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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

ABSTRACT: In this retrospective review of 100 patients with primary invasive acral melanoma, we examined whether narrow-margin excision is warranted for acral melanoma. Patients treated with surgical margins recommended by the National Comprehensive Cancer Network (R-group) were compared to those treated with narrow margins (N-group). A total of 65 patients underwent narrow-margin excision. Positive margin status or local recurrence rarely occurred regardless of the excision margins, whereas fatal events frequently occurred, particularly among the patients with T4 melanoma. The mortality rates of N- and R-group with T1-3 melanomas were similar (1.36 and 1.28 per 100 person-years, respectively). However, patients with T4 melanoma treated with narrow-margin excision had a higher mortality rate (11.44 vs. 5.03 per 100 person-years). Kaplan-Meier analyses showed a worse prognosis in the N-group (p = 0.045) but this group had thicker Breslow thickness (4.21 mm vs. 2.03 mm, p = 0.0013). A multivariate analysis showed that Breslow thickness was an independent risk factor, but surgical margin was not a risk factor for melanoma-specific survival or disease-free survival. In conclusion, although we could not find a difference between the narrow-margin excision and recommended-margin excision in this study, we suggest following current recommendations of guidelines. Our study warrants the prospective collection of data on acral melanoma to better define the prognosis of this infrequent type of melanoma.

SUBMITTER: Ito T

PROVIDER: S-EPMC7408916 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

Ito Takamichi T Kaku-Ito Yumiko Y Wada-Ohno Maiko M Furue Masutaka M

Journal of clinical medicine 20200716 7

In this retrospective review of 100 patients with primary invasive acral melanoma, we examined whether narrow-margin excision is warranted for acral melanoma. Patients treated with surgical margins recommended by the National Comprehensive Cancer Network (R-group) were compared to those treated with narrow margins (N-group). A total of 65 patients underwent narrow-margin excision. Positive margin status or local recurrence rarely occurred regardless of the excision margins, whereas fatal events ...[more]

PMID: 32708762

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Project description:Although the National Comprehensive Cancer Network (NCCN) guidelines include clear recommendations for the appropriate resection margins in non-acral cutaneous melanoma, the required margin for acral melanoma is controversial. In this retrospective study, we aimed to investigate whether narrow-margin excision is warranted for thick acral melanoma. Records from 277 melanoma patients with stage T3-T4 disease who underwent radical surgery in three centers in China from September 2010 to October 2018 were reviewed. Clinicopathologic data, including age, gender, excision margin (1-2 cm versus ≥ 2 cm), Clark level, Breslow thickness, ulceration, N stage and adjuvant therapy, were included for survival analysis. The patients were followed up until death or March 31, 2021. Log-rank and Cox regression analyses were used to identify prognostic factors for overall survival (OS), disease-free survival (DFS) and local and in-transit recurrence-free survival (LITRFS). Among all enrolled patients, 207 (74.7%) had acral melanoma, and 70 (25.3%) had non-acral cutaneous melanoma. No significant difference in baseline characteristics was identified between non-acral and acral melanoma, except for age (p = 0.004), gender (p = 0.009) and ulceration (p = 0.048). In non-acral melanoma, a resection margin of 1-2 cm was a poor independent prognostic factor for OS [p = 0.015; hazard ratio (HR) (95% CI), 0.26 (0.009-0.77)] and LITRFS [p = 0.013; HR (95% CI), 0.19 (0.05-0.71)] but not for DFS [p = 0.143; HR (95% CI), 0.51 (0.21-1.25)]. Forty-three (20.8%) patients in the acral melanoma group had a 1-2-cm resection margin. The resection margin was not correlated with patients' OS (p = 0.196 by log-rank analysis, p = 0.865 by multivariate survival analysis), DFS (p = 0.080 by log-rank analysis, p = 0.758 by multivariate survival analysis) or LITRFS (p = 0.354 by log-rank analysis) in acral melanoma. As recommended in the NCCN guidelines, a resection margin ≥ 2 cm is required for non-acral cutaneous melanoma. Meanwhile, a narrow resection margin (1-2 cm) may be safe for patients with acral melanoma.

