Patterns of recurrence following complete response to regional chemotherapy for in-transit melanoma.
ABSTRACT Even after complete response (CR) to regional chemotherapy for in-transit melanoma, many patients develop recurrence. Understanding the probability, location, and timing of recurrences can optimize management strategies for this patient population.
A prospective database identified patients who underwent 81 first-time hyperthermic isolated limb perfusions (HILPs) and 133 first-time isolated limb infusions (ILIs). Response was defined using the response evaluation criteria in solid tumors; recurrence was defined as development of new disease after in-field CR.
HILP exhibited a significantly higher CR rate than ILI (44 vs. 28 %, p = .01). Among 36 HILP-CRs and 37 ILI-CRs, the 3-year recurrence rate was 65 % (95 % confidence interval [95 % CI]: 43-79 %) and 85 % (95 % CI: 63-94%), respectively. Median time to first recurrence was longer for HILP-CR than ILI-CR (23 vs. 8 months, p = .02). There was no statistically significant difference in median time to in-field recurrence between HILP-CR and ILI-CR (46 vs. 25 months, p = .15), but HILP-CR showed a longer median time to out-of-field recurrence (42 vs. 14 months, p = .02). Finally, the overall survival (OS) difference between HILP-CR and ILI-CR (3-year survival: 77 vs. 54 %) did not achieve statistical significance (p = .10).
In the largest series comparing patterns of recurrence, we demonstrate that out-of-field recurrence after CR to HILP occurs later than after CR to ILI, though control of in-field disease remains similar. There remains no statistically significant difference in overall survival after CR to the 2 procedures.
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ABSTRACT: Background Even after negative sentinel lymph node biopsy (SLNB) for primary melanoma, patients who develop in-transit melanoma (ITM) or local recurrences (LR) may have subclinical regional lymph node involvement. Study Design A prospective database identified 33 patients with ITM/LR who underwent Tc-99m sulfur colloid lymphoscintography (LS) alone (n=15) or in conjunction with lymphazurin dye (n=18) administered only if the ITM/LR was concurrently excised. Results Seventy nine percent (26/33) of patients undergoing SLNB in this study had prior removal of LNs in the same lymph node basin as the expected drainage of the IT or LR at the time of diagnosis of their primary melanoma. LS at time of presentation with ITM/LR was successful in 94% (31/33) cases, and at least one SLN was found intraoperatively in 97% (30/31) cases. The SLNB was positive in 33% (10/30) of these cases. Completion LN dissection was performed in 90% (9/10) of cases. Nine patients with negative SLNB and ITM underwent regional chemotherapy. Patients in this study with a positive SLN at the time the IT/LR was mapped had a significantly shorter time to the development of distant metastatic disease compared to those with negative SLNs. Conclusion In this study, we demonstrate the technical feasibility and clinical utility of repeat SLNB for recurrent melanoma. Performing SLNB can not only optimize local, regional, and systemic treatment strategies for patients with LR or ITM but also appears to provide important prognostic information.Journal of the American College of Surgeons 01/2013; · 4.50 Impact Factor
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ABSTRACT: Isolated limb infusion (ILI) is a limb-preserving treatment for in-transit extremity melanoma. The benefit of resecting residual disease after ILI is unclear. A multi-institutional experience was analyzed comparing patients who underwent ILI plus resection of residual disease (ILI + RES) versus ILI-alone. A total of 176 patients were included, 154 with ILI-alone and 22 with 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, 15 (68 %) had a partial response (PR), 2 (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 after ILI had improved DFS versus those with SD or PD after ILI, p < 0.0001. Resection of residual disease after ILI offers a DFS and OS similar to those who have a CR after ILI-alone. It may offer a treatment strategy that benefits patients undergoing ILI.Annals of Surgical Oncology 10/2013; · 4.12 Impact Factor
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ABSTRACT: Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established. A prospective, single-institution database of 243 patients with in-transit melanoma (1995-2013) was queried for patients who had progression of disease after RC with melphalan and subsequently received systemic immunotherapy. Fifteen patients received IL-2 only, 12 received ipilimumab only, and 6 received IL-2 followed by ipilimumab. Fisher's exact test was used to determine if there was a difference in number of complete responders after immunotherapy. With IL-2 alone, all patients progressed. After ipilimumab alone, three patients had a complete response and nine had progressive disease. Six additional patients received IL-2 first then ipilimumab. All six progressed on IL-2 but three went on to have a complete response to ipilimumab while three progressed. The use of ipilimumab at any time in patients who progressed after RC was associated with higher rate of complete response compared to use of IL-2 alone (33 vs. 0 %; p = 0.021). Patients with progression after regional therapy for melanoma may benefit from immunologic therapy. In this group of patients, immune checkpoint blockade with ipilimumab has a higher complete response rate than T cell stimulation with IL-2, with no complete responders in the IL-2 only group. Furthermore, the complete response rate for ipilimumab in our cohort is higher than reported response rates in the literature for ipilimumab alone, suggesting that the effects of immunotherapy may be bolstered by previous regional treatment.Annals of Surgical Oncology 04/2014; · 4.12 Impact Factor