Page 25 - ARNM-2-2

Advances in Radiotherapy
& Nuclear Medicine Melanoma brain metastatic treatment

plus radiotherapy achieved a significantly higher rate than The use of ipilimumab has been associated with a higher
ICI combination therapy (OR = 1.41, 95% CI: 1.20 – 1.67, risk of RDN. Reported rates of RDN after administration
P < 0.01). Grade 3 or 4 CNS-related adverse event rates of combined treatment vary between studies, with a 6.8%
were not significantly different between the three arms. rate in melanoma BM patients treated with SRS plus
pembrolizumab (risk of RDN remained unaffected by the
A key point in disease management using combined 39
treatments is the administration timing for both timing between the treatments) and a 16.7% rate after
5 months. Concurrent strategies do not seem to lead to an
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radiation and ICI. Although there is no unanimous increased rate of RDN at 9 – 12 months compared to non-
agreement, concurrent treatment is usually defined concurrent strategies, but the rate tends to increase with
as the administration of radiotherapy and ICI within longer follow-up at 4 years compared to SRS alone, and at
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30 days or 4 weeks. A narrow window of 2 weeks to 3 years compared to non-concurrent strategies (HR = 4.47,
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implement combined treatments has also been reported. 95% CI: 1.57 – 12.73, P = 0.005). Similarly, an increased
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Importantly, treatment timing is correlated with efficacy, rate of grade 3 – 4 adverse events was also found with
with a shorter temporal gap between the administrations longer follow-up at 50 months amomg patients receiving
of the component therapies giving much better outcomes. 32 concurrent treatments. 33
Kiess et al. described an improvement in 1-year OS
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with SRS delivered concurrent or before ICI compared 4. Conclusion and future perspectives
to its non-concurrent counterpart (65% vs. 56% vs. 40% Melanoma BM is becoming an increasingly common
1-year OS rates, respectively, P = 0.008). Concurrent clinical problem due, in part, to the longer lifespan
treatment has been identified as an independent predictor bestowed by new systemic therapies. A multidisciplinary
factor for regional PFS (HR = 0.17, P < 0.0001) compared assessment and approach is essential to offering the most
to non-concurrent treatment, and concurrent strategy efficient form of therapy to patients at every critical point
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has been reported to result in higher reductions in lesion throughout the disease course. Several international
volume at 1.5, 3, and 6 months (P < 0.0001). 35 guidelines and consensus have been published for the
In a cohort of 58 melanoma BM treated with SRS treatment of BM. While these guidelines do not specifically
and ICI, Skrepnik et al. found that compared with the address melanoma, many of the recommendations can
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non-concurrent treatment, the concurrent treatment did be safely adapted because these guidelines are shaped
not remarkably lengthen OS but significantly improved from integration of evidence stemming from studies
regional brain control (75% vs. 23.5 %; P = 0.03) and featuring a significant portion of patients with melanoma
prolonged median CNS progression time (not reached BM. Combining high doses of targeted radiation with
vs. 5.7 months; P = 0.02). In addition, decreased distant immunotherapy is one of the treatment strategies that
brain failure has been described with concurrent strategies pique the most attention in the management of melanoma
compared to non-concurrent strategies (HR = 0.15, 95% BM. This strategy has been described as superior in terms
CI: 0.05 – 0.47, P = 0.0011). 37 of local control and survival, without causing a notable
increase in toxicity. Nevertheless, optimal dosage of
According to a meta-analysis by Lehrer et al. , the radiation, ICI administration timing, treatment sequence,
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concurrent strategy could significantly increase 1-year OS and the interval between treatments remain controversial.
(64.6% vs. 51.6%, P = 0.00027) and manifest a tendency The sequence of treatments is considered a critical aspect
to achieve higher 1-year local control (89.2% vs. 67.8%, deserving further investigation. Theoretically, radiation
P = 0.09) when compared to the non-concurrent treatment. before ICI administration could be advantageous over the
Even compared to ICI administration before or after SRS, opposite strategy, as it may improve blood–brain barrier
concurrent treatment also led to higher 1-year regional permeability, allowing increased ICI penetration and
brain control: 12.3% (95% CI: 4.0 – 31.9%) vs. 29.4% creating a proper microenvironment for ICI action. These
(95% CI: 18.2 – 43.7%) vs. 38.1% (95% CI: 20.1 – 60.1%), factors are crucial points for consideration when designing
respectively (P = 0.049). a treatment strategy.
Radionecrosis (RDN) emerges as a major health safety Although combined focal radiotherapy and ICI for
concern among treated patients. Unless histopathologically BM are purportedly safe and well tolerated, safety reports
examined, RDN can be radiologically confused with local regarding these treatments are yet to be delineated. The
relapse and/or immunotherapy changes. According to emergence of symptomatic RDN is one of the side effects
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Leher et al. , RDN has an overall estimated incidence that have sparked the greatest attention because it is a
rate of 5.3% (95% CI: 0.3 – 15.7%), and a meta-analysis by harmful post-treatment consequence of great clinical
Trapani et al. revealed slightly higher rates of 8.7 – 16.7%. concern. In addition to the local effects of high radiation
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Volume 2 Issue 2 (2024) 5 doi: 10.36922/arnm.3499