Venous thromboembolism in metastatic castration-resistant cancer patients

[pjoshea13]

New Italian study below [1].

"Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC.

"This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio(SHR).

"At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12months of 17.1% ...

"Elevated ptDNA, visceral metastasis, prior chemotherapy and LDH were significantly associated with higher VTE incidence compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, ... 44.4 vs 14.8% ... 24.7 vs 4.5% ... and 30.0 vs 13.5%.., respectively).

"In the multivariate analysis including ptDNA level, visceral metastases, number of lesions, serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78 ...).

"These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA."

***

21 out of 180 is high!

Instead of waiting until one needs to get the ER ASAP, why not monitor D-dimer? Although it can be elevated for other reasons, zero means no blood clot.

Nattokinase can be used to control D-dimer, or one can ask for an anticoagulant. Note that nattokinase dissolves clots, whereas anticoagulants increase clotting times.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/346...

Int J Cancer

. 2021 Oct 3. doi: 10.1002/ijc.33834. Online ahead of print.

Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients

Vincenza Conteduca 1 2 , Emanuela Scarpi 1 , Daniel Wetterskog 3 , Nicole Brighi 1 , Fabio Ferroni 1 , Alice Rossi 1 , Alessandro Romanel 4 , Giorgia Gurioli 1 , Sara Bleve 1 , Caterina Gianni 1 , Giuseppe Schepisi 1 , Cristian Lolli 1 , Pietro Cortesi 1 , Federica Matteucci 1 , Domenico Barone 1 , Giovanni Paganelli 1 , Francesca Demichelis 4 , Himisha Beltran 5 , Gerhardt Attard 3 , Ugo De Giorgi 1

Affiliations collapse

Affiliations

1 IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014, Meldola, Italy.

2 Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy.

3 University College London Cancer Institute, London, UK.

4 Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.

5 Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

PMID: 34605002 DOI: 10.1002/ijc.33834

Abstract

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio(SHR). At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12months of 17.1% (95% confidence interval [CI] 10.3-23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and LDH were significantly associated with higher VTE incidence compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, P=.0003; 44.4 vs 14.8%, P=.015; 24.7 vs 4.5%, P=.006; and 30.0 vs 13.5%, P=.05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions, serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95%CI 1.63-20.44, P=.006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA. This article is protected by copyright. All rights reserved.

Keywords: AR-directed signaling inhibitors; biomarker; metastatic castration-resistant prostate cancer; plasma tumor DNA; venous thromboembolism.

This article is protected by copyright. All rights reserved.

[lcfcpolo]

Hi Patrick. Thank you for posting this. I'm in the category of having recurring DVTs before my diagnosis. Indeed it was only after my second DVT that my PSA was checked and the rest is history. Advanced Prostate Cancer, as my PSA was 1,311.I take the anticoagulant, Apixaban (Eliquis). I guess I have 3 thoughts:

1. Everyone with Prostate Cancer (PC) diagnosis, please do ask for D-dimmer tests regularly or at least monitor very closely. This report appears to confirm this risk is real.

2. Nattokinase. Are there any reports / papers that this is safer or more advantageous than using a anticoagulant if treating existing DVTs when you have PC?

3. Are there any other treatments, Standard Of Care or otherwise that may benefit a patient who has Advanced PC and has recurring DVTs. Thank you.

[pjoshea13 in reply to lcfcpolo]

Nattokinase has a similar structure & function as plasmin. While plasmin will get rid of a clot eventually (perhaps in months), it can only work if future clotting is inhibited. Anticoagulants allow plasmin to do its slow job, but they are double-edged swords. An accident might lead to a bleed-out. With Warfarin, a handful of vitamin K caps or a K injection will quickly restore normal coagulation. With the newer more-favored drugs, I don't know what the protocols are.

It has been many years since my double DVT. 3 months of Warfarin allowed one vein to clear. I was supposed to do 6 months but my doctor allowed me to switch to nattokinase. My n=1 trial convinced me that it works - & I do feel that it is safer, since my coagulation time is normal.

-Patrick

[MateoBeach]

PtDNA seems to be the way to assess for carcinogenic DVT and the need for anticoagulant prophylaxis.

[Hidden]

Thanks, Patrick. How much nattokinase do you take? I have capsules made by Zenavea that are 2,000 FU (100 mg). Do you think 1/day is enough?

[pjoshea13 in reply to Hidden]

You have to monitor D-dimer to find out what you need. I have to take 6 x 2,000 FU before bed. There is no standard dose.

-Patrick

[Hidden in reply to pjoshea13]

Thanks, Patrick. Let's see if the doctor will order a D-dimer!