Melanoma-specific Survival Research Articles

Study of Microsatellite Instability by Immunohistochemistry in a Cohort of Patients With Melanoma.

Microsatellite instability (MSI) has prognostic value and impacts therapy strategies in several malignancies. Data regarding MSI in melanoma are scarce. The aim of this study was to assess MSI through the analysis of MMR protein expression in patients with melanoma. An observational retrospective single-center study was designed based on patients with primary melanoma. We assessed MSI through immunohistochemical staining with anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2 on full-thickness excision tissue. Ninety-three patients were included in this study. The complete absence of nuclear staining in tumoral cells was extremely rare, with only one melanoma not expressing MSH6. Most melanomas showed an expression index for MLH1 (77.7%), MSH2 (87.2%), and PMS2 (78.6%) ≥ 75%. Most melanomas (57.8%) exhibited an MSH6 expression index in the range of 1%-74%. A lowMSH6 expression index and a reduced combined MMR protein expression index (MMR-e) were significantly associated with higher melanoma-specific survival. A mildPMS2 staining intensity was significantly associated with a higher melanoma-specific survival. The patients with high MMR-e who received immunotherapy progressed and died more frequently than those with reduced MMR-e (75% vs. 33.3%). More studies are needed to further define the role of MSI in melanoma prognosis and response to immunotherapy.

Enhanced Risk Stratification for Sentinel Lymph Node Biopsy in Head and Neck Melanoma Using the Merlin Assay (CP-GEP).

Sentinel lymph node biopsy (SLNB) for head and neck melanomas involves complex challenges due to intricate lymphatic networks and delicate anatomic structures. The Merlin Assay (CP-GEP), merging clinicopathologic data with gene expression profiling, offers a non-invasive method to identify patients who have a low risk for nodal metastasis, potentially sparing these low-risk patients from surgical procedures. This study evaluated 250 clinically node-negative patients with stage I, II, or III melanoma from the Mayo Clinic and University Hospitals Cleveland Medical Center who had tumors in the head and neck region diagnosed between 2004 and 2021. All the patients underwent SLNB. The Merlin Assay, using the CP-GEP model, combines patient age at diagnosis, Breslow thickness, and gene expression of eight specific genes from the primary tumor to predict the risk of nodal metastasis. The SLNB positivity rate was 14% overall, and CP-GEP predicted a possible 40.8% reduction in SLNB procedures with a negative predictive value (NPV) of 98%. For 215 SLNB-negative patients (5-year recurrence-free survival [RFS] of 76.9%, distant metastasis-free survival [DMFS] of 84.3%, and melanoma-specific survival [MSS] of 90.6%), CP-GEP improved risk stratification by identifying 100 patients as low risk with 5-year RFS of 86.1%, DMFS of 92.7%, and MSS of 95.3%. Among 167 T1-T2 patients, the SLNB positivity rate was 8.4%, and CP-GEP achieved an SLNB reduction rate of 56.3% with an NPV of 98.9%. The Merlin Assay effectively categorizes head and neck melanoma patients by risk, enabling more accurate clinical decision-making regarding SLNB and follow-up evaluation, especially for early-stage melanoma patients.

First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data.

Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases.

Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. A total of 551 patients were treated, with ILI/ILP (n=356), ICI (n=125), and TVEC (n=70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p =.002). Breslow thickness was lowest with TVEC (p =.007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p =.01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p =.029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p =.003). ILI/ILP had shorter local PFS (HR, 1.72; p =.012), PFS (HR, 1.79; p <.001), distant metastasis-free survival (DMFS) (HR, 1.75; p =.014), overall survival (HR, 1.82; p =.009), and melanoma-specific survival (HR, 2.29; p =.004). Stage IIIB disease had longer DMFS (HR, 0.24; p <.001) compared to IIIC/D. TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.

