Non-Expert Markings of Active Chronic Graft-Versus-Host Disease Photographs: Optimal Metrics of Training Effects.

Lack of reliable measures of cutaneous chronic graft-versus-host disease (cGVHD) remains a significant challenge. Non-expert assistance in marking photographs of active disease could aid the development of automated segmentation algorithms, but validated metrics to evaluate training effects are lacking. We studied absolute and relative error of marked body surface area (BSA), redness, and the Dice index as potential metrics of non-expert improvement. Three non-experts underwent an extensive training program led by a board-certified dermatologist to mark cGVHD in photographs. At the end of the 4-month training, the dermatologist confirmed that each trainee had learned to accurately mark cGVHD. The trainees' inter- and intra-rater intraclass correlation coefficient estimates were "substantial" to "almost perfect" for both BSA and total redness. For fifteen 3D photos of patients with cGVHD, the trainees' median absolute (relative) BSA error compared to expert marking dropped from 20 cm2 (29%) pre-training to 14 cm2 (24%) post-training. Total redness error decreased from 122 a*·cm2 (26%) to 95 a*·cm2 (21%). By contrast, median Dice index did not reflect improvement (0.76 to 0.75). Both absolute and relative BSA and redness errors similarly and stably reflected improvements from this training program, which the Dice index failed to capture.

Clinical and Histopathologic Characteristics of Metastatic and Locally Advanced Cutaneous Basal Cell Carcinomas.

ABSTRACT: Locally advanced or metastatic basal cell carcinomas (laBCCs or mBCCs) are rare, with few case series providing information on their epidemiology. We aimed to describe the clinical and histologic features of locally advanced and metastatic basal cell carcinomas. Forty cases of laBCC or mBCC were identified by searching Vanderbilt's database from 1984 to January 2019. A retrospective chart review was performed. Pathology slides were available for 23 cases (13 mBCCs and 10 laBCCs). Twenty-one of 23 cases were Clark level IV or V, with a mean depth of invasion of >7 mm for both types. The mean mitotic rate was 4.4 mitoses/mm2 for laBCCs and 3.3 mitoses/mm2 for mBCCs. Ulceration was identified in 7 laBCC and 8 mBCC cases. Perineural invasion was present in 2 laBCC and 6 mBCC cases, with 3 mBCCs invading nerves >0.1 mm. Of 13 mBCC cases, histologic subtypes included infiltrative (n = 9), nodular (n = 7), morpheaform (n = 4), and superficial (n = 2), with multiple patterns present in some specimens. 10 of 13 patients with mBCC had local recurrence before metastasis. In summary, we identified several potential markers of high-risk BCC, including perineural invasion, deep invasion, elevated mitotic rate, and local recurrence of the primary tumor.

Porcine Urinary Bladder Extracellular Matrix for Treatment of Periocular Skin Defects.

PURPOSE: To describe the experience of 4 oculoplastic surgeons with porcine bladder matrix for periocular anterior lamella and donor site skin defects either as stand-alone treatment or in conjunction with other reconstructive procedures. The authors hypothesized that defect size and location influence the requirement for additional matrix treatments or ancillary procedures. METHODS: Following the Institutional Review Board approval, the authors conducted a retrospective review of 17 patients treated with porcine bladder matrix at 2 oculoplastic practices between 2016 and 2018. Powdered matrix was applied to the skin defect and overlaid with a matrix sheet. Subsequent rounds of matrix treatment or other reconstructive procedures were performed as necessary. Defect size and location were correlated to the number of ancillary matrix treatments or surgical procedures via univariate analysis. RESULTS: Twenty-five sites (21 primary and 4 donor) in 17 individuals (8-95 years, M = 58.8 years, 10 males) were treated with porcine bladder matrix. All wounds healed successfully. Additional matrix treatments were administered at 5 sites. Ancillary procedures were performed for 7 sites. Upper lid involvement and larger defect size tended to require additional ancillary procedures (p = 0.006), while lower eyelid and other periocular defects required fewer procedures (p < 0.001). CONCLUSION: Porcine bladder matrices are useful adjuncts to healing periocular anterior lamella defects in various settings. Such repairs are useful in nonsurgical candidates, but must take into account varying levels of complexity based on lesion location. Smaller defects are more conducive to application of matrices as stand-alone treatment, while larger or upper eyelid defects often require additional procedures.

