Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review. Consensus was achieved through modified Delphi methodology. The steering committee included five dermatologists, three medical oncologists, two head and neck surgeons, one radiation oncologist, and a patient advocacy group representative. The steering committee aligned on the following clinical topics: diagnosis and identification of patients considered not candidates for surgery; staging systems and risk stratification in cutaneous squamous cell carcinoma; the role of radiation therapy, surgery, and systemic therapy in the management of advanced disease, with a focus on immunotherapy; referral patterns; survivorship care; and inclusion of the patient's perspective. Consensus was achieved on 34 recommendations addressing 12 key clinical questions. The Expert Cutaneous Squamous Cell Carcinoma Leadership steering committee's evidence-based consensus recommendations may provide healthcare professionals with practically oriented guidance to help optimize outcomes for patients with advanced cutaneous squamous cell carcinoma.

Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management.

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women's Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.

Immunohistochemistry utilization in the diagnosis of melanoma.

BACKGROUND: The use of immunohistochemical (IHC) stains in dermatopathology is commonplace; however, little is known regarding utilization trends in melanoma diagnosis. Current Medicare local coverage determinations (LCDs) state that most pigmented lesions, including melanoma, can be diagnosed using H&E alone. METHODS: Histopathology reports for all biopsy-proven melanomas excised between January 1, 2017 and June 30, 2018, at a single dermatology clinic, were identified with the following parameters abstracted: laboratory/dermatopathologist rendering the diagnosis, whether IHC was performed, type/number of stains utilized, presence/depth of invasion, and melanoma subtype. The association of characteristics with IHC utilization was evaluated using χ2 test for categorical variables. RESULTS: Three hundred and fifty six eligible melanomas were identified. IHC was employed in 228 (64%) of the diagnoses. Invasive melanoma was diagnosed in 199 cases (55.9%) while 157 (44.1%) were identified as melanoma in situ (MIS). Of the 228 that utilized IHC, 117 were performed on invasive melanoma (58.8%) and 111 were performed on MIS (70.7%). CONCLUSION: Our findings suggest a higher IHC usage for the diagnosis of melanoma than previously reported. Existing LCDs regarding IHC utilization in melanoma do not reflect the current state of practice. Further investigation regarding IHC utilization and the development of appropriate-use criteria for melanoma IHC is necessary.

Level of Evidence Review for a Gene Expression Profile Test for Cutaneous Melanoma.

BACKGROUND: The advent of molecular medicine may allow for individualized cancer prognostication, which should enable better clinical management and, hopefully, improve patient outcomes. A 31-gene expression profile (31-GEP) test is currently available for patients diagnosed with cutaneous melanoma; this test helps inform patients' individual treatment plans, especially when combined with traditional biomarkers. OBJECTIVE: The objective of this study was to review the current literature and establish the level of evidence for a cutaneous melanoma 31-GEP test. METHODS: A review of seven development and validation studies for the 31-GEP test was conducted. The respective strengths and weaknesses of each study were applied to the level of evidence criteria from major organizations that publish guidelines for melanoma management: American Joint Committee on Cancer, National Comprehensive Cancer Network, and American Academy of Dermatology. RESULTS: Evaluating each study led to classifying the 31-GEP test as level I/II, I-IIIB, and IIA according to American Joint Committee on Cancer, National Comprehensive Cancer Network, and American Academy of Dermatology criteria, respectively. This stands in contrast to the official unrated status conferred by the American Joint Committee on Cancer and National Comprehensive Cancer Network and the II/IIIC rating designated by the American Academy of Dermatology. CONCLUSIONS: Differences between the authors' findings and official published ratings may be attributed to chronological issues, as many of the studies were not yet published when the aforementioned organizations conducted their reviews. There was also difficulty in applying the National Comprehensive Cancer Network criteria to this prognostic test, as their guidelines were intended for evaluation of predictive markers. Nevertheless, based upon the most current data available, integration of the 31-GEP test into clinical practice may be warranted in certain clinical situations.

Radiation therapy for widespread actinic keratoses.

OBJECTIVE: To profile 16 patients with widespread and resistant actinic keratoses (AKs) treated with radiation therapy. DESIGN: Chart review and phone interviews of 16 patients who were treated with radiation therapy between 2003 and 2010. SETTING: A specialized dermatological practice primarily treating patients with skin cancer. PARTICIPANTS: The study population at the time of treatment was aged 70 to 87 with a mean age of 79.6 years and included 14 men and two women. MEASUREMENTS: Patients were followed at two weeks and six months after treatment to assess clinical outcome. All adverse effects were recorded. Patients were contacted for phone interview to assess patient satisfaction after treatment. RESULTS: Patients all had significant reduction of AKs in the radiation field with a majority (90%) reporting they were "very satisfied" with their treatment outcome. Of 16 patients at two weeks post-treatment, 13 had complete clinical resolution of their AK after radiation therapy. Three of 16 patients had significant reduction (50-99%) in AK in the treatment field. Patients reported improved quality of life, a reduced need for frequent clinic visits, and long-term remission from the development of new AKs within the treatment field. CONCLUSION: Patients meeting suggested specific criteria developed by the authors may be treated successfully with radiation therapy with good outcomes at six-month follow up and high levels of patient satisfaction.