The Prognostic Value of the 31-Gene Expression Profile Test in Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

Cutaneous melanoma is an increasingly common and potentially lethal form of skin cancer. Current staging systems based on clinical and pathological features have limitations in accurately predicting outcomes, particularly for early-stage disease. The 31-gene expression profile (31-GEP) test has emerged as a promising tool for improving risk stratification in melanoma patients. We conducted a systematic review and meta-analysis of studies evaluating the prognostic performance of the 31-GEP test in cutaneous melanoma. A comprehensive literature search was performed in multiple databases. Studies reporting survival outcomes stratified by 31-GEP class were included. Random-effects models were used to determine survival estimates across studies. Thirteen studies comprising 14,760 patients were included in the meta-analysis. The 31-GEP test consistently stratified patients into risk groups with significantly different outcomes. The 5-year melanoma-specific survival rates were 99.8% (95% CI: 98-100%) for Class 1A, 97.6% (95% CI: 92.4-99.3%) for Class 1B/2A, and 83.4% (95% CI: 66.5-92.7%) for Class 2B. Similar trends were observed for recurrence-free and distant metastasis-free survival. This meta-analysis supports the prognostic utility of the 31-GEP test in cutaneous melanoma prognostication. The test consistently stratified patients into clinically meaningful risk groups across multiple survival metrics. These findings support the potential clinical utility of the 31-GEP test in enhancing current staging systems and informing personalized management strategies for melanoma patients.

Does the interval between melanoma diagnosis and surgery have an impact on outcomes? A systematic review and meta-analysis

Studies report conflicting effects of the time interval between cutaneous melanoma excision and subsequent sentinel lymph node biopsy (SLNB). We conducted a meta-analysis to investigate the effects of time interval from diagnosis to SLNB on overall survival (OS), melanoma-specific survival (MSS) and recurrence-free survival (RFS). MethodsWe screened public databases for relevant studies published from January 1997 to April 2024. The study followed PRISMA guidelines (PROSPERO CRD42021240045). Risk of Bias for individual studies (Cochrane Collaboration ROBINS-E), and heterogeneity between studies (RevMan Web v7.4.0) were assessed. Pooled relative hazard ratios (HR) were calculated, and summaries of evidence were presented with GRADE. Results19,741 articles were identified. 13 studies had data for quantitative analysis including 66,283 patients. The cutoff for “early” SLNB was ≤43 days.MSS and RFS was worse in patients who underwent early SLNB with HR 0.75 (95 %CI 0.62–0.92) and 0.87 (95 %CI 0.77–0.98) respectively, but with significant cohort biases. The early and late groups had similar OS (HR 0.88 (95 %CI 0.76–1.02)). Where SLN positive patients were reported, there was no difference in MSS (HR 1.11 (95 %CI 0.75–1.66)) and RFS (HR 0.99 (95 %CI 0.88–1.11)). Some studies had significant confounding biases, with high-risk melanomas being over-represented in early SLNB cohorts. ConclusionsPatients undergoing SLNB for melanoma do not have demonstrable long-term advantages when performed <6 weeks compared to those between 6 and 12 weeks after primary excision biopsy. Clinicians and patients should gain confidence that SLNB performed up to 12 weeks does not negatively influence their long-term outcomes.

Long-term outcomes of nodal surveillance practices in sentinel node positive melanoma: An early post MSLT-II cohort

BackgroundThe Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), published in 2017, demonstrated equivalent melanoma-specific survival between nodal surveillance and completion lymph node dissection (CLND) for sentinel lymph node (SLN) positive melanoma. This study evaluated outcomes of nodal surveillance in an early post-MSLT-II institutional cohort. MethodsIncluded patients received nodal surveillance from 2017 to 2023. Primary outcomes were nodal basin and any site recurrence. Kaplan Meier curves and Cox proportional hazard models were used to evaluate recurrence-free survial and associated factors. ResultsThis 212 patient cohort (median age 61 years, 57.7 ​% male, 96.7 ​% white) had median primary tumor depth of 1.9 ​mm and one positive SLN. Sixty-three patients (29.7 ​%) recurred at 23 month median follow-up. Sixty percent received adjuvant therapy. Any site and nodal basin recurrence-free survival were 58.3 ​% and 80.9 ​% at 3 years. On adjusted analysis, older age and head/neck primary site were associated with worse recurrence-free survival. ConclusionLong-term outcomes at a single institution were comparable to clinical trial findings. Nodal surveillance remains a feasible management strategy for SLN ​+ ​melanoma.

