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  1. Article ; Online: Local and Systemic Management Options for Melanoma Brain Metastases.

    Amouzegar, Afsaneh / Tawbi, Hussein A

    Cancer journal (Sudbury, Mass.)

    2024  Volume 30, Issue 2, Page(s) 102–107

    Abstract: Abstract: Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and ... ...

    Abstract Abstract: Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and breakthrough systemic therapies including immunotherapy and targeted therapies have improved the outcomes of patients with metastatic melanoma, management of patients with melanoma brain metastases (MBMs) remains challenging. Notably, patients with MBMs have historically been excluded from clinical trials, limiting insights into their specific treatment responses. Encouragingly, a growing body of evidence shows the potential of systemic therapies to yield durable intracranial responses in these patients, highlighting the need for inclusion of patients with MBMs in future clinical trials. This is pivotal for expediting the advancement of novel therapies tailored to this distinct patient population. In this review, we will highlight the evolving landscape of MBM management, focusing on local and systemic treatment strategies.
    MeSH term(s) Humans ; Melanoma/drug therapy ; Brain Neoplasms/therapy ; Combined Modality Therapy ; Immunotherapy ; Radiosurgery
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2018400-1
    ISSN 1540-336X ; 1528-9117 ; 1081-4442
    ISSN (online) 1540-336X
    ISSN 1528-9117 ; 1081-4442
    DOI 10.1097/PPO.0000000000000711
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Retraction and republication-TRICOTEL: defining symptomatic brain metastases in clinical trials.

    Dummer, Reinhard / Tawbi, Hussein

    The Lancet. Oncology

    2023  Volume 24, Issue 8, Page(s) e327

    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Letter
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(23)00292-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The standard of care for brain metastases in melanoma.

    Tawbi, Hussein

    Clinical advances in hematology & oncology : H&O

    2020  Volume 18, Issue 1, Page(s) 28–31

    MeSH term(s) Brain Neoplasms/secondary ; Brain Neoplasms/therapy ; Humans ; Melanoma/pathology ; Melanoma/therapy ; Neoplasm Metastasis ; Standard of Care
    Language English
    Publishing date 2020-06-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2271951-9
    ISSN 1543-0790
    ISSN 1543-0790
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  4. Article ; Online: A promising start for checkpoint inhibitors in childhood malignancies.

    Tawbi, Hussein

    The Lancet. Oncology

    2019  Volume 21, Issue 1, Page(s) 13–14

    MeSH term(s) Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; Child ; Humans ; Lymphoma ; Melanoma
    Chemical Substances Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; pembrolizumab (DPT0O3T46P)
    Language English
    Publishing date 2019-12-04
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(19)30803-4
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  5. Article: The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition.

    Kreidieh, Firas Y / Tawbi, Hussein A

    Therapeutic advances in medical oncology

    2023  Volume 15, Page(s) 17588359231186027

    Abstract: Despite major advances with immunotherapy and targeted therapy in the past decade, metastatic melanoma continues to be a deadly disease for close to half of all patients. Over the past decade, advancement in immune profiling and a deeper understanding of ...

