Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and death.

BACKGROUND: Despite approximately 4400 locally advanced US cases annually, high-stage basal cell carcinoma (BCC) is ill-defined. OBJECTIVE: To develop a tumor (T) staging system for BCC that will predict metastasis/death and compare its performance with that of the American Joint Committee on Cancer 8th edition (AJCC8) T-staging system. METHODS: Brigham and Women's Hospital (BWH) T staging was developed from a previously published nested cohort of 488 primary BCCs. Tumors were staged via BWH and AJCC8 T-staging systems, and predictions of metastasis and/or death were compared. RESULTS: The BWH and AJCC8 T-staging systems both captured all metastases/deaths in high T stages (BWH, T2; AJCC8, T3/T4). BWH T2 included 54% fewer cases ≥2 cm than AJCC8 T3/T4. BWH had a higher specificity (0.92 vs 0.80; P < .001) and positive predictive value (24% vs 11%, P < .001) for identifying cases at risk for metastasis/death, and the C-statistic was superior for BWH (P < .001). The BWH T2 10-year cumulative incidence of metastasis/death was 37% (95% confidence interval, 21%-60%). LIMITATIONS: Two-center cohort. CONCLUSIONS: BWH and AJCC 8 BCC staging both capture all metastases and deaths in the upper stages. However, BWH staging does so in half the number of cases, thus minimizing inappropriate up-staging. The risk of metastasis or death in BWH T2 BCC is sufficient to warrant surveillance for recurrence and clinical trials of adjuvant therapy.

Evaluation of the utility of localized adjuvant radiation for node-negative primary cutaneous squamous cell carcinoma with clear histologic margins.

BACKGROUND: Though the National Comprehensive Cancer Network recommends consideration of localized adjuvant radiation after clear-margin surgery for cutaneous squamous cell carcinoma (cSCC) with large-caliber (≥0.1-mm) nerve invasion (LCNI) and other high-risk features, only a single small study has compared surgery plus adjuvant radiation therapy (S+ART) to surgical monotherapy (SM) for cSCC. OBJECTIVE: Compare S+ART to SM for primary cSCCs with LCNI and other risk factors. METHODS: Matched retrospective cohort study of primary cSCCs (matched on sex, age, immune status, type of surgery, diameter, differentiation, depth, and LCNI) treated with S+ART versus SM. A subgroup analysis of cSCCs with LCNI was performed. RESULTS: In total, 62 cSCCs were included in matched analysis (31 S+ART and 31 SM) and 33 cSCCs in the LCNI analysis (16 S+ART and 17 SM). There were no significant differences in local recurrence, metastasis, or death from disease in either analysis. Risk of local recurrence was low (8%, 7/89), with 3 of the local recurrences being effectively treated upon recurrence. LIMITATIONS: Single academic center and nonrandomized design. CONCLUSION: Adjuvant radiation did not improve outcomes compared with SM due to a low baseline risk of recurrence, although adjuvant radiation for named nerve invasion and LCNI of ≥3 nerves has been shown to improve outcomes in a prior study. Randomized studies are needed to define the subset of cSCC for whom adjuvant radiation has utility.

Factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter.

BACKGROUND: Basal cell carcinoma (BCC) recurrence and metastatic rates are known to be very low. The risk factors for these rare outcomes are subsequently not well studied. OBJECTIVE: To identify risk factors independently associated with local recurrence (LR) and metastasis and/or death (M/D) in large (≥2 cm) BCC. METHODS: BCCs histologically confirmed between 2000 and 2009 were retrospectively screened for tumor diameter at 2 academic centers. Medical records of all large BCCs and an equal number of randomly selected small BCCs were reviewed for LR and M/D. RESULTS: Included were 248 large BCC and 248 small BCC tumors. Large BCCs had a significantly higher risk of LR and M/D than small BCCs (LR: 8.9% vs 0.8%, P < .001; M/D: 6.5% vs. 0%, P < .001). Because the risks were so low in small BCCs, they were excluded from further analysis. On multivariable logistic regression, head/neck location (odds ratio [OR], 9.7; 95% confidence interval [CI], 3.0-31.3) and depth beyond fat (OR, 3.1; 95% CI, 1.0-9.6) were associated with LR in large BCCs. Risk of LR was lower with Mohs micrographic surgery (OR, 0.14; 95% CI, 0.04-0.5). Head/neck location (OR, 5.3; 95% CI, 1.2-23.2), tumor diameter ≥4 cm (OR, 11.9; 95% CI, 2.4-59.4), and depth beyond fat (OR, 28.6; 95% CI, 6.7-121) were significant predictors of M/D in large BCCs. LIMITATIONS: Retrospective cohort design. CONCLUSIONS: Large BCCs, particularly those with additional risk factors, have a high enough risk of recurrence and metastasis to warrant further investigation to optimize management.

Detection of subclinical disease with baseline and surveillance imaging in high-risk cutaneous squamous cell carcinomas.

