Saturday, July 7, 2018

Circulating tumor cells/DNA in melanoma!!! Have I not mentioned this a ZILLION times????

There are many blood (and other fluid) markers, all much easier to collect that actual tumor samples, that can be used to diagnosis melanoma, determine tumor type, prognosis and response to therapy.  Here's a link to zillions of posts:  Neutrophil-to-lymphocyte ratio and outcomes in melanoma. Yep, AGAIN!!!!!  More here:  Simple blood tests that tells us where we are with our melanoma....AGAIN (and again, and again, and again)!!!

And there is this (with tons of links within) on circulating tumor cells/DNA alone:  ASCO 2017: Circulating DNA to measure response in melanoma

Now, these:

Circulating Tumor Cells in Stage IV Melanoma Patients. Hall, Ross, Bowman, et al.J Am Coll Surg. 2018 May 7.
Management of stage IV melanoma patients remains a challenge. In spite of promising new therapies, many patients develop resistance and progression. The aim of this pilot study was to determine if CTCs are associated with shortened (180-day) progression-free survival (PFS) following a baseline CTC assessment in stage IV melanoma patients.

A baseline CTC assessment was performed in 93 stage IV melanoma patients using a commercially available immunomagnetic system. The presence of greater than/equal to 1 CTC was considered a positive result. A Cox multivariable regression model was used to evaluate the association between presence of CTCs at baseline and PFS, after adjusting for covariables. Kaplan-Meier curves and a log-rank test were used to summarize and compare unadjusted PFS for patients stratified by CTC positivity.

Median follow-up was 17 months; mean age was 55 years. Thirteen of 93 (14%) patients had no evidence of disease (NED) at baseline CTC assessment. One or more CTC was detected in 39/93 (42%) of patients at baseline. CTCs were not associated with primary melanoma features or NED status. Twenty-eight of 93 (30%) patients progressed within 180 days of baseline draw, with 20/39 (51%) of the CTC positive patients relapsing compared to 8/54 (15%) of the CTC negative patients. In adjusted Cox models, a significant association was found suggesting worse PFS within 180 days for CTC positive patients at baseline (vs. CTC negative).

One or more CTCs at baseline were associated with progression within 180 days in stage IV melanoma patients. This information warrants further study of CTCs as a means of identifying patients at high-risk for disease progression.

Measuring circulating tumor cells can predict response and progression!! And, this.....

Quantitative monitoring of circulating tumor DNA predicts response of cutaneous metastatic melanoma to anti-PD1 immunotherapy.  Herbreteau, Vallee, Knol, et al. Oncotarget. 2018 May 18.

Immunotherapies have changed the medical management of metastatic melanoma. However, the early detection of patients who do not respond to these treatments is a key issue. We evaluated the quantitative monitoring of circulating tumor DNA (ctDNA) as an early predictor of response to anti-PD1. Patients treated with anti-PD1 for metastatic mutated melanoma were selected. The somatic alteration detected on the tumor tissue was quantified on plasma DNA by digital PCR (dPCR) at treatment initiation, after 2 and 4 weeks of treatment, and then every 4 weeks until progression. The absence of biological response (defined as a significant decrease in the amount of ctDNA relative to the baseline level) after 2 weeks of treatment was associated with a lack of clinical benefit under anti-PD1. In the presence of a biological response at week 2, detection of subsequent biological progression (significant increase in the amount of ctDNA relative to its nadir) was 100% predictive of progressive disease, on average 75 days prior to radiological detection. Patients with a persistent biological response beyond week 16 did not experience any progressive disease and exhibited sustained responses. In conclusion, we show that quantitative monitoring of ctDNA, using criteria accounting for dPCR measurement imprecision, allows the early and specific detection of patients who do not respond to anti-PD1 therapy.

When circulating tumor DNA was monitored in patients treated with immunotherapy, no significant decrease in the ctDNA measured in the blood was associated with lack of benefit from anti-PD-1 AND an increase in the ctDNA "was 100% predictive of progressive disease, on average 75 days prior to radiological detection."  Think what being able to change treatments, from one that is not working to one that might serve you better, 75 days sooner, could mean for patient outcomes!!!  And, there's this:

Evaluating Circulating Tumor DNA From the Cerebrospinal Fluid of Patients With Melanoma and Leptomeningeal Disease. Ballester, Glitza, Douse, et al.  J Neuropathol Exp Neurol. 2018 Jun 4.  

Circulating tumor DNA (ctDNA) refers to tumor-derived cell-free DNA that circulates in body fluids. Fluid samples are easier to collect than tumor tissue, and are amenable to serial collection at multiple time points during the course of a patient's illness. Studies have demonstrated the feasibility of performing mutation profiling from blood samples in cancer patients. However, detection of ctDNA in the blood of patients with brain tumors is suboptimal. Cerebrospinal fluid (CSF) can be obtained via lumbar puncture or intraventricular catheter, and may be a suitable fluid to assess ctDNA in patients with brain tumors. We detected melanoma-associated mutations by droplet-digital PCR (ddPCR) and next-generation sequencing in ctDNA obtained from the CSF (CSF-ctDNA) of melanoma patients with leptomeningeal disease. There is a strong correlation between mutation detection by ddPCR, the presence of circulating tumor cells in CSF and abnormalities in the MRI. However, approximately 30% of CSF samples that were negative or indeterminate for the presence of tumor cells by microscopic examination were positive for CSF-ctDNA by ddPCR. Our results demonstrate that CSF is a suitable fluid for evaluating ctDNA and ddPCR is superior to CSF-cytology for analysis of CSF in melanoma patients with leptomeningeal disease.

Here researchers are simply noting that the cerebral spinal fluid can be monitored in the same manner blood samples can be.

I have been noting these reports for YEARS!!!!!!!!!!!!!!!!!!  If I am aware of these options, then oncologists should know about these study results and assay possibilities far better than I.  These minimally invasive, but highly informative tests, should be readily available and utilized as part of the arsenal to diagnosis, predict response, determine progression, find appropriate therapy, and ultimately save lives of melanoma patients ~ TODAY!!!!  - c

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