Prognostic Value of the Neutrophil-to-lymphocyte Ratio, Platelet-to- lymphocyte Ratio and Monocyte-to-lymphocyte Ratio in Melanoma Patients: A Cohort Study.

The prognostic value of the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio in patients with melanoma has yielded controversial results in the literature. A retrospective single-centre cohort study was conducted from 1998 to 2020, including patients diagnosed with invasive melanoma. A total of 2,721 patients were included in the study. The median follow-up was 8.23 years (IQR 4.41-13.25). The median baseline neutrophil- lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio values increased significantly (p < 0.001) with the increasing American Joint Committee on Cancer stage. The optimal cut-off values for neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio were determined as 2.1, 184 and 0.2, respectively. In the multivariate analysis, high levels of neutrophil-lymphocyte ratio (≥ 2.1), platelet-lymphocyte ratio (≥ 184) and monocyte-lymphocyte ratio (≥ 0.2) were independently associated with significantly shorter melanoma-specific survival (neutrophil-lymphocyte ratio: HR 1.30, 95% CI 1.06-1.60, p = 0.013; platelet-lymphocyte ratio: HR 1.37, 95% CI 1.06-1.76, p = 0.014; monocyte- lymphocyte ratio: HR 1.29, 95% CI 1.05-1.58, p = 0.015) and overall survival (neutrophil-lymphocyte ratio: HR 1.39, 95% CI 1.19-1.64, p < 0.001; platelet- lymphocyte ratio: HR 1.44, 95% CI 1.19-1.74, p < 0.001; monocyte-lymphocyte ratio: HR 1.42, 95% CI 1.21-1.66, p < 0.001). High levels of neutrophil- lymphocyte ratio and monocyte-lymphocyte ratio were also associated with poor relapse-free survival, while platelet-lymphocyte ratio was not. In conclusion, baseline neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio were identified as independent predictors for the prognosis of melanoma.

Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience.

AIMS: The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. METHODS AND RESULTS: A total of 71 neoplasms showing spitzoid features (Spitz-like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in-situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF-mutated naevus/low-grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow-up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression-free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). CONCLUSIONS: The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.

The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

BACKGROUND: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. METHODS: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. RESULTS: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). CONCLUSIONS: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma.

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists' diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists' confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists' willingness to adopt such XAI systems, promoting future use in the clinic.

A Narrative Review: Opportunities and Challenges in Artificial Intelligence Skin Image Analyses Using Total Body Photography.

Artificial intelligence (AI) algorithms for skin lesion classification have reported accuracy at par with and even outperformance of expert dermatologists in experimental settings. However, the majority of algorithms do not represent real-world clinical approach where skin phenotype and clinical background information are considered. We review the current state of AI for skin lesion classification and present opportunities and challenges when applied to total body photography (TBP). AI in TBP analysis presents opportunities for intrapatient assessment of skin phenotype and holistic risk assessment by incorporating patient-level metadata, although challenges exist for protecting patient privacy in algorithm development and improving explainable AI methods.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma.

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.

Melanoma-specific survival is worse in the elderly: a multicentric cohort study.

We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P  < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P  < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P  < 0.001), as were nodular melanoma and acral lentiginous melanoma ( P  < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan-Meier survival curves showed longer melanoma-specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P  = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.

Spaghetti Technique Versus Wide Local Excision for Lentigo Maligna Affecting the Head and Neck Regions: Surgical Outcome and Descriptive Analysis of 79 Cases from a Single Practice Cohort.

INTRODUCTION: Lentigo maligna is a subtype of melanoma in situ that typically affects the head and neck region with an increasing incidence. Margin-controlled techniques, such as spaghetti technique (ST), have gained popularity over wide local excision (WLE) with a margin of 5 mm. OBJECTIVES: To evaluate the outcomes of lentigo maligna cases in the head and neck area treated by either WLE or ST in a tertiary referral hospital. The secondary goal was to describe the demographic and clinical characteristics of our series. METHODS: Cohort study of patients diagnosed with lentigo maligna on the head and neck region between January 2014 and February 2022 in a tertiary hospital. RESULTS: In total, 79 lentigo maligna were studied, corresponding to 77 patients. Fifty-three lesions (67%) were treated with WLE and 26 (33%) with ST. The mean age of the patients was 73 years and 58% were men. Most of the tumors were located on the cheek (50%) and mean lesion diameter was 2.2 cm for the ST group and 1.2 cm for the WLE group. Mean duration follow-up was 44 months. There were two local recurrences in the WLE group (2/53; 3.7%) and none in the ST group. CONCLUSIONS: Both WLE and ST are appropriate surgical approaches for lentigo maligna. ST offers an efficient alternative to Mohs surgery for treating lentigo maligna in the head and neck area, especially when guided by reflectance confocal microscopy.

Topographical and Chronological Analysis of Thin Cutaneous Melanoma's Progressions: A Multicentric Study.

