Neutrophil-to-Lymphocyte ratio [NLR] & Abiraterone.

[pjoshea13]

New Japanese study below.

I reviewed the NLR-PCa literature as of a year ago in:

"Inflammation. [1] Neutrophil-to-Lymphocyte Ratio [NLR]".

Basically, as with other markers of inflammation, the NLR is predictive of survival, regardless of type of treatment.

I believe that, while cancer creates the inflammatory environment, inflammation is not just an indication of how bad things are, but a condition that should be treated. The root cause is chronic activation of pro-survival NF-kB (nuclear factor-kappaB). Inhibit NF-kB & many pro-survival proteins will be inhibited. The pro-inflammatory enzymes that operate on the arachidonic acid in the PCa lipid rafts will be inhibited. & a reduction in inflammation markers will be indicative that heat has been taken out of the cancer. This should ultimately be reflected in survival stats.

In the new study of CRPC men taking Zytiga:

"The NLR cut-off point was determined to be 3.76 for the OS, and divided into the high NLR group of 34 patients and the low NLR group of 56 patients. A PSA response was obtained in 8 patients (23.5%) in the high NLR group and in 24 (42.9%) in the low NLR group."

"a high NLR [NLR ≥3.76; median OS: 8.4 months ... 6.325-10.475 months] was correlated with a risk of mortality compared with a low NLR (NLR <3.76; median OS {overall survival} not reached)."

NF-kB inhibitors include any & all of the usual polyphenols that are taken by men with PCa.

Nalakrats achieved a C-Reactive Protein level of zero with his regimen. Unheard of. Everyone seems to have some degree of subclinical inflammation. He hasn't reported his NLR, but it is probably very low. The lower the better. & I believe that it can always be driven lower.

Inflammation is easy to monitor, & it is easy to see if a handful of polyphenols has an effect on it.

-Patrick

ncbi.nlm.nih.gov/pubmed/295...

Mol Clin Oncol. 2018 Apr;8(4):592-594. doi: 10.3892/mco.2018.1573. Epub 2018 Feb 13.

Baseline neutrophil-to-lymphocyte ratio predicts the prognosis of castration-resistant prostate cancer treated with abiraterone acetate.

Yasui M1, Hasegawa Y2, Kawahara T1, Kumano Y1, Miyoshi Y1, Matsubara N2, Uemura H1.

Author information

1

Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama 232-0024, Japan.

2

Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan.

Abstract

Abiraterone acetate (AA), a CYP17 inhibitor, now has a crucial role in the treatment of castration-resistant prostate cancer (CRPC), and previous studies have reported several prognostic clinical factors for AA treatment. The neutrophil-to-lymphocyte ratio (NLR) has also been investigated for a CRPC treatments in a few reports, however it has not been identified to be a prognostic factor for AA treatment in Japanese patients. The present study aimed to assess the association of the baseline NLR with the overall survival (OS) in CPRC patients treated by AA. The present study retrospectively reviewed a total of 90 consecutive patients with CRPC treated with AA from 2011 to 2016 at Yokohama City University Medical Center and National Cancer Center Hospital East. The primary endpoint of the study was the OS, which was defined as the survival from the start of AA administration. The secondary endpoint was the prostate-specific antigen (PSA) response. PSA response was defined as a reduction in antigen levels of >50%. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days prior to the initiation of AA therapy. The NLR cut-off point was determined to be 3.76 for the OS, and divided into the high NLR group of 34 patients and the low NLR group of 56 patients. A PSA response was obtained in 8 patients (23.5%) in the high NLR group and in 24 (42.9%) in the low NLR group. The difference of PSA response between the two groups was significant (P=0.037). Kaplan-Meier curves demonstrated that a high NLR [NLR ≥3.76; median OS: 8.4 months; 95% confidence interval (CI): 6.325-10.475 months] was correlated with a risk of mortality compared with a low NLR (NLR <3.76; median OS not reached). A multivariate analysis demonstrated that the NLR was an independent predictor for the OS (hazard ratio: 2.682; 95% CI: 1.143-6.293; P=0.023). The findings suggest that the NLR may be a useful novel biomarker for predicting the prognosis of CRPC patients treated with AA.

KEYWORDS:

CRPC; NLR; abiraterone acetate

PMID: 29541468 PMCID: PMC5838297 DOI: 10.3892/mco.2018.1573

[snoraste]

Patrick,

Am I reading it correctly that it suggests a somewhat direct link between “diet” and OS?

[pjoshea13 in reply to snoraste]

I didn't get a connection.

But a high omega-6 & omega6:3 ratio intake will create a pro-inflammatory state.

In particular, the lipid rafts will be comparatively loaded with arachidonic acid. Which means PCa cells will be on an inflammatory hair trigger.

But NF-kB is the core problem, since it is always activated.

-Patrick

[snoraste in reply to pjoshea13]

I guess my confusion is the connection between NF-kB inhibitors, such as polyphenols, to lowering of NLR, which leads to a better clinical OS. If you believe they did their selection and math right, wouldn’t that be a rational conclusion (impact of diet on OS)?

[pjoshea13 in reply to snoraste]

I see what you are saying, but one would need pharma-levels of polyphenols to control cancer-activated NF-kB IMO. -Patrick

[snoraste in reply to pjoshea13]

Perhaps. But clearly there’s a correlation and that’s the real interesting part to me. It also appeals to me intuitively based on my personal experience. My PSA doubled in sep2017 in about a month and a half till mid Oct. I started my new regiment of diet and exercise right at that point, and the next PSA reading the following month was lower. No other medications or hormone therapy in the interim. So while a far cry from the scientific proof, it’s certainly telling something about my individual response in the short term. That’s why I was intrigued by your post.

[snoraste]

Also a second question, how do you clinically measure the ratio?

[Hidden in reply to snoraste]

These are checked in the White Blood Cell Differential blood test. It's a fairly standard blood test, especially for cancer patients undergoing treatment. And then it's just a simple calculation N/L.

[snoraste in reply to snoraste]

I figured it out - never mind this question

[Hidden in reply to snoraste]

I just did mine for the heck of it:

N= 3K

L= 3.9K

Ratio = .77

[snoraste in reply to Hidden]

Mine shows as percentages - I thought it was the ratio of the percentages -

[Hidden in reply to snoraste]

You need the absolute count. That is sometimes not provided.

[snoraste in reply to Hidden]

I’ll follow up with my doc - thanks

[Hidden in reply to snoraste]

I screwed up, it's not the Complete Blood Count, the test is the White Blood Cell Differential. Many times these are done together, but they are separate tests.

[snoraste in reply to Hidden]

Figured it out on my labs - it’s listed as absolute lymph and neut.

[Hidden]

Thanks Patrick.

I read about this last year. Here's another more general article on subject:

ncbi.nlm.nih.gov/pmc/articl...

[gusgold]

Nalakrats claims to have a C-Reactive Protein level of 0 but Nal's daughter sent me a recent pic of Nalakrats because she is worried he has gone off the deep end

Gus

thumbs.dreamstime.com/z/cra...