BACKGROUND: There are limited studies on imaging for management of high-risk cutaneous squamous cell carcinoma (HRCSSC). OBJECTIVE: To evaluate the impact of baseline (ie, at diagnosis) and surveillance (ie, subsequent time points after diagnosis) imaging on management of HRCSCCs. METHODS: All primary CSSCs treated at Brigham and Women's Hospital Mohs Surgery Clinic and Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic from January 1, 2017 through June 1, 2019, were reviewed to identify tumors that underwent baseline or surveillance imaging. Tumors that underwent imaging were reviewed to determine the impact of imaging on management and ability of imaging to identify subclinical disease. RESULTS: Eighty-three patients underwent imaging for 87 primary HRCSCCs, of which 48 (58%) underwent surveillance imaging. A total of 146 (59%) abnormal results were obtained from 248 imaging studies. Management was altered by 42 (24%) studies. Imaging detected subclinical disease in 21% of cases studied. A majority (56%) of detections were not seen initially but rather during surveillance imaging in the 2 years after treatment. LIMITATIONS: Single institution retrospective design. CONCLUSIONS: Imaging identifies subclinical disease in HRCSCC. Prospective studies are needed to determine best practices for screening and surveillance in HRCSCC.

A comparison of skin cancer screening and treatment costs at a Massachusetts cancer center, 2008 versus 2013.

BACKGROUND: Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing. OBJECTIVE: To tabulate the costs of skin cancer-related care (SCRC), including both screening and treatment, at an academic cancer center at 2 time points. METHODS: Cost data (insurance and patient payments) at an academic cancer center from 2008 and 2013 were queried for International Classification of Diseases, Ninth Revision, codes pertaining to skin cancer. Screening costs were separated from treatment costs through associated Current Procedural Terminology codes. RESULTS: The total annual cost of SCRC increased by 64%, the number of patients receiving SCRC increased by 45%, and the mean cost per patient treated increased by 13%. Screening accounted for 17% and 16% of total annual costs in 2008 and 2013, respectively. The mean cost per patient with melanoma increased by 84%, which was the largest increase among skin cancer diagnoses. In 2013, the few patients with melanoma who were treated with ipilimumab (n = 48 [4% of patients with melanoma]) accounted for 42% of melanoma treatment costs and 20% of SCRC costs. LIMITATIONS: Prescription costs were unavailable. CONCLUSIONS: Melanoma costs have increased as a result of the introduction of ipilimumab. Ongoing studies are needed to monitor the cost-effectiveness of SCRC at a national level.

The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management.

BACKGROUND: There is limited evidence on the utility of radiologic imaging for prognostic staging of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: Review utilization of radiologic imaging of high-stage CSCCs to evaluate whether imaging impacted management and outcomes. METHODS: Tumors classified as Brigham and Women's Hospital (BWH) tumor (T) stage T2B or T3 over a 13-year period were reviewed to identify whether imaging was performed and whether results affected treatment. Disease-related outcomes (DRO: local recurrence, nodal metastasis, death from disease) were compared between patients by type of imaging used. RESULTS: 108 high-stage CSCCs in 98 patients were included. Imaging (mostly computed tomography, 79%) was utilized in 45 (46%) patients and management was altered in 16 (33%) patients who underwent imaging. Patients that received no imaging were at higher risk of developing nodal metastases (nonimaging, 30%; imaging, 13%; P = .041) and any DRO (nonimaging, 42%; imaging, 20%; P = .028) compared to the imaging group. Imaging was associated with a lower risk for DRO (subhazard ratio, 0.5; 95% CI 0.2-0.9; P = .046) adjusted for BWH T stage, sex, and location. LIMITATIONS: Single institution retrospective design and changes in technology overtime. CONCLUSIONS: Radiologic imaging of high-stage CSCC may influence management and appears to positively impact outcomes. Further prospective studies are needed to establish which patients benefit from imaging.

Before or after: is there a connection between the use of adjunctive nonmelanoma skin cancer treatments and subsequent invasive tumors?

Although the therapeutic gold standard for basal cell carcinomas (BCCs) is surgical excision, imiquimod, fluorouracil cream, and photodynamic therapy are frequently used. All 3 modalities have been shown to be efficacious for the treatment of superficial BCCs as well as other nonmelanoma skin cancers; however, recent reports have emerged implicating these agents in causing more aggressive recurrent subtypes of BCCs. Here we review this literature as well as offer an alternative explanation for these tumors.

Identifying an Education Gap in Wound Care Training in United States Dermatology.

IMPORTANCE: As restoration of the integument is paramount to wound healing, dermatologists should be central to managing wounds; yet this is often not the case. If a training gap exists during residency training, this may account for the observed discrepancy. OBJECTIVES: To identify United States (US) dermatology residents' impressions regarding their preparedness to care for wounds, and to assess the amount and type of training devoted to wound care during residency. DESIGN, SETTING, AND PARTICIPANTS: An online survey among current US dermatology residents enrolled in a residency training program. MAIN OUTCOMES AND MEASURES: The primary goal was to determine whether dermatology residents believe more wound care education is needed, evaluate preparedness to care for wounds, and identify future plans to manage wounds. RESULTS: Responses were received from 175 of 517 (33.8%) US Dermatology residents contacted. The majority of residents did not feel prepared to manage acute (78.3%) and chronic (84.6%) wounds. Over three quarters (77.1%) felt that more education is needed. Fewer than half (49.1% and 35.4%) of residents planned to care for acute and chronic wounds, respectively, when in practice. CONCLUSIONS AND RELEVANCE: There is a gap in wound care education in US dermatology residency training. This translates to a low percentage of dermatology residents planning to care for wounds in future practice. Dermatology residents need to receive focused wound care training in order to translate the underpinnings of wound healing biology and ultimately better serve patients.

Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women's Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma.

Importance: Brigham and Women's tumor classification (BWH) better predicts poor outcomes than American Joint Committee on Cancer (AJCC) 7th edition (AJCC 7). AJCC 8th edition (AJCC 8) has not been evaluated. Objectives: To compare BWH and AJCC 8 tumor classifications for head and neck cutaneous squamous cell carcinoma (HNCSCC). Design, Setting, and Participants: A total of 459 patients with 680 HNCSCCs in this cohort study were staged via BWH and AJCC 8 classifications and poor outcomes (ie, local recurrence [LR], nodal metastasis [NM], disease specific death [DSD], and overall survival [OS]) were compared. The study was carried out at a single academic tertiary care center in Boston, Massachusetts. Main Outcomes and Measures: Distinctiveness (outcome differences between tumor class), homogeneity (outcome similarity within tumor class), monotonicity (outcome worsening with increasing tumor class), and C statistic. Results: A total of 680 HNCSCCs in 459 patients were included in this study, of which 313 (68%) were men with the mean (SD) age of 70.2 (12.7) years. The AJCC 8 (T3/T4) and BWH (T2b/T3) high tumor classes accounted for 121 (18%) vs 63 (9%), 17 (71%) vs 16 (70%), and 11 (85%) vs 12 (92%) of total cases, metastases, and deaths, respectively. The AJCC 8 T2 and T3 comprised 23% of cases and had statistically indistinguishable outcomes. The BWH had higher specificity (93%) and positive predictive value (30%) for identifying cases at risk for metastasis or death. C statistics showed BWH to be superior in predicting NM and DSD (P = .01 and P = .005, respectively), but there was no difference for LR and OS. Conclusions and Relevance: Lack of distinction between AJCC T2 and T3 resulted in a 23% subset of HNCSCCs with significant risk of metastasis and death-too large of a group for routine nodal staging or consideration of adjuvant therapy. The BWH identifies the same number of poor outcomes in a 9% subset of HNCSCCs, thus minimizing inappropriate upstaging of low-risk disease.

Cutaneous Squamous Cell Carcinoma in Transketolase Deficiency.

This case report describes a patient in their late 30s with a history of transketolase deficiency who presented with a new diagnosis of squamous cell carcinoma.

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data.

Importance: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) has been associated with an increased risk of poor outcomes. Patients with PNI may present with clinical symptoms and/or radiologic evidence of PNI (clinical PNI [CPNI]), yet most patients are asymptomatic and PNI is often found on histologic examination (incidental PNI [IPNI]). Evidence-based estimates of the risks of disease-related outcomes comparing IPNI and CPNI are limited in the dermatology literature. Objectives: To review and synthesize outcomes data for patients with CSCC and CPNI or IPNI. Data Sources: A systematic review was conducted in MEDLINE and EMBASE for English-language articles published since inception to November 11, 2016. Study Selection: All studies that reported a disease-related outcome (local recurrence, nodal metastasis, distant metastasis, or disease-specific death) of CSCCs with CPNI and IPNI were included. Data Extraction and Synthesis: Articles were screened for eligibility, and any possible discrepancies in this screening were resolved. Data extracted included study characteristics, tumor characteristics, treatments performed, and disease-related outcomes. Overall risks of disease-related outcomes were generated by pooling patients from eligible studies. χ2 Statistics and Fisher exact tests were used to evaluate differences in disease-related outcomes. Main Outcomes and Measures: Risks of disease-related outcomes and 5-year recurrence-free, disease-specific, and overall survival. Results: A total of 12 studies containing 241 patients with CPNI and 381 patients with IPNI were included in the systematic review and analysis. The overall risks of local recurrence and disease-specific death were significantly higher in patients with CSCC and CPNI compared with those with CSCC and IPNI (local recurrence, 37% vs 17%; P < .001; disease-specific death, 27% vs 6%; P < .001). The risks of nodal metastasis and distant metastasis did not differ significantly by PNI classification. Patients with CSCC and CPNI had poorer mean 5-year recurrence-free survival and disease-specific survival compared with patients with IPNI (recurrence-free survival, 61% vs 76%; P = .009; disease-specific survival, 70% vs 88%; P = .002). Conclusions and Relevance: Patients with CSCC and CPNI are at an increased risk of local recurrence and disease-specific death compared with patients with CSCC and IPNI and have a 30% risk of death. Patients with PNI may benefit from increased long-term surveillance. Further studies are needed to establish standardized guidelines on follow-up and dermatologic surveillance in this high-risk patient population.