Prognostic value of patient-reported outcomes in advanced or metastatic melanoma patients treated with immunotherapy: Findings from the CheckMate-067 study

ObjectivePatient-reported outcomes (PROs) that predict survival in cancer patients have yet to be realized as practical tools for clinicians to make better treatment decisions. To identify such PROs in adults with advanced melanoma treated with immunotherapy, this study used 7.5-year follow-up data from CheckMate-067, a phase 3, randomized, double-blind study of nivolumab or nivolumab plus ipilimumab versus ipilimumab. MethodsPRO data assessed using the European Organization of Research for the Treatment of Cancer Core-30 and EQ-5D-3L at baseline and during subsequent visits after treatment initiation were pooled across treatment arms. Associations between baseline PRO or change from baseline (CFB) scores with survival outcomes (progression-free survival [PFS], overall survival [OS], and melanoma-specific survival [MSS]) were examined using Cox proportional hazards models for PFS or OS and cause-specific hazard models for MSS. ResultsBaseline and CFB scores for most PRO domains, especially for physical functioning, global health status/quality of life (GHS/QoL), fatigue, and EQ-5D visual analog scale (VAS), were prognostic of all survival outcomes. Achieving meaningful improvement/maintenance of baseline PRO scores at 12 weeks following treatment initiation predicted better survival outcomes than with meaningful worsening from baseline. ConclusionsPROs at baseline and during treatment, particularly for physical functioning, GHS/QoL, fatigue, and EQ-VAS, were prognostic of survival outcomes. This knowledge may accelerate development of prognostic tools to manage treatment in patients with previously untreated unresectable or metastatic melanoma who undergo immunotherapy.

The Prognostic Significance of Tumoral Melanosis.

Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent. We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS). TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS. TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Analysis of Calculated Liver Scores for Long-Term Outcome in 423 Cutaneous Melanoma Patients.

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan-Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37-126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5-126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14-5.75; HR 2.94, 95% CI 1.42-6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms.

Next day sentinel node biopsy for melanoma after lymphoscintigraphy using 99mTc-labelled nanocolloid does not adversely affect long-term outcomes.

Sentinel Lymph Node Biopsy (SLNB) is an important management tool for early-stage melanoma. Different radiopharmaceuticals are used internationally to localise the sentinel node using lymphoscintigraphy (LSG) before surgery. Recent reports have suggested that a delayed interval between LSG and SLNB using 99mTc-labelled nanocolloid tracer has an adverse survival impact, but not with 99mTc-labelled antimony sulphide colloid. This study aims to analyse survival outcome in a prospective cohort of melanoma patients undergoing same day or next day SLNB after LSG using 99mTc-labelled nanocolloid. Outcome data were reviewed for patients undergoing SLNB, stratified by time interval between LSG and SLNB at a single UK academic centre. Kaplan-Meier survival analysis was used to assess overall survival (OS), melanoma-specific survival (MSS) and progression-free survival (PFS). Cox multivariable regression analysis identified independent risk factors. 925 patients had LSG using the 99mTc-nanocolloid tracer between 2009 and 2019, with a median follow-up of 6.36years. No difference was seen on univariate analysis in OS, MSS, PFS, or nodal recurrence between patients undergoing same day or next day SLNB (Log-rank P = 0.437, 0.293, 0.587, 0.342 respectively). In addition, nodal recurrence as first site or anytime site of recurrence in SLNB negative patients was similar between the groups (Log-rank P = 0.093 and 0.457 respectively). Stratified analysis of time did not demonstrate an outcome difference (MSS Log-rank P = 0.938). Cox multivariable regression did not show time interval to independently influence OS, MSS or PFS. We do not find a significant effect on long-term outcomes when SLNB is performed the day after LSG with 99mTc-labelled nanocolloid tracer. We infer that tracer migration is not clinically significant within 24h of injection based on long term clinical outcome data.

