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Relevant Articles About Research and Clinical Trials in Skin Cancer

RELATED :BCC (Basal Cell Carcinoma):Melanoma:SCC (Squamous Cell Carcinoma)

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MelanomaNSCLC (Non-Small Cell Lung Cancer)Other CancersSCC (Squamous Cell Carcinoma)Biological: T3011Combination Product: T3011 + pembrolizumabRecruitingAustraliaUnited States 0NCT04370587Phase 1Phase 2
A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

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GNA/BAP1 Mutation Impact on Protein & mRNA Expression in UM

KEY TAKEAWAYS

  • The study aimed to identify genetic causes of protein and mRNA expression variations in UM cell lines.
  • Researchers noted that Mel285 and Mel290 differ from other UM cell lines and may not be suitable for therapeutic testing.

Uveal melanoma (UM) cell lines are being extensively utilized for preclinical research because not all cell lines exhibit typical GNAQ or GNA11 hotspot mutations.

Maria Chiara Gelmi and the team aimed to better classify UM-cell lines by determining whether genetic causes can explain their protein and mRNA expression profiles, with a special emphasis on cell lines without the typical GNAQ or GNA11 hotspot mutations.

Researchers designed this study to assess the protein and mRNA expression in 14 UM cell lines and detect the presence of single nucleotide variants and small insertions and deletions with next-generation sequencing (NGS) and copy number alterations with a single nucleotide polymorphism (SNP) array.

They merged the lists of differentially expressed proteins and genes and created shared lists by keeping only terms with concordant mRNA and protein expression and further performed the enrichment analyses on the shared lists.

Results revealed that cell lines Mel285 and Mel290 were distinct from GNAQ/GNA11-mutated cell lines and exhibited downregulation of melanosome-related markers. Both cell lines lacked typical UM mutations but had putatively deleterious variants in various genes: Mel285 had mutations in CTNNB1, PPP1R10, LIMCH1, and APC, while Mel290 had mutations in ARID1A, PPP1R10, SPG11, and RNF43.

Additionally, Mel285 showed chromosomal losses including 1p, 3p, partial 3q, 6, and partial 8p, whereas Mel290 showed losses of 1p and 6.

Moreover, the upregulated terms in Mel285 and Mel290 did not indicate a clear alternative origin while in the remaining 12 cell lines, expression profiles were related to BAP1 expression.

The study concluded that, despite Mel285 and Mel290 exhibiting copy number alterations characteristic of UM, multi-omics analyses showed that they belong to a distinct group compared to the other UM cell lines analyzed. Therefore, they may not serve as representative models for testing potential therapeutic targets for UM.

The study was supported by the Bontius Foundation, Oogfonds, the Sam Fund, the Leiden University Fund, P.A. Jager-van Gelder Fund, the Blinden-Penning Foundation, and the Scientific Association for Retinoblastoma and Ocular Oncology.

Source: https://pubmed.ncbi.nlm.nih.gov/39042403/

Gelmi MC, de Ru AH, van Veelen PA, et al. (2024). “Protein and mRNA Expression in Uveal Melanoma Cell Lines Are Related to GNA and BAP1 Mutation Status.” Invest Ophthalmol Vis Sci. 2024 Jul 1;65(8):37. doi: 10.1167/iovs.65.8.37. PMID: 39042403.

68GA-NOTA-XH05 for Targeting LAG-3 in Melanoma Imaging

KEY TAKEAWAYS

  • The study aimed to evaluate the use of novel peptide-based PET tracer 68Ga-NOTA-XH05 in assessing LAG-3 expression in melanoma post-CpG oligonucleotide treatment.
  • The study highlighted 68Ga-NOTA-XH05’s potential in detecting LAG-3 and assessing immunotherapy response.

Lymphocyte activation gene 3 (LAG-3) is generally expressed on activated immune cells and has emerged as a promising target for immune checkpoint blockade. However, inconsistent results have been reported corresponding to the association between patient prognosis and LAG-3 expression in tumors. This indicates the urgent need for digging deeper to unveil the role of LAG-3 expression levels in melanoma therapies.

Peizhe Yuan and the team aimed to investigate the utility of the novel peptide-based positron emission tomography (PET) tracer 68Ga-NOTA-XH05 in non-invasively detecting LAG-3 expression in melanoma after CpG oligonucleotide treatment.

Researchers prepared, purified, and identified 68Ga-NOTA-XH05 by high-performance liquid chromatography and performed the cell uptake and blocking assays to verify the specificity of the tracer, in vitro.

The expression analysis of LAG-3 in B16-F10 subcutaneous tumors was evaluated by flow cytometry, the tracer uptake was utilized for establishing a correlation between LAG-3 expression and tracer uptake for the affirmation of the tracer specificity.

