Factors affecting survival after complete response to isolated limb perfusion in patients with in-transit melanoma.

Abstract

BACKGROUND:

Isolated limb perfusion (ILP) results in complete response (CR) rates of 60% to 90% in patients with regionally advanced melanoma. Survival after a CR may be influenced by various factors, particularly out-of-field disease in iliac lymph nodes (ILN) identified during lower-extremity ILP. We examined clinical and pathological parameters, including ILN status and outcome, for patients with in-transit melanoma who had a CR to ILP.

METHODS:

From May 1992 to July 1997, 50 patients (16 men and 34 women; median age, 57 years) with stage IIIA or IIIAB melanoma had a CR to a 90-minute hyperthermic iliac ILP with melphalan (10 mg/L limb volume, n = 20) or melphalan and tumor necrosis factor (4-6 mg+/-200 microg interferon; n = 30). Clinical and pathological parameters were analyzed by univariate and Cox proportional hazards models to determine which were associated with survival or in-field recurrence.

RESULTS:

The median in-field recurrence-free survival in the cohort of 50 patients after a CR to ILP was 1.4 years, and the actuarial 5-year in-field recurrence-free survival was 30%. By univariate analysis, there was a trend for improved outcome with female sex and stage IIIA (vs. IIIAB) at initial diagnosis was associated with improved survival after a CR to ILP (P = .056 and .012, respectively). Eleven (22%) of 50 patients had positive ILNs identified and resected at ILP. The probability of overall in-field recurrence was 70% after 4 years, and there was no difference between those with or without positive ILNs; median time to in-field recurrence was 13 and 19 months, respectively (P = .62). Similarly, overall survival was not influenced by positive ILN status (median [months]: +ILN, 69 vs. -ILN, 58; P = .68). Of note, Cox models identified that the risk of death was significantly greater in those with a history of prior systemic therapy (hazard ratio: 2.67 [95% confidence interval, 1.17-6.11]; P = .02) and those with an in-transit lesion size > or =1.4 cm2 (hazard ratio, 3.12 [95% confidence interval, 1.30-7.5]; P = .011). When these two variables were combined, there was a highly significant association with shortened survival (P = .002 by log-rank test).

CONCLUSIONS:

These data indicate that for patients undergoing ILP and in whom positive ILNs are found and resected, ILP is justified. In addition, patients who have a CR after ILP and have a history of prior treatment or larger lesions should be considered for adjuvant systemic therapy.

• Authors: T G Zogakis, D L Bartlett, S K Libutti, D J Liewehr, S M Steinberg, D L Fraker, H R Alexander
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 8 Issue 10 Pg. 771-8 (Dec 2001) ISSN: 1068-9265 [Print] United States
• PMID: 11776490 (Publication Type: Journal Article)

Chemical References

• Tumor Necrosis Factor-alpha
• Interferons
• Melphalan

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Chemotherapy, Cancer, Regional Perfusion (methods)
• Disease-Free Survival
• Extremities (blood supply)
• Female
• Humans
• Hyperthermia, Induced (methods)
• Interferons (administration & dosage)
• Lymphatic Metastasis
• Male
• Melanoma (drug therapy, mortality, secondary)
• Melphalan (administration & dosage)
• Middle Aged
• Neoplasm Staging
• Skin Neoplasms (drug therapy, mortality, pathology)
• Tumor Necrosis Factor-alpha (administration & dosage)