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions. We randomly assigned patients with previously untreated advanced melanoma, in a 1:1:1 ratio, to one of the following regimens: nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks; nivolumab (3 mg per kilogram) every 2 weeks plus placebo; or ipilimumab (3 mg per kilogram) every 3 weeks for four doses plus placebo. Treatment was continued until the occurrence of disease progression, unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to BRAF mutation status, metastasis stage, and programmed death ligand 1 expression. Here, we report the final, 10-year results of this trial, including results for overall survival and melanoma-specific survival, as well as durability of response. With a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) for nivolumab plus ipilimumab as compared with ipilimumab and was 0.63 (95% CI, 0.52 to 0.76) for nivolumab as compared with ipilimumab. Median melanoma-specific survival was more than 120 months with nivolumab plus ipilimumab (not reached, with 37% of the patients alive at the end of the trial), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab. The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma. (Funded by Bristol Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy

Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity. Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS). Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included. Locoregional control, distant metastasis-free survival, melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. Of 3007 CHNM and 10,637 CMOS patients, CHNM had more adverse pathological features (median age 65.9 vs 58.5, P<.001; median Breslow thickness 1.7mm vs 1.2mm, P<.001; and ulceration 21.2% vs 18.2%, P<.001). CHNM had worse locoregional control (hazard ratio (HR) 1.17, P<.001) and distant metastasis-free survival (HR 1.25, P<.001) but there were no significant differences in MSS or OS. Among stage IV patients who received immune checkpoint inhibitor, CHNM had better MSS (HR 0.56, P=.001) and OS (HR 0.57, P<.001) on multivariable analyses. Retrospective study, offset by prospective data collection. CHNM is associated with a distinct clinicopathological and prognostic profile.

51667 31-GEP testing is associated with improved melanoma-specific survival relative to untested patients: an analysis of patients

51667 31-GEP testing is associated with improved melanoma-specific survival relative to untested patients: an analysis of patients <65 years old

31-GEP (DecisionDx): a review of clinical utility and performance in a Mayo Clinic cohort.

Cutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31-GEP test (DecisionDx-Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31-GEP test in a real-world setting. Patients with CM who underwent 31-GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31-GEP testing on clinical decision-making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan-Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse-free survival (RFS) and melanoma-specific survival (MSS). The study included 65 CM patients. Dermatologists ordered more than 80% of 31-GEP tests. In 81.5% of cases, 31-GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre-SLNB 31-GEP results. Among patients with stage I-IIA melanoma, 25% of those with high-risk 31-GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low-risk than in high-risk 31-GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31-GEP classes, suggesting limited prognostic value. The 31-GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

Acral Melanoma Incidence and Survival Trends in 1990-2020: A Nationwide, Population-based Study.

Acral melanoma is a clinical subtype of melanoma with high mortality, on which research is limited in scope. This study aimed to assess incidence trends and melanoma-specific survival rates for acral melanoma in the Swedish population from 1990 to 2020.This cross-sectional study included patients with an acral melanoma diagnosis from 1990 to 2020 from the nationwide, population-based Swedish Melanoma Registry. Analyses on acral melanoma melanoma-specific survival rates were adjusted for age, sex, histopathological subtype, and tumour thickness. Clinicopathological features and melanoma-specific survival rates were compared between diagnostic periods: 1990-1999, 2000-2009, and 2010-2020, respectively. Changes in standardized incidence rates in 1996-2020 were evaluated separately for males and females. In total, 1,000 acral melanomas in 999 patients were included in the study. No significant yearly change in standardized incidence rates for either males or females was observed, even though the absolute number of cases increased. Factors such as male sex, age ≥ 70 years, and Breslow thickness > 1.0 were independently linked to lower melanoma-specific survival. The 5-year melanoma-specific survival across the studied period ranged from 75.8% to 77.9% for females, and from 62.4% to 71.7% for males.

Long-Term Survival in Patients With Advanced Melanoma

Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival. To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials. Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023. Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab. Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR). A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69). This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.

Proof of concept that melanoma nuclear count compares favourably with the benchmark histological prognostic feature, Breslow thickness.

