Determinants of Outcome in Melanoma Patients With Cerebral Metastases

Fife, Kate; Colman, Marjorie H.; Stevens, Graham; Firth, Ian; Moon, Dominic H.; Shannon, Kerwin F.; Harman, Richard; Petersen‐Schaefer, Karin; Zacest, Andrew C.; Besser, Michal J.; Milton, G. W.; McCarthy, W. H.; Thompson, John F.

doi:10.1200/jco.2004.08.140

Cited by 396 publications

(373 citation statements)

References 36 publications

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“…16 The reported objective response rates of symptomatic brain metastases from melanoma to WBRT range from 11% to 14%. 2,[7][8][9][10]16 These data indicate that WBRT is of little benefit in the majority of patients who have symptomatic brain metastases from melanoma. In addition, the duration of such treatment will take a substantial part of the rest of these patients lives, and its side effects, like fatigue, nausea, and hair loss, signify an additional burden for these patients.…”

Section: Toxicitymentioning

confidence: 98%

“…[4][5][6] The standard treatment for patients with symptomatic brain metastasis and active extracranial metastases consists of whole-brain RT (WBRT) in combination with corticosteroids that, nonetheless, is barely effective (the median survival is about 3, and most treated patients dye of neurologic disease). 1,2,[7][8][9] In fact, the objective response rate of symptomatic brain metastasis from melanoma to conventional WBRT probably is not greater than 15% 7,10 ; and, for the majority of patients, the burden of such treatment may have more negative impact on the quality of life than the doubtful benefit to survival compared with corticosteroids and other supportive measures. Data about the efficacy of RT in patients with asymptomatic brain metastasis from melanoma are lacking.…”

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confidence: 99%

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Temozolomide in advanced malignant melanoma with small brain metastases

Boogerd

Gast

Dalesio

2007

Cancer

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BACKGROUND.The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT.METHODS.Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma. Patients with brain metastasis that measured >2 cm, extensive edema, and localization in the brain stem were excluded from the study. For the current analysis, patients with leptomeningeal metastasis and patients who received previous stereotactic RT were excluded. In patients who achieved a systemic response or stabilization to temozolomide, the response of brain metastasis and the necessity for palliative cranial RT were evaluated.RESULTS.Among 179 patients who received temozolomide for advanced melanoma, 52 patients with brain metastasis were evaluable. Stabilization of systemic metastasis was noted in 7 of 52 patients (13%), and there were 6 responses (5 partial responses and 1 complete response; 11%); thus, in those 13 patients, 6 had stabilization of brain metastasis (11%) and 5 had a response (2 partial responses and 3 complete responses; 9%). Immunotherapy did not influence the neurologic response. The median time to neurologic progression was 7 months (range 2–15, months). RT for cerebral recurrence was required in 2 patients. The median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4–6.8 months). Intracranial hemorrhagic complications were not observed.CONCLUSIONS.The current results indicated that it is feasible to treat patients who have advanced melanoma and small brain metastasis with temozolomide as the single treatment. The small subset of patients with systemic response usually showed durable stabilization or a response of brain metastasis. With this approach, neurologic disease can be controlled, and cranial irradiation may be deferred and even withheld in most of patients. Cancer 2007. © 2006 American Cancer Society.

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Section: Toxicitymentioning

confidence: 98%

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confidence: 99%

Temozolomide in advanced malignant melanoma with small brain metastases

Boogerd

Gast

Dalesio

2007

Cancer

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“…Medications that have activity in brain metastases include the BRAF kinase inhibitors dabrafenib and vemurafenib and the MEK inhibitor trametinib. This is critical considering that median duration of survival is 4 months in patients with melanoma brain metastases in previously reported series [57]. A multicenter phase II trial of dabrafenib in patients with BRAF-mutant melanoma with brain metastases found the drug to have significant activity in the central nervous system.…”

Section: Melanoma and Immunotherapymentioning

confidence: 99%

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

et al. 2016

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Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patient's disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles.The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation.There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases.This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS. The Oncologist 2016;21:244-251 Implications for Practice: Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy.

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“…In our population brain metastases were first detected by PET/CT in 2 and by MRI or CCT in 9 of 11 patients. Detecting and staging for brain metastases in melanoma patients is important for choosing individual therapy which can consist of surgery, radiotherapy or chemotherapy or combinations of these strategies (35,36).…”

Section: Fdg-pet/ct Is Increasingly Used For Therapy Assessment Of DImentioning

confidence: 99%

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

Strobel

Dummer

Steinert

et al. 2008

Eur J Nucl Med Mol Imaging

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PURPOSE: This study aims to compare the use of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B in chemotherapy response assessment of stage IV melanoma patients. METHODS: In 25 patients with stage IV melanoma, FDG-PET/CT and S-100B after 2-3 months (three cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B. Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases, MRI or CCT was performed. RESULTS: There was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CT responders (n = 10) compared with PET/CT non-responders (n = 15; p = 0.072) with remarkably better 1-year OS of 80% compared to 40% (p = 0.048). There was a significant longer PFS of PET/CT responders compared with PET/CT non-responders (p = 0.002). S-100B was normal at baseline in eight of 22 patients where it was available. Chemotherapy response assessment with S-100B failed to show correlation with OS or PFS. Eleven patients developed brain metastases during treatment, first detected by PET/CT in two and by MRI or CCT in nine of 11 patients. Appearance of brain metastases was associated with a poor survival. CONCLUSIONS: 18F-FDG-PET/CT and CT alone are equally suitable for chemotherapy response assessment in melanoma patients and clearly superior to S-100B. PET/CT responders have better early survival, but this is shortlived due to late therapy failure-often with brain recurrence. Additional brain MRI for therapy response assessment in such high-risk patients is mandatory to detect brain metastases missed by PET/CT. Chemotherapy Response Assessment in MethodsIn 25 patients with stage IV melanoma FDG-PET/CT and S-100B after 2-3 months (3 cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B.Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases MRI or CCT was performed. ResultsThere was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CTresponders (n=10) compared with PET/CT non-responders (n=15) (p=.072) with remarkably better 1-year OS of 80% compared to 40% (p=.048). There was a significant longer PFS of PET/CT-responders compared with PET/CT nonresponders (p=.002). S-100B was normal at baseline in 8 of 22 patients where it was available. Chemotherapy response assessment with S -100B failed to show correlation with OS or PFS. 11 patients developed brain metastases during treatment, first detected by PET/CT in 2 and by MRI or CCT in 9 of 11 patients.Appearance of brain metastases was associated with a poor survival.

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Determinants of Outcome in Melanoma Patients With Cerebral Metastases

Abstract: This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Cited by 396 publications

References 36 publications

Temozolomide in advanced malignant melanoma with small brain metastases

Temozolomide in advanced malignant melanoma with small brain metastases

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

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