Discussion
death, tumor, bleeding, epilepsy, edema, hydrocephalus, DVT, neurological deficits, glioblastoma, CFS
DISEASE PROGRESSION, TUMOR, BLEEDING, POST-OPERATIVE HEMORRHAGE, EPILEPSY, EDEMA, DISEASE, HYDROCEPHALUS, RECRUITMENT, COMPLICATION, CYSTIC DEGENERATION, CSF LEAKAGE, LEAKAGE, GLIOBLASTOMA, COMPLICATIONS, DVT
The main findings of this pilot study are: (1) randomization seems feasible in this patient population and adherence to the study protocol and follow-up procedures was good; (2) combining stereotactic biopsy with LITT in the same session is feasible and does not cause any delay in planning surgery or starting adjuvant therapy; (3) the safety profile of the procedure appears in line with results reported in literature for LITT [The inclusion rate of screened patients was 66%, and most of them (85%) were willing to be randomized, which shows that patients are motivated to participate to the study. None of the patients withdrew after the treatment, which suggests that the follow-up procedures were well tolerated. As inclusions were considerably hindered at the beginning of the trial due to the COVID-19 pandemic, our recruitment rate was lower than anticipated with 18 patients in 15 months instead of 20 patients in 12 months.Two serious complications (CD ≥ 3) occurred in two LITT patients. One case of post-ablation edema leading to hydrocephalus necessitating shunting and new neurological deficits, and one case of progressive post-operative hemorrhage resulting in death. Post-ablation edema is a known complication in LITT (8.82–35.5%) [Other reported AEs such as DVT and epilepsy were not considered directly related to the procedure as all of them presented more than 30 days after ablation and are often described in patients with glioblastoma [Median KPS and mean QoL scores seem to worsen and mean tumor volumes seem to increase over 3 months in both groups. This probably reflects the aggressive and progressive nature of the disease. No conclusion on differences between the two groups can be drawn given the number of included patients. Even though a trend toward less growth with stable median KPS and quality of life was noticed, an appropriate powered study is necessary to determine the effect of LITT on disease progression.This feasibility study helped the design of a full-scale multicenter RCT. Five key lessons emerged from our pilot study.First, multifocality and cystic degeneration were initially considered as exclusion criteria, in line with previously published series [Second, after the post-operative hemorrhage complication, an amendment to the study protocol was made to interrupt the procedure in case of significant bleeding after biopsy. We are aware that in some centers biopsy and ablation are performed in two different sessions, but in our opinion this approach causes several disadvantages, exposing patients twice to a surgical procedure and general anesthesia, delaying the start of adjuvant therapy and incrementing costs.Third, we noted that prevention of peroperative CSF leakage is essential to avoid laser misplacement. In one case an intraoperative revision was necessary because of an inadequate laser probe position. The inaccuracy was probably due to a combination of a navigation registration error and perioperative cerebrospinal fluid (CFS) leakage, and we were able to correct the position by navigating on the intraoperative MRI. We therefore advise to use the intraoperative MRI scan in case of replacing the probes.Fourth, evaluation of real ablation volume on post-operative MRI is challenging in patients with glioblastoma, as ablation zone appears as a peripherally enhancing rim on T1-weighted contrast-enhanced images [Fifth, 2 out of 14 patients (14%) were unable to complete the QoL questionnaires since their clinical condition was too poor or because the patient had died. In future studies, it should be considered that data on QoL from the clinically most compromised patients might be incomplete.The major strength of our study is that, as far as we are aware, this is the first prospectively controlled (feasibility) study for LITT in patients with newly diagnosed glioblastoma. As opposed to previous non controlled series, we provide more reliable insights in general applicability of this technique and practicability of designing a larger clinical trial in this population. The most important limitation of this pilot study is the small sample size collected from a single center limiting any precise comparison between groups or extrapolation to other centers. Furthermore, the recruitment rate was affected by the COVID-19 pandemic, so some uncertainty remains about the inclusion rate in the future.