Locoregional Management of in-Transit Metastasis in Melanoma: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline

Abstract

Objective The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastases (ITM) from melanoma.
 
 Methods The guideline was developed by the Program in Evidence-Based Care (PEBC) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group (DSG). Recommendations were drafted by the Working Group based on a systematic review of publications in MEDLINE and Embase. The document underwent patient and caregiver-specific consultation and was circulated to the Melanoma DSG and the PEBC Report Approval Panel for internal review; the revised document underwent external review.
 
 Recommendations
 Minimal ITM were defined as lesions in a location with limited spread (generally 1 to 4 lesions); lesions are generally superficial, often clustered together, and surgically resectable. Moderate disease was defined as > 5 lesions covering a wider area or when new in-transit lesions develop rapidly (over weeks). Maximal disease was defined as large-volume disease with multiple (more than 15 to 20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.
 
 1. In patients presenting with minimal ITM, complete surgical excision with negative pathological margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.
 2. In patients presenting with moderate, unresectable ITM consider using the following approach for localized treatment: intralesional interleukin-2 or talimogene laherparepvec as first choice, topical diphenylcyclopropenone as second choice, or radiation therapy as third choice. There is insufficient evidence to recommend intralesional bacille Calmette-Guerin or carbon dioxide laser ablation outside of a research setting.
 3. In patients presenting with maximal ITM confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.
 4. In cases where local, regional, or surgical treatments for ITM may be ineffective, unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [18F]FDG PET/CT

“…Moreover, the identification of the exact number and site of in-transit metastases is fundamental for the choice of the optimal therapy: ITMs are typically resected if less than 3–4 lesions and none larger than 5 cm; otherwise, locoregional treatment should be evaluated, with a preference for TVEC in the torso or head/neck ITM. Systemic therapy should be chosen with a concurrent clinically evident metastatic or nodal disease with or without the aforementioned simultaneous specific ITM treatment [ 16 , 35 ]. In these terms, the positive impact that BSREM, comparing to OSEM reconstruction, could have in the evaluation of [ 18 F]FDG PET/CT images is evident.…”

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced Wild-Type BRAF Melanoma Patients

“…11 With respect to the choice between HILP and ILI, although phase III prospective randomized trials comparing these two procedures have not yet been initiated, there is general consensus that HILP is more effective than ILI but is more complex and associates with more adverse events. 1 It is for these reasons that our multidisciplinary board recommended the HILP procedure for the treatment of locoregional limb metastases in patients < 76 y old, with an ECOG performance status < 2, and the ILI procedure for the treatment of patients > 75 y old and/or ECOG performance status ≥ 2. This procedure selection bias was considered and weighted in both the logistic regression model used to evaluate the effect of patient/tumour variables on response and the multivariate Cox regression model used to evaluate PFS and OS.…”

“…Approximately 4% of locoregional metastases cumulatively localise to inferior limb, inguinal and pelvic regions, with synchronous inferior limb, inguinal region and/or pelvic involvement observed in approximately 2% of cases. [1][2][3] Over the past 15 y, local, regional and systemic treatments for locoregional metastatic melanoma have evolved and highvolume specialist centres now provide local, regional, and systemic therapeutic options. However, these therapeutic options are not uniformly recommended by current international guidelines 1 , 4-10 ; in particular, there are guideline differences in recommended local therapeutic procedures and both Japanese 10 and some European guidelines 7 do not recommend locoregional chemotherapy.…”

“…Local treatments include surgical resection, electro-chemotherapy (ECT), ablative, topical and intralesional therapies. [11][12][13] Regional treatment options include regional radiation therapy 14 and locoregional chemotherapy by hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI) for locoregional melanoma metastases located in the limbs, 1 or hypoxic pelvic and limb perfusion (HPLP) for cases of synchronous inferior limb and inguinal region and/or pelvic involvement. 15 Systemic treatments, currently proposed for locoregional metastases judged to be unresectable for technical or clinical reasons, include single or combinations of agents with local and/or regional treatments.…”

Molecular Aspects of the Isolated Limb Infusion Procedure

“…These measures, and the mild hyperthermia, improve the take up of the cytotoxic agents by the exposed tissues, augmenting tumour responses. In case locally advanced melanomas or sarcomas are confined to a limb, these patients can often be effectively treated by high-dose loco-regional chemotherapy administered by either hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI), although these procedures are not uniformly recommended by current American, European and Australian guidelines [1,[4][5][6][7][8][9][10][11]. Both HILP and ILI are well-established treatments in the neoadjuvant setting to improve resectability for sarcoma, as well as an adjuvant or palliative treatment when melanoma ITMs or local recurrences of sarcoma are present.…”