    Abstract Despite major advances with immunotherapy and targeted therapy in the past decade, metastatic melanoma continues to be a deadly disease for close to half of all patients. Over the past decade, advancement in immune profiling and a deeper understanding of the immune tumor microenvironment (TME) have enabled the development of novel approaches targeting and a multitude of targets being investigated for the immunotherapy of melanoma. However, to date, immune checkpoint blockade has remained the most successful with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, alone or in combination, yielding the most robust and durable clinical outcome in patients with metastatic melanoma. The highest rate of durable responses is achieved with the combination with PD-1 and CTLA-4 inhibition, and is effective in a variety of settings including brain metastases; however, it comes at the expense of a multitude of life-threatening toxicities occurring in up to 60% of patients. This has also established melanoma as the forefront of immuno-oncology (IO) drug development, and the search for novel checkpoints has been ongoing with multiple relevant targets including T-cell immunoglobulin and mucinodomain containing-3 (TIM-3), LAG-3, V-domain immunoglobulin suppressor T-cell activation (VISTA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), among others. Lymphocyte activation gene-3 (LAG-3), which is a co-inhibitory receptor on T cells that suppress their activation, has revolutionized immunomodulation in melanoma. The 'game changing' results from the RELATIVITY-047 trial validated LAG-3 blockade as a relevant biological target and established it as the third clinically relevant immune checkpoint. Importantly, LAG-3 inhibition in combination with PD-1 inhibition offered impressive efficacy with modest increases in toxicity over single agent PD-1 inhibitor and has been U.S. Food and Drug Administration approved for the first-line therapy of patients with metastatic melanoma. The efficacy of this combination in patients with untreated brain or leptomeningeal metastases or with rare melanoma types, such as uveal melanoma, remains to be established. The challenge remains to elucidate specific mechanisms of response and resistance to LAG-3 blockade and to extend its benefits to other malignancies. Ongoing trials are studying the combination of LAG-3 antibodies with PD-1 inhibitors in multiple cancers and settings. The low toxicity of the combination may also allow for further layering of additional therapeutic approaches such as chemotherapy, oncolytic viruses, cellular therapies, and possibly novel cytokines, among others.
    Language English
    Publishing date 2023-07-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2503443-1
    ISSN 1758-8359 ; 1758-8340
    ISSN (online) 1758-8359
    ISSN 1758-8340
    DOI 10.1177/17588359231186027
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  6. Article ; Online: Symptomatic melanoma CNS metastases in the TRICOTEL study - Authors' reply.

    Dummer, Reinhard / Tawbi, Hussein

    The Lancet. Oncology

    2022  Volume 23, Issue 11, Page(s) e482

    MeSH term(s) Humans ; Melanoma/secondary ; Skin Neoplasms ; Neoplasms, Second Primary ; Brain Neoplasms/therapy ; Brain Neoplasms/secondary
    Language English
    Publishing date 2022-10-31
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(22)00647-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5696: Show issues Location:
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  7. Article: Current and emerging options for patients with melanoma brain metastases.

    Kreidieh, Firas Y / Tawbi, Hussein A

    Clinical advances in hematology & oncology : H&O

    2022  Volume 20, Issue 10, Page(s) 619–627

    Abstract: Melanoma is the most aggressive skin cancer, with a high incidence of metastatic spread and a predilection for metastases to the brain. It represents the third most common origin of brain metastases after breast and lung cancer. With the advent of ... ...

    Abstract Melanoma is the most aggressive skin cancer, with a high incidence of metastatic spread and a predilection for metastases to the brain. It represents the third most common origin of brain metastases after breast and lung cancer. With the advent of targeted therapy and immunotherapy in melanoma, along with improved local therapy options such as stereotactic radiosurgery (SRS), the treatment of melanoma brain metastases (MBM) has led to significant improvements in outcome. In this review, we provide an overview of management options for patients with MBM while highlighting emerging treatment options. Surgery may be considered for patients with symptomatic MBM, whereas SRS is considered standard for patients with 1 to 4 brain lesions. Combination immunotherapy has led to durable intracranial responses and improved long-term outcomes for patients with asymptomatic MBM. The data available to date have shown that patients with MBM can have a durable response and overall response that are similar to those of patients without brain metastases, and additional trials are ongoing. Mounting evidence suggests that patients with MBM should be considered for inclusion in clinical trials, which range from early-phase trials to phase 3 studies, to accelerate much-needed drug development in this population.
    MeSH term(s) Brain Neoplasms/secondary ; Humans ; Immunotherapy ; Melanoma/pathology ; Radiosurgery ; Retrospective Studies ; Skin Neoplasms/pathology ; Skin Neoplasms/therapy
    Language English
    Publishing date 2022-10-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2271951-9
    ISSN 1543-0790
    ISSN 1543-0790
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  8. Article ; Online: Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity.