Project description:BackgroundAcral melanoma is a rare type of melanoma that affects world populations irrespective of skin color and has worse survival than other cutaneous melanomas. It has relatively few single nucleotide mutations without the UV signature of cutaneous melanomas, but instead has a genetic landscape characterized by structural rearrangements and amplifications. BRAF mutations are less common than in other cutaneous melanomas, and knowledge about alternative therapeutic targets is incomplete.MethodsTo identify alternative therapeutic targets, we performed targeted deep-sequencing on 122 acral melanomas. We confirmed the loss of the tumor suppressors p16 and NF1 by immunohistochemistry in select cases.ResultsIn addition to BRAF (21.3%), NRAS (27.9%), and KIT (11.5%) mutations, we identified a broad array of MAPK pathway activating alterations, including fusions of BRAF (2.5%), NTRK3 (2.5%), ALK (0.8%), and PRKCA (0.8%), which can be targeted by available inhibitors. Inactivation of NF1 occurred in 18 cases (14.8%). Inactivation of the NF1 cooperating factor SPRED1 occurred in eight cases (6.6%) as an alternative mechanism of disrupting the negative regulation of RAS. Amplifications recurrently affected narrow loci containing PAK1 and GAB2 (n = 27, 22.1%), CDK4 (n = 27, 22.1%), CCND1 (n = 24, 19.7%), EP300 (n = 20, 16.4%), YAP1 (n = 15, 12.3%), MDM2 (n = 13, 10.7%), and TERT (n = 13, 10.7%) providing additional and possibly complementary therapeutic targets. Acral melanomas with BRAFV600E mutations harbored fewer genomic amplifications and were more common in patients with European ancestry.ConclusionOur findings support a new, molecularly based subclassification of acral melanoma with potential therapeutic implications: BRAFV600E mutant acral melanomas with characteristics similar to nonacral melanomas that could benefit from BRAF inhibitor therapy, and non-BRAFV600E mutant acral melanomas. Acral melanomas without BRAFV600E mutations harbor a broad array of therapeutically relevant alterations. Expanded molecular profiling would increase the detection of potentially targetable alterations for this subtype of acral melanoma.

Project description:ImportanceMelanoma guidelines recommend surgical excision with 10-mm margins for T1 melanoma. However, this procedure may be problematic at sites close to critical structures such as the scalp, face, external genitalia, acral, periumbilical, and perineal areas.ObjectiveTo compare outcomes of wide (10-mm margins) vs narrow (5-mm margins) excision in patients with T1a melanoma near critical structures.Design, setting, and participantsThis cohort study was a retrospective comparison of 1341 consecutive patients aged 18 years or older from the National Cancer Institute of Milan, Italy, diagnosed between 2001 and 2020 with T1a cutaneous melanoma close to critical structures who accepted wide excision vs narrow excision.ExposuresLocal recurrence and melanoma-specific mortality (MSM) rates with 5-mm vs 10-mm excision margins.Main outcomes and measuresThe primary aim of the study was to ascertain whether a narrower (5-mm) vs wider (10-mm) excision margin was associated with local recurrence and MSM. The secondary aim was to compare the need for reconstructive surgery in the groups defined by excision margin width. Between April 28 and August 7, 2022, associations were assessed by weighted Cox and Fine-Gray univariable and multivariable models.ResultsA total of 1179 patients met the inclusion criteria (median [IQR] age, 50.0 [39.5-63.0] years; female, 610 [51.7%]; male, 569 [49.3%]). Six hundred twenty-six patients (53.1%) received a wide excision (434 [69.3%] with linear repair and 192 [30.7%] with flap or graft reconstruction) and 553 (46.9%) received a narrow excision (491 [88.8%] with linear repair and 62 [11.2%] with flap or graft reconstruction). The weighted 10-year MSM was 1.8% (95% CI, 0.8%-4.2%) in the wide group and 4.2% (95% CI, 2.2%-7.9%) in the narrow group; the weighted 10-year local recurrence rate was 5.7% (95% CI, 3.9%-8.3%) in the wide group and 6.7% (95% CI, 4.7%-9.5%) in the narrow group. Breslow thickness greater than 0.4 mm (subdistribution hazard ratio [sHR] for 0.6 vs 0.4 mm, 2.42; 95% CI, 1.59-3.68; P < .001) and mitotic rate greater than 1/mm2 (sHR for a single increment, 3.35; 95% CI, 2.59-4.32; P < .001) were associated with worse MSM. Multivariable analysis showed that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.Conclusions and relevanceThe study's findings suggest that local excision with 5-mm margins for T1a melanoma may not be associated with an increased risk of local recurrence. Breslow thickness greater than 0.4 mm, mitotic rate greater than 1/mm2, and acral lentiginous melanoma and lentigo maligna melanoma subtypes were associated with a higher risk of recurrence. These findings may be useful for future melanoma treatment guidelines.

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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

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