Outcomes after progression of disease with anti-PD-1/PD-L1 therapy for patients with advanced melanoma.

BACKGROUND: Greater than one-half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti-PD-1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti-PD-1 therapy. METHODS: The authors evaluated 383 consecutively treated patients who received anti-PD-1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival were assessed. RESULTS: Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%). CONCLUSIONS: The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.

Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease.

Importance: Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification. Objective: To compare the prognostic value of body surface area (BSA) and National Institutes of Health (NIH) Skin Score on survival outcomes stratified by erythema and sclerosis subtypes of cGVHD. Design, Setting, and Participants: Multicenter prospective cohort study from the Chronic Graft-vs-Host Disease Consortium including 9 medical centers in the US, enrolled from 2007 through 2012 and followed until 2018. Participants were adults and children with a diagnosis of cGVHD requiring systemic immunosuppression and with skin involvement during the study period, who had longitudinal follow-up. Data analysis was performed from April 2019 to April 2022. Exposures: Patients underwent continuous BSA estimation and categorical NIH Skin Score grading of cutaneous cGVHD at enrollment and every 3 to 6 months thereafter. Main Outcomes and Measures: Nonrelapse mortality (NRM) and overall survival (OS), compared between BSA and NIH Skin Score longitudinal prognostic models, adjusted for age, race, conditioning intensity, patient sex, and donor sex. Results: Of 469 patients with cGVHD, 267 (57%) (105 female [39%]; mean [SD] age, 51 [12] years) had cutaneous cGVHD at enrollment, and 89 (19%) developed skin involvement subsequently. Erythema-type disease had earlier onset and was more responsive to treatment compared with sclerosis-type disease. Most cases (77 of 112 [69%]) of sclerotic disease occurred without prior erythema. Erythema-type cGVHD at first follow-up visit was associated with NRM (hazard ratio, 1.33 per 10% BSA increase; 95% CI, 1.19-1.48; P < .001) and OS (hazard ratio, 1.28 per 10% BSA increase; 95% CI, 1.14-1.44; P < .001), while sclerosis-type cGVHD had no significant association with mortality. The model with erythema BSA collected at baseline and first follow-up visits retained 75% of the total prognostic information (from all covariates including BSA and NIH Skin Score) for NRM and 73% for OS, with no statistical difference between prognostic models (likelihood ratio test χ2, 5.9; P = .05). Conversely, NIH Skin Score collected at the same intervals lost significant prognostic information (likelihood ratio test χ2, 14.7; P < .001). The model incorporating NIH Skin Score instead of erythema BSA accounted for only 38% of the total information for NRM and 58% for OS. Conclusions and Relevance: In this prospective cohort study, erythema-type cutaneous cGVHD was associated with increased risk of mortality. Erythema BSA collected at baseline and follow-up predicted survival more accurately than the NIH Skin Score in patients requiring immunosuppression. Accurate assessment of erythema BSA may assist in identifying patients with cutaneous cGVHD at high risk for mortality.

Validity of Using Billing Codes From Electronic Health Records to Estimate Skin Cancer Counts.

IMPORTANCE: Patients can develop multiple skin cancers, and their medical data can be spread over multiple health care systems. This fragmented care, combined with the lack of skin cancer registries, has limited our ability both to provide accurate estimates of incidence and to study the pathogenesis of multiple skin cancers. OBJECTIVE: To assess whether standard diagnostic and procedural codes present in the electronic health records at a single health care system are a valid proxy for estimating the number of overall skin cancers. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of patients seen at a single-center tertiary care hospital (ie, Vanderbilt University Medical Center) between July 1, 2008, and June 30, 2018. All patients with at least 1 electronic health record-based diagnostic or procedural code for any skin cancer and at least 1 pathology report of a skin cancer. EXPOSURE: The number of International Classification of Disease (ICD) or Current Procedural Terminology (CPT) codes relating to skin cancer. MAIN OUTCOMES AND MEASURES: Pearson correlation coefficient and R2 were calculated for the total number of ICD or CPT codes for skin cancer and histologically verified skin cancers. RESULTS: In this cohort study of 35 901 patients, the mean (SD) age was 70.4 (14.4) years, 20 404 (56.8%) were men, and 31 623 (88.1%) were White individuals. Of these patients, 6307 had at least 1 ICD or CPT code or pathology report for a skin cancer, of whom 5688 patients had both a CPT code related to skin malignancy and a histologically verified skin cancer. There was a strong linear correlation between the number of CPT codes and pathology records (r = 0.87). There was a poor correlation between the number of ICD codes and pathology records (r = 0.22). CONCLUSIONS AND RELEVANCE: This cohort study found that the use of ICD codes was a poor proxy measure for the number of skin cancers per patient. In contrast, CPT codes accounted for more than 75% of the variability in the number of skin cancers (R2 = 0.76) and were a better proxy measure for the total number of skin cancers per patient.

