Hepatic and Overall Progression-Free Survival After Percutaneous Hepatic Perfusion (PHP) as First-Line or Second-Line Therapy for Metastatic Uveal Melanoma.

BACKGROUND: Uveal melanoma often metastasizes to the liver, portending a poor prognosis. Melphalan/hepatic delivery system (HDS) via percutaneous hepatic perfusion (PHP) is a minimally invasive means of circulating high-dose chemotherapy through the affected liver. This study evaluated melphalan/HDS use as either first-line or second-line treatment to guide treatment sequencing. PATIENTS AND METHODS: A retrospective review included patients with hepatic-dominant metastatic uveal melanoma who underwent melphalan/HDS treatment via PHP from 2008 to 2023. RESULTS: A total of 30 patients were identified; 53.3% female, with a median age of 63.5 years (37-78 years). Median follow-up time was 14.5 months. First-line therapies included melphalan/HDS (n = 17), liver-directed (n = 7), and immunotherapy (n = 6). Second-line therapies included melphalan/HDS (n = 6), immunotherapy (n = 5), and liver-directed (n = 3). Median hepatic progression-free survival (hPFS) for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 17.6/8.8/9.2 months, respectively (P = 0.002). Median hPFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was not reached/14.7/7.5 months, respectively (P < 0.001). Median overall PFS for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 15.4/8.8/9.2 months, respectively (P = 0.04). Median overall PFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was 22.2/14.7/7.5 months, respectively (P = 0.001). CONCLUSIONS: Melphalan/HDS via PHP for metastatic uveal melanoma to the liver was found to have significantly improved hPFS and overall PFS when used as first-line therapy compared with immunotherapy or liver-directed therapy. PHP continued to demonstrate improved hPFS and PFS when used as second-line therapy compared with second-line immunotherapy or liver-directed therapy.

Isolated Limb Infusion for Limb-Threatening Sarcomas.

BACKGROUND: Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. METHODS: A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. RESULTS: The study identified 61 patients (52.5% female; median age, 73 years; range, 20-94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR + PR + stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P < 0.0001). The responders (CR + PR) had significantly longer PFS than the non-responders (SD + PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1-12.9; P < 0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P < 0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9-12.0; P < 0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P = 0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1-6.8; P = 0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P = 0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P = 0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR + PR + SD (HR, 3.0; 95% CI 1.0-8.7; P = 0.04). CONCLUSIONS: The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS.

Radar-Guided Localization and Resection for Metastatic Nodal and Soft Tissue Melanoma: A Single-Institution Retrospective Study.

BACKGROUND: Radar-guided localization (RGL) offers a wire-free, nonradioactive surgical guidance method consisting of a small percutaneously-placed radar reflector and handheld probe. This study investigates the feasibility, timing, and outcomes of RGL for melanoma metastasectomy. METHODS: We retrospectively identified patients at our cancer center who underwent RGL resection of metastatic melanoma between December 2020-June 2023. Data pertaining to patients' melanoma history, management, reflector placement and retrieval, and follow-up was extracted from patient charts and analyzed using descriptive statistics. RESULTS: Twenty-three RGL cases were performed in patients with stage III-IV locoregional or oligometastatic disease, 10 of whom had reflectors placed prior to neoadjuvant therapy. Procedures included soft tissue nodule removals (8), index lymph node removals (13), and therapeutic lymph node dissections (2). Reflectors were located and retrieved intraoperatively in 96% of cases from a range of 2 to 282 days after placement; the last reflector was not able to be located during surgery via probe or intraoperative ultrasound. One retrieved reflector had migrated from the index lesion, thus overall success rate of reflector and associated index lesion removal was 21 of 23 (91%). All RGL-localized and retrieved index lesions that contained viable tumor (10) had microscopically negative margins. There were no complications attributable to reflector insertion and no unexpected complications of RGL surgery. CONCLUSION: In our practice, RGL is a safe and effective surgical localization method for soft tissue and nodal melanoma metastases. The inert nature of the reflector enables implantation prior to neoadjuvant therapy with utility in index lymph node removal.

