Saturday, February 24, 2018

More blood tests to determine prognosis as well as response to therapy in melanoma patients!!!

It is becoming more and more clear (at least to me!!!!!!!!!) that there are all sorts of ways of looking at blood markers in order to diagnose, predict progression and response, as well as evaluate response to a particular treatment in melanoma patients.  Here is my latest post with a zillion links within:  Circulating tumor DNA to help differentiate true progression of melanoma vs pseudoprogression in patients treated with anti-PD-1  Now, there's this ~

Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. Zager, Gastman, Leachman, et al.  BMC Cancer. 2018 Feb 5.

The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients.

This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival.
The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively. The GEP was a significant predictor of RFS and DMFS in univariate analysis , along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status . GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate .

The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

Think how great this sort of information would be when trying to determine whether or not to utilize adjuvant therapy!!!

But, that's not all!  There's also this ~

Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy.  Hong, Sullivan, Kalinich, et al.  Proc Natl Acad Sci U S A. 2018 Feb 16.

A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival and overall survival. Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.

Wouldn't it be great to know where you stand 7 weeks into therapy?  You wouldn't waste time (and in melanoma world that "time" can make all the difference!!!) with a therapy that is not working for you!!!

Blood draws with more detailed info than repeated radiological studies!!!  C'mon man!!!  Let's get some consensus and make these tests available for patients in need! - c

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