Monocentric evaluation of Ki-67 labeling index in combination with a modified RPA score as a prognostic factor for survival in IDH-wildtype glioblastoma patients treated with radiochemotherapy.

PURPOSE: The prognosis for glioblastoma patients remains dismal despite intensive research on better treatment options. Molecular and immunohistochemical markers are increasingly being investigated as understanding of their role in disease progression grows. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to have prognostic and therapeutic relevance for glioblastoma patients. Other markers implicated in tumor formation and/or malignancy are p53, Alpha thalassemia/mental retardation syndrome X-linked (ATRX), Epidermal Growth Factor Receptor splice variant III (EGFRvIII), and Ki-67, with loss of nuclear ATRX expression and lower Ki-67 index being associated with prolonged survival. For p53 and EGFRvIII the data are contradictory. Our aim was to investigate the markers mentioned above regarding progression-free (PFS) and overall survival (OS) to evaluate their viability as independent prognostic markers for our patient collective. METHODS: In this retrospective study, we collected data on patients undergoing radiotherapy due to isocitrate dehydrogenase (IDH) wildtype glioblastoma at a single university hospital between 2014 and 2020. RESULTS: Our findings confirm Ki-67 labeling index ≤ 20% as an independent prognostic factor for prolonged PFS as well as MGMT promoter methylation for both prolonged PFS and OS, in consideration of age and Eastern Cooperative Oncology Group (ECOG) status, chemotherapy treatment, and total radiation dose for PFS as well as additionally sex, resection status, and receipt of treatment for progression or recurrence for OS. Additionally, Ki-67 labeling index ≤ 20% showed a significant correlation with prolonged OS in univariate analysis. Modification of the recursive partitioning analysis (RPA) score to include Ki-67 labeling index resulted in a classification with the possible ability to distinguish long-term-survivors from patients with unfavorable prognosis. CONCLUSION: MGMT promoter methylation and Ki-67 labeling index were independent predictors of survival in our collective. We see further studies pooling patient collectives to reach larger patient numbers concerning Ki-67 labeling index as being warranted.

Adaptation of a hexapod-based robotic system for extended endoscope-assisted transsphenoidal skull base surgery.

OBJECTIVE: To adapt a hexapod-based robotic system for use in extended endoscope-assisted transsphenoidal skull base surgery. METHODS: A robotic system (Evolution 1, Universal Robot Systems, Schwerin, Germany) based on a hexapod design with an attached seventh axis is used as instrument holder. The instrument interface is operated via a joystick control. An endoscope is applied to the instrument interface, which is tracked by a navigation system (Stealth, Medtronic, USA). RESULTS: The instrument holder was modified so that it could be applied in transsphenoidal surgery. Furthermore, translation and pivoting movements of the system were implemented, also a quick change between microscope and robotic-controlled endoscope was made possible. After extensive phantom testing two patients with large invasive pituitary adenomas were operated on using the robotic endoscope assistance during transsphenoidal surgery. The robotic assistance allowed the use of two additional instruments under endoscopic view. For example, drilling, suctioning, application of punches, as well as microsurgical tumor removal could be performed under endoscopic view. CONCLUSION: A robotic system could be adapted for use in endoscope-assisted transsphenoidal skull base surgery allowing simultaneous use of two instruments under endoscopic view. This opens new possibilities to extend transsphenoidal skull base surgery.