During the ICTHIC webinar “Clinical insights in CAT to include COVID‐19“, prof Andrez Muñoz shared data from the TESEO registry. Here, we summarize the key points of his presentation.
Prof. Muñoz’s presentation and the full webinar are found here.
If you want some more background information on the TESEO registry, please see “The TESEO registry and how it can help patients with CAT.”
The need for a CAT-specific registry
A limited number of randomized clinical trials in cancer-associated thrombosis (CAT) exist regarding treatment and prophylaxis. In addition, the available clinical trials provide limited data of CAT with a limited number of sub-analyses.
Global registries worldwide exist, such as RIETE (NCT02832245), the world’s largest database on patients with venous thromboembolism (VTE), or Garfield (NCT02155491), the global anticoagulant registry in the VTE field. We could obtain some interesting data from these registries that were not observed in the last decade of randomized clinical trials.
For example, we learned that different cancer types are not the same because they carry a different risk of bleeding and thromboembolic recurrence using data from the RIETE registry [1]. This helped our clinical practice.
We know that cancer variables (type of tumor, stage of the disease, etc.) are major drivers for VTE in cancer patients. But we have also learned that molecular data or mutations can impact the patient’s VTE risk.
Recent data showed that specific mutations could modulate the risk of VTE by enhancing or reducing it, such as the IDH1 mutation in gliomas [2]. Additionally, these mutations can have a different impact depending on the tumor being analyzed. For example, the IDH1 mutation that seems to be a protective factor in gliomas does not affect hepatobiliary cancer [2].
Starting from these data, it is clearly necessary to have a specific approach based on cancer variables for cancer patients. In this setting, a particular CAT registry is much needed. Therefore, in 2018, the TESEO registry was initiated. It is a prospective international-specific registry of CAT, promoted by the Spanish Society of Medical Oncologists (SEOM), and includes 43 centers in Spain and two centers in Portugal. It involved 2200 patients by September 2021.
Unpublished data from the TESEO registry
Risk of VTE and cancer type
Data from the TESEO registry show that lung and colorectal cancer are the two leading tumor types [3], which is consistent with the RIETE registry and the randomized clinical trials, such as the Caravaggio trial (NCT03045406). Breast cancer is the third most common neoplasm; it has a low VTE risk but is prevalent in the clinic [3].
A significant risk of VTE is associated with bile duct and gallbladder cancers, which are not common tumors but have a VTE risk comparable to the highest risk tumors (lung and colorectal cancer) and are not included in risk assessment models (as the Korana score) [3].
Risk of VTE and anticancer treatments
Classical chemotherapies are still the leading anticancer systemic therapy, although other systemic therapies are expanding in oncology. The most common drugs are platinum analogs (cisplatin, oxaliplatin, and carboplatin) plus fluoropyrimidines [3].
Checkpoint inhibitors (pembrolizumab and nivolumab) are emerging as common drugs in cancer patients with VTE, as they are the standard drugs used in many cancers. However, we still do not have data to infer their role in enhancing VTE risk because evidence from randomized clinical trials or meta-analyses is still lacking [3].
Risk of VTE over time
It is known that the highest risk for VTE is in the first 6 months from the cancer diagnosis. This is undoubtedly true for pancreatic or lung cancer but not for breast or ovarian cancer. Data show that people with ovarian or breast cancer experience fewer thromboembolic events in the first 6 months after diagnosis, compared to other cancers, but have a long-term risk of VTE, with peaks at more than 20 months after diagnosis [3].
This means that not all patients with cancer face the same pattern of occurrence of VTE, and they do not face the same risk during the cancer journey.
Risk of VTE and cancer stage
The same differences in VTE risk can be observed for the cancer stage. VTE events tend to be early in localized stages with reactivations during relapse. Stage IV cancer tends to have a longer tail of events. Time to thrombosis since cancer diagnosis ranged from 3.8 months (95% CI: 0.8–202) for stage I to 10 months (95% CI: 0–163) in stage IV [3].
In addition, VTE recurrence varies with stage. For example, the median time to recurrent VTE was 0.8 months (95% CI: 0.3–7.7) in stages I–III and 2.0 months (95% CI: 0.3–14.9) in stage IV [3].
VTE risk and cancer histology
Adenocarcinoma is the major risk factor regarding tumor histology. A total of 71% of the patients involved in the TESEO registry have adenocarcinoma, an important VTE risk factor [3].
Despite being very aggressive tumors, squamous cell carcinoma and small-cell carcinoma can be considered low VTE risk histology categories compared with adenocarcinomas [3].
Risk of VTE compared to stage and primary site
For lung cancer patients, almost 80% of events occur in a late stage (stage IV) with poor prognosis; for patients with breast cancer, almost 50% of VTE occur in stages I–III with a good prognosis [3].
For this reason, it is very important to have a specific VTE risk assessment model for patients with breast cancer to provide the correct prophylaxis and limit VTE-related poor outcomes.
Type of event detection
50.3% of the VTE in the TESEO registry were unsuspected, of which 57.1% were truly asymptomatic [3].
The main source of symptoms was the VTE itself (43.8%), followed by the tumor (17.7%) and toxicity related to antineoplastic therapies (2.1%). Also, most patients (60.8%) presented with pulmonary embolism (PE).
Analyzing the 6-month overall survival (OS), unsuspected pulmonary embolism (PE) had a better prognosis than suspected PE. Patients with unsuspected PE with outpatient management (unsuspected asymptomatic PE) have better OS (6-month OS rates of 80.9%, 95% CI, 75.1-87.2) than people with unsuspected PE (with symptoms) hospitalized for a different medical reason (6-month OS rate of 55.9%, 95% CI, 43.8- 71.5) and suspected PE (6-month OS rates of 55.5%, 95% CI, 48.2-64.7) [3].
There is no difference in overall survival between patients with unsuspected PE hospitalized for different medical reasons and suspected PE [3]. These data confirm the better long-term prognosis of unsuspected, truly asymptomatic PE, compared to unsuspected PE with symptoms but admitted for other medical reasons and suspected PE [3].
No significant differences in overall survival have been shown between patients with suspected and unsuspected VTE (OS rate of 9.9, 95% CI, 7.3-non-computable, and 14.4 months, 95% CI, 12.6-non-computable, respectively. p=0.00038). [3].
VTE recurrence
Patients with active cancer have three-times higher risk of recurrent VTE compared with patients with no active cancer, which means that anticoagulation should be maintained in this category of patients, in agreement with the guidelines [3]
In addition, more severe VTE events have a higher recurrence rate than less severe events [3].
VTE and death
In total, 73% of deaths were caused by cancer itself, but 16.3% had a mixed cause, with VTE possibly involved. This highlights the importance of taking VTE risk into special consideration because adequate treatment can prevent it [3].
Conclusion
TESEO registry provides further insights in CAT that complement data from other VTE registries and randomized clinical trials. VTE, recurrent VTE, and bleeding risk in cancer are linked to cancer biology and variables. For this reason, it is important to collect as much specific data as possible to better understand and predict VTE in patients with cancer.
References
1- Mahé I, Chidiac J, Bertoletti L, et al. The Clinical Course of Venous Thromboembolism May Differ According to Cancer Site. Am J Med. 2017;130(3):337-347.
2- Dunbar A, Bolton KL, Devlin SM, et al. Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors. Blood. 2021;137(15):2103-2113.
3- Carmona-Bayonas A, Gómez D, Martínez de Castro E, et al. A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry. Eur J Intern Med. 2020;78:41-49.