    Burton, Elizabeth M / Tawbi, Hussein A

    Cancer discovery

    2021  Volume 11, Issue 5, Page(s) 1008–1010

    Abstract: Although combination anti-PD-1 and anti-CTLA4 mAbs have revolutionized outcomes for many cancers, their utility has been limited due to significant immune-related toxicities and the emergence of resistance. In this issue ... ...

    Abstract Although combination anti-PD-1 and anti-CTLA4 mAbs have revolutionized outcomes for many cancers, their utility has been limited due to significant immune-related toxicities and the emergence of resistance. In this issue of
    MeSH term(s) Antibodies, Bispecific ; CTLA-4 Antigen ; Immunotherapy ; Programmed Cell Death 1 Receptor ; T-Lymphocytes
    Chemical Substances Antibodies, Bispecific ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2021-04-29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-21-0257
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6916: Show issues Location:
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  9. Article ; Online: Nonsurgical Management of Melanoma Brain Metastasis: Current Therapeutics, Challenges, and Strategies for Progress.

    Makawita, Shalini / Tawbi, Hussein A

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2021  Volume 41, Page(s) 79–90

    Abstract: This review aims to provide an overview of nonsurgical treatment strategies for central nervous system metastases in melanoma as well as discuss treatment challenges and future directions. Recent strategies for melanoma brain metastases have involved ... ...

    Abstract This review aims to provide an overview of nonsurgical treatment strategies for central nervous system metastases in melanoma as well as discuss treatment challenges and future directions. Recent strategies for melanoma brain metastases have involved proving the intracranial activity of approved therapies as well as identifying novel drug targets. BRAF/MEK combination therapy has intracranial activity in those with
    MeSH term(s) Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Brain Neoplasms/therapy ; Combined Modality Therapy ; Humans ; Immunotherapy ; Melanoma/diagnosis ; Melanoma/genetics ; Melanoma/therapy ; Radiosurgery
    Language English
    Publishing date 2021-05-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.1200/EDBK_321137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Emergent immunotherapy approaches for brain metastases.

    Wang, Jianbo / Tawbi, Hussein A

    Neuro-oncology advances

    2021  Volume 3, Issue Suppl 5, Page(s) v43–v51

    Abstract: Brain metastases from solid tumors are increasing in incidence, especially as outcomes of systemic therapies continue to extend patients' overall survival. The long-held notion that the brain is an immune sanctuary has now been largely refuted with ... ...

    Abstract Brain metastases from solid tumors are increasing in incidence, especially as outcomes of systemic therapies continue to extend patients' overall survival. The long-held notion that the brain is an immune sanctuary has now been largely refuted with increasing evidence that immunotherapy can induce durable responses in brain metastases. Single agent immune checkpoint inhibition with anti-CTLA4 and anti-PD1 antibodies induces durable responses in 15%-20% in melanoma brain metastases as long as patients are asymptomatic and do not require corticosteroids. The combination of anti-CTLA4 with anti-PD-1 antibodies induces an intracranial response in over 50% of asymptomatic melanoma patients, and much lower rate of otherwise durable responses (20%) in symptomatic patients or those on steroids. Data in other cancers, such as renal cell carcinoma, are accumulating indicating a role for immunotherapy. Emerging immunotherapy approaches will have to focus on increasing response rates, decreasing toxicity, and decreasing steroid dependency. The path to those advances will have to include a better understanding of the mechanisms of response and resistance to immunotherapy in brain metastases, the use of novel agents such as anti-LAG3 checkpoint inhibitors, targeted therapy (oncogene directed or TKIs), and possibly surgery and SRS to improve the outcomes of patients with brain metastases.
    Language English
    Publishing date 2021-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 3009682-0
    ISSN 2632-2498 ; 2632-2498
    ISSN (online) 2632-2498
    ISSN 2632-2498
    DOI 10.1093/noajnl/vdab138
    Database MEDical Literature Analysis and Retrieval System OnLINE

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