Cancer patients are at high risk of suffering a thrombotic event that can worsen their prognosis and quality of life. Researchers from the Research Group on Genomics of Complex Diseases of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, led by Dr. José Manuel Soria, and the Medical Oncology Service of the Gregorio Marañón General University Hospital in Madrid, led by Dr. Andrés Muñoz, within the framework of the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM) have developed and validated a new tool or score, called ONCOTHROMB, which for the first time combines clinical data and genomics of the patient. This tool has shown an excellent predictive capacity of the risk of suffering venous thromboembolic events by cancer patients undergoing chemotherapy outpatient treatment.
One in five cancer patients eventually develops a thrombosis, especially during the first months of treatment. To reduce this risk, alternatives such as low molecular weight heparin or the new oral anticoagulants are currently available on the market. The challenge is to find out which patients can really benefit from this treatment in order to improve their prognosis and at the same time prevent other patients from the risk of bleeding as a result of the treatment.
“Our score is able to identify 34% of patients who will suffer a thromboembolic event, and 94% of those who will not develop a thrombotic event and, therefore, we do not need to treat with anticoagulants” points out Dr. Soria, co-author of this work.
“This new diagnostic tool applies an algorithm, based on the analysis of nine genetic variants of coagulation factors that is combined with three classic clinical risk factors (tumor type, disease stage, and body mass index) of each cancer patient. This makes it possible to identify patients with a high, moderate or low risk level. It is important to highlight that this study is a pioneer in the world in the application of genetics in measuring the risk of thrombosis in cancer”, explains Dr. Andrés Muñoz, co-author of the project.
The study analyzed data from 364 patients from the Spanish ONCOTHROMB 12-01 cohort. As detailed by the researchers, clinical data associated with the risk of venous thromboembolic events were collected at the time of diagnosis, including the Khorana score, which is the only scale available to date to assess the risk of thrombosis in these patients. patients, but whose predictive value is very limited.
In addition, genotypes for the 51 genetic variants known to be associated with thrombosis were studied, and multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to thrombosis risk. The tool has been validated with a cohort of Austrian patients (Vienna-CATS).
The researchers were able to verify that nine specific genetic variants, in addition to the location and stage of the tumor, as well as a body mass index greater than 25 kg/m2 were associated with an increased risk of thrombosis.
“With the new tool provided by this study, it is estimated that cases of thrombosis can be reduced by up to 70% by being able to apply preventive treatments that will prevent their appearance and therefore improve complications and the quality of life of patients. It should also be noted that this complication is more typical of a series of cancers: lung, pancreas, stomach, kidney, ovarian, colorectal, and brain tumor,” says Dr. Muñoz from the Gregorio Marañón Hospital.
The results, published in the prestigious Journal of Clinical Oncology, show that it is an effective tool to help oncologists guide clinical decisions on the optimal intensity of anticoagulant treatment to prevent thromboembolic events in these patients. “We can consider that this scale is the first stone that lays the foundations of personalized medicine in the field of cancer and thrombosis”, in the words of Dr. Soria, lead author of this work.
Thrombosis is a very relevant clinical situation in cancer patients. The mere presence of a tumor already represents an added risk of presenting thrombotic events, but when these patients are also receiving treatment with chemotherapy, the probability of thrombosis is even higher.
Currently, oncologists usually indicate anticoagulant treatment in those patients in whom there is a history of thrombosis, either due to a family history or due to having developed previous events.
One of the great advantages of the ONCOTHROMB scale is that it can be used from the moment of diagnosis. “This tool can be especially useful when cancer is diagnosed, since from a clinical point of view, venous thrombosis in a cancer patient has a very negative impact on survival and quality of life, hence the need to identify as soon as possible the risk of thrombosis in the initial stage of the disease”, says Dr. Muñoz.
“When the oncologist requests a biopsy, an analysis, a PET scan, a CT scan or any other battery of diagnostic tests, he can also request this score to determine the risk of thrombosis. Therefore, when he begins to treat the patient, he could already indicate the anticoagulant in case he needed it ”.
In addition, “it has also been possible to demonstrate that this tool predicts thrombotic events in these patients in the long term, up to 18 months, with which its predictive capacity is much more reliable and useful for clinical practice”, explains Dr. Muñoz.
Currently, both the American and European Societies of Clinical Oncology (ASCO and ESMO, respectively) guidelines indicate that it is important to stratify the risk of thrombosis in cancer patients using validated tools. “Well, here we make our scale available to the scientific community, which will be very useful for this purpose”, concludes Dr. Soria.
This study has been funded by the Carlos III Health Institute, the Spanish Society of Medical Oncology, the Spanish Society of Thrombosis and Haemostasis, and the ActivaTT Association for Health.
Andres Muñoz, Cihan Ay, Ella Grilz, Sonia López, Carme Font, Vanesa Pachón, Victòria Castelló, Virginia Martínez-Marín, Mercedes Salgado, Eva Martínez, Julia Calzas, Laura Ortega, Ana Rupérez, Eduardo Salas, Jose Manuel Soria. Clinical-genetic risk score for predicting cancer-associated venous thromboembolism: a development and validation study involving two independent prospective cohorts. Journal of Clinical Oncology DOI 10.1200/JCO.22.00255
