Hidde M. Kroon

Efficacy of repeat isolated limb infusion with melphalan and actinomycin D for recurrent melanoma.

Isolated limb infusion (ILI) is an effective and minimally invasive treatment option for delivering regional chemotherapy in patients with metastatic melanoma confined to a limb. Recurrent or progressive disease after an ILI, however, presents a challenge for further treatment. The value of repeat ILI in this situation has not been well documented.

Isolated limb infusion: a review.

Isolated limb perfusion is the preferred treatment option for locally advanced melanoma and sarcoma confined to a limb. This treatment results in high response rates with a satisfying duration of response in both tumours. A drawback of isolated limb perfusion, however, is the invasive and complex character of the procedure.

Treatment of melanoma metastases in a limb by isolated limb perfusion and isolated limb infusion

In‐transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option. J. Surg. Oncol. 2011; 104:397–404.

Safety and Efficacy of Isolated Limb Infusion With Cytotoxic Drugs in Elderly Patients With Advanced Locoregional Melanoma

Introduction:The treatment of elderly patients with advanced metastatic melanoma confined to a limb remains controversial. Isolated limb infusion (ILI) is an effective minimally invasive alternative to isolated limb perfusion (ILP) and is therefore a potentially valuable therapeutic option for this group. Methods:From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin-D was used. Results:Eighty-six patients (46%) were ≥75 years of age (range: 75–93). The patient characteristics in both groups were comparable except that the older group comprised more women (71% vs. 54%; P = 0.02) and had a lower body mass index (median: 24.4 vs. 26.4; P = 0.008). Complete response rates were 34% for those ≥75 years and 41% in the younger group (P = 0.28). There was no difference in limb recurrence free interval after a complete response (median: 24 months for both groups; P = 0.51) or in survival (median: 36 months for <75, 39 months for ≥75; P = 0.36) between both groups. Older patients experienced less limb toxicity after the procedure (Wieberdink grade III/IV toxicity in 36%) compared with younger patients (51%; P = 0.009) while systemic toxicity, complications, and long-term morbidity were similar. Conclusions:Elderly patients with advanced metastatic melanoma of the limb experience the same or lower toxicity after ILI compared with younger patients while response rates, limb recurrence free interval, survival, and morbidity are similar. ILI is an attractive alternative to the more laborious ILP, especially for older patients.

Isolated limb infusion with melphalan and actinomycin D for melanoma: a systematic review.

Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure‐related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response. J. Surg. Oncol. 2014 109:348–351.

A Propensity Score Matched Analysis of Open Versus Minimally Invasive Transthoracic Esophagectomy in the Netherlands

Objective: The aim of this study was to compare open esophagectomy (OE) with minimally invasive esophagectomy (MIE) in a population-based setting. Background: Randomized controlled trials and cohort studies have shown that MIE is associated with reduced pulmonary complications and shorter hospital stay as compared to OE. Methods: Patients who underwent transthoracic esophagectomy for cancer between 2011 and 2015 were selected from the national Dutch Upper Gastrointestinal Cancer Audit. Hybrid, transhiatal, and emergency procedures were excluded. Patients who underwent OE were compared with those treated by MIE. Propensity score matching was used to correct for differences in baseline characteristics. The primary endpoint was postoperative pulmonary complications; secondary endpoints were morbidity, mortality, convalescence, and pathology. Results: Some 1727 patients were included. After propensity score matching the percentage of patients with 1 or more complications was 62.6% after OE (N = 433) and 60.2% after MIE (N = 433) (P = 0.468). Pulmonary complication rate did not differ between groups: 34.2% (OE) versus 35.6% (MIE) (P = 0.669). Anastomotic leak (15.5% vs 21.2%, P = 0.028) and reintervention rates (21.1% vs 28.2%, P = 0.017) were higher after MIE. Mortality was 3.0% in the OE group and 4.7% in the MIE group (P = 0.209). Median hospital stay was shorter after MIE (14 vs 13 days, P = 0.001). Percentages of R0 resections (93%) did not differ between groups. The median (range) lymph node count was 18 (2–53) (OE) versus 20 (2–52) (MIE) (P < 0.001). Conclusions: This population-based study showed that mortality and pulmonary complications were similar for OE and MIE. Anastomotic leaks and reinterventions were more frequently observed after MIE. MIE was associated with a shorter hospital stay.

Isolated limb infusion: technical aspects.

To describe the technique of isolated limb infusion (ILI) for regional high dose chemotherapy in patients with advanced malignancies confined to a limb, as currently practiced at Melanoma Institute Australia (MIA).

Australian multi-center experience outside of the Sydney Melanoma Unit of isolated limb infusion chemotherapy for melanoma.

Isolated limb infusion (ILI) is a minimally invasive alternative to isolated limb perfusion (ILP) for delivering high‐dose regional chemotherapy to treat locally advanced limb melanoma. The current study aimed to evaluate the applicability of ILI in four Australian tertiary referral centers outside of its originating institution, the Sydney Melanoma Unit (SMU; currently known as the Melanoma Institute Australia).

Perfusion and infusion for melanoma in-transit metastases in the era of effective systemic therapy.

The management of melanoma in-transit metastases (IT-mets) is challenging. For many years, the absence of effective systemic therapy has prompted physicians to focus on regional therapies for melanoma confined to the limb. The introduction of isolated limb perfusion (ILP) and isolated limb infusion (ILI) has enabled effective delivery of cytotoxic drugs in an isolated circuit, so as to overcome systemic toxicity and maximize local response. Both techniques have evolved over years and both tumor necrosis factor (TNF)-alpha-based ILP and ILI have distinct indications. The development of new systemic treatment options for patients with melanoma in the past decade has shed a new light on melanoma therapy. The present manuscript focuses on the modern role of ILI and ILP in the treatment of patients with melanoma with in-transit metastases in the era of effective systemic therapy. The response and control rates of ILI/ILP are still superior to rates achieved with systemic agents. The extent of disease in patients with stage III disease, however, warrants effective systemic treatment to prolong survival. There is great potential in combining rapid response therapy such as ILI/ILP with systemic agents for sustainable response. Trial results are eagerly awaited.

Isolated Limb Infusion for Recurrent and Locally Metastatic Limb Melanoma

Recurrent and metastatic melanoma confined to a limb is a frequently encountered clinical problem in patients with initial primary limb melanoma. Regional chemotherapy using isolated limb perfusion (ILP) provides effective treatment, but is invasive, complex, and costly. Isolated limb infusion (ILI) chemotherapy is a simple, minimally invasive, and effective alternative to ILP.