StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a pilot study.

PURPOSE: Previous literature has produced heterogeneous results on StrataXRT for prevention of acute radiation dermatitis (RD) in breast cancer. This pilot study aimed to assess the feasibility and efficacy of StrataXRT in a cancer center. METHODS: The study consisted of five cohorts: (1) patients with large breasts treated with local radiation therapy (RT) either in the supine position or (2) the prone position, (3) patients receiving locoregional breast RT with any breast size, and (4) patients receiving chest wall RT, either locally or (5) locoregionally. The primary endpoint of the study was RD grade as assessed using the Common Terminology Criteria for Adverse Events. Secondary endpoints included incidence of moist desquamation (MD), patient- and clinician-reported skin assessments, patient quality of life as assessed by the Skindex-16, and patient satisfaction. These outcomes were compared with those from a published trial from the same institution assessing standard of care and Mepitel Film (MF) as prevention of breast RD. RESULTS: Forty-five patients receiving RT to the breast or chest wall were enrolled. Two withdrew, leaving 43 evaluable patients. Overall, two (4.7%) patients had grade 3 RD, 14 (32.6%) had grade 2 RD, and 27 (62.8%) had grade 1 RD. Ten patients (23.3%) developed MD during/after RT. CONCLUSION: StrataXRT is effective in preventing grade 3 RD in patients, and the most promising results were observed within the prone cohort. Further research includes evaluating the efficacy of StrataXRT against the standard of care for the prophylaxis of RD. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov (identifier: NCT05594498) on October 13, 2022.

A Customized 3D-Printed Bolus for High-Risk Breast Cancer with Skin Infiltration: A Pilot Study.

BACKGROUND: In high-risk breast cancer patients with skin infiltration, the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential inadequate dose distribution of a standard bolus due to air gaps between the bolus and the skin. In this pilot study, we introduced into clinical practice the use of a personalized 3D-printed bolus filled with ultrasound transmission gel. METHODS: Seven patients undergoing radiotherapy after mastectomy were selected. A 3D-printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and, subsequently, on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control were assessed. RESULTS: Overall, for the clinical cases, the percentage median difference between the measured and calculated doses was -2.7% (-7.0-4.9%). The median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. CONCLUSIONS: A personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus' consistency and provide accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study, and further investigations are needed.

Hypofractionated versus Conventional Postmastectomy Irradiation for Breast Cancer: Comparison of Acute Skin Toxicity.

Purpose: Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors. Methods: This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot. Results: Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity. Conclusion: Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, and economic benefits, supporting its clinical promotion.

Risk Factor Analysis for Anti-epidermal Growth Factor Receptor Monoclonal Antibody-induced Problematic Skin Toxicities in Patients With Liver Metastatic Colorectal Cancer.

BACKGROUND/AIM: We previously reported that patients with metastatic colorectal cancer (mCRC) and baseline liver metastasis are at a higher risk of developing grade ≥2 overall skin toxicities when treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This study aimed to identify additional factors associated with skin toxicities induced by anti-EGFR treatment in patients with liver metastatic CRC. PATIENTS AND METHODS: Patients with liver metastatic CRC who initially received anti-EGFR monoclonal antibody-containing treatment (n=77) were retrospectively assessed. The primary endpoint was to identify the factor(s) responsible for the development of grade ≥2 overall skin toxicities. Additionally, factors for grade ≥2 rash and paronychia were evaluated. RESULTS: The incidence of grade ≥2 overall skin symptoms, rash, and paronychia was 62.3%, 31.2%, and 28.6%, respectively. Multivariate Cox proportional hazard regression analyses revealed that age <65 years and anemia were independent baseline risk factors for grade ≥2 overall skin toxicities (adjusted hazard ratio 2.09, 95% confidence interval=1.10-3.97, p=0.02 for age; 2.36, 1.20-4.61, p=0.01 for anemia). In contrast, combination prophylaxis using systemic minocycline and corticosteroid ointment was a preventive factor (0.47, 0.25-0.88, p=0.02). Males and age <65 years were baseline risk factors for grade ≥2 rash, and combination prophylaxis was identified as a preventive factor. No factors were identified for paronychia. CONCLUSION: Age <65 years and anemia were identified as independent baseline risk factors. Additionally, combination prophylaxis was found to be a preventive factor against anti-EGFR monoclonal antibody-induced grade ≥2 overall skin toxicities in patients with liver metastatic CRC.

Mepitel film for the prevention of radiation dermatitis: A comprehensive review of its efficacy, side effects, physics measurements, patient- and clinician-reported outcomes.

