracranial disease and age. Class 1 with the best prognosis included patients
younger than 65 years, with control of extracranial disease, and with performance status > 60 in Karnofsky
performance status (KPS) score. Class 3 with the poorest prognosis included patients with KPS < 70 regardless
of the presence of all other factors. Class 2 with intermediate prognosis included patients who did not meet
the criteria of classes 1 or 3 . These three prognostic factors are still the basis of all contemporary, more
[9]
refined prognostic scores, even if new factors are included. However, in the original RTOG database, only
4% of patients had SCLC histology . Retrospective studies have confirmed the validity of the prognostic
[9]
stratification of BM from SCLC according to the RTOG RPA class criteria. In 132 SCLC patients who received
WBRT, the median survival for classes 1, 2, and 3 was 2, 4.5, and 2 months, respectively (P = 0.003). However,
there were only eight (4%) patients in class 1 . In 154 patients with BM of whom 98% received WBRT as
[2]
part of their treatment, the median survival for classes 1, 2, and 3 was 8.6, 4.2, and 2.3 months, respectively
(P = 0.002). Only 5% of patients from this group met the criteria of RPA class 1 . The rarity of RPA class 1
[2]
among patients treated for BM from SCLC is related to the aggressiveness of the primary tumor. Brain-only
metastases from SCLC with cured primary are an extremely rare event, as demonstrated by EORTC phase II
trial, in which the accrual of patients with brain-only metastases was so slow that the study was stopped before
the required number of patients was reached .
[4]

In the more contemporary disease-specific graded prognostic assessment (DS-GPA), the prognostic factors
for patients with BM were attributed separately for respective primary tumors. For lung cancer, based on
the results of 1833 NSCLC and 281 SCLC patients, apart from the prognostic factors from RTOG RPA class
(extracranial disease, age and KPS) the number of BM (1 vs. 2-3 vs. > 3) reached prognostic significance.
When patients with SCLC were analyzed separately, the number of BM was also significantly prognostic for
survival . The retrospective study demonstrated that median survival for 30 patients with single BM was
[10]
7 months compared with 2.9 months for 98 patients with multiple BM from SCLC (P = 0.005) . In another
[2]
small retrospective study, the number of BM also had an impact on survival . The prognostic significance
[11]
of the number of BM for SCLC may be counterintuitive, because we still treat this disease with WBRT based