Simple blood tests that tells us where we are with our melanoma....AGAIN (and again, and again, and again)!!!

I have been yelling about simple blood tests that give good information to melanoma patients for YEARS!!  I think my first post was in 2015.  Here is some of what I said and a link to that February post (with a zillion links within): "Yep.  It's me again, Margaret.  I'm still yelling about simple blood draws that can provide critical information related to the diagnosis of, feasibility of treatment for, response to treatment, and prognosis generally in melanoma patients!"  Simple blood tests that tell us how melanoma patients are responding to therapy and identify their disease in the first place....AGAIN!!!!

On a rather disheartening note ~ At a recent symposium for melanoma patients in Atlanta, facilitated by Northside and MRF, with "melanoma specialists" from Emory and Northside Hospital, I asked the panel what they were utilizing in regard to blood assays in diagnosing, monitoring, and implementing treatment for their patients.  They looked at me like deer in the headlights!!  One blathered on about it only being useful in regard to diagnosing BRAF status, not being "validated", blah, blah, blah. Seriously???  I call - B.S.!!!!  Some of these tests are not particularly special, like the NLR (neutrophil-to-lymphocyte ratio) for instance.  This is easily attained and computed via a simple CBC (complete blood count) drawn at every lab in this country a zillion times a day.  AND...we have looked at this data long enough to know that it is true!!!

Okay.  I'll quit yelling.  Now, there's this ~

Neutrophil-to-lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Ma, Kuzman, Ray, et al.  Sci Rep. 2018 Mar 6. 

Neutrophil-to-lymphocyte ratio is a strong predictor for overall survival and disease free survival in many cancers. Our study is the first investigation aiming to determine the predictive value of neutrophil-to-lymphocyte ratio on prognosis of patients with stage III melanoma. This retrospective study utilized a cohort of 107 patients with stage III melanoma treated at Huntsman Cancer Institute, University of Utah, from May 2002 to March 2016. The optimal cutoff of neutrophil-to-lymphocyte ratio was determined by the significance of log-rank tests. A total of 97 log-rank tests were conducted to find the optimal cutoff. Disease free survival was assessed using the Kaplan-Meier method, and univariable and multivariable Cox models were applied to evaluate the predictive value of neutrophil-to-lymphocyte ratio. 2.5 was identified as the optimal cutoff. Kaplan-Meier curve showed that the disease free survival rate of the low value group was significantly higher compared to that of high value group. After adjusting for confounders and other prognostic factors, the neutrophil-to-lymphocyte ratio greater than or = to 2.5 remained a strong predictor for disease recurrence in patients with stage III melanoma.

Liquid biopsy to monitor melanoma patients. Gaiser, von Bunoff, Gebhardt, Utikal. J Dtsch Dermatol Ges. 2018 Mar 7.

During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression. Consequently, reliable methods for monitoring disease progression or treatment resistance are necessary. Localized and advanced cancers may generate circulating tumor cells and circulating tumor DNA (ctDNA) that can be detected and quantified from peripheral blood samples (liquid biopsy). For melanoma patients, liquid biopsy results may be useful as novel predictive biomarkers to guide therapeutic decisions, particularly in the context of mutation-based targeted therapies. The challenges of using liquid biopsy include strict criteria for the phenotypic nature of circulating MM cells or their fragments and the instability of ctDNA in blood. The limitations of liquid biopsy in routine diagnostic testing are discussed in this review.

Liquid Profiling of Circulating Tumor DNA in Plasma of Melanoma Patients for Companion Diagnostics and Monitoring of BRAF Inhibitor Therapy. Haselmann, Gebhardt, Brechtel, et al.Clin Chem. 2018 Feb 26. 

The current standard for determining eligibility of patients with metastatic melanoma for BRAF-targeted therapy is tissue-based testing of BRAF mutations. As patients are rarely rebiopsied, detection in blood might be advantageous by enabling a comprehensive assessment of tumor mutational status in real time and thereby representing a noninvasive biomarker for monitoring BRAF therapy.

In all, 634 stage I to IV melanoma patients were enrolled at 2 centers, and 1406 plasma samples were prospectively collected. Patients were assigned to 3 separate study cohorts: study 1 for assessment of circulating tumor DNA (ctDNA) as part of companion diagnostics, study 2 for assessment of ctDNA for patients with low tumor burden and for follow-up, and study 3 for monitoring of resistance to BRAF inhibitor (BRAFi) or mitogen-activated protein kinase inhibitor therapy.

Overall, a high degree of concordance between plasma and tissue testing results was observed at 90.9% (study 1) and 90.1% (study 2), respectively. Interestingly, discrepant results were in some cases associated with nonresponse to BRAFi (n = 3) or a secondary BRAF-mutant malignancy (n = 5). Importantly, ctDNA results correlated with the clinical course of disease in 95.7% and with response to treatment. Significantly, the detection of BRAF mutant ctDNA preceded relapse assessed by Response Evaluation Criteria in Solid Tumors, and was more specific than serum S100 and lactate dehydrogenase.

Blood-based testing compares favorably with standard-of-care tissue-based BRAF mutation testing. Importantly, blood-based BRAF testing correlates with the clinical course, even for early-stage patients, and may be used to predict response to treatment, recurrence, and resistance before radioimaging under BRAFi therapy, thereby enabling considerable improvements in patient treatment.

Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy. Gonzalez-Cao, Mayo de Las Casas, Jordana, et al. Melanoma Res. 2018 Feb 23.

Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome. In patients with persistent BRAF mutations (n=12), progression-free survival and overall survival were 3.5 months and 5.3 months compared with 16.6 months and 21.9 months in patients with BRAF negativization (n=16), and 15.1 months and NR in patients who maintained their initial negative status (n=12). The median duration of response in patients with radiological response, but persistence of BRAFV600 in early-cfDNA (n=5) was 4 months. Our study indicates that serial BRAF testing in the blood of advanced melanoma identifies patients refractory to therapy.

And these are just a handful of reports!!!   They don't even address other blood assays of which we know a great deal, including CD4+ T cells, microRNA, gene expressions, and circulating melanoma cells. I am just one little woman sitting in Chattanooga, TN!!  With melanoma.  Without a salary for this effort.  But with a computer and basic common sense!  You "melanoma experts" need to do better!!!  Get with the program.  These tests are available, have important implications for melanoma patients, and we need YOU to get on board and start incorporating them in your management of melanoma patients NOW!  Some folks don't have the luxury of waiting around for you to get off your hands!  Liquid blood assays WILL be utilized to diagnosis, monitor and evaluate melanoma patients for appropriate treatment choices!!  They are not likely to be the sole, end-all-be-all answer to all things melanoma, but will certainly be an essential component of basic care.  We need you peeps to make it so...SOONER...rather than later.  C'mon, man!!!!  (It's good that ratties have long tails!  We need them!) - c