Risks of Multiple Skin Cancers in Organ Transplant Recipients: A Cohort Study in 2 Administrative Data Sets.

IMPORTANCE: There are limited reports on the risks of multiple primary skin cancers in organ transplant recipients (OTRs). OBJECTIVE: To determine the risks over time and risk factors for OTRs developing (1) any skin cancer posttransplant, (2) a subsequent skin cancer after the first posttransplant skin cancer in the data sets used in the study, and (3) 10 or more skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from Optum deidentified electronic health record data set (7.7 million patients) and Truven Health MarketScan insurance claims data set (161 million patients) from 2007 to 2017. Skin cancers were identified using diagnosis plus treatment codes for basal cell carcinoma, squamous cell carcinoma, and melanoma; OTRs were identified using 4 or more diagnosis codes for organ transplant. Data analysis took place from January 1, 2007, to December 31, 2017. MAIN OUTCOMES AND MEASURES: Cumulative risks of (1) any skin cancer treatment posttransplant, (2) a subsequent skin cancer treatment after the first posttransplant skin cancer treatment in our data, and (3) 10 or more skin cancer treatments in OTRs. A Wei-Lin-Weissfeld marginal model was used to evaluate risk factors for any skin cancer. RESULTS: A total of 7390 OTRs in Optum and 133 651 in MarketScan were identified, 4.5% and 13.3% of which had had at least 1 skin cancer treatment, respectively. At 2 years after the initial posttransplant skin cancer in the data sets, OTRs had a 44.0% to 57.0% risk of a subsequent skin cancer treatment and a 3.7% to 6.6% risk of having 10 or more skin cancer treatments. Statistically significant risk factors for any skin cancer included age, history of skin cancer, and history of actinic keratosis in both data sets, and male sex and thoracic transplant in MarketScan. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, approximately half of the OTRs who developed at least 1 posttransplant skin cancer developed a subsequent skin cancer within 2 years, and approximately 1 in 20 developed 10 or more skin cancers. Identifying OTRs at highest risk for multiple primary skin cancers may help target strategies for prevention and early detection.

Optimal biomechanical parameters for measuring sclerotic chronic graft-versus-host disease.

Skin biomechanical parameters (dynamic stiffness, frequency, relaxation time, creep, and decrement) measured using a myotonometer (MyotonPRO) could inform management of sclerotic disease. To determine which biomechanical parameter(s) can accurately differentiate sclerotic chronic graft-versus-host disease (cGVHD) patients from post-hematopoietic cell transplant (post-HCT) controls, 15 sclerotic cGVHD patients and 11 post-HCT controls were measured with the myotonometer on 18 anatomic sites. Logistic regression and two machine learning algorithms, LASSO regression and random forest, were developed to classify subjects. In univariable analysis, frequency had the highest overfit-corrected area under the receiver operating characteristic curve (AUC 0.91). Backward stepwise selection and random forest machine learning identified frequency and relaxation time as the optimal parameters for differentiating sclerotic cGVHD patients from post-HCT controls. LASSO regression selected the combination of frequency and relaxation time (overfit-corrected AUC 0.87). Discriminatory ability was maintained when only the sites accessible while the patient is supine (12 sites) were used. We report the distribution of values for these highly discriminative biomechanical parameters, which could inform assessment of disease severity in future quantitative biomechanical studies of sclerotic cGVHD.