Intracerebral immunotherapy for brain tumors.

e13522 Background: Immunotherapy is a promising approach for the treatment of brain tumors, but available data are still inconclusive. The main drawback is represented by transport across the blood–brain barrier of high molecular weight drugs. Convection-enhanced delivery (CED) has been designed to overcome some difficulties. We wondered whether a CED strategy based on the use of novel immune checkpoint inhibitors could be effective. Methods: Frameless biopsy by fluorescein tracer and neuronavigation-assisted system, followed by an injection of nivolumab 40mg/4mL into the brain lesion, were offered to patients with: a) high grade gliomas (HGG) inoperable or progressed during or after standard treatment (i.e. surgery and radio-chemotherapy); b) HGG at first diagnosis or after disease progression treated with radical surgery (nivolumab delivered in the surgical cavity after tumor removal); c) other brain tumors or solitary metastases judged suitable for surgical procedure. PD-L1 expression was assessed in all patients, but it was not a strict criterion for accrual. Standard therapy, usually based on chemotherapy, radiotherapy or both, was sequentially administered to patients able to tolerate such an approach. End-points were safety, response rate, disease control, predictive value of PD-L1 expression. This is a non-sponsored monocentric, real life, basket trial approved by Ethical Committee (EudraCT number: 2018-001560-33). Results: Since August 2018, 17 patients with brain tumors (16 HGG and 1 heavily pretreated medulloblastoma) and 5 patients with brain metastasis (of lung and gastrointestinal cancers) were enrolled. Median age was 63 years (range 26-83). After a median follow up of three months (range 1-6), all patients are alive and in good clinical conditions. No signs of neurologic toxicity due to intracerebral nivolumab were observed. Brain MRI performed at 4 to 12 weeks after nivolumab CED revealed findings suggesting a perivascular lymphocyte infiltration. Correlation between PD-L1 expression and treatment efficacy will be evaluated over time. Conclusions: Intracerebral nivolumab appears to be a feasible and safe option for patients with HGG and brain metastases at the dose investigated in the study. Long-term follow up could contribute to well understand the role of this strategy. Clinical trial information: 2018-001560-33.

Efficacy, Safety, and Duration of a Frameless Fiducial-Less Brain Biopsy versus Frame-based Stereotactic Biopsy: A Prospective Randomized Study

Background/Objective We compared the efficacy, duration, safety, length of hospital stay of a frameless fiducial-less brain biopsy with those of the standard frame-based stereotactic biopsy. Patients and Methods This prospective cohort study enrolled 56 adult patients: (1) for whom no conclusive diagnosis could be reached noninvasively; (2a) who had lesions involving deep-seated and eloquent areas, multifocal lesions, or lesions for which craniotomy and lesion removal was not indicated, or (2b) were poor candidates for craniotomy (> 80 years of age and/or with serious comorbidities). Frameless and frame-based biopsy were performed in 28 patients each Results A diagnosis was not made in four cases (14.3%) of the frame-based biopsy group and in three cases (10.7%) of the frameless biopsy group, in spite of accurate targeting (p = 1.0). The mean duration of the whole procedure (preparatory steps outside the operating room [OR], inside the OR, surgery) was 111.3 minutes for the frame-based biopsy and 79.1 minutes for the frameless biopsy (p = 0.001). No statistically significant differences between the two methods were found concerning new neurologic symptoms, new abnormal findings in postoperative computed tomography (CT) and length of postoperative hospital stay (LOS). The smallest diameter of a successfully biopsied lesion was 15 mm for both groups. Conclusions The frameless fiducial-less brain biopsy was equally efficacious and safe compared with the standard stereotactic frame-based biopsy. The overall duration of frameless biopsy is shorter than that of frame-based biopsy, mainly because the preparatory steps in frameless biopsy require less time. However, the overall time spent in the OR did not differ between the two groups. The LOS also did not differ significantly.