Melanoma Management最新文献

Poly (ADP-ribose) polymerase inhibitors (PARPi) have shown efficacy in treating cancers with homologous recombination deficiency (HRD), including subsets of melanoma. However, the potential synergy between PARPi and standard melanoma therapies remains understudied. Here, we report two cases of advanced metastatic melanoma refractory to standard-of-care treatment that demonstrated durable partial responses following the addition of PARPi in combination with immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors. Both patients exhibited homologous recombination repair (HRR) pathway mutations and tolerated the combinatory regimens well, achieving progression-free survival of more than 11 months. Mechanistically, PARPi may enhance immunogenicity to ICI therapy via activation of the cyclic GMP-AMP synthase-stimulator of interferon (cGAS-STING) pathway and modulation of programmed death ligand 1 (PD-L1) expression. Preclinical studies also support synergism between PARPi and BRAF/MEK-targeted therapies. This report highlights the potential for PARPi to be integrated into advanced melanoma treatment, particularly in HRD tumors and in combination with ICI and targeted therapies. Although limited by the small sample size, our findings support the rationale for ongoing clinical trials evaluating PARPi-based combinations and underscore the need for further studies to clarify the optimal sequencing and combinations of therapy.

Background: Melanoma is one of the most fatal skin cancers, with rising incidence and mortality worldwide. From diagnosis to treatment, patient experiences often involve anxiety, symptom burden, and limited access to information which profoundly impacts health outcomes.

Objective: This systematic review aims to identify and analyze major barriers melanoma patients face throughout their healthcare journey.

Methods: Studies were identified from PubMed, Scopus, Web of Science, Embase, and Cochrane Library, supplemented by manual hand-searching. Eligible studies focused on the experiences of melanoma patients, addressed knowledge gaps and barriers to care throughout the patient journey, and were published in English between 2013 and 2023. Screening and extraction were conducted independently and in duplicate. The methodological quality of the included studies was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

Results: Out of 2,257 screened articles, 183 met the inclusion criteria. Studies were categorized into four major themes: intersectionality, treatment, diagnosis/prognosis, and patient/societal burden. Commonly explored subcategories included self-examination, risk factors, and drug efficacy.

Conclusions: Melanoma patients experience significant gaps throughout their healthcare journey. Identifying areas of improvement in current practices is the first step toward developing targeted solutions that improve the patient experience and quality of life.

Melanoma incidence has increased over recent decades, yet mortality has been relatively stable. This pattern has raised concern that many newly diagnosed melanomas, particularly melanoma in situ, may reflect overdiagnosis rather than a true increase in disease burden. Screening can detect melanoma earlier but is likely associated with overdiagnosis and overdetection, which may lead to excess morbidity with little survival benefit. This review examines global trends in melanoma incidence and mortality, the effects of screening programs, and the consequences of overdiagnosis. We evaluate both population-based and risk-directed screening strategies and assess diagnostic tools such as dermoscopy, total body photography, and artificial intelligence devices. Further research is needed to determine how these adjunctive technologies can be effectively integrated into screening strategies to improve clinical outcomes.

Cutaneous melanoma is a highly aggressive skin cancer with rising incidence, driven by risk factors such as ultraviolet exposure, genetic predisposition, and immunosuppression. While surgical excision remains the primary treatment, interest in chemoprevention strategies is growing. Numerous natural and synthetic agents have shown preclinical promise, but evaluating their effectiveness is challenging due to their systemic effects on multiple cell types. This review provides a focused examination of the melanocyte-specific mechanisms of select agents that have been tested in clinical trials for melanoma chemoprevention. We discuss various molecular and cellular mechanisms driving the anti-melanoma properties of nonsteroidal anti-inflammatory drugs, statins, sulforaphane, vitamin D, and N-acetylcysteine. Despite promising preclinical and early clinical data, challenges remain regarding precise mechanisms, optimal dosing, long-term safety, and patient selection. Future research should focus on refining melanoma prevention strategies through well-designed clinical trials and personalized approaches integrating genetic and molecular risk factors.

Subungual melanoma accounts for 1.9% of cutaneous melanomas. Amelanotic cases, comprising 15-25%, poses a significant diagnostic challenge because it can be misdiagnosed as other traumatic, inflammatory, or neoplastic conditions. This often leads to delayed diagnosis and subsequently, a poor prognosis. We present a case of an 83-year-old woman with a bleeding, painful and progressive lesion on the nail area of her right middle finger initially misdiagnosed as paronychia at a rural clinic four months ago. An incisional biopsy confirmed the diagnosis of amelanotic subungual melanoma. Amputation of the affected finger was performed successfully. Imaging studies showed no metastatic disease. This case underscores the importance of early recognition and management of subungual melanoma, particularly in remote rural areas, to optimize patient outcomes.

