Abstract 2847: Quantitative assessment of circulating BRAF DNA in stage IV melanoma patients undergoing BRAF inhibitor treatment

Author(s):  
David Polsky ◽  
Jyothi Sakuntala Tadepalli ◽  
Gregory Chang ◽  
Nathaniel Fleming ◽  
Yongzhao Shao ◽  
...  
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yukiko Kiniwa ◽  
Kenta Nakamura ◽  
Asuka Mikoshiba ◽  
Atsuko Ashida ◽  
Yasuyuki Akiyama ◽  
...  

Abstract Background While molecularly targeted therapies and immune checkpoint inhibitors have improved the prognosis of advanced melanoma, biomarkers are required to monitor drug responses. Circulating tumor cells (CTCs) are released from primary and/or metastatic tumors into the peripheral blood. We examined whether CTCs have potential as biomarkers by checking the number of CTCs, as well as the BRAF genotype of individual CTCs, in melanoma patients undergoing BRAF/MEK inhibitor treatment. Methods CTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). The numbers of CTCs were analyzed in fifteen patients with stage 0–III melanoma. Furthermore, changes in CTC numbers were assessed in five patients with stage IV melanoma at four time points during BRAF/MEK inhibitor treatment, and the BRAF genotype was analyzed in CTCs isolated from one patient. Results We examined CTCs in patients with stage 0–III (five samples per stage: stage 0–I, stage II, and stage III), and detected CTCs even in patients with early disease (stage 0 and I). Interestingly, recurrence occurred in the lymph nodes of one stage I patient 2 years after the detection of a high number of CTCs in the patient’s blood. The total number of CTCs in four of five patients with stage IV melanoma fluctuated in response to BRAF/MEK inhibitor treatment, suggesting that CTC number has potential for use as a drug response marker in advanced disease patients. Interestingly, one of those patients had CTCs harboring seven different BRAF genotypes, and the mutated CTCs disappeared upon BRAF/MEK inhibitor treatment, except for those harboring BRAFA598V. Conclusions CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect patients’ responses to BRAF/MEK inhibitor treatment. Furthermore, genetic heterogeneity of BRAF may contribute to resistance to BRAF/MEK inhibitors. Our findings demonstrate the usefulness of CTC analysis for monitoring responses to targeted therapies in melanoma patients, and for understanding the mechanism of drug resistance.


2018 ◽  
Vol 38 (11) ◽  
pp. 6393-6397 ◽  
Author(s):  
KALLE MATTILA ◽  
PIRITA RAANTA ◽  
VALTTERI LAHTELA ◽  
SEPPO PYRHÖNEN ◽  
ILKKA KOSKIVUO ◽  
...  

2018 ◽  
Vol 227 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Carolyn S. Hall ◽  
Merrick Ross ◽  
Jessica B. Bowman Bauldry ◽  
Joshua Upshaw ◽  
Mandar G. Karhade ◽  
...  

2020 ◽  
Vol 18 (11) ◽  
pp. 1270-1277
Author(s):  
Klaus Eisendle ◽  
Georg Weinlich ◽  
Susanne Ebner ◽  
Markus Forstner ◽  
Daniela Reider ◽  
...  

2007 ◽  
Vol 30 (8) ◽  
pp. 831-838 ◽  
Author(s):  
Hitoe Torisu-Itakura ◽  
Jonathan H. Lee ◽  
Young Huynh ◽  
Xing Ye ◽  
Richard Essner ◽  
...  

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 7572-7572
Author(s):  
S. G. Holtan ◽  
R. D. Rao ◽  
E. Creagan ◽  
J. Kaur ◽  
H. Pitot ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8600-8600
Author(s):  
Nicole M. Rochet ◽  
Luis F. Porrata ◽  
Lisa A. Kottschade ◽  
Travis Edward Grotz ◽  
Svetomir Markovic