Further PET imaging and biodistribution studies post-CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumorigenated subjects were executed for the assessment of the ability of  68Ga-NOTA-XH05 in immunotherapy efficacy monitoring and the abscopal effect of CpG.

Results revealed that following purification, 68Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis demonstrated a positive correlation between LAG-3 expression in tumors and the uptake of 68Ga-NOTA-XH05. This finding supports the tracer’s potential for targeting LAG-3 expression in melanoma.

In B16-F10 tumorigenated subjects treated with CpG, PET imaging using 68Ga-NOTA-XH05 showed a higher tumor-to-blood ratio (TBR) compared to the control group. The increased TBR values in CpG-treated tumorigenated subjects were significant enough to differentiate between responders and non-responders. This suggests that 68Ga-NOTA-XH05 may be an effective tool for monitoring the efficacy of CpG immunotherapy.

Furthermore, in a bilateral subcutaneous tumor line where only the right-sided tumors received an intratumoral injection of CpG, the TBR values of the left-sided tumors were significantly higher than those in the control group. This indicates that 68Ga-NOTA-XH05 could effectively monitor the systemic effects of local CpG injection, demonstrating its potential utility in assessing the abscopal effect in melanoma treatment.

The study concluded by highlighting the capability of 68Ga-NOTA-XH05 in the detection and assessment of LAG-3 expression levels within tumors and evaluating response to immunotherapy, thus hinting at a promising clinical translational implication.

This study was funded by the National Natural Science Foundation of China (81801738, 82030052), the Hubei Provincial Natural Science Foundation (2022CFB063), and Key Research and Development Program of Hubei Province (2023BCB016).

Source: https://pubmed.ncbi.nlm.nih.gov/39043603/

Yuan P, Long Y, Wei N, et al. (2024). “Peptide-based PET tracer targeting LAG-3 for evaluating the efficacy of immunotherapy in melanoma.” J Immunother Cancer. 2024 Jul 23;12(7):e009010. doi: 10.1136/jitc-2024-009010. PMID: 39043603.

END and Occult Metastasis in cT2N0 Maxillary Sinus Cancer

KEY TAKEAWAYS

  • The study aimed to assess the impact of END on the prognosis and explore subgroup-specific biomarkers for pts with cT2N0 MS-SCC.
  • The key outcomes of the study were to evaluate the effect of END on DSS and OS.
  • Researchers validated that END did not confer significant survival benefits in cT2N0 MS-SCC.

Maxillary sinus squamous cell carcinoma (MS-SCC) is a rare malignancy, yet it constitutes the predominant cancer type affecting the nasal cavity and paranasal sinus. Due to its typically asymptomatic early stages, over 80% of newly diagnosed MS-SCC cases present at an advanced T3/4 stage. Standard curative treatment involves surgical intervention alongside radiotherapy, often complemented by chemotherapy.

Jingjing Wang and the team aimed to evaluate the effect of elective neck dissection (END) on the prognosis of patients (pts) diagnosed with cT2N0 MS-SCC and identify predictive factors associated with the occurrence of occult metastasis in this specific patient group.

Researchers conducted a retrospective analysis using SEER database data, focusing on pts diagnosed with cT2N0 MS-SCC. Those pts were divided into 2 groups: those who underwent END and those who did not.

They utilized data from the SEER database to investigate the impact of END on disease-specific survival (DSS) and overall survival (OS) in pts with cT2N0 MS-SCC.

About 180 pts meeting inclusion criteria were analyzed after exclusion based on specific parameters. The study employed propensity score matching to compare outcomes between pts who underwent END and those who did not. Statistical analyses included univariate and multivariable models, presenting HR with 95% confidence intervals (CI). Ethical approval and patient consent were waived due to the study’s use of publicly accessible data from the SEER database.

The study assessed the impact of END on DSS and OS using propensity score matching. Multivariate logistic regression analysis was employed to identify predictors of occult metastasis. In total, the study included 180 pts, with 40 cases undergoing END.

Results indicated that following propensity score matching, there were no significant differences in DSS OS rates between pts who underwent END and those who did not. Occult metastasis was observed in 9 pts, corresponding to a rate of 22.5%.

High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (HR 1.52, 95% CI 1.17-2.00). Overall, cT2N0 MS-SCC exhibited an occult metastasis rate of 22.5%, with histologic grade identified as the primary determinant of occult metastasis.

These findings concluded that END did not provide a significant survival benefit in cT2N0 MS-SCC.

The study was funded by the Henan provincial Medical Science and Technology Research Project (No.LHGJ20220196) and Project of Science and Technology in Science and Technology Department of Henan Province (No. 232102310285).

