Faculty Bibliography

PURPOSE/OBJECTIVE:Chemotherapy-induced alopecia (CIA) affects approximately 65% of patients receiving chemotherapy and has a negative impact on quality of life (QoL). Scalp cooling (SC) is the only FDA-cleared intervention for CIA. This systematic review and meta-analysis evaluated SC adverse events (AEs), reasons for discontinuation, and scalp metastasis incidence. METHODS:Meta-analyses using random-effects models estimated pooled prevalences of SC AEs, SC discontinuation, and reasons for discontinuation. A generalized linear mixed model was used to estimate the incidence of scalp metastasis. RESULTS:Sixty-seven studies met the inclusion criteria. The most common AEs were generalized chills (42%, 95% confidence interval (CI) 26-58%), cap heaviness (35%, 95% CI 18-52%), and headache (30%, 95% CI 21-39%). The SC discontinuation rate was 18% (95% CI 13-23%). The most common reasons for discontinuation were progressive alopecia (15%, 95% CI 10-20%) and reasons unrelated to SC (9%, 95% CI 5-13%). The most frequent AEs leading to SC discontinuation were headache (4%, 95% CI 2-6%), cold intolerance (4%, 95% CI 3-5%), and general discomfort (4%, 95% CI 2-7%). Secondary analysis of scalp metastases yielded an incidence of 0.15% (95% CI 0.05-0.47%). Analysis of FDA Manufacturer and User Facility Device Experience (MAUDE) database medical device reports revealed that user error contributed to cold thermal injuries. Prevalence estimates were limited by significant heterogeneity between studies, reflecting variations in study methodology and real-world SC practices. CONCLUSION/CONCLUSIONS:SC is generally well tolerated with minimal safety concerns. Clinical comfort strategies like supportive medications and improved patient education could enhance SC tolerability and support its implementation.

BACKGROUND/UNASSIGNED:Chemotherapy-induced alopecia (CIA) significantly impacts patients' quality of life. While low-dose oral minoxidil (LDOM) shows promise in treating CIA after chemotherapy completion, its safety and efficacy when given during active chemotherapy remain unclear. This review examined existing literature on CIA pathogenesis, minoxidil's mechanism of action, and LDOM efficacy to explore its potential use during chemotherapy. SUMMARY/UNASSIGNED:Recent retrospective studies demonstrated LDOMs good tolerability in cancer patients post-chemotherapy, with minimal adverse effects. Scalp cooling, the only Food and Drug Administration-cleared intervention to mitigate CIA, is thought to reduce chemotherapeutic delivery to the hair follicles, whereas minoxidil, a vasodilator, increases blood flow to the follicle. Despite these differing mechanisms, preclinical studies suggest potential benefits of LDOM during chemotherapy. One study demonstrated a protective effect of subcutaneous minoxidil against cytarabine-induced alopecia, while another showed faster regrowth with systemic minoxidil administered concurrently with paclitaxel. LDOM may, therefore, exert benefits through mechanisms beyond vasodilation, potentially by its impact on the hair cycle. Studies on topical minoxidil during chemotherapy show variable results, possibly due to poor adherence or variations in application practices - limitations LDOM could address. KEY MESSAGES/UNASSIGNED:Given the psychological impact of CIA and limited treatments, investigation of LDOM's safety and efficacy when initiated during chemotherapy is warranted.

Radiation recall dermatitis is a known but rare adverse effect that is characterized by the development of dermatitis in the region of prior irradiated tissue triggered by exposure to a systemic agent. Capivasertib is a small-molecule inhibitor targeting the phosphatidylinositol 3-kinase/protein kinase B pathway recently approved in locally advanced and metastatic breast cancer; however, the safety of its use in the setting of palliative radiation is currently unclear. Here, we report a case of radiation recall dermatitis in a patient with metastatic breast cancer on capivasertib with history of radiation to the right lower extremity managed with corticosteroids, antibiotics, and switching to alpelisib.

Erdheim"“Chester disease (ECD) is a rare, non-Langerhans histiocytic disease, with the manifestation of cutaneous lesions becoming further recognised and understood. Most commonly presenting with xanthelasma-like lesions, cutaneous manifestations are the first noticeable sign of ECD in a significant number of patients. Other commonly reported cutaneous lesions of ECD include panniculitis-like lesions and granuloma annulare-like lesions. While previously reported papular lesions of ECD include crusty yellow and erythematous papules, small, pink to fleshy coloured papules, and verruca plana-like papules, papulonodular eruptions consistent with fibrous histiocytomas are a rare and underreported sequala of ECD. Here, we report an 86-year-old male with a history of prostate and bladder cancer who presented with eruptive fibrous histiocytomas, prompting workup that lead to a diagnosis of ECD. The patient received expedited imaging given the rare association of eruptive fibrohistiocytic lesions with malignancy, revealing diffuse perinephric and urothelial soft tissue thickening and enhancement, which was biopsied and found to harbour the BRAF V600E mutation. One could reasonably hypothesise that the pathologic mechanism occurring in the perinephric and urothelial soft tissue areas of this patient bodes similarities to the cutaneous sites consistent with the fibrohistiocytic lesions. This may present a potential clue to the poorly understood origin and pathogenesis of ECD.

PURPOSE/OBJECTIVE:Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS/METHODS:We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS:A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS:Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

INTRODUCTION/BACKGROUND:The purpose of this study is to systematically review data pertaining to breast cancer and radiation-induced skin reactions in patients with skin of color (SOC), as well as data pertaining to objective measurements of skin pigmentation in the assessment of radiation dermatitis (RD). METHODS AND MATERIALS/METHODS:We conducted a systematic review utilizing MEDLINE electronic databases to identify published studies until August 2022. Key inclusion criteria included studies that described RD in breast cancer with data pertaining to skin of color and/or characterization of pigmentation changes after radiation. RESULTS:We identified 17 prospective cohort studies, 7 cross-sectional studies, 5 retrospective studies and 4 randomized controlled trials. Prospective cohort and retrospective series demonstrate worse RD in African American (AA) patients using subjective physician-graded scales. There is more limited data in patients representing other non-White racial subgroups with SOC. 2 studies utilize patient reported outcomes and 15 studies utilize objective methods to characterize pigmentation change after radiation. There are no prospective and randomized studies that objectively describe pigmentation changes with radiotherapy in SOC. CONCLUSIONS:AA patients appear to have worse RD outcomes, though this is not uniformly observed across all studies. There are no studies that describe objective measures of RD and include baseline skin pigmentation as a variable, limiting the ability to draw uniform conclusions on the rate and impact of RD in SOC. We highlight the importance of objectively characterizing SOC and pigmentation changes before, during and after radiotherapy to understand the incidence and severity of RD in SOC.