Dietary supplements: altered coagulation and effects on bruising.

BACKGROUND: Patient use of dietary supplements that alter coagulation or have an effect on bruising is becoming increasingly common. OBJECTIVE: To identify and describe dietary supplements that alter coagulation or are reported to alter bruising during and after surgical procedures. METHODS: The MEDLINE, Cochrane Collaboration, and International Bibliographic Information on Dietary Supplements databases were searched for articles using the search words "bruising," "bleeding," "coagulation," "hemostasis," "herbal medicine," "alternative medicine," and "dietary supplement." Additional sources were obtained from manual searches of recent journal articles. RESULTS: In vivo and in vitro evidence supports the notion that many dietary supplements alter coagulation. Limited evidence is available to support anecdotal claims of diminished postoperative bruising after the use of dietary supplements. CONCLUSION: Surgeons should be aware that many of their patients are taking dietary supplements that may alter coagulation. Because most patients will not readily volunteer this information, specific steps should be taken to obtain it prior to more extensive surgical procedures.

Evaluation of the American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma and proposal of a new staging system.

PURPOSE: To identify and propose corrections for deficiencies in the American Joint Committee on Cancer (AJCC) system for staging cutaneous squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Prognostic factors for CSCC were identified by retrospective analysis of the published literature. Limitations and deficiencies in the current AJCC staging system for CSCC were then determined using these prognostic factors. RESULTS: Size, histologic differentiation, location, previous treatment, depth of invasion, tumor thickness, histologic subtype, perineural spread, and scar etiology are the most powerful tumor prognostic indicators in patients with localized disease. The most important prognostic factors for patients with nodal metastases are the location, number, and size of the positive lymph nodes. Proposed changes for the T classification include increased stratification of tumor size, identification of patients with perineural invasion, and the addition of tumor thickness or depth of invasion. The N classification has been expanded to include the number and size of nodal metastases. CONCLUSION: The current AJCC staging system for carcinoma of the skin has deficiencies that limit its use for CSCC. The proposed TMN staging system for CSCC more accurately reflects the prognosis and natural history of CSCC.

Histopathologic evaluation of cutaneous squamous cell carcinoma: results of a survey among dermatopathologists.

BACKGROUND: There are numerous histopathologic features related to prognosis in cutaneous squamous cell carcinoma (CSCC). We hypothesize that there is no uniform approach toward the reporting of these features. This may be related to differing opinions on their prognostic use. METHODS: A written survey concerning the microscopic evaluation of CSCC was sent to 120 dermatopathologists in the United States and Canada. Respondents were asked whether they comment on specific microscopic features of CSCC, and whether they believe that each specific feature can predict prognosis. RESULTS: The response rate was 78%. Histologic type, and the presence of perineural or vascular/lymphatic invasion, is reported by most dermatopathologists (90%, 96%, and 95%, respectively). These features are also thought to predict prognosis by the majority of respondents. Only 54% report histologic grade, and 49% think grade predicts prognosis. Depth is reported anatomically by 63%, but by only 8% in actual millimeters of invasion. However, 55% think tumor depth predicts prognosis. A total of 43% report the presence of an associated actinic keratosis, although very few (16%) think it predicts prognosis. Very few comment on the presence of inflammation. CONCLUSIONS: Histopathologic reporting of CSCC is not uniform among dermatopathologists. Also, there appears to be differing opinions on the use of certain histopathologic features for predicting prognosis.

Use of alternative therapies by patients undergoing surgery for nonmelanoma skin cancer.

BACKGROUND: The use of alternative therapies is becoming increasingly common and may result in unwanted side effects and drug interactions. OBJECTIVE: To determine the frequency of alternative medicine use by patients undergoing Mohs surgery for nonmelanoma skin cancer. METHODS: A written survey concerning use of alternative therapies was given to patients undergoing Mohs surgery for nonmelanoma skin cancer. A follow-up telephone survey was used to clarify positive responses. RESULTS: Thirty-six of 192 (18.8%) patients with nonmelanoma skin cancer reported using some type of alternative therapy. Almost all patients were using these therapies for conditions unrelated to their nonmelanoma skin cancer. Herbs and botanicals were the most common type of alternative therapy utilized. CONCLUSION: Physicians performing Mohs surgery should be aware that a significant number of their patients use alternative therapies. Since most patients do not readily volunteer information about alternative medicine usage, specific steps should be taken to obtain this information.