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Kirakli et al. J Cancer Metastasis Treat 2019;5:10 I http://dx.doi.org/10.20517/2394-4722.2018.73 Page 3 of 12

Solitary metastases: surgery vs. SRS
In the absence of head to head randomized data, most of the retrospective studies comparing surgery vs. SRS
reported similar outcomes in brain control or survival in solitary resectable brain metastases [19,20] . It’s hard
to make a decision when there is no indication for surgical decompression or need for histologic diagnosis.
One small randomized study with 64 patients with solitary metastases, compared SRS to microsurgery plus
[21]
WBRT. OS and 1 year local control were similar . Recently, in secondary analysis of EORTC 22952 trial in
abstract form which randomized patients to SRS or surgery with or without adjuvant WBRT, it was reported
[22]
that early control was better with SRS but late control favored surgery .

Solitary metastasis: only SRS after surgery
Postoperative SRS vs. WBRT after resection of brain metastases
The absence of survival advantage and recognized neurotoxicity of adjuvant WBRT after surgery have led
[6]
to postoperative SRS to surgical cavity . But there has been some challenges in the use of SRS without
WBRT after surgical resection. First, the use has increased in trend although the data have been mainly
[25]
derived from retrospective series [23,24] and one prospective phase II trial . The results of these studies report
around 80% local control in 1 year suggest similar control rates with adjuvant WBRT. The only randomised
data on this subject has been available from Kepka’s multicenter trial, which did not demonstrate the non-
inferiority of postsurgical SRS compared to postsurgical WBRT in patients with solitary brain metastasis.
The difference in neurocognitive failure at 6 months (primary end-point) was in favour of WBRT. Besides,
although it was not the primary end-point; the patients in postsurgical SRS arm compared to postsurgical
WBRT were found to have increased neurological deaths (66% vs. 31%, P = 0.015, HR: 2.51) and decreased
[26]
2 years overall survival (10% vs. 37%, P = 0.046, HR: 1.8), respectively . The second challenge is that
there have been some reports on dural-based leptomeningeal recurrences along the surgical tract after
[27]
postoperative SRS [27,28] . Atalar et al. reported 13% leptomeningeal recurrence rate at a median of 5 months
after SRS directed to postsurgical resection cavity. It’s hard to define target volume for postoperative SRS.
[29]
Tumor cell dissemination along the surgical tract is another challenge. Recently, Soliman et al. reported a
consensus guideline on delineation of CTV for postsurgical cavity SRS.

Preoperative SRS
In the context of leptomeningeal recurrences after postoperative SRS, preoperative SRS followed by surgical
resection in 48 h is evolving as a new paradigm. The theoretical benefits are decreased radionecrosis and
decreased leptomeningeal recurrences as a result of better definition of target volume by delineation of
intact metastasis, a smaller margin volume and sterilization of surgical bed [6,30] . The results of preoperative
SRS in 47 oligometastatic (1-3 brain metastases) patients before surgical resection have been reported by
[5]
Asher et al. NSCLC patients were 37.2% of the cohort. The median dose was 14 Gy. The expansion margin
of gross target volüme to planned target volüme was not used. There wasn’t any difficulty during surgery or
increased postoperative complication. In spite of the inclusion of relatively large lesions (median dimension
3
3.04 cm and median volume 8.49 cm ), local control rates were 97.8%, 85.6% and 71.8% at 6, 12 and 24
months, respectively. Six of the 8 local relapsing patients were the ones who had either significant dural
attachement or adherence to dural veins which might make an implication on the need for higher doses in
such cases instead of dose reduction. There wasn’t any leptomeningeal failure which confirms the hypothesis
of the study. The authors concluded that preoperative SRS might be a better treatment at least for “high risk”
[5]
[31]
patients . A phase II trial is going on this subject .
Oligometastases: WBRT alone vs. WBRT plus SRS boost
In line with the intensification of local therapy Radiation Therapy Oncology Group (RTOG) conducted a
phase 3 trial (RTOG 9508) which randomized 331 patients with 1-3 brain metastases to WBRT vs. WBRT
plus SRS. Lung cancer patients were 64% of the patient cohort. SRS boost in conjunction to WBRT showed
survival benefit in patients with 1 metastatic lesion (6.4 months vs. 4.9 months, P = 0.0393). The addition of