Shared decision-making quality and decisional regret in patients with low-risk superficial basal cell carcinoma: A prospective, multicenter cohort study.

Background: Many therapies are available to treat low-risk superficial basal cell carcinoma (lr-sBCC), which may complicate the shared decision-making (SDM) process. Objective: To assess the SDM process of patients and physicians when deciding lr-sBCC therapy as well as the factors that may influence the SDM process. Methods: A prospective, multicenter cohort study was conducted over 18 months, from October 2018 to April 2020, in 3 tertiary university hospitals and 1 private hospital. Results: This study included 107 patients. There was a weak positive correlation between Shared Decision-Making Questionnaire-Patient version (SDM-Q-9) and Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) (Spearman's correlation coefficient [rs] [105] = 0.21; P = .03). Most patients (71%) chose a nonsurgical treatment after the SDM process. Patients with higher satisfaction with the SDM had lower decisional conflict and decisional regret (P < .001). Patients aged >80 years had higher rates of significant decisional conflict. When evaluating treatment decisions, the highest median score for decisional conflict (22, IQR [16]; P = .01) was observed among patients who chose a surgical excision. Limitations: Patients may have self-selected to participate. Conclusion: This study suggests that some patients may prefer less invasive therapies for lr-sBCC. The SDM process may reduce decisional conflict and decisional regret.

Detection of novel therapies using a multi-national, multi-institutional registry of cutaneous immune-related adverse events and management.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias. METHODS: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv. RESULTS: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated. CONCLUSION: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.

Drug reactions with eosinophilia and systemic symptoms induced by immune checkpoint inhibitors: an international cohort of 13 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.

Shared decision making for patients with breast and gynecologic malignancies undergoing chemotherapy associated with persistent alopecia.

Objective: To assess patient-perceived involvement in shared decision making among those diagnosed with breast or gynecologic malignancies undergoing chemotherapy associated with persistent chemotherapy-induced alopecia (pCIA). We also sought to identify factors that influence shared decision making. Methods: We recruited patients from the Gynecologic Medical Oncology and Breast Medicine Services at a large academic center for this prospective cohort study. All patients were scheduled to start chemotherapy between June 1, 2017 and December 31, 2017. Following medical consultation, including discussion of the risk of pCIA, patients completed the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Clinical and sociodemographic information was also collected. Univariate analysis was used to evaluate SDM-Q-9 total scores and their constituents for all variables. Results: Sixty-one patients completed the survey. The median total SDM-Q-9 score was 95.6 (95% CI: 90-100). Most patients (n = 57, 93%) reported a high level of involvement (SDM-Q-9 total score > 66). There was no difference in total scores between patients with breast compared with gynecologic cancer (P > .05). By individual item, the scores for item Q1 ("My doctor made clear that a decision needs to be made") were significantly lower for Black patients and those with advanced disease (P < .05). Conclusions: Most patients indicated they were adequately involved in shared decision making regarding chemotherapy treatment options and their risk for pCIA. Patients from underrepresented populations and those with advanced disease may benefit from additional support from their clinicians to better address the anticipated psychosocial impacts of pCIA and facilitate the provision of optimal and equitable care.

Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients.

BACKGROUND: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). OBJECTIVES: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. METHODS: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. RESULTS: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01-0·76] and vitiligo (OR 0·07, 95% CI 0·006-0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02-0·31), lichenoid reactions (OR 0·15, 95% CI 0·03-0·77) and eczematous reactions (OR 0·24, 95% CI 0·07-0·78), all compared with pruritic rash. CONCLUSIONS: Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated.

Histopathology of Dermatologic Complications of Tattoos.

ABSTRACT: Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.

Assessment and Treatment Outcomes of Persistent Radiation-Induced Alopecia in Patients With Cancer.

Importance: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described. Objective: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma. Design, Setting, and Participants: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA. Main Outcomes and Measures: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans. Results: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, -0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (-0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction. Conclusions and Relevance: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.

Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Nonmelanoma Skin Cancer in Childhood and Young Adult Cancer Survivors Previously Treated With Radiotherapy.

BACKGROUND: Radiotherapy (RT) is a risk factor for nonmelanoma skin cancer (NMSC), specifically basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but whether features, histology, or recurrence of NMSC after RT resemble those observed in the general population is unknown. METHODS: A retrospective review (1994-2017) was performed within the Adult Long-Term Follow-Up Program and Dermatology Service at Memorial Sloan Kettering Cancer Center. Demographics, clinical features, histology, treatment, and recurrence were collected for this patient cohort that was under close medical surveillance. Pathology images were reviewed when available. RESULTS: A total of 946 survivors (mean age, 40 years [SD, 13]) were assessed for NMSC. The mean age at first cancer diagnosis was 16 years (range, 0-40 years [11]), and the most common diagnosis was Hodgkin lymphoma (34%; n=318). In 63 survivors, 281 primary in-field lesions occurred, of which 273 (97%) were BCC and 8 (3%) were SCC. Mean intervals from time of RT to BCC and SCC diagnosis were 24 years (range, 2-44 years) and 32 years (range, 14-46 years), respectively. The most common clinical presentation of BCC was macule (47%; n=67), and the most common histologic subtypes were superficial for BCC (48%; n=131) and in situ for SCC (55%; n=5). Mohs surgery predominated therapeutically (42%; n=117), the mean duration of follow-up after treatment was 6 years (range, 12 days-23 years), and the 5-year recurrence rate was 1% (n=1). CONCLUSIONS: Most NMSCs arising in sites of prior RT were of low-risk subtypes. Recurrence was similar to that observed in the general population. Current guidelines recommend surgical intervention for tumors arising in sites of prior RT because they are considered to be at high risk for recurrence. These findings suggest that an expanded role for less aggressive therapy may be appropriate, but further research is needed.

