As knowledge increases, wonder deepens

Despite the growing interest in the field of cancer-associated thrombosis (CAT) in the last years, there are still many open questions awaiting clarification. Most recent clinical practice guidelines highlight the need of further research in different aspects. Hopefully, the launch of ICTHIC Magazine will help to broaden the knowledge, share experiences and eventually improve patient care.

Attractive areas of clinical research to focus attention in future numbers of ICTHIC Magazine could be some of the following:

Stratification of thrombosis risk. To date the only validated tool is the Khorana score. However, its positive predictive value is suboptimal. The addition of biomarkers (for instance D-dimer) or hereditary thrombophilia seems to increase its predictive power but there is still room for improvement. Indeed, selection of at-risk patients is essential to settle the indications of pharmacological thromboprophylaxis in this population.

Bleeding risk assessment. Cancer patients also show an increased bleeding risk compared to patients without cancer. A limitation to assess the risk/benefit balance of thromboprophylaxis is the lack of bleeding scores for this specific population.

VTE prevention. Besides the above-mentioned need of stratification, there is concern about optimizing the use of antithrombotic prophylaxis. The paucity of quality evidence justifies the overall underuse reported by different research groups. Strategies aimed to favor the appropriate prescription of VTE prophylaxis are needed.

Treatment of VTE. Low molecular weight heparins (LMWH) are the drug of choice for the initial and long-term (6 months) treatment of CAT. In patients with active cancer, due to the high incidence of recurrent VTE, prolonged anticoagulant therapy is recommended. The best treatment for the extended therapy is unknown. On the other hand, recent investigations suggest that incidental/unsuspected events should be treated as symptomatic VTE. However, uncertainty exists about optimal management of isolated subsegmental PE or distal DVT. Furthermore, the treatment of CAT can be particularly challenging in some settings frequently found in patients with malignancies such as thrombocytopenia, primary or secondary central nervous system involvement, recent bleeding o recurrent VTE despite anticoagulant therapy. Unfortunately, one cannot expect to count with randomized clinical trials shedding light on these topics in a near future. In return, well-conducted registries may provide data of great value from a clinical point of view.

Role of direct oral anticoagulants (DOAC). In the general population with VTE, DOAC have been shown to be as effective and safer than vitamin-K antagonists. Substudies in the reduced cancer subgroup included in those pivotal clinical trials yielded similar results. However, indirect comparisons beteween DOAC and LMWH are of little value, due to relevant differences in the characteristics of recruited patients. Currently, several phase-III studies comparing DOAC vs LMWH in patients with CAT are ongoing. Their results will definitely clarify this point. But then other questions will gain the interest of clinicians and researchers, for example, do ACOD show antineoplastic properties as suggested for LMWH?

Finally, the benefits of screening for occult cancer in patients with unprovoked VTE have been questioned by some recent reports. However, the impact of an screening strategy may differ in selected populations such as older patients (>50 years-old), in whom the risk of hidden malignancy is higher.

This introductory text for the first issue of ICTHIC Magazine is merely a brief reflection on the many gaps that need to be filled. The scenario may become even more complex since a debate exists over generalization of recommendations to all cancer patients or the need of individualization according to the site of malignancy or the stage.

Multidisciplinary collaborative networking must be encouraged to reach new horizons. This is reponsibility of all stakeholders: researchers, physicians, scientific societies, industry, governments, patients’ associations and society at large.

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