Glioblastoma - Category, Glioblastoma (GBM)
Conditions
Keywords
LITT, Laser Interstitial Thermal Therapy, ultra-early recurrence, GMB, GMB recurrence, GMB ultra-early recurrence
Brief summary
Glioblastoma (GBM) remains aggressive despite standard therapy (surgery (CRET) + RT/CT). Over 40% of patients develop recurrence between surgery and pre-RT MRI, with median overall survival (OS) of 13.3m and 24.4m for patients with and without recurrence in pre-RT MRI, respectively. Reoperation is avoided as it delays adjuvant therapy. LITT offers a minimally invasive alternative that may: * Treat recurrence without delaying RT/CT * Potentially sensitize tumors to subsequent therapy This study tests if LITT can be practically integrated within the critical 1-week window between pre-RT MRI and radiotherapy initiation, maintaining the adjuvant schedule.
Detailed description
Background: GBM is frequent and still has a poor prognosis. Standard therapy consists of complete resection of enhancing tumor (CRET) followed by RT and CT. At the institution, patients planned for RT undergo a pre-radiotherapy planning MRI. As recently published, \>40% of patients exhibit contrast-enhancing tumor recurrence in the short interval between early postoperative MRI and pre-RT MRI, despite CRET in the initial surgery. This ultra-early recurrence is strongly associated with shorter OS: in the cohort, median overall survival (OS) was 13.3m and 24.4m for patients with and without recurrence in pre-RT MRI, respectively. Hence, pre-radiation GBM recurrence is a frequent event with detrimental consequences for patients. Reoperation in this setting is rarely performed as it delays adjuvant treatment, which worsen prognosis further. LITT is an established, minimally invasive treatment form for brain lesions such as glioblastoma recurrences and metastases. LITT may offer a solution to this dilemma as its minimal invasiveness enables to ablate the recurrent tumor without delaying treatment. As an additional benefit, LITT may work as a potent sensitizer to subsequent RT and CT. A key challenge in the implementation of LITT in this setting is the tight scheduling window (maximum 1 week) between pre-radiotherapy planning MRI and start of radiotherapy. In order not to delay adjuvant treatment, LITT should optimally be performed within this time window. To be feasible, both planning and execution of LITT, including coordination of intraoperative MRI and engineering support, must occur within this short timeframe. This feasibility study aims to prospectively investigate whether LITT can be integrated into the existing care pathway without postponing of adjuvant treatment. This may lay the groundwork for future clinical trials. Objective: The aim is to test feasibility of integrating scheduling, planning and execution of LITT into the standard treatment course of patients with CRET-resected glioblastoma scheduled to receive concomitant radio-chemotherapy. The primary objective of this feasibility study is to evaluate the feasibility of performing LITT for ultra-early recurrence following GBM resection without delaying adjuvant radio-chemotherapy. Secondary objectives are collected to estimate the effect size of pre-RT LITT on median overall survival compared to patients with ultra-early recurrence who do not receive LITT, and to historic controls; the purpose of these endpoints is to guide power calculations of a subsequent phase II trial. Methods: This is a prospective, single-arm, monocentric feasibility study conducted at the University Department of Neurosurgery, Inselspital, Bern. The study is exploratory in nature and aims to generate foundational data for a larger, multi-centric phase II trial. At the University Hospital of Bern, all patients are presented to the tumor board after surgery for brain tumors. All patients with histologically confirmed glioblastoma and without residual contrast enhancement (CRET) meeting the inclusion criteria for study participation will be asked for consent and, where applicable, included in the trial. All patients showing ultra-early recurrence on planning MRI and meeting the inclusion criteria for LITT will be considered to undergo LITT before the beginning of radiotherapy. Patients without recurrence ("no recurrence" group) and patients with recurrence who do not undergo LITT ("recurrence/no LITT" group) will serve as internal control groups.
