During our webinar “Update on Oncology & Thrombosis to include COVID‐19”, the interest from the audience was so high that we decided to report the discussion that emerged from the presentation.
Dr. Font presented an update from the EPIPHANY study
Cancer has been found to be an independent predictor of death (overall 30-day mortality) in patients with acute pulmonary embolism (PE). Approximately 50% of cancer-related PE is unsuspected (UPE) or incidentally diagnosed. The EPIPHANY project aimed to:
- Identify clinical and radiological variables potentially predictive of adverse outcomes in cancer patients with PE
- Develop a specific risk-stratification model for patients with cancer-related PE, including acute symptomatic and incidental events.
The study provided new information regarding the clinical features and clinical and radiological variables to predict outcomes within 15, 30 and 90 days in patients with cancer-associated PE.
The data presented by Dr Font confirm that UPE accounts for up to 50% of PE diagnoses in cancer patients (58% in our cohort). Two risk assessment models have been developed to stratify cancer patients with PE:
- The EPIPHANY Risk: 6 covariates – electronic support
- The ‘4S’ rule (setting, suspicion, symptoms, signs) using bedside variables
These novel proposed models should be validated in external prospective cohorts. However, they may be useful for risk stratification in patients in prospective interventional trials for the selection of patients with cancer-associated PE for outpatient management and the assessment of optimal ‘3D’ anticoagulation: Drug–Dose–Duration.
Questions and answers
Question: Could you comment on treatment with DOAC vs LMWH?
Dr Font: Almost all the patients included in the EPIPHANY received low-molecular-weight heparin (LMWH) during the first 3 months since the inclusions ended in 2014 when direct oral anticoagulants (DOACs) were not yet used in this population. Some patients received fibrinolytic or unfractionated heparin.
Question: Was there a risk stratification by an underlying cancer diagnosis (advanced, metastasis), other comorbidities in UPE?
Dr Font: We compared the baseline characteristics (Figure 1) according to the different proposed work-up scenarios (‘4S’ rule) in the prospectively assessed group of 497 patients.
Figure 1: baseline characteristics according to the different proposed work-up scenarios (‘4S’ rule) in the prospectively assessed group of 497 patients.
Of note, the proportion of metastatic disease was greater in patients with UPE (80% in truly asymptomatic UPE [TA-UPE] and 86% in UPE with symptoms [UPE-S]) compared with patients with symptomatic PE with 73% of patients with metastatic cancer (p=0.016; Figure 2).
Figure 2: Baseline characteristics in 497 prospectively assessed patients according to work-up scenarios
In the inclusion criteria for the study, we included patients with active cancer (localized or metastatic) or patients receiving adjuvant chemotherapy (no other adjuvant therapies or patients with cancer in remission).
Apart from the presence of symptoms, vital signs and inpatients vs outpatients, there were differences in the three groups regarding: Eastern Cooperative Oncology Group (ECOG) performance status (better in the TA-UPE group), surgery (greater in the symptomatic PE group), and chemotherapy and biological therapies, which were more common in the TA-UPE group.
Interestingly, no differences were observed regarding the comorbidities studied (chronic obstructive pulmonary disease, chronic heart disease, venous thromboembolism history).
We compared the 30-day mortality rates and the overall survival according to the three scenarios without risk stratification for other variables.
Question: Was the location of the PE different between symptomatic vs asymptomatic? Did asymptomatic PE involve smaller branches of the pulmonary arteries?
Dr Font: In Figure 2, the radiological findings show that patients with acute symptomatic PE had bilateral lung involvement, multiple and troncular PE more frequently, whereas lobar and segmentary PE in more proximal locations were more frequent in the TA-UPE.
Prof Wang spoke about drug–drug interactions (DDIs) in the real-world setting
Drug–drug interactions are commonly cautioned but with very little data to guide best practice. Multiple concurrent drug therapies that could have DDIs is also common in the real-life setting.
There is a need for research to investigate and prioritize relevant DDI, outcomes of DDI, and optimal monitoring and management strategies. In addition, it is recommended to review concurrent medications for possible DDIs.
