PLATO-VTE - an INVENT Endorsed Study, recently completed study recruitment. We sat down for a Q&A with PhD Student & Lead Investigator Dr. Noémie Kraaijpoel to talk about the milestone and next steps for the study.
INVENT-VTE: This is a novel study to evaluate tumor-educated platelets in patients with unprovoked VTE. What motivated you to do this study?
We know from previous studies that in patients with unprovoked venous thromboembolism (VTE), the risk of occult cancer detection is high; about 5% in the year following VTE diagnosis.
Over the past decades, many different approaches to screen for occult cancer have been evaluated in these patients, with the aim to detect an underlying cancer at an earlier, potentially curable stage. Screening strategies are often classified as either ‘limited’ or ‘extensive’, wherein limited screening usually consists of at least a thorough medical history and physical examination, basic blood work-up, and a chest X-ray. The extensive screening strategies commonly combined the limited work-up to more diagnostic imaging (e.g. CT abdomen or whole-body PET-CT) or tumor markers (e.g. PSA, CEA, or CA-125). As the individual studies did not show benefit of an extensive strategy over a more limited approach, current guidance suggests to only perform limited cancer screening in patients with unprovoked VTE.
However, a recent individual patient data meta-analysis of Dr. Van Es and colleagues found that patients receiving extensive screening were two times more likely to be diagnosed with cancer initially than those receiving a more limited screening. This shows that patients with unprovoked VTE may benefit from an extensive screening approach, as it may potentially detect cancer at an earlier stage, thereby possibly reducing cancer-related morbidity and mortality. Yet, as about a quarter of cancers are still missed upon screening, the current techniques used for extensive screening are suboptimal, and novel approaches are needed to identify those patients who may benefit from additional tests.
Biomarkers for cancer are promising screening tools as they avoid radiation and may detect a broad variety of cancers. Platelet mRNA sequencing is a novel pan-cancer detection test, developed by prof. Würdinger and colleagues, which revolves around the mRNA signature of platelets that is altered in the presence of a tumor. The potential of this test was demonstrated in a study of 228 patients with various cancers and 55 healthy donors, in which platelet mRNA profiling was associated with a sensitivity of 97% and a specificity of 94% for detecting cancer. The PLATO-VTE study is the first to clinically evaluate the diagnostic potential of this test. We expect that platelet mRNA sequencing can accurately identify cancers which are missed by the currently recommended limited screening approach.
Now that recruitment for the study is complete, when do you expect analysis to be completed and results to be available?
The last patient has been recruited in July 2019, and 12-month follow-up of this patient will be completed in July 2020. We will hopefully be able to publish the results soon thereafter
In terms of International collaboration, what has your experience been with conducting the study in multiple countries? Were there any notable advantages or barriers that you encountered?
We have been very fortunate to collaborate with a highly dedicated team of researchers in Canada and Europe. Most of the centers previously participated in cancer screening studies and the local investigators really want to move this field forward. Collaboration is key to any large cohort or trial, and I truly believe that it opens doors to new collaborations or studies. I am certain that we will invite the PLATO-VTE group to collaborate in the near future. The only barrier we experienced was from the local Ethics Review Boards, as it sometimes takes several months before study approval is granted
Lastly, in regards to future research, do you have plans for another study to build on the results of this study?
If the PLATO-VTE study shows good diagnostic accuracy of platelet mRNA sequencing for the detection of cancer, the results will be used to design a large randomized controlled trial assessing the efficacy of platelet mRNA sequencing to detect occult cancer in patients with unprovoked VTE.