Scientific Background: Patients suffering from BM from SCLC have a poor prognosis with a
median survival ranging between 2-14 months. Treatment options for BM in SCLC are usually
limited to WBRT, steroids or palliative chemotherapy. SCLC patients demonstrate an exception
in the treatment of BM, because treatment options for a limited number of BM from other solid
tumors commonly include surgery or SRS with or without WBRT. Even though SCLC is a
radiosensitive tumor, higher doses are commonly not applied. Locally ablative treatments like
SRS or surgery are less frequently used in patients with BM from SCLC as compared to other
types of cancer due to the high incidence of brain metastases in SCLC and the increased
likelihood of a diffuse failure pattern. It is of general belief that BM from SCLC are rarely
solitary and usually occur at multiple sites. The investigators could not confirm these
findings from this analysis as they found 1-5 BM in 39 % of their patients. WBRT, with a
treatment time of about two weeks, is commonly the technique of choice for SCLC patients with
any number of BM. In a recent Japanese trial, prophylactic cranial irradiation did not result
in longer overall survival compared with observation in patients with early disease (ED)
SCLC. PCI is therefore no longer recommended for patients with ED SCLC when patients receive
regularly MRI examinations during follow-up.
Though, the initial response to cranial irradiation is good, especially in the synchronous
setting, SCLC patients are at high risk of developing intracranial recurrence. In the
investigators´ retrospective analysis median Overall survival (OS) after re-WBRT was only 2
months and the median OS after SRS was 6 months. These results are similar as compared to
results for re-irradiation after PCI. In a recent analysis the investigators reported a
prolonged survival for patients treated with SRS in the recurrent setting after previous PCI
with a median survival of 5 months.
Therefore, the number of patients with oligometastatic cerebral disease might rise. Based on
recursive partitioning Analysis (RPA) classification, the investigators found a median
survival after WBRT of 17 months in RPA class I, 7 months in class II and 3 months in class
III (p<0.0001), which is comparable to previous analyses using graded prognostic assessment
(GPA) scoring. This is further of special interest as patients in RPA class I had a
comparable or even better outcome than patients with non-cerebral disease treated with PCI.
On the other hand, patients with RPA class III should be carefully selected for WBRT and
treatment should be weighed against supportive therapy with steroids alone. This implicates
that patient selection is mandatory, even in SCLC, and that the general paradigm of WBRT
needs to be reevaluated.
Trial Objectives: The purpose of this trial is to explore the neurocognitive response in
patients with brain metastases from SCLC treated with WBRT or SRS. The investigators proposed
that patients treated with SRS would have inferior neurocognitive function based on the
Hopkins Verbal Learning Test-Revised (HVLT-R) compared with patients treated with SRS alone.
Patients Selection: Patients with a diagnosis of brain metastases from SCLC will be evaluated
and screened based on the protocol. All patients fulfilling the inclusion and exclusion
criteria will be informed about the possibility to participate in the study. Registration for
the study must be performed prior to beginning of RT. 56 patients will be enrolled in this
exploratory clinical trial.
Trial Design: This pilot trial will be conducted as a single-center prospective, randomized,
two-arm Phase II study.