There are a variety of tools available to localize melanoma that had spread to deep layers of the skin or lymph nodes that can guide surgeons to the cancer when the tumor cannot be felt. We evaluated a marker that reflects radar signals that has been studied in breast surgery but not in melanoma. The marker was placed in the tumor before surgery and was located during surgery using a handheld probe, guiding the surgeon to the correct location. An advantage of the radar-reflecting marker we studied is that since it is safe to stay in the body, it can be placed ahead of the use of cancer medications and can keep track of the tumor as it responds to treatment. In a review of 23 surgeries in which the radar-reflecting marker was used, there was one case where the marker migrated away from the tumor and one case where the marker was not able to be located. Monitoring or alternative definitive treatment was provided in each of these cases. Overall, we found the marker to be an effective tumor localization tool for surgeons and safe for patients. Other marker options available are unable or less suitable to be placed a long time in advance of surgery due to either technical or safety reasons, so the radar-reflecting marker is especially useful when it is placed in a tumor ahead of medical treatment leading up to planned surgical treatment.

Evaluating the role of level 3 axillary lymph node dissection in metastatic melanoma: Can we predict involvement?

BACKGROUND AND OBJECTIVES: MSLT-2 and DECOG-SLT established that immediate complete axillary lymph node dissection (CLND) did not correlate with an increase in melanoma-specific survival when compared with active ultrasound observation in patients with sentinel lymph node (SLN)-positive disease. After those trials, there was a shift toward performing CLND only for clinically node-positive disease. With these changes, we sought to determine the role of level III axillary lymph nodes in bulky disease and how the use of neoadjuvant therapy may impact the rate of positivity in level III axillary nodes. METHODS: We performed a retrospective chart review on all patients who underwent axillary CLND for cutaneous melanoma by one surgeon at an academic center from 2014 to 2022. These patients underwent CLND based on either having SLN+ disease or having clinically palpable or radiographically bulky disease. RESULTS: Of 95 patients included, there were 7 (7.3%) patients with level III positivity. One was SLN+ (1.0%), while 3 (3.1%) had bulky disease and neoadjuvant therapy, and 3 (3.1%) had bulky disease without neoadjuvant therapy. No preoperative factors were identified that predicted level III involvement. After performing CLND, the patients who had clinically palpable or radiographically bulky disease and neoadjuvant therapy had higher percent necrosis of nodes in levels I and II but not III. At 5 years, overall survival and recurrence-free survival were improved in those without level III involvement (58% and 64%, respectively) when compared to those with level III involvement (41% and 50%), though this was not statistically significant. CONCLUSIONS: Further study may identify better prognostic factors for level III positivity, allowing for the possibility of dissecting only levels I and II or even replacing CLND with targeted node dissections.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: A multicenter cohort study.

BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. OBJECTIVE: To determine factors associated with SLN+ in patients with T1a melanoma. METHODS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into ≤42 (25% quartile cutoff) and >42 years. RESULTS: Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age ≤42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and ≥2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with ≥2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%. LIMITATIONS: Retrospective study. CONCLUSION: SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.

Assessing the Efficacy of Imiquimod Use in Patients With Persistent Locally Advanced Melanoma In Situ

BACKGROUND: The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. METHODS: Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. RESULTS: Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. CONCLUSION: Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.

Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity?