Interventions
DEVICELITT
Patients undergoing MR-guided Laser Interstitial Thermal Therapy (LITT) between pre-RT MRI and RT.
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed glioblastoma, IDH-wildtype, regardless of MGMT status * ≥18 years of age * CRET * Karnofsky Performance Status (KPS) ≥70 * No contra-indication for radio-chemotherapy * Scheduled for adjuvant radio-chemotherapy at University Hospital of Bern * Able to provide informed consent * No contra-indication for LITT * No pregnancy or active breast-feeding * No known coagulopathy independent of medication * No dissemination or multifocal disease * Patients lacking capacity to consent or considered vulnerable (e.g., minors, those under legal protection) are not included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients who successfully complete the planned treatment | from enrollment to the end of radiotherapy, an average of 8 weeks | Proportion of CRET patients who successfully complete the planned treatment protocol without protocol violation, until the end of radiation therapy. A protocol violation is defined as any of the following: a delay of more than 7 days in the scheduled pre-RT MRI, LITT procedure, or RT initiation, or an interruption of RT due to a LITT-related event. The study teams aims to describe logistical and organizational difficulties (coordination of intraoperative MRI-availability, engineering support). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complications of LITT | from enrollment to the end of radiotherapy, an average of 8 weeks | Any deviation from the normal postoperative course, including any new appearance of blood during LITT MRI, any seeding along the trajectory of the probe, any pathological wound condition such as dehiscence or infection |
| Delay of Radiotherapy | assessed the day of radiation start, ranging from 3 to 6 weeks after GBM resection | Measurement of the time-lag between planning MRI and beginning of radiation, and comparsion to pre-planned radiation start |
| Use of steroids | from enrollment to the end of radiotherapy, an average of 8 weeks | Use of steroids: Binary (yes/no) and, if applicable, dose and duration |
| Evolution of radiation necrosis | from enrollment to the end of radiotherapy, an average of 8 weeks | Any increase of the size of the contrast enhancing lesion |
| Evolution of target lesion | from enrollment to the end of radiotherapy, an average of 8 weeks | Any increase of the size of the contrast enhancing lesion |
| Evolution of pseudoprogression | from enrollment to the end of radiotherapy, an average of 8 weeks | Any increase of the size of the contrast enhancing lesion |
| Time to local recurrence | from enrollment to the end of radiotherapy, an average of 8 weeks | Time from detection of relapse to detection of local glioblastoma recurrence (lesion within/at the borders of the surgical cavity or associated FLAIR/T2 hyperintensity) |
| Time to distant recurrence | from enrollment to the end of radiotherapy, an average of 8 weeks | Time from detection of relapse to detection of distant glioblastoma recurrence (outside the borders of the surgical cavity or associated FLAIR/T2 hyperintensity) |
| Median overall survival | from enrollment to date of death, assessed up to the end of the study period (end of ratiotherapy for the last included patient) | Median overall survival measured from first surgery to death |
| Site of recurrence | assessed the day of radiation start, ranging from 3 to 6 weeks after GBM resection | Spatial position of the recurrence (local adjacent, distant) |
| Recruitment rate | at study completion (date of end of radiotherapy for the last included patient, approximately 2 years after enrollment of the first participant | Proportion of CRET patients who agree to participate |
| Progression rate | pre RT-MRI | Proportion of recruited patients who present with progression on pre-RT MRI |
| Inclusion rate | pre RT-MRI | Rate of recruited patients who agree to receiving LITT |
| Treatment rate | at study completion (date of end of radiotherapy for the last included patient, approximately 2 years after enrollment of the first participant | Rate of recruited patients who receive LITT |
Countries
Switzerland
Contacts
CONTACTPhilippe Schucht, MD
CONTACTAlexis P. R. Terrapon, MD
PRINCIPAL_INVESTIGATORPhilippe Schucht, MD
Inselspital Bern, Department of Neurosurgery
Outcome results
None listed