Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update

Roccuzzo, Gabriele; Bongiovanni, Eleonora; Tonella, Luca; Pala, Valentina; Marchisio, Sara; Ricci, Alessia; Senetta, Rebecca; Bertero, Luca; Ribero, Simone; Berrino, Enrico; Marchiò, Caterina; Sapino, Anna; Quaglino, Pietro; Cassoni, Paola

doi:10.1080/14737159.2024.2314574

Cited by 4 publications

(2 citation statements)

References 132 publications

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“…Despite these limitations, the findings of this study provide important insights into the potential role of a regional approach to TVEC and RT in stimulating systemic immune responses. Future study designs incorporating TVEC and RT as an immunomodulator should also incorporate biomarkers to better predict treatment response and potentially select those who are more likely to progress locally versus systemically in guiding the appropriate local and/or systemic treatment modality [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma

Tam,

Ladbury,

Kassardjian

et al. 2024

Cancers

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Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte–macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan–Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0–58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively (p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1–not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0–NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4–26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7–NR mos) (p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly.

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Section: Discussionmentioning

confidence: 99%

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma

Tam,

Ladbury,

Kassardjian

et al. 2024

Cancers

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“…Moreover, the comprehensive profiling of miRNA expression in different stages of melanoma, from melanocytes to metastatic melanoma cells, has been shown to provide valuable insights into the role of specific miRNAs. This profiling helps in understanding how miRNAs contribute to tumor growth, angiogenesis, metastasis, drug resistance, and immune responses to cancer [37,38].…”

Section: Literature Findingsmentioning

confidence: 99%

Molecular Markers in Melanoma Progression: A Study on the Expression of miRNA Gene Subtypes in Tumoral vs. Benign Nevi

Prodan,

Costescu,

Elagez

et al. 2024

Current Oncology

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This study investigates the differential expression of miRNA gene subtypes in tumoral versus benign nevi in individuals with melanoma, aiming to identify clinically significant correlations that could serve as reliable markers for assessing tumor stage and progression. Conducted between 2019 and 2022, this descriptive, quantitative observational research analyzed 90 formalin-fixed paraffin-embedded (FFPE) samples from the Pius Brinzeu County Emergency Clinical Hospital, Timisoara, including 45 samples of advanced-stage melanoma and 45 samples of pigmented nevi. miRNA purification and analysis were performed using the miRNeasy Kit and the Human Cancer PathwayFinder miScript miRNA PCR Array, with statistical analysis (including logistic regression) to determine associations with cancer staging, such as high Breslow index risk, number of mitoses, and vascular invasion. After the analysis and comparison of 180 miRNA gene subtypes, we selected 10 of the most upregulated and 10 most downregulated genes. The results revealed that hsa-miR-133b, hsa-miR-335-5p, hsa-miR-200a-3p, and hsa-miR-885-5p were significantly upregulated in melanoma samples, with fold changes ranging from 1.09 to 1.12. Conversely, hsa-miR-451a and hsa-miR-29b-3p showed notable downregulation in melanoma, with fold changes of 0.90 and 0.92, respectively. Additionally, logistic regression analysis identified hsa-miR-29b-3p (OR = 2.51) and hsa-miR-200a-3p (OR = 2.10) as significantly associated with an increased risk of a high Breslow index, while hsa-miR-127-3p and hsa-miR-451a were associated with a reduced risk. Conclusively, this study underscores the significant alterations in miRNA expression in melanoma compared to benign nevi and highlights the potential of specific miRNAs as biomarkers for melanoma progression. The identification of miRNAs with significant associations to melanoma characteristics suggests their utility in developing non-invasive, cost-effective diagnostic tools and in guiding therapeutic decisions, potentially improving patient outcomes in melanoma management.

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Monitoring circulating tumor DNA liquid biopsy in stage III BRAF-mutant melanoma patients undergoing adjuvant treatment

Marchisio,

Ricci,

Roccuzzo

et al. 2024

J Transl Med

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Background The introduction of adjuvant therapies for patients with resected cutaneous melanoma (CM) has increased the need for sensitive biomarkers for risk stratification and disease monitoring. This study aims to investigate the utility of circulating tumor DNA (ctDNA) assessment in predicting and reflecting disease status during adjuvant therapy. Methods We enrolled 32 patients with resected BRAF-mutated stage III CM receiving adjuvant targeted therapy or immunotherapy. Plasma samples of patients were collected at the baseline (treatment initiation) and during the therapy, and BRAF-mutated ctDNA was quantified by droplet digital PCR (ddPCR). Results Baseline ctDNA was detected in 11/32 (34.4%) patients and predicted postoperative high risk of relapse [HR 3.79, 95% CI 1.20–12.00, p = 0.023]. The three-year overall survival (OS) rate was 54.6% (95% CI 22.9–77.9) versus 95% (95% CI 69.5–99.3) in ctDNA-positive and negative groups, respectively, with significantly worse OS for ctDNA-positive patients [HR 7.92, 95% CI 1.56–40.36, p = 0.013]. Among the baseline ctDNA-positive group (high-risk patients), longitudinal ctDNA detection during adjuvant therapy reflected the clinical outcomes. Only non-relapsing patients cleared their plasma ctDNA by the end of the treatment, while persistent ctDNA detection provided early evidence of disease recurrence. Conclusions ctDNA detection shows promising results in the post-operative setting for identifying cutaneous melanoma patients at the highest risk of relapse and for real-time monitoring of patients’ clinical status and treatment response.

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Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update

Cited by 4 publications

References 132 publications

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma

Molecular Markers in Melanoma Progression: A Study on the Expression of miRNA Gene Subtypes in Tumoral vs. Benign Nevi

Monitoring circulating tumor DNA liquid biopsy in stage III BRAF-mutant melanoma patients undergoing adjuvant treatment

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