Page 24 - ARNM-2-2

Advances in Radiotherapy
& Nuclear Medicine Melanoma brain metastatic treatment

Table 1. (Continued)
Author (year) Number Number Strategies Treatment Main results Main conclusions
of studies of patients included in the arms
included included analyses
studies, and alone (HR=0.595, significantly increase
1 phase I 95% CI: 0.489 – 0.723, grade 3 – 4 neurological
study) P < 0.001 adverse events.
Grade ≥3 neurologic ICI+RT did not
adverse events for ICI+RT significantly increase
versus RT alone (RR=1.425, grade ≥3 radiation
95% CI: 0.485 – 4.183, necrosis.
P=0.519)
Grade ≥ 3 radiation
necrosis for ICI+RT versus
RT alone (RR=2.73 [95%
CI: 0.59 – 12.59; P=0.199])
Su et al. 28 11 studies 4154 (98% RT (WBRT or SRS+ICI OS of SRS+ICI group longer ICI alone showed a higher
melanoma SRS) versus ICI than that of ICI group OS benefit in BM patients
patients) ICI (ipilimumab/ alone (HR=1.72, than targeted therapy
prembrolizumab/ ICI versus 95% CI: 1.41 – 2.11, P=0.22) alone.
nivolumab) TT OS of ICI group longer Total survival time of
TT (BRAF or than that of non-ICI group patients with SRS+ICI
MEK inhibitors) (HR=7.78, was longer than that of
95% CI: 6.85 – 8.83) patients with single ICI.
Badrigilan et al. 32 16 1465 (only RT (SRS) SRS alone OS for ICI versus no-ICI SRS+ICI improves
retrospective melanoma in ICI (ipilimumab/ versus (HR=0.66, patients’ clinical and
studies 13 studies) prembrolizumab/ ICI+SRS 95% CI: 0.55 – 0.8) radiological outcomes.
nivolumab) (either OS for concurrent therapy The effectiveness of the
concurrently versus non-concurrent combination is subject
or non- therapy (HR=1.43, P=0.008) to the identification of
concurrently, and 1-year LBC (HR =1.91, an optimal therapeutic
or ICI before P=0.04) window
SRS or ICI OS for concurrent therapy
after SRS) versus ICI before SRS
(HR=2.55, P=0.0003)
Abbreviations: BM: Brain metastases; CI: Confident interval; DCR: Disease control rate; HR: Hazard ratio; RR: Risk ratio; ICI: Immune checkpoint
inhibitor; LBC: Local brain control; LC: Local control; ORR: Overall response rate; OS: Overall survival; RT: Radiotherapy; SRS: Stereotactic
radiosurgery; TT: Target therapy; WBRT: Whole brain radiotherapy.

strategies in monotherapy. One of the first meta-analyses WBRT subgroup, OS was improved in the radiation plus ICI
in the field was published by Petrelli et al. in 2019. A total cohort (HR = 0.53, 95% CI: 0.44 – 0.63). Concordant results
25
27
of 33 studies were reviewed, encompassing 87% of the were also reported by Najafi et al. in a meta-analysis that
melanoma cases. The studied patients received different included 28 studies with a high proportion of melanoma
forms of radiation treatments, which include SRS/HFSRT patients. The addition of ICIs to radiation led to an increase
(56.9%) and WBRT alone (19.4%) or combined with in OS compared to radiotherapy alone (HR = 0.39, 95% CI:
SRS (23.7%). Despite the high WBRT rate and the 0.34 – 0.44), along with an acceptable toxicity profile.
clinical differences among the radiation techniques, Similar effects have been reported when comparing
combined treatment of ICI with radiotherapy resulted in combined treatment to ICI monotherapy. A meta-analysis
a statistically significant improvement in overall survival by Su et al. also reported better OS with SRS plus ICI
28
(OS) when compared to radiotherapy alone (hazard ratio compared to ICI alone. Compared to ICI monotherapy,
[HR] = 0.54, 95% confidence interval [CI]: 0.44 – 0.67]). ICI double combination and ICI plus radiotherapy have
He et al. also described the survival benefit demonstrated led to significantly higher intracranial ORR (odds ratio
26
by the combined therapeutic strategy, which significantly [OR]: 1.32, 95% CI: 1.17 – 1.49, and OR = 1.48, 95%
improved OS, regardless of whether it was defined from CI: 1.32 – 1.65, respectively, P < 0.01) with no significant
diagnosis (HR = 0.55, 95% CI: 0.48 – 0.64) or from difference between both combined treatment strategies.
29
treatment (HR = 0.45, 95% CI: 0.39 – 0.52). Even in the In terms of intracranial disease control rate (DCR), ICI

Volume 2 Issue 2 (2024) 4 doi: 10.36922/arnm.3499