Breslow thickness (BT) is the most important histological prognostic feature for melanoma prognosis, but it only captures tumour size in one dimension. Adding a further measurement in a different axis has been shown to improve prognostic value. It seems reasonable that further prognostic value could be obtained by estimating the number of invasive melanoma cells using nuclear count. The aim of this study was to show proof of concept that nuclear count has prognostic value independent of BT. Melanoma cell nuclei were labelled with SRY-related HMG-box 10 (SOX10) protein, the sections scanned and StarDist machine-learning algorithm used to count nuclei in 102 cases of primary cutaneous melanoma. Prognostic value was assessed using survival analyses. Nuclear count correlated strongly with T category, BT and calculated tumour area (each P < 0.001), suggesting that it was a valid marker of melanoma burden. Nuclear count was a predictor for overall survival in univariable analysis [hazard ratio (HR) = 2.25, confidence interval (CI) = 1.66-3.06, P < 0.001] and multivariable analysis (HR = 2.60, CI = 1.59-4.24, P < 0.001). BT and ulceration were significant in univariable analyses, but not in multivariable models with nuclear count. Models containing nuclear count showed the best fit. Similar results were seen for melanoma-specific and metastasis-free survival. Nuclear count was able to stratify melanomas within a given T stage. This study demonstrated proof of concept that counting melanoma nuclei may be an improved measure of invasive tumour burden compared to BT. Future studies will need to refine methods of nuclear detection and also to confirm its prognostic value.

Association between warfarin and survival in invasive melanoma: a population-based cohort study

BackgroundWarfarin has been shown to reduce cancer risk via Vitamin K related AXL tyrosine kinase inhibition. Although AXL has been implicated in disease progression and therapy resistance in preclinical melanoma models, there are no clinical studies evaluating the impact of warfarin on melanoma prognosis. Hence, we sought to evaluate the relationship between warfarin and survival in melanoma. MethodsWe conducted a retrospective population-based cohort study of melanoma patients aged ≥ 65 years diagnosed between 2009–2013 from the Surveillance, Epidemiology, and End Results-Medicare database. Patients were grouped according to warfarin therapy 6 months prior and after melanoma diagnosis. Univariable and multivariable Cox proportional hazards models were used to compare overall (OS) and melanoma-specific survival (MSS) between groups. ResultsOverall, 10,778 patients with invasive melanoma were included. 13.2 % were prescribed warfarin, with atrial fibrillation being the most common indication (74.1 %). Warfarin prescription was associated with older age, male sex, and a greater number of comorbidities (all p < 0.001). Patients prescribed warfarin more frequently presented with ulceration, T3 and T4 disease, and stage II disease (all p < 0.05). Warfarin prescription was associated with greater MSS and OS in multivariable models (MSS adjusted hazard ratio [aHR] 0.72, 95 % CI 0.54–0.96, p = 0.02; OS aHR 0.88, 95 % CI 0.79–0.99, p = 0.04). ConclusionsWarfarin was associated with greater MSS and OS among melanoma patients. These findings highlight the potential for Vitamin K related pathways to impact cancer specific activity. Further study of AXL and Vitamin K inhibition will be of significant interest in melanoma, targeted strategies actively under investigation.

Breslow density ability to predict melanoma survival: should it be used in clinical practice?

Breslow density (BD) is an estimation of melanoma volume, which has emerged as a novel histopathological prognostic biomarker. Our aim was to evaluate the role of BD as predictor of patients´ survival and assess its prognostic value in relation to overall survival (OS), disease-free survival (DFS), melanoma-specific survival (MSS) and metastasis-free survival (MFS). A retrospective observational study in a cohort of 107 patients with invasive melanoma was conducted. Kaplan-Meier and Log-rank tests were used for 10-year survival analysis. The ability of BD and Breslow thickness (BT) to predict survival was assessed using receiver operating characteristic curves. The average follow-up was 115 months excluding deaths. BD ≥65% showed lower survival rates compared with the BD<65% group (log-rank test p<0.001). Area under the curve (AUC) of BD ≥65% was higher than BT's for all studied survival rates except for melanoma-specific survival, in which absolute BD showed the highest value. BD is proposed as a simple, valuable and inexpensive histopathological feature that could provide with valuable information to current melanoma staging, since it has proved a statistically significant prognostic value in relation to survival in melanoma patients, and comparable 10-year survival prediction ability to BT.