Source: https://pubmed.ncbi.nlm.nih.gov/39004629/

Wang J, Fang Q, Zhang X, et al. (2024). “Role of elective neck dissection in cT2N0 maxillary sinus squamous cell carcinoma.” Sci Rep. 2024 Jul 14;14(1):16230. doi: 10.1038/s41598-024-66179-7. PMID: 39004629; PMCID: PMC11247074.

Standardizing Melanoma Inguinal Lymphadenectomy Complications

Standardizing Melanoma Inguinal Lymphadenectomy Complications

KEY TAKEAWAYS

  • The study aimed to standardize the classification and reporting of perioperative complications in inguinal lymph node dissection through the CALI group.
  • Researchers concluded that CALI standardizes inguinal lymph node dissection complication reporting for melanoma, vulval, and penile cancer treatments.

Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes.

René Sotelo and the team aimed to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events (AEs) in lymphadenectomy of the inguinal area (CALI) group.

They conducted an inclusive analysis using a modified 3-round Delphi consensus approach involving a global panel of experts in inguinal lymph node dissection for melanoma, penile, and vulval cancer. The expert group comprised general surgeons, urologists, and oncologists specializing in gynecology and surgery.

The survey evaluated expert consensus on perioperative complications associated with inguinal lymph node dissection. Panel interrater agreement and consistency were measured by overall percentage agreement and Cronbach’s α.

About 47 experienced consultants participated: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons, and 4 (8.5%) gynecology oncologists. Among them, 31 (66%), 10 (21.3%), and 22 (46.8%) treat penile cancer, vulval cancer, and melanoma with inguinal lymph node dissection, respectively. 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into 5 macrocategories.

Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer, and penile cancer.

The study concluded that the complications and AEs in lymphadenectomy of the inguinal area classification system serve as a standardized tool for assessing and reporting complications during inguinal lymph node dissection in melanoma, vulval, and penile cancer treatment.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/38987232

Sotelo R, Sayegh AS, Medina LG, et al. (2024). “Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.” BJS Open. 2024 Jul 2;8(4):zrae056. doi: 10.1093/bjsopen/zrae056. PMID: 38987232; PMCID: PMC11236483.

Diabetes Affects Tumor Thickness & Ulceration in Melanoma Diagnosis

KEY TAKEAWAYS

  • The study aimed to evaluate the association between type 2 diabetes and malignant melanoma.
  • Researchers found no link between diabetes & melanoma; they found its link to thicker tumors and ulceration at diagnosis.

In high-income countries, diabetes related cancers, including melanoma are 1 of the most common causes of diabetes-related deaths. More extensive studies are required to establish a clear link between diabetes and site-specific cancers.

Jens Ejrnæs Tønder and the team aimed to assess the association between diabetes, specifically type 2 diabetes, and malignant melanoma through a systematic review and meta-analysis.

Researchers systematically searched up to february 22, 2023, as per the eligibility criteria set up to identify exploratory research instances based on the association between diabetes (including type 2 diabetes) and malignant melanoma outcomes like incidence, stage, and melanoma-specific mortality.

PubMed, the cochrane library, and the Web of Science were the primary databases searched subsequently, the 2 independent reviewers thoroughly evaluated identified articles followed by quality -assessment was performed using the newcastle-ottawa scale, designed for observational studies.

Meta-analyses were subsequently carried out using RevMan 5.4.1, which focused on assessing melanoma risk using adjusted risk estimates and examining the melanoma stage using a dichotomous model. This comprehensive approach aimed to clarify the association between diabetes and malignant melanoma across various dimensions of disease progression and outcome.

The literature search identified 20 studies eligible for inclusion in the systematic review and meta-analysis. Of these, 14 contributed data for analyzing melanoma risk, 3 focused on melanoma thickness and ulceration, and 4 examined melanoma-specific survival outcomes.

The meta-analyses revealed that there was no statistically significant impact of diabetes on the overall risk of developing melanoma (RR: 1.05, 95%CI: 0.99-1.12, P = 0.10). However, the analysis revealed that individuals with type 2 diabetes were more likely to present with more advanced melanoma stages at the time of diagnosis. Specifically, the risk of Breslow thickness greater than 1 mm was significantly higher (RR 1.35, 95%CI: 1.22-1.49, P < 0.001), and there was also an increased risk of ulceration (RR 1.30, 95%CI: 1.00-1.68, P = 0.05).

A meta-analysis examining the association between diabetes and melanoma-specific mortality was not feasible due to the heterogeneity in study designs and outcome reporting among the included studies. Future research focusing on standardized methodologies could provide further insights into this aspect of the relationship between diabetes and melanoma outcomes.

The study concluded that although there was no link between diabetes and melanoma, an association between tumor thickness and the presence of ulceration at the time of diagnosis was established during this study. Further exploration of these facts requires more extensive research in this area.

Authors did not receive any grants or funding for this study.

