Impact of Sequencing Radiation Therapy and Immune Checkpoint Inhibitors in the Treatment of Melanoma Brain Metastases.
Int J Radiat Oncol Biol Phys
; 108(1): 157-163, 2020 09 01.
Article
en En
| MEDLINE
| ID: mdl-32057994
ABSTRACT
PURPOSE:
Melanoma brain metastases (MBM) occur in â¼50% of melanoma patients. Although both radiation therapy (RT) and immune checkpoint inhibitor (ICI) are used alone or in combination for MBM treatment, the role of this combination and how these treatments could best be sequenced remains unclear. METHODS AND MATERIALS We conducted a retrospective analysis of patients with resected MBM who underwent treatment with RT, ICI, or a combination of RT and ICI. Among the latter, we specifically investigated the differential gene expression via RNA-sequencing between patients who received RT first then ICI (RT â ICI) versus ICI first then RT (ICI â RT). We used a glycoprotein-transduced syngeneic melanoma mouse model for validation experiments.RESULTS:
We found that for patients with resected MBM, a combination of RT and ICI confers superior survival compared with RT alone. Specifically, we found that RT â ICI was superior compared with ICI â RT. Transcriptome analysis of resected MBM revealed that the RT â ICI cohort demonstrated deregulation of genes involved in apoptotic signaling and key modulators of inflammation that are most implicated in nuclear factor kappa-light-chain-enhancer of activated B cells signaling. In a preclinical model, we showed that RT followed by anti-programmed death-ligand 1 therapy was superior to the reverse sequence of therapy, supporting the observations we made in patients with MBM.CONCLUSIONS:
Our study provides initial insights into the optimal sequence of RT and ICI in the treatment of MBM after surgical resection. Prospective studies examining the best sequence of RT and ICI are necessary, and our study contributes to the rationale to pursue these.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Inhibidores de Puntos de Control Inmunológico
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Melanoma
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Int J Radiat Oncol Biol Phys
Año:
2020
Tipo del documento:
Article