Safety and feasibility of the use of cryoablation in patients with brain neoplasm

There are only limited surgical treatment options like microneurosurgery or
biopsy for brain tumors . However, very recently several cases have been
presentedin the literature using a cryoablation technique. Cryoablation offers
precise and safe lesion targeting with minimal blood loss, is minimally
invasive and the ice-cone formation within the tumor can be monitored by
several imaging techniques. Cryoablation could also potentially be used for
non-resectable tumors. Furthermore, cryoablation could have a potential
immunological effect in some malignant brain tumors and have been shown to open
blood brain barrier which could be very interesting for drug targeting.
Cryoablation could thus be of high value in the minimal invasive treatment of
several brain tumors.

This study is performed to investigate the safety and feasibility of
cryoablation during operation in adults in several brain tumors like gliomas,
meningiomas, and brain metastasis. The primary objective is to assess safety in
terms of complications rate & morbidity and feasibility, such as operation
time, blood loss during intervention and practicability. The secondary
objective is to analyse the confirmation of reaching macroscopic tumor edges
using intraoperative ultrasound or CT-scan, progression free survival, and
overall survival during the entire study period.

This study is set up as an open label, prospective pilot study (Phase I study).
The study will include 30 patients with gliomas, meningiomas, or brain
metastasis in at the ErasmusMC brain tumor center. In all patients, the tumor
will be operated conform standard procedure. Upon exposure of the tumor, a
biopsy will be taken. Then one or a number of cryoprobes that will be required
for tumor ablation will be inserted in the tumor. After proper positioning, the
cryoablation will start. The ice formation will be monitored continuously,
using cone-beam CT and/or intraoperative ultrasound. Prior to cryoprobe
placement, there will be one scan. During cryoprobe placement, a variable
number of scans may be necessary. After cryoprobe placement, there will be one
scan to confirm the position. Additionally, there will be one scan during each
freezing cycle (1 or 2 cycles per operation), and one scan after removing the
cryoprobes. The duration of each freezing cycle will be a maximum of 10
minutes, followed by active thawing. After resection of the necrotic tumor, the
patients will receive the standard treatment and follow up.

See study design

All patients included in this study will receive the same (neo-)adjuvant
therapy (if necessary) as patients who did not participate in this study.
Depending on the size of the tumor, cryoablation takes approximately 30 minutes
to complete. However, we expect that the total operating time will be
considerably shorter as the cryoablation effect on the tumor should shorten the
tumor resection time. Cryoablation is already used for the treatment of
prostate carcinoma, kidney carcinoma and several lung cancers often with better
results than other surgical treatments. Although only few clinical cases have
been published, cryoablation seems not to increase complications or mortality
rates in brain surgery.
Patient with brain tumors could benefit significantly from this therapy in
terms of operation time and blood loss. Cryoablation could also potentially be
used for non-resectable tumors or very vascularized tumors. Furthermore, the
supposed immunological effect and opening of the blood-brain barrier could be
very interesting in combination with adjuvant therapies in the future.
Regarding the use of cone-beam CT: by taking additional scans, the placement of
cryoprobes can be even more precise, increasing the possibility of achieving a
larger ablation zone. Additionally, cryoablation is often performed with the
assistance of cone-beam CT in other pathologies. Considering the age (often
60+) and limited life expectancy of a significant portion of the patients
(including glioma patients and patients with brain metastases), it can be
assumed that the radiation burden is acceptable.