Source: https://pubmed.ncbi.nlm.nih.gov/38972968/

Tønder JE, Bønnelykke-Behrndtz ML, Laurberg T, et al. (2024). “Melanoma risk, tumour stage, and melanoma-specific mortality in individuals with diabetes: a systematic review and meta-analysis.” BMC Cancer. 2024 Jul 7;24(1):812. doi: 10.1186/s12885-024-12598-8. PMID: 38972968; PMCID: PMC11229239.

TRM CD8 T Cells & cDC1: Key Players in Melanoma Protection

KEY TAKEAWAYS

  • The study aimed to investigate the role of TRM CD8 T cells, cDC1, and TCF1 expression in orchestrating melanoma control and response to CBI.
  • Researchers noticed distinct TCF1+ and TaCF1- TRM CD8 T cell subsets and cDC1s crucial for melanoma control and response to CBI.

Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance.

Tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) have been highlighted for their significant roles in cancer protection. Recent transcriptomic studies emphasize the pivotal role of TCF7+ T cells, which encode TCF1 and are crucial for effective immunotherapy response. However, uncertainty persists regarding the existence and function of TCF1+ TRM T cells, given evidence suggesting TCF1 downregulation for tissue residency activation.

Saraí G De León-Rodríguez and the team aimed to assess the role of TRM CD8 T cells, cDC1, and the distinct TCF1+ and TCF1- TRM subsets in melanoma control and response to CBI.

They evaluated TRM CD8 T cells and cDC1 in 2 patients with melanoma cohorts: 1 immunotherapy-naive and the other receiving immunotherapy by using multiplexed immunofluorescence and spectral flow cytometry. The 1 cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders.

In the study, 2 CD8+ TRM subsets, TCF1+ and TCF1-, correlate with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67, while TCF1- TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1- subset displaying increased expression of exhaustion markers.

A close spatial correlation between cDC1s and TRMs is observed, with TCF1+ TRM/cDC1 pairs enriched in the stroma and TCF1- TRM/cDC1 pairs in tumor areas. Notably, these TCF1- TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1- TRM subsets, alongside cDC1, prove relevant to CBI response.

The study concluded that TRM CD8 T cells and cDC1 play pivotal roles in melanoma protection. It highlighted functionally distinctive TCF1+ and TCF1- TRM subsets, essential for both melanoma control and effective response to CBI.

This study was funded by CONAHCyT-PRONACES 302962.

Source: https://pubmed.ncbi.nlm.nih.gov/38969523/

De León-Rodríguez SG, Aguilar-Flores C, Gajón JA, et al. (2024). “TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response.” J Immunother Cancer. 2024 Jul 5;12(7):e008739. doi: 10.1136/jitc-2023-008739. PMID: 38969523; PMCID: PMC11227852.

Efficacy and Safety of Adjuvant ICI in Elderly Melanoma

KEY TAKEAWAYS

  • The study aimed to assess adjuvant ICI in patients with elderly melanoma ≥ 75 years compared to younger patients.
  • Researchers observed higher toxicity and reduced efficacy of adjuvant ICI.

Immune checkpoint inhibitors (ICI) have demonstrated safety and efficacy in adjuvant treatment of melanoma, yet data specific to elderly patients aged 75 years or older remains limited.

A Gawaz and the team aimed to compare the efficacy and safety profiles of adjuvant ICI in patients aged ≥ 75 years vs those < 75 years in a real-world setting.

Researchers performed an inclusive analysis of clinical data from 456 patients treated with adjuvant ICI between January 1st, 2018, and December 20th, 2022. Patients were categorized based on age: 117 patients aged ≥ 75 years and 339 patients aged < 75 years. The study aimed to compare the occurrence of immune-related adverse events (irAE) and disease-free survival (DFS) between these age groups.

The study concluded that adjuvant ICI were generally well tolerated across age groups, with similar overall occurrence of irAE. However, elderly patients (≥ 75 years) experienced a notably higher incidence of skin, nephrological toxicity, and colitis/diarrhea compared to younger patients.

Additionally, patients aged ≥ 75 years demonstrated a significantly shorter DFS, suggesting reduced efficacy of adjuvant ICI in this population. Given these findings, caution is warranted when considering adjuvant ICI therapy for elderly patients with melanoma.

The study received an open-access funding from the University of Tübingen.

Source: https://pubmed.ncbi.nlm.nih.gov/38969911/

Gawaz A, Wolff I, Nanz L, et al. (2024). “Efficacy of adjuvant immune checkpoint inhibitors pembrolizumab or nivolumab in melanoma patients ≥ 75 years: results of a real-world cohort including 456 patients.” Cancer Immunol Immunother. 2024 Jul 5;73(9):185. doi: 10.1007/s00262-024-03750-1. PMID: 38969911; PMCID: PMC11226568.

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