Does sentinel lymph node status have prognostic significance in patients with acral lentiginous melanoma?

BACKGROUND: The prognostic benefit of sentinel lymph node biopsy (SLNB) and factors predictive of survival specifically in patients with acral lentiginous melanoma (ALM) are unknown. METHODS: The SEER database was queried for ALM cases that underwent SLNB from 1998 to 2013. Clinicopathological factors were correlated with SLN status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: Median age for the 753 ALM study patients was 65 years, and 48.2% were male. Median thickness was 2 mm with 38.1% of cases having ulceration. SLN metastases were detected in 194 of 753 cases (25.7%). Multivariable analysis showed that thickness, Clark level IV-V, and ulceration significantly predicted for SLN metastasis (P < 0.05). For patients with positive SLN, 5-year OS and MSS were significantly worse at 48.1% and 58.9%, respectively, compared with 78.7% and 88.5%, respectively, for patients with negative SLN (P < 0.0001). On multivariable analyses, older age, male gender, increasing thickness, ulceration, and a positive SLN significantly predicted for worse OS and MSS (all P < 0.05). CONCLUSION: This study confirms the important role of SLNB in ALM. SLN metastases are seen in 25.7% of ALM cases, providing significant prognostic information. In addition, thickness, ulceration status, and SLNB status significantly predict survival in patients with ALM.

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma.

BACKGROUND: Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI. METHODS: We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded. RESULTS: Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6% (P = 0.001). Five-year DSS after local therapy was 93% versus 31%, respectively (P = 0.046). CONCLUSIONS: Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.

Eliminating Preoperative Lymphoscintigraphy in Extremity Melanomas.

BACKGROUND: Preoperative lymphoscintigraphy (LSG) is an imaging procedure routinely used to identify the draining nodal basin in melanomas. At our institute, we have traditionally performed preoperative LSG followed by intraoperative LSG for logistical and evaluative reasons. We sought to determine if preoperative LSG could be safely eliminated in the treatment of extremity melanomas, which exhibit consistent and predictable lymphatic drainage patterns. METHODS: We reviewed the Yale Melanoma Registry 1308012545 for cutaneous extremity melanomas treated at our institution. From this registry, we calculated the incidence of atypical lymph node drainage patterns outside the axillary and inguinal regions. Based on these data, we eliminated preoperative LSG in 21 cases (8 upper extremities and 13 lower extremities). Additionally, we calculated the potential hospital charge reduction of forgoing preoperative LSG. RESULTS: Upper and lower extremity melanomas treated at our institution exhibited atypical lymph node drainage at a rate of 3.4% and 2.0%, respectively. The sites of atypical drainage were to the epitrochlear and popliteal regions. In all 21 cases where preoperative LSG was eliminated, we were able to correctly identify the sentinel lymph node. The potential hospital charge reduction of forgoing preoperative LSG totaled $2,393. CONCLUSIONS: Preoperative LSG can be safely eliminated in the management of upper and lower extremity melanomas. Exceptions may be considered for primary lesions of the posterior calf, ankle, and heel as well as for patients with history of prior surgery or radiation. Forgoing preoperative LSG results in a hospital charge reduction of $2,393 and provides additional benefits to the patient. Ultimately, there is potential for significant charge reduction if applied across health care systems.

Use of Indocyanine Green for Sentinel Lymph Node Biopsy: Case Series and Methods Comparison.

INTRODUCTION: Sentinel lymph node biopsy is indicated for patients with biopsy-proven thickness melanoma greater than 1.0 mm. Use of lymphoscintigraphy along with vital blue dyes is the gold standard for identifying sentinel lymph nodes intraoperatively. Indocyanine green (ICG) has recently been used as a method of identifying sentinel lymph nodes. We herein describe a case series of patients who have successfully undergone ICG-assisted sentinel lymph node biopsy for melanoma. We compare 2 imaging systems that are used for ICG-assisted sentinel lymph node biopsy. METHODS: Fourteen patients underwent ICG-assisted sentinel lymph node biopsy for melanoma using the SPY Elite system (Novadaq, Mississigua, Canada) and the Hamamatsu PDE-Neo probe system (Mitaka USA, Park City, Utah). We analyzed costs for 2 systems that utilize ICG for sentinel lymph node biopsies. RESULTS: Intraoperative use of ICG for sentinel lymph node biopsies was successful in correctly identifying sentinel lymph nodes. There was no difference between the Hamamatsu PDE-Neo probe and SPY Elite systems in the ability to detect sentinel lymph nodes; however, the former was associated with a lower operating cost and ease of use compared with the latter. CONCLUSION: ICG-assisted sentinel lymph biopsy using the SPY Elite or the Hamamatsu PDE-Neo probe systems for melanoma are comparable in terms of sentinel node detection. The Neo probe system delivers pertinent clinical data with the advantages of lower cost and ease of operation.

Malignant Melanoma: Beyond the Basics.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Discuss the initial management of cutaneous malignant melanoma with regard to diagnostic biopsy and currently accepted resection margins. 2. Be familiar with the management options for melanoma in specific situations such as subungual melanoma, auricular melanoma, and melanoma in the pregnant patient. 3. Discuss the differentiating characteristics of desmoplastic melanoma and its treatment options. 4. List the indications for sentinel lymph node biopsy and be aware of the ongoing trials and current literature. 5. Discuss the medical therapies available to patients with metastatic melanoma. SUMMARY: Management of the melanoma patient is a complex and evolving subject. Plastic surgeons should be aware of the recent changes in the field. Excisional biopsy remains the gold standard for diagnosis, although there is no evidence that use of other biopsy types alters survival or recurrence. Wide local excisions should be carried out with margins as recommended by National Comprehensive Cancer Network guidelines according to lesion Breslow depth, with sentinel lymph node biopsy being offered to all medically suitable candidates with intermediate thickness melanomas (1.0 to 4.0 mm), and with sentinel lymph node biopsy being considered for high-risk lesions (ulceration and/or high mitotic figures) with melanomas of 0.75 to 1.0 mm. Melanomas diagnosed during pregnancy can be treated with preoperative lymphoscintigraphy and wide local excision under local anesthesia, with sentinel lymph node biopsy under general anesthesia delayed until after delivery. Management of desmoplastic melanoma is currently controversial with regard to the indications for sentinel lymph node biopsy and the efficacy of postoperative radiation therapy. Subungual and auricular melanoma have evolved from being treated by amputation of the involved appendage to less radical procedures-ear reconstruction is now attempted in the absence of gross invasion into the perichondrium, and subungual melanomas may be treated with wide local excision down to and including the periosteum, with immediate full-thickness skin grafting over bone. Although surgical treatment remains the current gold standard, recent advances in immunotherapy and targeted molecular therapy for metastatic melanoma show great promise for the development of medical therapies for melanoma.