In-transit mets for melanoma are a type of Stage III regional metastatic disease, occurring in about 10% of melanoma patients, that are within or just below the skin as nodules within the lymph system and not in nodal basins. Unfortunately these lesions are an independent adverse prognostic factor and are frequently associated with distant metastasis....which makes sense when you think about where they reside. Isolated limb perfusion therapy has been utilized with some success. Here are a few of the latest articles:
In-transit Melanoma Metastasis: Incidence, Prognosis and the Role of Lymphadenectomy.
Read, Haydu, Saw, et al. Ann Surg Oncol. 2014 Sep 26.
11,614 patients with single primary cutaneous tumors were treated at Melanoma Institute in Australia between Jan 1994 and Dec 2009. Of these, 505 developed ITM. Their clinical characteristics, sentinel node status, disease pattern and progression as well as outcomes were analyzed.
Of this 505: Primary tumor thickness was 2.95mm. 39.4% were ulcerated.
ITM rates for patients with primary melanomas less than 1 mm = 0.4%, for those with primaries equal to or greater than 1 mm = 7.8%, and for those with sentinel node biopsy = 7.2%.
ITM rates for SN positive = 21.6%. For SN negative = 4.7%.
Median time from primary diagnosis to development of ITM = 17.9 months.
After dx, median survival time = 19.9 months. 5 year survival = 32.8%. 10 year survival = 27.5%.
Primary tumor site (head/neck and trunk) and ulceration were predictors for poorer survival.
Five year survival from the time of ITM ranged from 47.9% for non-ulcerated limb primary lesions to only 13.6% for ulcerated trunk lesions.
Elective lymph node dissection in clinically node negative patients with ITM did not significantly alter overall survival.
CONCLUSION: "This large study demonstrated that the diagnosis of melanoma ITM carries serious adverse prognostic implications and will assist in improving the accuracy of staging and prognostic estimates as well as treatment in these patients."
Burden of Disease Predicts Response to Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma. Muilenburg, Beasley, Thompson, et al. Ann Surg Oncol. 2014 Sep.
Isolated limb perfusion with melphalan is minimally invasive, effective treatment for in-transit melanoma. Databases from two academic centers were analyzed. Burden of disease was characterized as high or low (with low being ten or fewer lesions with none greater than 2 cm). Responses were measures at 3 months post isolated limb perfusion. 60 patients had low and 100 patients had a high burden of disease (BOD). Low BOD patients had an overall response rate of 73% and complete response of 50%. Patients with high BOD had only a 47% ORR and CR of 24%. Patients with a CR at 3 months demonstrated improved progression free survival, but overall survival was similar. Low BOD patients had an increased median PFS of 6.9 months vs 3.8 months and an increased median overall survival of 38.4 vs 30.9 months.
Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-transit Disease. Hassan, Petrella, Zhang, et al. Ann Surg Oncol. 2014 November.
Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. Retrospective collection of data on 31 patients treated with intralesional IL-2 for in-transit melanoma: Ten patients (32%) achieved complete response. 17 (55%) had a partial response. 4 (19%) had progressive disease. Higher CD8+ T cell infiltrates were noted in patients having a complete response vs that which was present in other lesions and improved progression free survival.
So, much like treatment data for melanoma generally, patients with the lowest disease burden and the greatest infiltration of T cells did best. No real surprises there. When thinking about this aspect of melanoma, I realized...this is a hard row to hoe, in the already difficult melanoma field. Wishing you all my best. - c
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