Guidelines of care for the management of primary cutaneous melanoma

Swetter, Susan M.; Tsao, Hensin; Bichakjian, Christopher K.; Curiel‐Lewandrowski, Clara; Elder, David E.; Gershenwald, Jeffrey E.; Guild, Valerie; Grant‐Kels, Jane M.; Halpern, Allan C.; Johnson, Timothy M.; Sober, Arthur J.; Thompson, John A.; Wisco, Oliver J.; Wyatt, Samantha; Hu, Shasa; Lamina, Toyin

doi:10.1016/j.jaad.2018.08.055

Cited by 451 publications

(532 citation statements)

References 335 publications

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“…As in melanomas at other anatomical sites, SLN mapping is standard‐of‐care for vulvar melanoma stage T1b (<0.8 mm with ulceration or 0.8–1.0 mm with or without ulceration) and in appropriate patients with tumour >1 mm in thickness (≥T2a). This technique may also be used in cases for T1a melanoma, if other adverse features are present …”

Section: Vulvamentioning

confidence: 99%

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Gynaecological malignancies and sentinel lymph node mapping: an update

Euscher

Malpica

2019

Histopathology

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Assessment of pelvic, para‐aortic or inguinal lymph nodes (LNs) provides not only important prognostic information, but also determines the need for adjuvant treatment. Sentinel lymph node (SLN) biopsy has the potential to provide this prognostic information, while reducing morbidity compared with extended LN dissection. This review discusses the clinical and pathological aspects of SLN biopsy in gynaecological cancer.

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Section: Vulvamentioning

confidence: 99%

“…This technique may also be used in cases for T1a melanoma, if other adverse features are present. 21…”

Section: Vulvamentioning

confidence: 99%

Gynaecological malignancies and sentinel lymph node mapping: an update

Euscher

Malpica

2019

Histopathology

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“…The signature uniquely demonstrated prognostic relevance in patients with stage I primary melanoma and further predicted poor outcomes in patients undergoing immunotherapy (16). However, owing at least in-part to a lack of prospective reproducible data, proving the clinical utility of such prognostic molecular tools remains a considerable challenge and there are currently no established prognostic biomarkers able to accurately identify truly high-risk patients (17).…”

Section: Introductionmentioning

confidence: 99%

Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

Garg

Couturier

Nsengimana

et al. 2020

Preprint

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PurposePredicting outcomes after resection of primary melanoma remains crude, primarily based on tumour thickness. We explored gene expression signatures for their ability to better predict outcomes.MethodsDifferential expression analysis of 194 primary melanomas resected from patients who either developed distant metastasis (n=89) or did not (n=105) was performed. We identified 121 metastasis-associated genes that were included in our prognostic signature, “Cam_121”. Several machine learning classification models were trained using nested leave- one-out cross validation (LOOCV) to test the signature’s capacity to predict metastases, as well as regression models to predict survival. The prognostic accuracy was externally validated in two independent datasets.ResultsCam_121 performed significantly better in predicting distant metastases than any of the models trained with the clinical covariates alone (pAccuracy=4.92×10−3), as well as those trained with two published prognostic signatures. Cam_121 expression score was strongly associated with progression-free survival (HR=1.7, p=3.44×10−6), overall survival (HR=1.73, p=7.71×10−6) and melanoma-specific survival (HR=1.59, p=0.02). Cam_121 expression score also negatively correlated with measures of immune cell infiltration (ρ=−0.73, p<2.2×10−16), with a higher score representing reduced tumour lymphocytic infiltration and a higher absolute 5-year risk of death in stage II melanoma.ConclusionsThe Cam_121 primary melanoma gene expression signature outperformed currently available alternatives in predicting the risk of distant recurrence. The signature confirmed (using unbiased approaches) the central prognostic importance of immune cell infiltration in long-term patient outcomes and could be used to identify stage II melanoma patients at highest risk of metastases and poor survival who might benefit most from adjuvant therapies.Translational relevancePredicting outcomes after resection of primary melanoma is currently based on traditional histopathological staging, however survival outcomes within these disease stages varies markedly. Since adjuvant systemic therapies are now being used routinely, accurate prognostic information is needed to better risk stratify patients and avoid unnecessary use of high cost, potentially harmful drugs, as well as to inform future adjuvant strategies. The Cam_121 gene expression signature appears to have this capability and warrants evaluation in prospective clinical trials.

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“…When diagnosed early, melanoma is treated with excision and Mohs surgery . Workup of melanoma includes skin biopsy, imaging with PET scan, and sentinel‐node biopsy and if sentinel node is positive, lymphnode dissection follows .…”

Section: Introductionmentioning

confidence: 99%

Blockade of CCR5 in melanoma: An alternative immune checkpoint modulator

Brehm

Bedogni

2019

Experimental Dermatology

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Melanoma is a deadly tumor, which in recent years has been successfully treated with immune checkpoint inhibitors as PD-1/PD-L1 and CTLA-4 inhibitors and targeted therapy as BRAF and MEK inhibitors. However, immunotherapy poses deleterious side effects and pursuit of new therapeutic targets is warranted. As knowledge of tumor immunology advances, such targets are being recognized.C-motif chemokine receptor-5 (CCR5) is a receptor found on immune cells whose effects impact the immune response both to induce inflammation and to activate suppressor cells causing an anti-inflammatory effect. CCR5 is well known as a target for HIV therapy where its blockade is efficient and safe, it is also known that its mutation CCR5delta32 is for the most part non-pathological to its carriers.In oncology, activation of the CCR5 receptor has been observed in high-stage disease and CCR5 blockade has been associated with an increased immune response. In this letter, we build up the rationale to utilize CCR5 as a therapeutic target for metastatic melanoma.

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Guidelines of care for the management of primary cutaneous melanoma

Cited by 451 publications

References 335 publications

Gynaecological malignancies and sentinel lymph node mapping: an update

Gynaecological malignancies and sentinel lymph node mapping: an update

Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

Blockade of CCR5 in melanoma: An alternative immune checkpoint modulator

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