If you want to read more on DDIs, check out “Investigating the drug−drug interactions occurring in cancer-associated thrombosis: use of checkpoint inhibitors and direct oral anticoagulants in a real-world setting.”
Questions and answers
Question: What do you think about the thrombotic risk of checkpoint inhibitors?
Prof Wang: There are a few of post-marketing studies that highlight a higher risk of thrombosis with these drugs compare to what declare by initial pre-marketing studies. So certainly we need to continue researching on these drugs and we need to be aware about the risks.
Question: If you have a colon cancer patient stage IV, with a KRAS mutation and with deep vein thrombosis (DVT), will you start DOACs and stop bevacizumab?
If the patient has DVT, I would certainly start an anticoagulation treatment, but the type of anticoagulant depends on the patient and the cancer type. To stop bevacizumab, we need to look at the patient and consider the cancer type to understand risk and benefits of interrupting the therapy. It is important not to compromise the patient’s treatment. An individualized approach is the best.
Question: In terms of safety, should platelet count cut-off triggers for platelet transfusion be adjusted according to different drug–drug interactions and cancer/tumor location (i.e., brain, GI tract)?
Prof Wang: This is certainly a great question and, this is commonly encountered in cancer patients. Unfortunately, we do not have strong evidence for the best management of anticoagulation in patients with thrombocytopenia, let alone when DDIs are a concern. I can provide you with what I do in my personal practice; however, this is not the only answer, and am happy to hear what others have done. I typically follow the 2018 ISTH guidance document on the treatment of cancer-associated thrombosis in patients with thrombocytopenia (https://doi.org/10.1111/jth.14015), and without further data to support this, I have not routinely adjusted platelet cut-off triggers for specific tumor locations or DDIs. In patients where the concern of bleeding risks is high due to DDIs, typically change of potentially interacting drugs, if possible, could be considered, after discussion with patients and his/her oncologist.
Prof Carrier shared the latest updates on COVID-19 and thrombosis
Prof. Carrier explained the evidence about the risk of venous thromboembolism (VTE) in patients with COVID-19 and discussed recent evidence for the prevention of VTE in hospitalized and critically ill patients with COVID-19.
We highly recommend you join our community and watch Prof. Carrier’s presentation here.
Questions and answers
Question: Is there any advocacy for half therapeutic dosing (75–100 IU/kg once daily) in COVID-19 ICU patients?
Prof Carrier: There is no randomized controlled trial evidence to support half therapeutic dosing in COVID-19 ICU patients, but it is controversial. The REMAP-CAP group is currently carrying out a randomized trial comparing prophylactic to intermediate dosing in COVID-19 ICU patients. Hopefully, we will have prospective data soon.
Question: What is your opinion regarding the use of DOACs in these patients?
Prof Carrier: I would only use DOACs if the patients are already on a DOAC at the time of hospitalization for COVID-19 (e.g., atrial fibrillation). If the patient is not already on anticoagulation, I use LMWH (or unfractionated heparin) for thromboprophylaxis. Heparinoids may have additional benefits than just anticoagulation (decrease viral entry, NETs, etc).
Question: These results are largely unexpected. Based on virtually all uncontrolled studies so far available, most international guidelines recommend against full-dose anticoagulation in COVID-19 patients free from thrombosis. Do you think that these studies have the potential to change clinical practice?
Prof Carrier: Yes. I think that upon publication, clinical practice guidelines will change. The pre-print manuscript should be available in a couple of weeks.
Question: How do you adjust the heparin dose in the presence of thrombocytopenia?
Prof Carrier: I do not use therapeutic dosing of LMWH in patients with platelet counts <50. Intermediate or prophylactic dosing is reasonable in patients with platelet counts between 20 and 50. Anticoagulation should be held in platelet counts <20.
Question: What do you think about aspirin in the pre-hospitalization phase?
Prof Carrier: It is a good hypothesis. Many studies are currently assessing anti-platelets in different settings (ICU, moderately ill, pre- and post-hospitalization). Hopefully, we will have more data soon.