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.

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.

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.

Endocrine Therapy-Induced Alopecia in Patients With Breast Cancer.

Importance: Endocrine therapy-induced alopecia (EIA) has been anecdotally reported but not systematically described. Objective: To characterize EIA in patients with breast cancer. Design, Setting, and Participants: Retrospective cohort study of 112 patients with breast cancer, diagnosed with EIA from January 1, 2009, to December 31, 2016, the patients were examined at the dermatology service in a large tertiary care hospital and comprehensive cancer center. Main Outcomes and Measures: The clinical features, alopecia-related quality of life (QoL), and response to minoxidil of EIA in patients with breast cancer were assessed. Data from the Hairdex Questionnaire was used to assess the impact of the alopecia on patients QoL. Higher score indicates lower QoL (0-100 score). Efficacy of minoxidil was measured at 3 or 6 months by a single-blinded investigator through standardized clinical photographs of the scalp. Results: A total of 112 female patients with breast cancer were included (median [range] age, 60 [34-90] years). A total of 104 patients (93%) had standardized clinical photographs; of these, 59 patients (53%) had trichoscopy images available at baseline, and 46 patients (41%) were assessed for response to minoxidil. Alopecia was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37 (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was similar to androgenetic alopecia. The predominant trichoscopic feature at baseline was the presence of vellus hairs and intermediate- and thick-diameter terminal hair shafts. A negative impact on QoL was reported, with a higher effect in the emotion domain according to the Hairdex score (mean [SD], 41.8 [21.3]; P < .001). After treatment with topical minoxidil, moderate or significant improvement in alopecia was observed in 37 of 46 patients (80%). Conclusions and Relevance: Endocrine therapies are associated with a pattern alopecia similar to androgenetic-type, consistent with the mechanism of action of causal agents. A significant negative impact on QoL was reported by patients, despite mostly mild alopecia severity.

Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients.

BACKGROUND: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. OBJECTIVE: To characterize inpatient dermatology consultations at a large comprehensive cancer center. METHODS: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January-December 2015. RESULTS: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35-8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. LIMITATIONS: The study's retrospective nature and single-institution setting are potential limitations. CONCLUSION: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.