Objective: This review aimed to summarize the benefits, side effects, physics measurements, and patient- and clinician-reported outcomes of Mepitel film (MF) in preventing radiation dermatitis (RD) for cancer patients. Methods: The online database PubMed was searched from inception to April 15, 2024 with the search terms "Mepitel film" or "Mepitel." Articles of any study design evaluating MF for the prevention of RD were included. Non-human studies were excluded. Results: The database search identified 119 articles and 13 of them were included in this review. Across these studies, MF was found to be beneficial in reducing RD and improved patient- and clinician-reported outcomes in breast and head and neck cancers. Side effects of MF included itchiness, acne, allergic reaction, tightness, discomfort, and poor film adherence, but patient dropouts were uncommon. MF did not cause a bolus effect or increased skin dose in physics measurements. Conclusions: MF is a safe and effective intervention for preventing acute RD. It should be recommended in breast cancer patients where the data is more robust. Further research is needed to evaluate MF's efficacy on patients with different skin tones, its cost-effectiveness, and identifying patients who most benefit from MF relative to other effective interventions.

Characterizing immune checkpoint inhibitor-related cutaneous adverse reactions: A comprehensive analysis of FDA adverse event reporting system (FAERS) database.

Background: The increasing adoption of immune checkpoint inhibitors (ICIs) in clinical settings highlights their efficacy in treating diverse conditions, while also emphasizing the potential for common cutaneous adverse reactions to arise. The aim of this study is to investigate a multitude of impacting factors and determinants among patients presenting with ICI-associated cutaneous adverse reactions. Methods: We conducted a comprehensive analysis of ICI-associated cutaneous adverse reactions using data from the FAERS. Our study spans from January 1, 2015, to March 31, 2023, focusing on ICIs, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents. Findings: Among the 334,293 reported irAR, 17,431 were identified as cutaneous adverse reactions (ARs). Predominant cutaneous ARs included rash (21.01 %), pruritus (11.22 %), and pemphigoid (3.90 %). Stevens-Johnson syndrome emerged as the most reported severe cutaneous adverse reaction (SCAR) (2.08 %). Anti-CTLA-4 agents exhibited higher cutaneous toxicity compared to anti-PD-1 and anti-PD-L1 agents. Anti-PD-1 agents demonstrated an elevated mortality rate. The combined use of ICIs with chemotherapy amplified the risk of SCAR and mortality. Targeted therapy was a risk factor for cutaneous ARs but was associated with reduced mortality. The median onset day for cutaneous toxicity was 21 days, while for SCAR, it was 23 days. Weight and age were identified as predictors of SCAR, cutaneous toxicity, and mortality. Skin cancer increased skin toxicity, while lung cancer heightened SCAR formation. The number of administered ICIs positively correlated with SCAR, skin toxicity, and mortality. Interpretation: This study highlights the significance of early identification and effective management of cutaneous toxicities, along with personalized follow-up care, as essential strategies for minimizing risks and preventing treatment disruptions.

Management of Skin Toxicities in Cancer Treatment: An Australian/New Zealand Perspective.

Cancer systemic therapeutics and radiotherapy are often associated with dermatological toxicities that may reduce patients' quality of life and impact their course of cancer treatment. These toxicities cover a wide range of conditions that can be complex to manage with increasing severity. This review provides details on twelve common dermatological toxicities encountered during cancer treatment and offers measures for their prevention and management, particularly in the Australian/New Zealand context where skincare requirements may differ to other regions due to higher cumulative sun damage caused by high ambient ultraviolet (UV) light exposure. Given the frequency of these dermatological toxicities, a proactive phase is envisaged where patients can actively try to prevent skin toxicities.

Enfortumab vedotin-related cutaneous toxicity correlates with overall survival in patients with urothelial cancer: a retrospective experience.

Introduction: Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR). Patients and methods: Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model. Results: Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925). Conclusion: In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.

Dose-toxicity surface histogram-based prediction of radiation dermatitis severity and shape.

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.

[Drug-related exanthema under immunotherapy and targeted oncological therapy]. / Arzneimittelexantheme unter Immun- und zielgerichteter onkologischer Therapie.

BACKGROUND: Oncological therapies can cause a variety of mucocutaneous adverse events. Exanthematous adverse events can be challenging in the context of the urgent need for cancer treatment due to their spread, sometimes rapid progression, and mucous membrane or organ involvement. MATERIALS AND METHODS: This article provides an overview of the most important exanthematic dermatoses as side effects of modern drug-based tumor therapies with diagnostic and therapeutic information for clinicians, taking into account the current literature and guidelines. RESULTS: Exanthematous adverse events of immune checkpoint inhibitors, EGFR antagonists, kinase inhibitors, bispecific T­cell engagers, and the CCR4 inhibitor mogamulizumab are reviewed in detail. CONCLUSIONS: Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.

Delayed onset skin toxicity reaction after peripherally inserted central catheter rupture in lower extremities combined with chemotherapy.

