A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities

Abstract

Background: Hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI) are well-accepted regional chemotherapy techniques for in-transit melanoma of extremity. The role and efficacy of repeat regional chemotherapy for recurrence and which salvage procedure is better remains debatable. We aimed to compare toxicities and clinical outcomes by procedure types and the sequence.

Methods: Data from 44 patients, who underwent repeat HILPs or ILIs from 3 institutions beginning 1997 to 2010, were retrospectively reviewed. Regional toxicity assessed by Wieberdink grade, systemic toxicity assessed by serum creatine phosphokinase level, length of hospital stay (LOS), response rates at 3 months after the procedure, and time to in-field progression (TTP) were analyzed.

Results: Of 44 patients, 46% were men and 54% women with a median age of 66 (range 29-85) years at diagnosis. The median follow-up was 21.4 (range 4-153) months. Of 70 ILIs and 28 HILPs, the following groups were identified: group A, ILI → ILI (n = 25); group B, ILI → HILP (n = 10); group C, HILP → ILI (n = 12); and group D, HILP → HILP (n = 3). The comparison of Wieberdink grade, serum creatine phosphokinase level, LOS, and response rate between procedures (HILP vs. ILI), between sequence (initial vs. repeat), and among their interactions showed no statistically significant differences. TTP after initial procedure did not differ between HILP and ILI (P = 0.08), and no survival difference was seen (P = 0.65) when TTP after repeat procedure was compared.

Conclusions: Most patients tolerated repeat regional chemotherapy without increased toxicity or LOS. No statistical difference in clinical outcomes was noted when comparing repeat procedures, even though repeat HILPs showed higher complete response compared to repeat ILIs.

Figure 1

a) The regional toxicity measured by Wieberdink toxicity grade after repeat procedures showed no statistical difference among 4 subgroups (p=0.09). b) No significant difference was detected for the peak creatine phosphokinase (U/L) (natural log transformed) after repeat procedures (p=0.71). c) No significant difference was observed for the length of stay after repeat procedures (p=0.71). [Boxplots were used to visualize the distribution for groups A to C. The box in the boxplot has lines at the lower quartile (25%), median (50%), and upper quartile values (75%) while the red circle marks the mean value. Whiskers extend from each end of the box to the most extreme values within 1.5 times the interquartile range from the ends of the box. The data with values beyond the ends of the whiskers, displayed with black circles, are potential outliers. For group D (N=3), due to small sample size, the data points (shown as triangles) were displayed for clarity.]

Figure 2

a) After initial procedures, no significant difference in time to in-field progression (TTP) between ILI and HILP was noted (p = 0.08). b) After repeat procedures, no sufficient survival impact from TTP difference between ILI and HILP was noted (p = 0.65).

Figure 3

Treatment algorithm for recurrent extremity melanoma after regional chemotherapy