A great portion of cutaneous melanoma's diagnoses nowadays is attributed to thin tumors with up to 1 mm in Breslow thickness (hereafter thin CMs), which occasionally metastasize. The objective of this study was to identify thin CM's metastatic patterns from a topographical and chronological standpoint. A total of 204 cases of metastatic thin CMs from five specialized centers were included in the study, and corresponding data were collected (clinical, epidemiological, histopathological information of primary tumor and the number, anatomical site, and time intervals of their progressions). First progressions occurred locally, in regional lymph nodes, and in a distant site in 24%, 15% and 61% of cases, respectively, with a median time to first progression of 3.10 years (IQR: 1.09-5.24). The median elapsed time between the first and second progression and between the second and third progression was 0.82 (IQR: 0.34-1.97) and 0.49 (IQR: 0.21-2.30) years, respectively, while the median survival time was about 4 years since first progression. Furthermore, the sequences of locations and time intervals of the progressions were associated with the clinicopathological and demographic features of the primary tumors along with the features of the preceding progressions. In conclusion, the findings of this study describe the natural history of thin CMs, thus highlighting the necessity to identify subgroups of thin CMs at a higher risk for metastasis and contributing to the optimization of the management and follow-up of thin CM patients.

Real-World Experience with Vismodegib on Advanced and Multiple BCCs: Data from the RELIVIS Study.

BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.

Prognostic factors for satellitosis or in-transit metastasis in cutaneous squamous cell carcinoma: A multicentric cohort study.

BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.

Analysis of dermoscopic changes of blue nevi on digital follow-up: A 21-year retrospective cohort study.

BACKGROUND: Blue nevi are benign dermal melanocytic proliferations that are often easy to recognize clinically. Rarely, these lesions can display atypical features, suggesting the presence of a malignant blue nevus or mimicking cutaneous metastases of melanoma. OBJECTIVE: To describe the clinical evolution of blue nevi over time and to assess the need for monitoring these lesions. METHODS: We conducted a retrospective cohort study of 103 patients who were followed between December 1998 and November 2019. An artificial intelligence algorithm was used to identify blue nevi from the databases of two digital epiluminescence devices. Changes in the area of each lesion were calculated with a segmentation neural network. RESULTS: We included 123 blue nevi from 103 patients. Most of the lesions segmented, 99 (91.7%), were considered stable. Of the 9 (8.3%) growing blue nevi identified, 2 (1.85%) showed significant growth. The studied growing blue nevi turned out to be cellular blue nevi, presented with a low tumour mutation burden and GNAQ c.626A>T alteration was identified in both lesions. LIMITATIONS: Some clinical variants of blue nevi might not be included. CONCLUSIONS: Most blue nevi remain stable during their evolution. Rarely, they can show progressive growth, although histopathological or molecular signs of malignancy have not been identified.

Prognostic role of microsatellites in melanoma and implications in the American Joint Committee on Cancer classification system: A cohort study.

BACKGROUND: There is limited information on microsatellite survival outcomes in patients with melanoma. OBJECTIVE: To evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites. METHODS: A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma. RESULTS: Of a total of 5216 patients, 108 (2.1%) had microsatellites at initial staging. Survival analysis showed that microsatellites were an independent risk factor with decreased overall survival (OS), melanoma-specific survival (MSS), and disease-free survival, with hazard ratios of 1.57, 1.76, and 1.76, respectively. Stratified analysis in patients with stage III melanoma showed a 5-year OS of 35% (95% CI, 17.3%-73.4%) and a MSS of 45% (95% CI, 23.1-87.5) for patients with stage IIIB melanoma with microsatellites. LIMITATIONS: Retrospective design of the study. CONCLUSION: Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival. Patients with stage IIIB melanoma with microsatellites had worse OS and MSS, whereas patients with stage IIIC melanoma had worse OS but not MSS.

Diagnostic Accuracy of Image-guided Biopsies for Diagnosis of Metastatic Melanoma in a Real-life Setting.

Early detection of melanoma metastasis is essential in order to initiate treatment and improve patient prognosis. The aim of this study was to determine the diagnostic accuracy of different image-guided biopsy techniques in patients with melanoma. A cohort study of patients diagnosed with melanoma who had undergone image-guided biopsies (ultrasound-guided fine-needle aspiration cytology, ultrasound-guided core-needle biopsy, computerized tomography--guided fine-needle aspiration cytology and computerized tomography-guided core-needle biopsy) to detect melanoma metastasis between 2004 and 2021 was conducted. The reference standard was histological confirmation and/or clinical-radiological follow-up. Sensitivity, specificity, positive and negative predictive values were calculated. A total of 600 image--guided biopsies performed on 460 patients were included for analysis. Locoregional lesions represented 459 (76.5%) biopsies, and 141 (23.5%) were distant lesions. Of the included biopsies, 49 (8.2%) were insufficient for diagnosis. Overall, sensitivity and specificity were 92% (95% confidence interval 89-94) and 96% (95% confidence interval 91-99), respectively. Sensitivity sub-analyses revealed lower diagnostic accuracy values in the lung, inguinal lymph nodes, and computerized tomography-guided lesions under 1 cm. Limitations include spontaneous metastasis regression and arbitrary minimum follow-up period. Image-guided biopsies in patients with melanoma have high sensitivity and specificity for detection of regional or distant metastasis. Tissue type, location and tumour burden may influence the diagnostic accuracy of the test.

Vitamin D deficiency in melanoma patients is associated with worse overall survival: a retrospective cohort study.

Recent interest has emerged in the protective role of vitamin D in melanoma survival and is the subject of multiple studies with heterogeneous results. Here, we present a retrospective cohort study of 264 patients with invasive melanoma from a tertiary university hospital. The aim of the study was to analyze the relationship between vitamin D levels and prognosis of melanoma patients. We found that lower vitamin D levels are independently associated with worse overall survival in melanoma patients in concordance with previous studies on other populations. Vitamin D deficiency could play a survival role in melanoma patients,. Future prospective studies are needed to investigate the effect of vitamin D supplementation on melanoma outcomes.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

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.