Herein, we present a patient who was undergoing chemotherapy for bilateral breast cancer and experienced delayed-onset skin toxicity reactions after rupture of a peripherally inserted central catheter (PICC) in the lower extremities. The objective of this case report is to provide the necessary nursing assessment for the risk awareness of the PICC internal rupture and the occurrence of central venous catheter extravasation, as well as to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs. Rupture of the PICC in the lower extremities was primarily attributed to the use of a silicone catheter and an excessive puncture angle. The nature of docetaxel and partial catheter rupture caused drug extravasation, leading to delayed skin toxicity. The use of a polyurethane catheter reduces the incidence of catheter rupture; hence, silicon catheters should be avoided. The central venous catheter is also at risk for the extravasation of chemotherapeutic agents. Moreover, docetaxel-induced delayed skin toxicity, which has a high incidence, should be treated as expected. Nurses and clinicians should be aware of PICC internal rupture and central venous catheter extravasation to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs.

A new G3BP1-GFP reporter system for assessing skin toxicity by real-time monitoring of stress granules in vitro.

The skin, the organ with the largest surface area in the body, is the most susceptible to chemical exposure from the external environment. In this study, we aimed to establish an in vitro skin toxicity monitoring system that utilizes the mechanism of stress granule (SG) formation induced by various cellular stresses. In HaCaT cells, a keratinocyte cell line that comprises the human skin, a green fluorescent protein (GFP) was knocked in at the C-terminal genomic locus of Ras GTPase-activating protein-binding protein 1 (G3BP1), a representative component of SGs. The G3BP1-GFP knock-in HaCaT cells and wild-type (WT) HaCaT cells formed SGs containing G3BP1-GFP upon exposure to arsenite and household chemicals, such as bisphenol A (BPA) and benzalkonium chloride (BAC), in real-time. In addition, the exposure of G3BP1-GFP knock-in HaCaT cells to BPA and BAC promoted the phosphorylation of eukaryotic initiation factor 2 alpha and protein kinase R-like endoplasmic reticulum kinase, which are cell signaling factors involved in SG formation, similar to WT HaCaT cells. In conclusion, this novel G3BP1-GFP knock-in human skin cell system can monitor SG formation in real-time and be utilized to assess skin toxicity to various substances.

A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac.

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.

Clinical Insights and Dermatological Recommendations for Non-Melanoma Skin Cancers (NMSCs) in Long-Term Hydroxyurea (HU) Therapy.

Hydroxyurea (HU), an anti-metabolite ribonucleotide reductase inhibitor, is commonly used to treat several myeloproliferative disorders, including polycythemia vera. However, patients receiving long-term treatment with HU may experience a variety of cutaneous side effects, with non-melanoma skin cancers (NMSCs) emerging as the most challenging and destructive. HU-induced carcinogenesis can be attributed to both the drug's mutagenic potential and impaired DNA repair following damage by external triggers such as ultraviolet light. We report a unique case of multiple aggressive NMSCs distributed within sun-exposed areas in an 81-year-old woman receiving chronic therapy with HU for 15 years. The case draws the clinician's attention to the increased incidence of NMSCs in this population and highlights the need for regular dermatologic monitoring. We also elaborate relevant insights and recommendations to assist healthcare providers in managing HU-related NMSCs development and progression.

Association between skin toxicity and efficacy of necitumumab in squamous non-small-cell lung cancer: a pooled analysis of two randomized clinical trials-SQUIRE and JFCM.

BACKGROUND: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM). MATERIALS AND METHODS: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints. RESULTS: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity. CONCLUSIONS: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.

Protecting the Antibacterial Coating of Urinal Catheters for Improving Safety.

Catheter-associated urinary tract infections (CAUTI) are among the most common bacterial infections associated with prolonged hospitalization and increased healthcare expenditures. Despite recent advances in the prevention and treatment of these infections, there are still many challenges remaining, among them the creation of a durable catheter coating, which prevents bacterial biofilm formation. The current work reports on a method of protecting medical tubing endowed with antibiofilm properties. Silicone catheters coated sonochemically with ZnO nanoparticles (NPs) demonstrated excellent antibiofilm effects. Toward approval by the European Medicines Agency, it was realized that the ZnO coating would not withstand the regulatory requirements of avoiding dissolution for 14 days in artificial urine examination. Namely, after exposure to urine for 14 days, the coating amount was reduced by 90%. Additional coatings with either carbon or silica maintained antibiofilm activity against Staphylococcus aureus while resisting dissolution in artificial urine for 14 days (C- or SiO2-protected catheters exhibited only 29% reduction). HR-SEM images of the protected catheters indicate the presence of the ZnO coating as well as the protective layer. Antibiofilm activity of all catheters was evaluated both before and after exposure to artificial urine. It was shown that before artificial urine exposure, all coated catheters showed high antibiofilm properties compared to the uncoated control. Exposure of ZnO-coated catheters, without the protective layer, to artificial urine had a significant effect exhibited by the decrease in antibiofilm activity by almost 2 orders of magnitude, compared to unexposed catheters. Toxicity studies performed using a reconstructed human epidermis demonstrated the safety of the improved coating. Exposure of the epidermis to ZnO catheter extracts in artificial urine affects tissue viability compared with control samples, which was not observed in the case of ZnO NPs coating with SiO2 or C. We suggest that silica and carbon coatings confer some protection against zinc ions release, improving ZnO coating safety.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.