BACKGROUND AND OBJECTIVES: Although minority race has been associated with worse cancer outcomes, the interaction of race with pathologic variables and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is not known. METHODS: Patients from the US Neuroendocrine Study Group (2000-2016) undergoing curative-intent resection of GEP-NETs were included. Given few patients of other races, only Black and White patients were analyzed. RESULTS: A total of 1143 patients were included. Median age was 58 years, 49% were male, 14% Black, and 86% White. Black patients were more likely to be uninsured (7% vs 2%, P = .011), and to have symptomatic bleeding (13% vs 7%, P = .009), emergency surgery (7% vs 3%, P = .006), and positive lymph nodes (LN) (47% vs 36%, P = .021). However, Black patients had improved 5-year recurrence-free survival (RFS) (90% vs 80%, P = .008). Quality of care was comparable between races, seen by similar LN yield, R0 resections, postoperative complications, and need for reoperation/readmission (all P > .05). While both races were more likely to have pancreas-NETs, Black patients had more small bowel-NETs (22% vs 13%, P < .001). LN positivity was prognostic for pancreas-NETs (5-year RFS 67% vs 83%, P = .001) but not for small-bowel NETs. CONCLUSIONS: Black patients with GEP-NETs had more adverse characteristics and higher LN positivity. Despite this, Black patients have improved RFS. This may be attributed to the epidemiologic differences in the primary site of GEP-NETs and variable prognostic value of LN-positive disease.

Betel Quid Use and Oral Cancer in a High-Risk Refugee Community in the USA: The Effectiveness of an Awareness Initiative.

Betel nut (BN) is a psychoactive oral carcinogen that is commonly used among Asian communities. This study aims to investigate BN usage patterns and the effectiveness of a visually guided educational initiative in a high-risk refugee population. All adult patients presenting to a private practice clinic, free community clinic, or health fair in the refugee community of Clarkston, Georgia during days when survey staff were present were approached for the study. Participants were first categorized into a familiar and unfamiliar cohort depending on participant-reported familiarity with BN. Depending on familiarity, subjects were then administered a pre-intervention test surveying health awareness for BN and usage patterns where relevant; subsequently, a visually guided educational brochure was reviewed, and a post-intervention test was administered. Results were statistically analyzed (STATA 12). Forty-eight participants were surveyed for the familiar cohort and 25 for the unfamiliar cohort. Among the familiar cohort, South and Southeast Asians comprised 91% of participants. On frequency of use, 42.8% reported social, 28.6% reported usage during celebrations only, and 28.6% reported daily. The most common reasons for use were for taste (40.9%), enjoyment (38.6%), and addiction (25%). Among the familiar cohort, 75% believed BN was harmful for health compared to 8% among the unfamiliar (p < 0.0001). In the familiar cohort, 52.3% believed BN alone could cause cancer compared to 4% among the unfamiliar (p < 0.0001). Following the educational intervention, 100% of participants believed BN mastication is harmful in both cohorts (p < 0.01), while 87.5% of participants in both cohorts recognized that BN alone could cause cancer (p < 0.0007). This study illustrates gaps in understanding regarding oral cancer and the health consequences of chronic BN mastication, as well as the efficacy of a visually guided educational brochure to improve participant knowledge among a high-risk refugee population.

Intralesional and Infusional Updates for Metastatic Melanoma.

Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of advanced melanoma, followed by the utilization of isolated extremity perfusion (ILP). Following this, intralesional oncolytic viruses, xanthene dyes, and cytokines were introduced for the management of in-transit metastases as well as unresectable, advanced melanoma. In 2015, the Food and Drug Administration (FDA) approved the first oncolytic intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of advanced melanoma. Additionally, immune checkpoint inhibition has demonstrated efficacy in the management of advanced melanomas, and this improvement in outcomes has been extrapolated to aid in the management of in-transit metastatic disease. Finally, percutaneous hepatic perfusion (PHP), also approved by the FDA, has been reported to have a significant impact on the treatment of hepatic disease in uveal melanoma. While some of these treatments have less utility due to inferior outcomes as well as higher toxicity profiles, there are selective patient profiles for which these therapies carry a role. This review highlights intralesional and infusional therapies for the management of metastatic melanoma.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.

IMPORTANCE: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma. OBJECTIVE: To determine the efficacy of adjuvant PD1 in resected AM or MM. DESIGN: An international, retrospective cohort study SETTING: Data up to November 2021 collected from 20 centres across 10 countries. PARTICIPANTS: One hundred and ninety four patients with resected stage III or IV1 AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis. MAIN OUTCOMES AND MEASURES: Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated. RESULTS: Forty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52-0.92, p = 0.0127)], DMFS [HR0.58 (0.38-0.89, p = 0.0134)] and OS [HR of 0.59 (0.38-0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69-2.68,p-value 0.3799], DMFS or OS. CONCLUSION AND RELEVANCE: After adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed.

Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress.

Locoregionally advanced and metastatic melanoma are complex diagnoses with a variety of available treatment options. Intralesional therapy for melanoma has been under investigation for decades; however, it has advanced precipitously in recent years. In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma. There has been significant progress since that time with other oncolytic viruses, toll-like receptor agonists, cytokines, xanthene dyes, and immune checkpoint inhibitors all under investigation as intralesional agents. Further to this, there has been exploration of numerous combinations of intralesional therapies and systemic therapies as various lines of therapy. Several of these combinations have been abandoned due to their lack of efficacy or safety concerns. This manuscript presents the various types of intralesional therapies that have reached phase 2 or later clinical trials in the past 5 years, including their mechanism of action, therapeutic combinations under investigation, and published results. The intention is to provide an overview of the progress that has been made, discuss ongoing trials worth following, and share our opinions on opportunities for further advancement.

Isolated Limb Infusion for Limb-Threatening, Unresectable Sarcoma: Past Progress, Current Applications, and Future Directions.

Treatment of soft tissue sarcomas (STSs) is complicated by disease heterogeneity. Further, it has not benefitted much from the recent therapeutic advances in other soft tissue malignancies. Surgical resection remains the gold standard in resectable disease, but unresectable, locally advanced STS requires alternative and multimodal approaches. Isolated limb infusion (ILI) provides regional chemotherapy to extremity STS and offers the potential for limb salvage. Despite being in use for nearly 3 decades, there is limited literature on ILI in STS. This review provides an overview of patient eligibility, the procedure, significant publications in this field, and opportunities for further progress.

A safety review of recently approved and late-stage trial treatments for metastatic melanoma: systemic and regional therapies.

INTRODUCTION: Advanced melanoma accounts for the majority of skin cancer-associated deaths. Over the past 15 years, there has been a dramatic change in the treatment options and prognosis for patients with advanced melanoma secondary to the development of novel systemic immunotherapies (IO) and targeted therapies. In addition to these novel systemic therapies, regional therapies (intralesional and perfusional) also continue to play a major role in the management of these patients. AREAS COVERED: In this article, we review recent updates in the management of advanced melanoma via Medline (PubMed) and Google Scholar, including recently published trials in the metastatic, adjuvant, and neoadjuvant settings. We also review recently published trials for regional therapies and discuss future directions in the management of patients with advanced melanoma. EXPERT OPINION: A significant portion of patients with advanced melanoma will develop recurrent or progressive disease following treatment with IO or targeted therapy. Therefore, identifying not only the appropriate therapeutic agent but also the sequence and duration of treatment is pivotal for these patients.

Isolated hyperthermic perfusions for cutaneous melanoma in-transit metastasis of the limb and uveal melanoma metastasis to the liver.

Patients with cutaneous melanoma can develop in-transit metastases (ITM), most often localized to limbs. For patients with uveal melanoma that develop metastatic disease, the overall majority develop isolated liver metastases. For these types of metastases, regional cancer therapies have evolved as effective treatments. Isolated limb perfusion (ILP), isolated limb infusion (ILI), isolated hepatic perfusion (IHP) and percutaneous hepatic perfusion (PHP) achieve a high local concentration of chemotherapy with minimal systemic exposure. This review discusses the mechanism and available literature on locoregional treatment modalities in the era of modern immunotherapy.

Oncolytic intralesional therapy for metastatic melanoma.

In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/or anatomic involvement. Oncolytic viral therapies are one category of non-surgical treatment options available for ITM. They induce tumor cell lysis and systemic anti-tumor activity through selective infection of tumor cells by naturally occurring or genetically modified factors. While there are numerous oncolytic viral therapies in various stages of development for the treatment of ITM, this discussion focuses on the mechanism and available literature for the two most established herpes virus-based therapies.