Patterns of failure following the excision of in‐transit lesions in melanoma and the influence of excisional margins

Gonzalez, Alexandra B.; Baum, Christian L.; Brewer, Jerry D.; Arpey, Christopher J.; Harmsen, William S.; Suman, Vera J.; Markovic, Svetomir N.; Jakub, James W.

doi:10.1002/jso.25176

Cited by 9 publications

(11 citation statements)

References 13 publications

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“…This finding has been reproduced in several other studies (41,42). This is not dissimilar from the death rate from stage III primary melanoma (40). Although the reasons why patients with a resected local recurrence often do not develop metastatic disease are not understood, this may be reflective of a protective immune response.…”

Section: Discussionsupporting

confidence: 70%

“…This is because local resectable recurrence does not necessarily indicate an aggressive biology in melanoma, whereas distant metastasis almost invariably does. Thus, in one recent study of patients who developed limited local resectable recurrence between 2005 and 2014, only 31% developed distant metastasis while 29% died of melanoma during the follow-up period (40). This finding has been reproduced in several other studies (41,42).…”

Section: Discussionmentioning

confidence: 64%

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Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Gartrell

Marks

Rizk

et al. 2019

Clinical Cancer Research

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Purpose: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population.Experimental Design: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan-Meier curves, and standard univariable and multivariable Cox proportional hazards models.Results: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC ¼ 0.695; P ¼ 0.008). We defined high-and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC ¼ 0.719; P ¼ 0.004 and AUC ¼ 0.698; P ¼ 0.004, respectively). Univariable Cox regression reveals that a highrisk MIP score correlates with DSS (P ¼ 0.015; HR ¼ 3.2).Conclusions: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II-III melanoma for enrollment in clinical trials. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): Figure 4. MIP correlates with DMFI and DSS using Cox regression analysis. A, Univariable and multivariable Cox analysis of DMFI. B, Univariable and multivariable Cox analysis of DSS. Values are significant at P 0.05 ( Ã , P 0.05; ÃÃ , P 0.01; ÃÃÃ , P 0.001).Gartrell et al.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 64%

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Gartrell

Marks

Rizk

et al. 2019

Clinical Cancer Research

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“…Among 130 patients with first time ITM treated with excision at our institution, 44 (34%) had no evidence of recurrence. Factors associated with subsequent recurrence were a DFI of <1 year and more than one IT lesion . A series from Duke University over a 27‐year period identified 648 patients who experienced a recurrence within 5 cm of the original primary melanoma resection scar .…”

Section: Introductionmentioning

confidence: 99%

“…While the ideal clinical and histologic margins of resection remain to be defined, the goal is a negative microscopic margin, and excising with a gross 5 mm margin is likely adequate . It is critical to understand the guidelines that dictate excision margins for a primary melanoma do not apply to IT events.…”

Section: Introductionmentioning

confidence: 99%

“…The argument for a more aggressive strategy is approximately two‐third of patients will experience a recurrence and this is above the threshold for which we would typically recommend adjuvant systemic therapy. In addition, approximately one‐fourth of patients will develop distant metastasis within 3 years and we currently have effective systemic therapies. One method to further individualize risk is a sentinel lymph node biopsy (SLNB).…”

Section: Introductionmentioning

confidence: 99%

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Management of local or regional non‐nodal disease

Racz

Block

Baum

et al. 2018

Journal of Surgical Oncology

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Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient. K E Y W O R D S diphenylcyclopropenone, in transit, intralesional therapy, limb perfusion, melanoma, stage III, talimogene laherparepvec 1 | INTRODUCTION Non-nodal locoregional metastasis in the setting of melanoma includes microsatellites, satellites, and in-transit metastasis (ITM). This pattern of spread is primarily the result of dermal and subcutaneous intralymphatic contamination. The presence of melanoma cells within this rich lymphatic plexus can result in recurrent disease anywhere from the primary site to the regional nodal basin and rarely retrograde, distal to the primary lesion. Historically, microsatellites were defined as microscopic foci identified on pathologic analysis, adjacent or deep to the primary. Clinically detected cutaneous and/or subcutaneous locoregional metastases were arbitrarily categorized based on their proximity to the primary melanoma; satellite lesions occurring within 2 cm of the primary and ITM lesions >2 cm from the melanoma. All these disease patterns have similar prognoses and the 8th edition of The American Joint Committee on Cancer Staging System has added clarity to this issue. 1The updated edition categorizes all regional nodal and intralymphatic disease as N1-N3 disease. Additionally, number of lesions differentiates N1-N3 and the subcategories a-c are distinguished based on clinically occult, clinically detected, matted and/or intralymphatic disease. One should make a distinction, when possible, between a true local recurrence, which represents subclinical persistent primary tumor after initial management; often in the setting of inadequate management such as incomplete resection, as opposed to intralymphatic disease. A true local recurrence portends a better prognosis than cutaneous metastases. 2 The distinction between distant skin, subcutaneous or lymph node metastasis is even more important as these are categorized as M1a, stage IV disease.In-transit metastases occur in 5% to 10% of patients with intermediate thickness melanoma [3][4][5][6][7] and have a propensity for the lower extremities. 8,9 In-transit metastasis often appear indolent and easily treatable, particularly when few in number. However, due to the aforementioned concept of lymphatic contamination, recurrence remains the rule and not the exception especially when management consists of targeted treatment of individual lesions rather than a more holistic approach that addresses the involved lymphatic network and nodal basin. Before embarking on treatment of new ITM, we obtain systemic imaging, PET scan preferred, to rule out clinically ...

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Exploiting molecular probes to perform near‐infrared fluorescence‐guided surgery

Zhang

2020

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Near-infrared (NIR) fluorescence imaging can provide real-time navigation for surgeons to discriminate boundaries between lesions and healthy tissue, which serves as a promising tool to enhance precise diagnosis and accurate excision during surgery. Molecular probes with NIR fluorescence can visualize diseased tissue in deep penetration with improved signal-to-noise ratio, which considerably encourages the active participation of NIR fluorescence-guided surgery in the operating room. Although a great quantity of fluorescent probes has been employed in clinical trials, the U.S. Food and Drug Administration only approves an extremely narrow number of contrast agents for clinical use so far. Currently, there remain two significant problems to be addressed in surgical resection: accurate identification of diseased tissue and the preservation of adjacent vital structures. Here, molecular probes with NIR fluorescence are systematically reviewed to offer possible solutions to these two problems. Targeting strategies of fluorescent probes are introduced, where the strengths and weaknesses of each strategy are presented. Advances in fluorescent probes for the imaging of vital structures, such as nerve and ureter, are also summarized in this review. It is convinced that NIR fluorescence-guided surgery has the potential to improve current surgical resection and ameliorate the postoperative outcomes of diverse diseases.

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Patterns of failure following the excision of in‐transit lesions in melanoma and the influence of excisional margins

Abstract: Patients with greater than 1 IT lesion and a DFI less than 1 year are at a higher risk of failure after surgical excision of a first IT event. Very few failures were isolated local disease within 2 cm of the IT resection scar, regardless of IT excision margin.

Cited by 9 publications

References 13 publications

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Management of local or regional non‐nodal disease

Exploiting molecular probes to perform near‐infrared fluorescence‐guided surgery

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