Hepatic artery infusion of melphalan in patients with liver metastases from ocular melanoma

Boone, Brian A.; Perkins, Samantha; Bandi, Rupal; Santos, Ernesto; McCluskey, Kevin; Bartlett, David L.; Pingpank, James F.

doi:10.1002/jso.24984

Cited by 13 publications

(10 citation statements)

References 58 publications

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“…Siegel et al [ 58 ], also using fotemustine, reported an OS of up to 22 months, although it is not known how many of the patients included in the study received first-line therapy. On the other hand, the study by Boone et al [ 49 ], the most recent in this group, barely reached 3 months of OS with melphalan.…”

Section: Resultsmentioning

confidence: 65%

“…The median survival of the studies included in this review is around 15 months [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. The multi-center trial of Leyvraz et al [ 29 ] with fotemustine, one of the most powerful treatments in the review, is a perfect example of these results, with overall survival (OS) of 14 months and a PFI of 4.5.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Metastatic Uveal Melanoma: Systematic Review

Rodriguez-Vidal

Fernandez-Diaz

Fernandez-Marta

et al. 2020

Cancers

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Introduction: More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. Methods: A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan–Meier curves or numerically. Results: After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9–22 months), isolated liver perfusion (OS: 9, 6–27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6–17 months), immunotherapy (OS: 5–19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6–12 months), without being significant. Conclusions: The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.

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Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Treatment of Metastatic Uveal Melanoma: Systematic Review

Rodriguez-Vidal

Fernandez-Diaz

Fernandez-Marta

et al. 2020

Cancers

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“…For the palliative treatment of liver metastases in UM patients, HAIC is considered a valuable treatment option [ 1 , 11 ]. As regular repetitions of this intervention are a necessity, dose optimization deserves special consideration and might be beneficial for the patient, the interventional radiologist, and his team alike [ 12 – 15 ].…”

Section: Discussionmentioning

confidence: 99%

Radiation Dose Aspects of Hepatic Artery Infusion Chemotherapy in Uveal Melanoma Patients with Liver Metastases

Zensen

Opitz

Ludwig

et al. 2022

Cardiovasc Intervent Radiol

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Purpose In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investigate the radiation exposure of HAIC. Material and methods In this retrospective study, dose data from 841 procedures in 140 patients (mean age 65.3 ± 9.9 years, 74 female) who underwent HAIC between 06/2017 and 10/2021 at one of three different angiography systems were analyzed. Results In the overall population, dose area product (DAP) (median (IQR)) was 1773 cGy·cm2 (884–3688). DAP was significantly higher in the first intervention, where a complete diagnostic workup of the vasculature was performed, than in follow-up interventions: 5765 cGy·cm2 (3160–8804) versus 1502 cGy·cm2 (807–2712) (p < 0.0001). DAP also increased significantly with the number of infusion positions (median, (IQR)): one position 1301 cGy·cm2 (633–2717), two positions 1985 cGy·cm2 (1118–4074), three positions 6407 cGy·cm2 (2616–11590) (p < 0.0001). Conclusion In uveal melanoma patients with liver metastases undergoing HAIC, radiation exposure is significantly higher both at the first intervention compared to follow-up interventions, but also with increasing number of infusion positions. Level of evidence: 3

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“…There were also 5.7% of patients in the RCT that discontinued treatment because of hepatic toxicity, diagnosed by hyperbilirubinemia (5.7%), increase in ALT (2.9%), and increase in AST (2.9%) [ 16 ]. One retrospective review of 14 patients who underwent PHP found 1 patient who had hepatic failure that resulted in death [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Fulminant Hepatic Failure after Chemosaturation with Percutaneous Hepatic Perfusion and Nivolumab in a Patient with Metastatic Uveal Melanoma

Teal

Yorio

2021

Case Reports in Oncological Medicine

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Immune checkpoint inhibitors, such as nivolumab, a programmed death receptor-1 (PD-1) inhibitor, have dramatically improved the treatment of advanced melanomas. Chemosaturation with percutaneous hepatic perfusion (PHP) delivers chemotherapy in high doses directly to the liver and is a potentially effective treatment modality in metastatic uveal melanoma with liver metastases. Its safety and effectiveness have not been studied in patients also receiving immunotherapy. A 46-year-old male with a history of uveal melanoma of the right eye was found to have liver metastases. He was treated with PHP using high-dose melphalan for 6 months with a partial response followed by progression. Two months after his last PHP treatment, the patient was started on nivolumab. After two doses of nivolumab, the patient developed severe hepatitis that progressed to fulminant hepatic failure and death despite treatment with high-dose corticosteroids and mycophenolate mofetil. Nivolumab and other immune checkpoint inhibitors have been effective in treating advanced melanoma and extending life. However, there are serious immune adverse events that can occur. While hepatitis after taking nivolumab has been documented, fulminant hepatic failure is rare. We believe that prior PHP treatment contributed to the severity of the hepatitis and, ultimately, fulminant hepatic failure. To our knowledge, this is the only case of fulminant hepatic failure secondary to a checkpoint inhibitor with preceding PHP. Specific precautions should be made in patients who have been exposed to PHP in the past, and further studies should be done to assess the safety of using checkpoint inhibitors after PHP.

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Hepatic artery infusion of melphalan in patients with liver metastases from ocular melanoma

Abstract: HAI of melphalan is safe and feasible for patients with metastatic ocular melanoma. Further study to determine the optimal utilization of this treatment approach is warranted.

Cited by 13 publications

References 58 publications

Treatment of Metastatic Uveal Melanoma: Systematic Review

Treatment of Metastatic Uveal Melanoma: Systematic Review

Radiation Dose Aspects of Hepatic Artery Infusion Chemotherapy in Uveal Melanoma Patients with Liver Metastases

Fulminant Hepatic Failure after Chemosaturation with Percutaneous Hepatic Perfusion and Nivolumab in a Patient with Metastatic Uveal Melanoma

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