High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

Abstract Objective : We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. Results : BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07% to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

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Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma

10.20944/preprints202110.0145.v1 ◽

2021 ◽

Author(s):

Virginia Liberini ◽

Marco Rubatto ◽

Riccardo Mimmo ◽

Roberto Passera ◽

Francesco Ceci ◽

...

Keyword(s):

Fdg Pet ◽

Target Therapy ◽

Metabolic Parameters ◽

Whole Body ◽

First Line ◽

Pet Ct ◽

Line Target ◽

Melanoma Patients ◽

18F Fdg ◽

Fdg Pet Ct

Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: 44 melanoma patients who underwent [18F]FDG-PET/CT before first-line target therapy (28/50) or immunotherapy (16/50) were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared with Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. Results: Median(IQR) MTVwb and TLGwb were 13.1 mL and 72.4 respectively. Non-responders patients were 38/44, 26/28 and 12/16 at early evaluation, and in 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target and immunotherapy subgroup respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p<0.037) in the whole-cohort and target subgroup and also MTVwb and TLGwb (all p<0.022) in target subgroup. No significant differences were found for immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversy, MTVlfn, TLGlfn, MTVsoft+lfn, TLG-soft+lfn, MTVwb and TLGwb were significantly associated (all p<0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusion: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

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BRAF V600 mutation profiling in primary skin nodular melanoma in Indonesia: an analysis using high resolution pyrosequencing

10.21203/rs.2.20532/v3 ◽

2020 ◽

Author(s):

Hanggoro Tri Rinonce ◽

Rovi Panji Mustiko Aji ◽

Ni’mah Hayati ◽

Maria Fransiska Pudjohartono ◽

Bidari Kameswari ◽

...

Keyword(s):

High Resolution ◽

Allele Frequencies ◽

Variant Allele ◽

Nodular Melanoma ◽

Central Java ◽

Clinicopathological Variables ◽

Braf V600 Mutation ◽

Mutation Profiling

Abstract Objective: We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. Results: BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07% to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

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BRAF V600 mutation profiling in primary skin nodular melanoma in Indonesia: an analysis using high resolution pyrosequencing

10.21203/rs.2.20532/v1 ◽

2020 ◽

Author(s):

Hanggoro Tri Rinonce ◽

Rovi Panji Mustiko Aji ◽

Ni’mah Hayati ◽

Maria Fransiska Pudjohartono ◽

Bidari Kameswari ◽

...

Keyword(s):

High Resolution ◽

Allele Frequencies ◽

Variant Allele ◽

Nodular Melanoma ◽

Central Java ◽

Clinicopathological Variables ◽

Braf V600 Mutation ◽

Mutation Profiling

Abstract Objective : We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. Results : BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07% to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

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Quantitative Analysis and Monitoring of EZH2 Mutations Using Liquid Biopsy in Follicular Lymphoma

Genes ◽

10.3390/genes11070785 ◽

2020 ◽

Vol 11 (7) ◽

pp. 785

Author(s):

Ákos Nagy ◽

Bence Bátai ◽

Alexandra Balogh ◽

Sarolta Illés ◽

Gábor Mikala ◽

...

Keyword(s):

Follicular Lymphoma ◽

Mutation Analysis ◽

Liquid Biopsy ◽

Digital Pcr ◽

Circulating Tumor Dna ◽

Allele Frequencies ◽

Variant Allele ◽

Monitoring Tool ◽

Positron Emission ◽

Tumor Dna

Recent advances in molecular technologies enable sensitive and quantitative assessment of circulating tumor DNA, offering a noninvasive disease monitoring tool for patients with malignant disorders. Here, we demonstrated on four follicular lymphoma cases that circulating tumor DNA based EZH2 mutation analysis performed by a highly sensitive droplet digital PCR method may be a valuable treatment monitoring approach in EZH2 mutant follicular lymphoma. EZH2 variant allele frequencies changed in parallel with the volume of metabolically active tumor sites observed on 18F-fluorodeoxyglucose positron emission tomography combined with computer tomography (PET-CT) scans. Variant allele frequencies of EZH2 mutations decreased or were eliminated rapidly upon successful treatment, with treatment failure being associated with elevated EZH2 variant allele frequencies. We also demonstrated spatial heterogeneity in a patient with two different EZH2 mutations in distinct anatomical sites, with both mutations simultaneously detected in the liquid biopsy specimen. In summary, circulating tumor DNA based EZH2 mutation analysis offers a rapid, real-time, radiation-free monitoring tool for sensitive detection of EZH2 mutations deriving from different anatomical sites in follicular lymphoma patients receiving immunochemotherapy.

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Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

Cancers ◽

10.3390/cancers12071994 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1994 ◽

Cited By ~ 5

Author(s):

Alessandro A. E. Testori ◽

Silvia Chiellino ◽

Alexander C.J. van Akkooi

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Adjuvant Therapy ◽

Target Therapy ◽

Survival Rates ◽

Immune Checkpoint Blockade ◽

Severe Toxicity ◽

Toxic Side Effect ◽

The Past ◽

Melanoma Patients

This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years—anti-PD-1 or BRAF-directed therapy is the new standard of care.

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Risk prediction in cutaneous melanoma patients from their clinico-pathological features: superiority of clinical data over gene expression data

Heliyon ◽

10.1016/j.heliyon.2020.e04811 ◽

2020 ◽

Vol 6 (8) ◽

pp. e04811

Author(s):

Chakit Arora ◽

Dilraj Kaur ◽

Anjali Lathwal ◽

Gajendra P.S. Raghava

Keyword(s):

Gene Expression ◽

Risk Prediction ◽

Gene Expression Data ◽

Clinical Data ◽

Cutaneous Melanoma ◽

Expression Data ◽

Pathological Features ◽

Melanoma Patients

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Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma

Journal of Clinical Medicine ◽

10.3390/jcm10214994 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4994

Author(s):

Virginia Liberini ◽

Marco Rubatto ◽

Riccardo Mimmo ◽

Roberto Passera ◽

Francesco Ceci ◽

...

Keyword(s):

Fdg Pet ◽

Target Therapy ◽

Metabolic Parameters ◽

Whole Body ◽

First Line ◽

Pet Ct ◽

Line Target ◽

Melanoma Patients ◽

18F Fdg ◽

Fdg Pet Ct

Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann–Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan–Meier analysis. Results: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusions: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

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