Aims: In treating patients with melanoma, the order in which therapy is administered, choosing between targeted therapy and immune checkpoint inhibition, has garnered growing interest.

Patients and methods: We conducted a retrospective, real-world analysis of patients with advanced melanoma undergoing immunotherapy or targeted therapy as first-line at a single center.

Results: A total of 88 patients diagnosed with melanoma were identified. At 7 years, in this cohort, 68.4% (95% CI: 55.9%-83.6%) of patients were alive. In all, 47 tumors harbored BRAF mutations; 10 patients who did not receive therapy were excluded from this subgroup. Of the 37 patients with a BRAF mutation, 29 received first-line targeted therapy and 8 received first-line immunotherapy. At 2 years, 28 (76%) patients were alive and 9 (24%) had died. Of the 28 survivors, 22 received first-line targeted therapy and 6 received first-line immunotherapy. In addition, 29 patients were administered a MEK inhibitor in first line. Of these, 66.4% (95% CI: 48.3-91.2) of patients were alive at 7 years.

Conclusions: There was no significant difference between survival and first-line immunotherapy or first-line targeted therapy. Additional studies are required to establish whether front-line immunotherapy is linked to more effective long-term disease control compared to first-line targeted therapy.

Aim: This study summarized the existing evidence on the outcomes and safety of anti-PD-1s, anti-PD-L1s and anti-CTLA-4s in pediatric patients with melanoma.Materials & methods: MEDLINE^® and Embase were searched from database inception to 01-12-2023.Results: Of 1537 records identified, 27 studies (k) of 64 patients were included. Most studies were case reports (k = 16). All studies used anti-PD-1s (nivolumab, pembrolizumab) alone or anti-CTLA-4s (ipilimumab). Survival outcomes (k = 7), response outcomes (k = 15) and adverse events (k = 16) varied. Safety profiles of anti-PD-1s and anti-CTLA-4s were broadly similar to that seen in adults.Conclusion: Despite scarce, heterogenous data, this review can be a reference for clinicians. Future clinical trials should include adolescents to grow the evidence base on immune checkpoint inhibitors in pediatric melanoma.

Background: Melanoma, the deadliest skin cancer, presents significant challenges globally. This study examines survival factors among patients treated at a high-complexity oncology center in Colombia's coffee-growing region. Methods: Records from 2010 to 2021 were analyzed, capturing socio-demographics, clinical variables and survival outcomes via Kaplan-Meier and Cox regression. Results: Among 766 patients, factors influencing survival included sex, TNM stage, diagnostic stage, ulceration, metastasis, Breslow thickness ≥1 mm and positive nodes. Age, ulceration, distant stage at diagnosis and Breslow thickness ≥1 mm were associated with mortality. Conclusion: Colombian melanoma patients exhibit lower survival rates compared with global trends. Key survival determinants align with international literature. Enhanced photoprotection and early detection initiatives are imperative.

Aim: This study determined the characteristics of patients with early-stage melanoma (IA-IIA) who later had stage IV recurrence.Patients & methods: We retrospectively examined 880 melanoma patients and identified those who progressed to stage IV disease from an initial early-stage (n = 50).Results: We observed a median latent period of 4 years between early-stage diagnosis and metastatic disease. More patients (54%) developed metastatic disease 4 years or later from the initial diagnosis. 34% had regular dermatology appointments, and 30% had regular oncology follow-up. Lung and brain were the most common metastatic sites.Conclusion: Long term monitoring beyond 4 years and a low threshold for performing symptom-guided imaging, particularly if pulmonary or neurologic symptoms occur, may be prudent after early-stage melanoma diagnosis.

Aim: Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Methods: Six randomized case scenarios with diagnostic/clinical uncertainty were described with/without a benign or malignant diagnostic gene expression profile (GEP) result. Results: Clinical impact was assessed by reporting the mean increase/decrease of management changes normalized to baseline (n = 32 dermatologists). Benign GEP results prompted clinicians to decrease surgical margins (84.2%). Malignant GEP results escalated surgical excision recommendations (100%). A majority (72.2%) reduced and nearly all (98.9%) increased follow-up frequency for benign or malignant GEP results, respectively. There was an overall increase in management plan confidence with GEP results. Conclusion: Diagnostic GEP tests help guide clinical decision-making in a variety of diagnostically ambiguous or clinicopathologically discordant scenarios.