NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022

Schmults, Chrysalyne D.; Blitzblau, Rachel; Aasi, Sumaira Z.; Alam, Murad; Andersen, James S.; Baumann, Brian C.; Bordeaux, Jeremy S.; Chen, Pei-Ling; Chin, Robert; Contreras, Carlo M.; DiMaio, Dominick J.; Donigan, Jessica M.; Farma, Jeffrey M.; Ghosh, Karthik; Grekin, Roy C.; Harms, Kelly L.; Ho, Alan L.; Holder, Ashley M.; Lukens, John N.; Medina, Theresa; Nehal, Kishwer S.; Nghiem, Paul; Park, Soo Hyung; Patel, Tejesh; Puzanov, Igor; Scott, Jeffrey; Sekulić, Aleksandar; Shaha, Ashok R.; Srivastava, Divya; Stebbins, William G.; Thomas, Valencia D.; Xu, Yaohui; McCullough, Beth; Dwyer, Mary A.; Nguyen, Mai Q.

doi:10.6004/jnccn.2021.0059

Cited by 94 publications

(128 citation statements)

References 105 publications

(142 reference statements)

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“…National Comprehensive Cancer Network Guidelines recommend considering postoperative RT for those with negative margins who have extensive perineural or large-nerve involvement, and for those cases with positive margins. 18,19 20% (101/511) of the PNI cases had positive margins, and all such cases received RT. Of the 344 cases in the CSCC with PNI analysis, 7 BCC cases could not be separated from CSCC in 7 of the primary studies.…”

Section: Perineural Invasion Subanalysismentioning

confidence: 99%

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis

et al. 2022

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BACKGROUND Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9–4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4–14.1] vs 32.0% [25.0–39.0], p < .001), and recurrent BCC (4.4% [2.9–5.9] vs 11.9% [8.0–15.8], p < .001). CONCLUSION For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

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Section: Perineural Invasion Subanalysismentioning

confidence: 99%

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis

et al. 2022

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“…In cases of regional LNM, a neck dissection of ipsilateral cervical lymph nodes is advised, depending on the primary site including removal of the parotid gland ( 13 , 14 ). The extent of the advised neck dissection (i.e.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Tumor Characteristics and Location on the Extent of Lymph Node Metastases of Head and Neck Cutaneous Squamous Cell Carcinoma

Leer

Leus²,

Dijk³

et al. 2022

Front. Oncol.

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BackgroundThe extent of a neck dissection for patients with metastasis of cutaneous squamous cell carcinoma of the head and neck (HNcSCC) is still subject to debate and clear guidelines are lacking. Tumor characteristics like size, differentiation and tumor location are known risk factors for lymph node metastasis (LNM). There is some evidence that, depending on tumor location, LNM follows a specific pattern. This study aims to identify which tumor characteristics can predict the pattern and extent of LNM.MethodIn this cohort study 80 patients were included, who underwent a primary neck dissection for LNM of HNcSCC between 2003 and 2018 at the University Medical Center Groningen, the Netherlands. Retrospective data was collected for primary tumor characteristics and LNM and included surgical and follow-up data. Influence of tumor characteristics on the extent of LNM was analyzed using non-parametric tests. Logistic regression analysis were used to identify a metastasis pattern based on the primary tumor location.ResultsOnly primary tumor location was associated with the pattern of LNM. HNcSCC of the ear metastasized to level II (OR = 2.6) and the parotid gland (OR = 3.6). Cutaneous lip carcinoma metastasized to ipsilateral and contralateral level I (OR = 5.3). Posterior scalp tumors showed a metastasis pattern to level II (OR = 5.6); level III (OR = 11.2), level IV (OR = 4.7) and the parotid gland (OR = 10.8). Ear canal tumors showed a low risk of LNM for all levels. The extent of LNM was not related to age or any tumor characteristics i.e. tumor diameter, infiltration depth, differentiation grade, perineural growth and vascular invasion.ConclusionPrimary tumor location determines the LNM pattern. Whereas known unfavorable tumor characteristics did not relate to the extent of LNM. Location guided limited neck dissection combined with parotidectomy will treat most patients adequately.

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“…Currently, chemotherapy usage is limited to patients with metastatic melanoma after disease progression or drug intolerance with immunotherapy or oncogene-targeted agents (58). Cytotoxic treatment options include TMZ (alkylating agent), DITC (alkylating agent), paclitaxel (or albumin-bound paclitaxel) (microtubule inhibitor), and carboplatin (platinum agent and DNA cross-linker) (59). The most commonly used among these agents, TMZ (an oral prodrug of DITC) and DITC, have roughly equivalent activity against melanoma (60).…”

Section: Discussionmentioning

confidence: 99%

Wild-type IDH1 inhibition enhances chemotherapy response in melanoma

Zarei

Hajihassani

Hue

et al. 2022

Preprint

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Malignant melanoma is one of the most common types of cancer in the United States. Despite recent and well-described progress in melanoma treatment, advanced disease still carries a poor prognosis for many patients and chemotherapy has been appropriately abandoned as a front-line option. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme is protective to cancer cells under metabolic stress, including oxidative damage by conventional chemotherapy and nutrient limitation characteristic of the tumor microenvironment. Specifically, the cytosolic enzyme generates NADPH to maintain redox homeostasis. IDH1 also supports mitochondrial function through anaplerosis of its reaction product, α-ketoglutarate. We show that melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironment in natura. Similarly, findings were replicated in murine models of melanoma. Further, wtIDH1 inhibition was synergistic to conventional anti-melanoma chemotherapy in pre-clinical models. This work points to a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma.

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NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022

Cited by 94 publications

References 105 publications

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis

The Effect of Tumor Characteristics and Location on the Extent of Lymph Node Metastases of Head and Neck Cutaneous Squamous Cell Carcinoma

Wild-type IDH1 inhibition enhances chemotherapy response in melanoma

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