Management of brain metastases:

Systemic treatment, radiosurgery or

both? A chair introduction
GIUSEPPE MINNITI, MD, PhD
Department of Medicine, Surgery and
Neuroscience, University of Siena, Siena;
University of Pittsburgh, UPMC
Hillman Cancer Center San Pietro, Rome;
IRCCS Neuromed, Pozzilli (IS); Italy

Giuseppe Minniti
• Honoraria fees from Brainlab
• Honoraria fees from Accuray

Giuseppe Minniti
 Surgery Surgery should be considered when there are
acute symptoms of raised intracranial pressure
[EANO: III, C; ESMO: IV, B].
OI:https://doi.org/10.1016/j.annonc.2021.07.016

Radiotherapy SRS is recommended for patients with a limited

number (1-4) of BMs [EANO: I, A; ESMO: I, A].
SRS may be considered for patients with a higher
number of BMs (5-10) with a cumulative tumour
volume <15 ml [EANO: II, B; ESMO: II, B].
SRS to the resection cavity is recommended after
complete or incomplete resection of BMs [EANO:
I, A; ESMO: I, A].

Pharmacotherapy
based on histological and
molecular characteristics
of the primary tumour
and previous treatment
should be considered for
most patients with BMs
[EANO: IV, n/a; ESMO:
Giuseppe Minniti IV, B].
Clinical case 1:
Metastatic
melanoma

Patient presenting
with multiple brain
Pre-SRS, 1/2020
metastases
(symptomatic) from
a melanoma BRAF
mut in treatment with
dabrafenib and
trametinib
2 yrs after SRS (followed by systemic treatment)

Giuseppe Minniti
Clinical case 1:
Metastatic
SRS +o- The combination of ipilimumab and
melanoma systemic nivolumab should be the preferred
WBRT first-line treatment option also in
(past- therapies BRAF-mutated asymptomatic
Patient presenting 2015) (2015- patients [EANO: II, B; ESMO: II, B]
with multiple brain present) (2020-present)
metastases
(symptomatic) from
a melanoma BRAF
mut in treatment with
dabrafenib and
trametinib

Giuseppe Minniti
Clinical case 2:
Metastatic
NSCLC ALK-mut
4/2018, SRS to 11/2018, on 3/2020, starting
the cavity plus crizotinib alectinib
crizotinib
Patient presenting
with multiple brain
metastases from a
NSCLC, ALK-mut.
7/2021, alectinib, srs for 6/2022, alectinib,
further progression no active disease

Patients with NSCLC with actionable oncogenic driver

alterations such as EGFR or ALK or ROS1 rearrangement
SRS +o- and asymptomatic or oligosymptomatic BM should be treated
WBR systemic by upfront systemic targeted therapy [EANO: II, B; ESMO: III,
B].
T therapies In ALK-rearranged NSCLC patients with localised
(past- distant progression and ongoing systemic control,
2015) (2015- continuation of treatment with ALK TKI in
present) combination with local treatment of progressing
metastatic sites may be considered [III, B]
Giuseppe Minniti (present)
Clinical case 3:
Metastatic
HER2+ breast cancer

Patient presenting with

multiple brain metastases
from a HER2+ breast 2020, Pre-SRS
cancer on treatment with
pertuzumab and
trastuzumab

22 months after SRS (systemic treatment, T-DM1 )

Giuseppe Minniti
ESMO Clinical Practice Guideline for the diagnosis, Figure 3
staging and treatment of patients with metastatic
breast cancer
Authors: A. Gennari, F. André, C. H. Barrios, et al,
on behalf of the ESMO Guidelines Committee

Annals of Oncology 2021 321475-1495DOI: (10.1016/j.annonc.2021.09.019)

Annals of Oncology 2021 321475-1495DOI: (10.1016/j.annonc.2021.09.019)

Questions for the speakers

✓ Is the systemic therapy a «sufficient» treatment for patients

with BM sensitive to targeted therapy/immunotherapy?

✓ Is the combined treatment (SRS and systemic treatment)

better that single treatments? In such case, which is the
optimal timing?

✓ Is neurological/neurocognitive toxicity of new agents in

combination with RT of concern? How to manage toxicity?

Giuseppe Minniti
Thank you for your attention

Giuseppe Minniti