Eva M. Noorda

Isolated limb perfusion with tumor necrosis factor-α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

Since 1992, isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα‐ILP at their institution.

Safety and efficacy of isolated limb perfusion in elderly melanoma patients.

BackgroundOlder patients are assumed to have a higher risk of complications from isolated limb perfusion (ILP). A study was performed evaluating the safety and efficacy of ILP in patients older than 75 years with advanced melanoma of the limbs.MethodsA total of 218 therapeutic ILPs with melphalan with or without tumor necrosis factor α were performed in 202 patients with advanced measurable melanoma and were analyzed retrospectively. Fifty-three patients (28%) were 75 years or older.ResultsComplete response rates were 56% for those older than 75 years and 58% for the younger group (P=.79). Locoregional relapse occurred in 56% of the older group versus 51% in the younger group (P=.61). Limb toxicity, systemic toxicity, local complications, and long-term morbidity were similar in both age groups. Perioperative mortality was low, with one procedure-related death in the older group. Older patients stayed in the hospital for a median of 23 days (younger patients, 19 days;P<.01).ConclusionsILP results in similar response rates in the elderly with recurrent melanoma, without increased toxicity, complications, or long-term morbidity compared with younger patients. Older age in itself is not a contraindication for ILP.

Isolated Limb Perfusion Prolongs the Limb Recurrence-Free Interval After Several Episodes of Excisional Surgery for Locoregional Recurrent Melanoma

BackgroundThe influence of isolated limb perfusion (ILP) on the limb recurrence-free interval (LRFI) and the number of lesions per recurrence was studied for patients with frequently recurring regional in-transit metastases previously managed by excisional surgery.MethodsAll 43 patients who had their first ILP for a third or further limb recurrence were selected from our computer database of 451 patients who underwent therapeutic ILP for recurrent extremity melanoma in our centers. Eighteen patients had resectable and 25 had locally unresectable lesions at the time of ILP. The patients had a total of 269 intervals between treatment of their primary melanoma and last recurrence or last follow-up. Median follow-up was 35 months (interquartile range, 14–64 months).ResultsThe median LRFI decreases over time from primary melanoma to the third or further recurrence for which ILP was performed (P < 0.001). The median LRFI is 4.7 times longer (95% confidence interval [CI], 2.8–7.9; P < 0.001) after ILP in comparison with the last interval before ILP. Patients with resectable lesions have a median LRFI that is 5.9 times longer (95% CI, 2.7–13; P < 0.001). In all patients, the number of lesions increases by 22% per recurrence number (95% CI, 10%–35%; P = 0.02). At the same recurrence number, patients before ILP have a 2.6-fold higher (95% CI, 1.6–4.5) mean number of lesions than do patients after ILP (P < 0.001).ConclusionsILP lengthens the LRFI and decreases the number of lesions per recurrence significantly in patients with repeatedly recurrent limb melanoma. Therefore, ILP could be a valuable adjunct to excisional surgery for in-transit metastases in these patients whose LRFIs tend to shorten over time.

Isolated limb perfusion: what is the evidence for its use?

Background: This study was conducted to assess the best available evidence for the use of isolated limb perfusion.Methods: Following the principles of Evidence-Based Medicine, we reviewed the best available evidence for isolated limb perfusion (ILP) for melanoma and soft tissue sarcoma (STS) of the limb.Results: Adjuvant ILP with melphalan (M-ILP) to wide local excision cannot be recommended for patients with primary melanoma with a limited regional benefit and no increase in overall survival (level 1b evidence). Prophylactic M-ILP next to the excision of recurrent melanoma has resulted in a nonsignificant decrease in recurrence rate (33% to 50%), with a significantly longer recurrence-free interval (10 to 17 months), but no survival benefit (level 2b evidence). Therapeutic M-ILP, with or without tumor-necrosis factor alpha and interferon gamma (T(I)M-ILP), seems indicated in unresectable melanoma (level 3 to 4 evidence). In unresectable STS of the limbs, limb salvage can be obtained in 57% to 86% of patients with neoadjuvant T(I)M-ILP (level 3 evidence). A comparison of level 3 to 4 studies on ILP and other neoadjuvant treatment modalities for unresectable STS shows that ILP results in the highest limb salvage rate with the lowest complication rate.Conclusions: Based on level 3 to 4 evidence, ILP is indicated in unresectable locoregional (recurrent) melanoma and unresectable STS of the limbs. Level 1 and 2b evidence does show an effect of prophylactic ILP on micrometastatic disease in locoregional (recurrent) melanoma of the limb. ILP seems the most effective limb sparing, neoadjuvant treatment modality when compared with other neoadjuvant treatment options for unresectable STS of the limb (level 3 to 4 evidence), although randomized studies are lacking.

Isolated Limb Perfusion for Melanoma

Isolated limb perfusion with high-dose chemotherapy is an accepted treatment modality to achieve locoregional control in advanced melanoma of the extremities. The drug of choice is melphalan. Tumor necrosis factor-alpha is frequently added to melphalan in bulky disease, and this combination may be an option for repeat perfusion for recurrent melanoma after a first perfusion. Results of perfusions performed with tissue temperatures between 37 degrees C and 38 degrees C seem to be equivalent to those of the perfusions performed under mild hyperthermic conditions. Perfusion cannot be recommended as an adjunct to wide local excision in patients who have primary melanoma. Adjuvant perfusion in repeatedly recurrent limb melanoma, however, may be of value because it lengthens the limb recurrence-free interval and decreases the number of lesions per recurrence significantly. Regional toxicity of perfusion should be mild when risk factors are taken into account.

Isolierte Extremitätenperfusion bei Melanomen

Das Verfahren der isolierten Extremitatenperfusion unter Verwendung eines mit Sauerstoff angereicherten extrakorporalen Kreislaufs wurde erstmals 1957 von Creech et al. an der Tulane University, New Orleans, angewendet [1]. Eine vollstandige Remission wurde bei einem 76 Jahre alten mannlichen Patienten mit extensiv rezidivierenden Melanomen am Bein erzielt und hielt an, bis der Patient schlieslich im Alter von 92 Jahren verstarb.