Assessment of Quality of Life and Treatment Outcomes of Patients With Persistent Postchemotherapy Alopecia.

Importance: Persistent alopecia occurs in a subset of patients undergoing chemotherapy, yet the quality of life (QOL) of these patients and their response to therapy have not been described in a large patient cohort. Objective: To characterize the clinical presentation of patients with persistent chemotherapy-induced alopecia (pCIA) or endocrine therapy-induced alopecia after chemotherapy (EIAC) and their QOL and treatment outcomes. Design, Setting, and Participants: A retrospective multicenter cohort of 192 women with cancer treated with cytotoxic agents who received a clinical diagnosis of persistent alopecia (98 with pCIA and 94 with EIAC) between January 1, 2009, and July 31, 2017, was analyzed. All patients were from the dermatology service in 2 comprehensive cancer centers and 1 tertiary-care hospital. Data on demographics, chemotherapy regimens, severity, clinical patterns, and response to hair-growth promoting agents were assessed. Data from the Hairdex questionnaire were used to assess the QOL of patients with alopecia. Main Outcomes and Measures: The clinical presentation, response to dermatologic therapy, and QOL of patients with pCIA were assessed and compared with those of patients with EIAC. Results: A total of 98 women with pCIA (median age, 56.5 years [range, 18-83 years]) and 94 women with EIAC (median age, 56 years [range, 29-84 years]) were included. The most common agents associated with pCIA were taxanes for 80 patients (82%); the most common agents associated with EIAC were aromatase inhibitors for 58 patients (62%). Diffuse alopecia was predominant in patients with pCIA compared with patients with EIAC (31 of 75 [41%] vs 23 of 92 [25%]; P = .04), with greater severity (Common Terminology Criteria for Adverse Events, version 4.0, grade 2) among patients with pCIA (29 of 75 [39%] vs 12 of 92 [13%]; P < .001). A negative emotional effect was reported by both groups. After treatment with topical minoxidil or spironolactone, moderate to significant improvement was observed for 36 of 54 patients with pCIA (67%) and for 32 of 42 patients with EIAC (76%). Conclusions and Relevance: Persistent chemotherapy-induced alopecia is frequently more severe and diffuse when compared with EIAC, and both groups of patients experienced a negative effect. A modest benefit was observed with dermatologic therapy. Additional studies are warranted to develop effective strategies for prevention and effective therapy for pCIA and EIAC.

In-vivo assessment of a case of cutaneous sarcoidosis using reflectance confocal microscopy.

Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that allows visualization of the epidermis and papillary dermis with cellular-level resolution. Granulomatous reactions such as sarcoidosis could be assessed using RCM. The identification of bright beaded-like structures that could correspond to reticulin fibers overlying granulomas, in association with dermoscopy, may be a very useful approach in the diagnosis of sarcoidosis and for the differentiation of this granulomatous entity with superficial cutaneous metastasis.

In-vivo assessment of a case of cutaneous sarcoidosis using reflectance confocal microscopy

Abstract: Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that allows visualization of the epidermis and papillary dermis with cellular-level resolution. Granulomatous reactions such as sarcoidosis could be assessed using RCM. The identification of bright beaded-like structures that could correspond to reticulin fibers overlying granulomas, in association with dermoscopy, may be a very useful approach in the diagnosis of sarcoidosis and for the differentiation of this granulomatous entity with superficial cutaneous metastasis.

Hair disorders in patients with cancer.

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders, including alopecia, hirsutism, hypertrichosis, and pigmentary and textural hair changes. The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy-induced alopecia has been well documented primarily in the oncology literature; however, the effect of other alterations, such as radiation-induced alopecia, hirsutism, and changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in oncology patients, including the underlying pathophysiological mechanisms, severity grading scales, patient-reported quality of life questionnaires, management strategies, and future translational research opportunities.

Hair disorders in cancer survivors.

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, postsurgery alopecia and localized hypertrichosis, and persistent stem cell transplantation and targeted therapy-induced alopecia. The information contained in this continuing medical education series should facilitate a better understanding on hair disorders in cancer survivors so that adequate support and therapies may be provided.

Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies.

PURPOSE: To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy. METHODS: All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review. RESULTS: There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case-control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of 5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effect of spironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied. CONCLUSIONS: Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.