Our central hypothesis is that the RNA content of TEPs allows for the identification of glioblastoma progression, including the differentiation from pseudo-progression and radionecrosis. For this we plan to use two parallel approaches, i.e. the TEP-…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in platelet RNA profile between blood taken at true progression
and blood taken at pseudoprogression/radionecrosis.
Secondary outcome
Established clinical prognostic factors and TEP-Glioblastoma-score will be
analyzed in univariate and multivariate models of progression free and overall
survival. Also, the effect of temozolomide and radiotherapy on the platelet RNA
profiles will be evaluated by comparing groups of samples collected at moment
of these therapies, and at moments when these therapies are not provided.
In addition, the tumor size will be correlated to the TEP-Glioblastoma-score,
and the levels of individual platelet RNAs.
Finally, gene ontology analyses will be performed, aiming to elucidate involved
molecular pathways in the platelets as a response to the intracranial tumor
status, including DAVID GO, and PANTHER GO, as described and performed by us
previously.
Background summary
Glioblastoma is one of the most lethal of all cancers with a median prognosis
of 16-18 months. The current standard of care consists of maximal safe
resection followed by combined radiation therapy with temozolomide chemotherapy
and adjuvant temozolomide courses. Due to its infiltrative growth pattern
glioblastomas virtually always recur sooner or later. Therapeutic options for
patients depend largely on interval between recurrence and initial treatment.
To make treatment decision even more complex in virtually all patient*s new
contrast-enhancing lesions will appear on the MRI scan at some point during
follow-up. Notably, not all new lesions denote tumor progression. During the
course of the disease up to 66% of patients experience contrast-enhancing
lesions on the MRI scan that resolve spontaneously over time without additional
treatment. These lesions result from therapy-induced radionecrosis and/or
oedema formation, a phenomenon also known as glioma pseudo-progression.
Follow-up with MRI scans is currently the standard to discriminate both
entities, but consequences of misdiagnosis may be severe, e.g. premature
therapy abrogation on one hand, too early or too late start of new treatment on
the other. More innovative approaches to discriminate these two very different
identities are urgently needed, at which stage liquid biopsies may offer a
potential solution. Blood platelets carry valuable up-to-date information on
glioblastoma-status as they are replenished every 7-10 days.
Study objective
Our central hypothesis is that the RNA content of TEPs allows for the
identification of glioblastoma progression, including the differentiation from
pseudo-progression and radionecrosis. For this we plan to use two parallel
approaches, i.e. the TEP-Glioblastoma-score and the *progressor versus
non-progressor*-test. Further validation of these platelet RNA-based scores may
provide an easily accessible companion diagnostics
test that could solve the most urgent need in management of glioblastoma
patients, e.g. reliable establishment of tumor progression, to date.
To test our hypothesis, we will collect longitudinal blood samples from
glioblastoma patients in two different countries, that is The Netherlands and
the United Kingdom. Samples collected in the Netherlands will be employed for
further optimization of both tests, aiming to reach >95% accuracy to correctly
detect the patient*s tumor status. Samples collected in the United Kingdom will
serve as an external validation series to confirm the generalizability of both
tests.
Study design
Investigator-initiated, observational study
Study burden and risks
A maximum of 18 mL of blood will be collected on average five times per
patient, depending on survival. Venipuncture can result in temporary pain and
the formation of a hematoma. We consider these effects to be relatively mild,
especially considering that on most occasions, blood will have to be drawn
anyway. We do not expect that the extra volume of blood taken will cause any
noticeable discomfort.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Radiologic suspicion of high grade glioma on MRI
Eligible for resection
Older than 18 years of age
Dutch speaking
Exclusion criteria
Known malignancy elsewhere in the body
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84923.000.24 |