Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases

Dohm, Ammoren; Nakashima, Jun; Kalagotla, Hruday; Jiang, Shirley; Tang, Joseph D.; Bhandari, Menal; Kim, Youngchul; Graham, Jasmine A.; Etame, Arnold B.; Liu, James K.; Tran, Nam; Vogelbaum, Michael A.; Wuthrick, Evan; Yu, Hsiang-Hsuan Michael; Oliver, Daniel; Ahmed, Kamran A.

doi:10.1016/j.ejca.2023.113287

Cited by 4 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of important clinical immunotherapy trials for melanoma patients with intracranial metastases are summarized in [9]. Clinical outcomes of melanoma patients with intracranial metastases treated with stereotactic radiosurgery and various systemic therapies have been analyzed in [10]. The overall 12 month survival rates for the combined anti-PD-1-CTLA4 therapy was 68%, 62% for BRAF/MEK inhibitor treatment, 59% for anti-PD-1 therapy, and 45% for anti-CTLA4 therapy compared to only 21% for BRAF inhibitor treatment and 15% for conventional chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs

Kraft,

Grützmann,

Meinhardt

et al. 2024

acta neuropathol commun

View full text Add to dashboard Cite

Melanoma is the most serious type of skin cancer that frequently spreads to other organs of the human body. Especially melanoma metastases to the brain (intracranial metastases) are hard to treat and a major cause of death of melanoma patients. Little is known about molecular alterations and altered mechanisms that distinguish intra- from extracranial melanoma metastases. So far, almost all existing studies compared intracranial metastases from one set of patients to extracranial metastases of an another set of melanoma patients. This neglects the important facts that each melanoma is highly individual and that intra- and extracranial melanoma metastases from the same patient are more similar to each other than to melanoma metastases from other patients in the same organ. To overcome this, we compared the gene expression profiles of 16 intracranial metastases to their corresponding 21 patient-matched extracranial metastases in a personalized way using a three-state Hidden Markov Model (HMM) to identify altered genes for each individual metastasis pair. This enabled three major findings by considering the predicted gene expression alterations across all patients: (i) most frequently altered pathways include cytokine-receptor interaction, calcium signaling, ECM-receptor interaction, cAMP signaling, Jak-STAT and PI3K/Akt signaling, (ii) immune-relevant signaling pathway genes were downregulated in intracranial metastases, and (iii) intracranial metastases were associated with a brain-like phenotype gene expression program. Further, the integration of all differentially expressed genes across the patient-matched melanoma metastasis pairs led to a set of 103 genes that were consistently down- or up-regulated in at least 11 of the 16 of the patients. This set of genes contained many genes involved in the regulation of immune responses, cell growth, cellular signaling and transport processes. An analysis of these genes in the TCGA melanoma cohort showed that the expression behavior of 11 genes was significantly associated with survival. Moreover, a comparison of the 103 genes to three closely related melanoma metastasis studies revealed a core set of eight genes that were consistently down- or upregulated in intra- compared to extracranial metastases in at least two of the three related studies (down: CILP, DPT, FGF7, LAMP3, MEOX2, TMEM119; up: GLDN, PMP2) including FGF7 that was also significantly associated with survival. Our findings contribute to a better characterization of genes and pathways that distinguish intra- from extracranial melanoma metastasis and provide important hints for future experimental studies to identify potential targets for new therapeutic approaches.

show abstract

Section: Introductionmentioning

confidence: 99%

Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs

Kraft,

Grützmann,

Meinhardt

et al. 2024

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

“…BRAF/MEK inhibitor combined strategies, including dabrafenib plus trametinib and encorafenib plus binimetinib, benefit advanced melanoma patients with BRAF gene mutations [ 43 , 44 ]. Meanwhile, the systematic strategy of combining BRAF/MEK inhibitors with radiotherapy and immunotherapy also brought hope to patients with melanoma MBM [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities

Zhou,

Gong,

et al. 2023

J Hematol Oncol

View full text Add to dashboard Cite

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor–brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.

show abstract

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery

Tang,

Mills,

Nakashima

et al. 2024

J Neurooncol

View full text Add to dashboard Cite

Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases

Cited by 4 publications

References 18 publications

Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs

Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs

Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery

Contact Info

Product

Resources

About