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Page 4 of 11 Kepka. J Cancer Metastasis Treat 2019;5:53 I http://dx.doi.org/10.20517/2394-4722.2018.114

patients with progression in the brain after or during first-line treatment. The data from this study showed
that omission of WBRT in the treatment of BM led to a significantly shorter time to progression in the brain
in patients managed without WBRT, with 8% vs. 35% of patients free of progression in the brain at 6 months in
those treated with and without WBRT, respectively. Overall survival was short (~ 3.5 months) in both groups .
[5]
The demonstrated risk of rapid progression in the brain without the use of WBRT suggests the benefit of
combining chemotherapy with WBRT also in these patients, regardless of the chemotherapy response-with
the awareness that no strong evidence for such an approach exists.

Histology of SCLC found during a craniotomy performed for brain tumor without prior diagnosis
of lung primary with this histology
This is a special case when the unexpected SCLC histology of a removed brain tumor leads to performing
diagnostic procedures to find a lung primary and evaluate its extension. When the lung primary is found,
further management does not differ from the scenario when BM are found during initial staging of SCLC,
namely chemotherapy followed by WBRT. Patients with BM from SCLC were not included in the trials on the
use of tumor bed radiosurgery with the omission of WBRT, because of the increased risk of dissemination
outside the tumor bed [17,18] . Thus, also in these cases, WBRT remains the standard of care. A special
presentation of BM SCLC represents a situation in which after removal of the brain tumor neither primary,
nor signs of extracranial extension are found despite meticulous diagnostic procedures including PET-CT
and bronchoscopy. In such a scenario, the justification for the use of chemotherapy may be questioned -
again, we have very limited evidence. The omission of chemotherapy as first-line treatment in such patients
with careful monitoring may be an option in more fragile patients.

BM developed during first-line treatment for ES-SCLC when no baseline brain imaging was
performed
Brain imaging in asymptomatic patients with ES-SCLC is not systematically performed. In the EORTC trial
which demonstrated a survival advantage with the use of PCI, brain imaging was not part of the standard
staging procedures and only 19% of randomized patients had baseline brain CT or MRI [8,19] . Obviously, if in
such patients during first-line chemotherapy symptomatic BM occur, WBRT is given and chemotherapy is
continued or discontinued after completion of brain irradiation depending on the systemic chemotherapy
response and performance status of the patient.

BM diagnosed before PCI for LS SCLC or ES SCLC in the case of pre-PCI MRI
Brain imaging has not always been a standard procedure before PCI qualification in either LS SCLC or ES
SCLC. Some prospective studies reported using CT scans, some did not require any imaging, and some did
not mention any requirements for imaging use . NCCN guidelines recommend pre-PCI MRI for patients
[20]
with response to initial therapy . These guidelines are strictly followed in the USA; as highlighted in a
[21]
recent survey, up to 96% out of 309 US radiation oncologists performed pre-PCI MRI . In contrast, some
[22]
European IASLC and ESTRO experts indicated in a survey on the practice of PCI use for ES SCLC that the
restrictions in reimbursement for MRI and problems with its availability were the main reasons of performing
PCI in such patients. With MRI surveillance, patients would avoid brain irradiation, unnecessary in some
cases . In one study, patients with initial diagnosis of LS SCLC had baseline MRI performed. Complete
[23]
responders who qualified for PCI after treatment completion had a second, pre-PCI MRI; 13 out of 40
(32.5%) patients had BM in pre-PCI MRI. Patients with pre-PCI detected BM had worse prognosis than those
without BM in pre-PCI MRI (17% vs. 74% for 1-year survival, respectively, P = 0.0001). This difference was
seen despite the higher and more intense WBRT doses in patients with BM. However, one major limitation
of this study was that PCI was applied late, that is, 4-10 months after diagnosis. Moreover, this finding does
not support the routine use of pre-PCI MRI, because even giving higher WBRT doses did not reverse the
poor prognosis in these patients . Similar observations from a larger group of patients were presented at
[24]
the IASLC World Conference on Lung Cancer in 2018. From 119 LS SCLC patients referred for PCI after