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DOACs in Brain Cancer?

Brain tumours have a risk of venous thromboembolism ranging between 15% and 30%.

For a long time in these patients the treatment of choice has been with LMWH, which has been shown to be more effective in the treatment of venous thromboembolism than warfarin.

Although direct anticoagulants (DOACs) are now widely used in cancer patients, there is limited data to support their use in patients with primary and metastatic brain tumours.

DOAC registration studies have included very few patients with brain tumours and there are currently no ongoing randomized trials in these patients.

In some categories of neoplastic patients (e.g., digestive, or gynaecological neoplasms), DOACs have been shown to be less safe than EBPM, with higher bleeding rates.

The risk of spontaneous bleeding from a brain tumour is far from negligible and the doctor prescribes anticoagulation at therapeutic doses in these patients, always with some apprehension.

Two retrospective studies compared the bleeding risk in patients with VTE and brain neoplasia (in 50% glioblastoma multiforme) taking DOAC (mainly rivaroxaban) and LMWH.

Even if the limited number of patients (about 300) does not allow relevant statistical analyses, the interesting data that emerges is that the number of major bleedings during anticoagulant therapy was significantly lower in patients in DOAC than in patients with LMWH (9% vs 26 %).

The few cerebral haemorrhages, of mild severity, were fewer in the group of patients treated with DOAC (4.5% vs 15%) and mainly in patients with primary brain neoplasia.

The only fatal intracranial haemorrhagic occurred in a patient with cerebral glioma in LMWH.

There were few bleeding events in patients with liver metastases.

There were no significant differences between DOAC and LMWH with regard to minor bleeding or thrombotic recurrence.

These results are encouraging, a retrospective cohort presents a strong bias related to patient selection.

The healthcare provider may have chosen to use LMWH in the most critically ill patients and therefore at greater risk of bleeding.

The ASCO guidelines do not place a contraindication to DOAC treatment in patients with VTE and brain cancer.

Currently the most important case series is in patients treated with rivaroxaban.

Diaz M, Jo J. Venous Thrombotic Events and Anticoagulation in Brain Tumor Patients. Curr Oncol Rep. 2022 Apr;24(4):493-500.

Swartz AW, Drappatz J. Safety of Direct Oral Anticoagulants in Central Nervous System Malignancies. Oncologist. 2021 May;26(5):427-432

Lee A, Oley F Jr, Lo M, Fong R, McGann M, Saunders I, Block S, Mahajan A, Pon TK. Direct oral anticoagulants or low-molecular-weight heparins for venous thromboembolism in patients with brain tumors. Thromb Res. 2021 Dec;208:148-155.

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Francis CW, Gates LE, Kakkar AK, Levine MN, Liebman HA, Tempero MA, Lyman GH, Falanga A. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520.

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