Resection of Residual Disease after Isolated Limb Infusion (ILI) Is Equivalent to a Complete Response after ILI-Alone in Advanced Extremity Melanoma

Abstract

Introduction Isolated limb infusion (ILI) is a limb-preserving treatment for in-transit extremity melanoma. The benefit of resecting residual disease following ILI is unclear. Methods A multi-institutional experience was analyzed comparing patients who underwent ILI plus resection of residual disease (ILI+RES) versus ILI-alone. Results 176 patients were included: 154 ILI-alone and 22 ILI+RES. There were no differences between the groups with respect to gender, age, extremity affected, or time from diagnosis to ILI. All surgical resections were performed as an outpatient procedure, separate from the ILI. Within the ILI+RES group, fifteen (68%) had a partial response (PR), two (9%) stable disease (SD), and 5 (23%) progressive disease (PD). The ILI-alone group had 52 (34%) CR, 30 (19%) PR, 15 (10%) SD, and 46 (30%) PD. Eleven (7%) ILI-alone patients did not have 3-month response available for review. Evaluating overall survival (OS) from date of ILI, the ILI-alone group had a median OS of 30.9 months, whereas the ILI+RES group had not reached median OS, p=0.304. Although the ILI+RES group had a slightly longer disease free survival (DFS) compared to those with a CR after ILI-alone (12.4 vs. 9.6), this was not statistically significant, p=0.978. Within the ILI+RES group, those with an initial PR following ILI had improved DFS vs. those with SD or PD following ILI, p<0.0001. Conclusion Resection of residual disease following ILI offers a DFS and OS similar to those who have a CR after ILI-alone, and may offer a treatment strategy that benefits more patients undergoing ILI.

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

“…ILI has also been trialed in sequence and in combination with other treatments, such as surgery, with no significant influence on OS. 85 However, recent results indicate that patients with a CR are more likely to experience durable PFS, distant metastatic-free survival and OS compared with their nonresponder counterparts and this has implications for subsequent treatments. 86 Of the modalities examined, HILP and ILI have been most extensively evaluated and include higher quality study designs.…”

“…However, due to the inclusion of those with locally recurrent melanoma or soft‐tissue sarcoma and the pooled nature of the reported data, this study was not formally included in the systematic review. ILI has also been trialed in sequence and in combination with other treatments, such as surgery, with no significant influence on OS . However, recent results indicate that patients with a CR are more likely to experience durable PFS, distant metastatic‐free survival and OS compared with their nonresponder counterparts and this has implications for subsequent treatments …”

The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options

“…Surgical resection of residual disease following ILI can be performed, and offers some additive benefits. In a study of 176 patients with IT disease where 154 were treated with ILI alone and 22 patients with ILI and surgery, the former had a 68% PR, while the latter had a 34% CR and a 19% PR [ 104 ]. The ILI alone group had a median overall survival (OS) of 30.9 months, whereas the ILI + surgery group did not reach median OS, but this difference was not statistically significant ( p = 0.304).…”

Neoadjuvant use of ipilimumab in locally advanced melanoma

“…For those with regionally advanced disease, treatment options include surgical resection and regional therapies including isolated limb infusion (ILI) and hyperthermic isolated limb perfusion (HILP) when resection is not feasible . Combinations of these modalities have been used when a complete response has not been obtained with limb infusion alone and have demonstrated similar outcomes among patients who obtain a complete response from limb infusion and those who have resection of residual disease when only a partial response is obtained .…”