8600 Background: The prognosis of stage IV melanoma patients remains poor. Published results have suggested that components of the complete blood count have significant prognostic value in several malignancies. Among the most studied were the absolute lymphocyte count (ALC), and absolute monocyte count (AMC) on clinical outcomes of patients with lymphoid malignancies. Thus, we sought to investigate if the pre-operative ALC (ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the risk of disease recurrence and survival after complete surgical resection of metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma patients followed at Mayo Clinic from 2000 to 2010. Log rank chi-square analysis was used to determine the best cut-off values for each pre-operative variable, while proportional hazards models were used to compared survival. Results: The median follow-up of the cohort was 24 months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as continuous variables, were all identified as prognostic factors for both relapse-free survival (RFS) and overall survival (OS). The best cut-off values for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05, respectively. Using Kaplan-Meier analysis, patients with an ALC-PO ≥ 1.9 x 109/L experienced superior OS and RFS compared with ALC-PO < 1.9 x 109/L patients [median OS of 58 months vs. 34 months, p < 0.04; median RFS of 14 months vs. 5 months, p < 0.009]. Conversely, a low AMC-PO (<0.62 x 109/L) was associated with better OS and RFS compared with higher AMC-PO (≥ 0.62 x 109/L): [median OS of 47 months vs. 14 months, p < 0.007; median RFS of 9 months vs. 5 months, p < 0.02]. When the ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with an ALC/AMC-PO ≥ 2.05 experienced a superior OS and RFS compared to patients with ALC/AMC-PO < 2.05: [median OS of 49 months vs. 12 months, p < 0.0001; median RFS of 10 months vs. 4 months, p < 0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent prognostic factor for RFS and OS (HR = 0.32, p < 0.003; HR = 0.23, p < 0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an independent prognostic factor for RFS and OS in patients undergoing resection of metastatic (stage IV) melanoma.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24055-e24055
Author(s):  
Benjamin Switzer ◽  
David James Savage ◽  
Jung Min Song ◽  
Carolyn Stanek ◽  
Pauline Funchain

e24055 Background: Despite an encouraging 99% five-year survival in patients diagnosed with early-stage melanoma, a higher proportion of fatal melanomas initially present with thin ( < 1mm) rather than thick ( > 4mm) melanoma.1 Therefore, early-stage melanoma survivorship remains a topic of high interest. We examined a cohort of early-stage melanomas which progressed to stage IV to inform survivorship and risk-stratification approaches in this large, understudied population. Methods: From a retrospective single-center study of 880 consecutive melanoma patients from 2016-2020, we identified new, non- de novo diagnoses of stage IV melanoma which progressed from an initial early-stage (IA-IIA) diagnosis. Descriptive data were collected via chart review on demographics, clinical features, presentation at time of progression, and follow up prior to progression. Results: A total of 50 patients met the inclusion criterion of an initial stage IA-IIA diagnosis with subsequent progression to stage IV melanoma. Primary early stage melanomas were diagnosed an average of 6.1 years prior to metastatic disease progression, with 46% (n = 23) diagnosed within 3 years, 22% (n = 11) between 4-6 years, 12% (n = 6) between 7-10 years, 8% (n = 4) between 10-12 years, and 12% (n = 6) beyond the 12 year mark from their initial early-stage diagnosis. Average age at time of diagnosis was 57.7 (median 60, range 21-68), and 62% (n = 31) were male. The two most common early-stage diagnostic sites were lower extremities (27.5%, n = 14) and back (23.5%, n = 12). The two most common sites of metastatic disease were lung (46%, n = 23) and brain (28%, n = 14). A total of 30% (n = 15) and 34% (n = 17) of this cohort maintained follow up with oncology and dermatology, respectively, prior to their stage IV diagnosis. Symptomatic disease lead to 80% (n = 40) of stage IV diagnoses, while 14% (n = 7) were diagnosed through routine oncologic or dermatologic follow up, and the final 6% were diagnosed incidentally. Conclusions: Early stage melanoma patients who develop stage IV disease exhibit wide ranges in onset of disease progression, thus survivorship plans for this group could include a combination of early provider screening and patient education for later presentations of metastatic disease. Due to relatively common metastatic involvement of the lung and brain, a high suspicion to screen for metastatic disease with symptoms involving these organs may be appropriate.


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