The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies

Read, Rebecca L.; Thompson, John F.

doi:10.1097/cmr.0000000000000740

Cited by 3 publications

(1 citation statement)

References 71 publications

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“…In-transit metastases (ITMs) affect 5-10% of all melanoma patients and are mainly located in the lower limbs (70%) [1]. In the case of a few small lesions, surgical excision is the treatment of choice, while bulky or rapidly recurrent lesions are best managed with locoregional and systemic therapies [2,3]. Before the introduction of systemic therapies, hyperthermic isolated limb perfusion (ILP) was the most effective treatment in case of multiple, bulky, recurrent in-transit disease [4,5].…”

Section: Introductionmentioning

confidence: 99%

Isolated Limb Perfusion and Immunotherapy in the Treatment of In-Transit Melanoma Metastases: Is It a Real Synergy?

Rastrelli,

Russano,

Cavallin

et al. 2024

JPM

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Background: Isolated limb hyperthermic-antiblastic perfusion (ILP) was the most effective local treatment for advanced in-transit melanoma, but the advent of modern effective immunotherapy (IT), such as immune checkpoint inhibitors, has changed the treatment landscape. Methods: This study evaluated the role of the association between ILP and IT in the treatment of locally advanced unresectable melanoma, particularly in relation to modern systemic therapies. We analyzed 187 consecutive patients who were treated with ILP (melphalan or melphalan associated with TNF-alpha) for advanced melanoma at the Veneto Institute of Oncology of Padua (Italy) and the Padua University Hospital (Italy) between June 1989 and September 2021. Overall survival (OS), disease-specific survival (DSS), local disease-free survival (local DFS) and distant disease-free survival (distant DFS) were evaluated. Local toxicity was classified according to the Wieberdink scale and surgical complications according to the Clavien–Dindo classification. Response to locoregional therapy was evaluated during follow-up according to the RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumor). Results: A total of 99 patients were treated with ILP and 88 with IT + ILP. The overall response rate was 67% in both groups. At 36 months, OS was 43% in the ILP group and 61% in the ILP + IT group (p = 0.02); DSS was 43% in the ILP group and 64% in the ILP + IT group (p = 0.02); local DFS was the 37% in ILP group and 53% in the ILP + IT group (p = 0.04); and distant DFS was 33% in the ILP group and 35% in the ILP + IT group (p = 0.40). Adjusting for age and lymph node involvement, receiving ILP + IT was associated with improved OS (p = 0.01) and DSS (p = 0.007) but not local DFS (p = 0.13) and distant DFS (p = 0.21). Conclusions: Our findings confirm the synergy between ILP and IT. ILP remains a valuable loco-regional treatment option in the era of effective systemic treatments. Further studies are needed to establish the optimal combination of loco-regional and systemic treatments and address the best timing of this combination to obtain the highest local response rate.

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Section: Introductionmentioning

confidence: 99%

Isolated Limb Perfusion and Immunotherapy in the Treatment of In-Transit Melanoma Metastases: Is It a Real Synergy?

Rastrelli,

Russano,

Cavallin

et al. 2024

JPM

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The Current State of Treatment and Future Directions in Cutaneous Malignant Melanoma

Ernst

Giubellino

2022

Biomedicines

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Malignant melanoma is the leading cause of death among cutaneous malignancies. While its incidence is increasing, the most recent cancer statistics show a small but clear decrease in mortality rate. This trend reflects the introduction of novel and more effective therapeutic regimens, including the two cornerstones of melanoma therapy: immunotherapies and targeted therapies. Immunotherapies exploit the highly immunogenic nature of melanoma by modulating and priming the patient’s own immune system to attack the tumor. Treatments combining immunotherapies with targeted therapies, which disable the carcinogenic products of mutated cancer cells, have further increased treatment efficacy and durability. Toxicity and resistance, however, remain critical challenges to the field. The present review summarizes past treatments and novel therapeutic interventions and discusses current clinical trials and future directions.

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Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry

Campana

Perić

Mascherini

et al. 2021

Cancers

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Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

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The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies

Cited by 3 publications

References 71 publications

Isolated Limb Perfusion and Immunotherapy in the Treatment of In-Transit Melanoma Metastases: Is It a Real Synergy?

Isolated Limb Perfusion and Immunotherapy in the Treatment of In-Transit Melanoma Metastases: Is It a Real Synergy?

The Current State of Treatment and Future Directions in Cutaneous Malignant Melanoma

Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry

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