Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

Assessment of cerebrovascular reserve with N-isopropyl-p-[123I]-iodoamphetamine time series analysis in patients with cerebrovascular disease.

ABSTRACT: Using N-isopropyl-p-[123I]-iodoamphetamine(123I-IMP) and single-photon emission computed tomography (SPECT), the relationship between cerebrovascular reserve and the 123I-IMP redistribution phenomenon was investigated.The 50 patients who matched the inclusion criteria were divided into control and ischemia groups, and the redistribution phenomenon was examined on resting images. The delayed images showed higher 123I-IMP accumulation in lesions in the middle cerebral artery(MCA) area and anterior cerebral artery(ACA) area, these watershed areas in the ischemia group than in the control group, confirming that the redistribution phenomenon exists with statistical significance (Wilcoxon test; control group vs ischemic group in the ACA area[P = .002], ACA-MCA watershed area(P = .014), MCA area(P = .025), and MCA-posterior cerebral artery(PCA) watershed area(P = .002). The patients were then divided into 4 types according to the Kuroda grading system, and the difference in the redistribution phenomenon was investigated between type III and the other 3 types.Compared with type I and type II, type III had a significantly lower rate of decrease in the radioisotope (RI) count, verifying the redistribution phenomenon (Student t test: type I vs type III in the ACA area(P = .008), ACA-MCA watershed area(P = .009), MCA area(P < .001), and MCA-PCA watershed area(P = .002); type II vs type III in the ACA area(P = .004), ACA-MCA watershed area(P = .2575), MCA area(P < .001), and MCA-PCA watershed area(P < .001). No significant difference between type III and type IV was observed in any area [(Student t test: type III vs type IV in the ACA area(P = .07), ACA-MCA watershed area(P = .38), MCA area(P = .05), and MCA-PCA watershed area(P = .24)].The redistribution phenomenon is associated with resting cerebral blood flow (CBF), but not necessarily with cerebral vascular reactivity (CVR).

Assessment of the Accuracy and Errors of Head-Up Display by an Optical Neuronavigation System in Brain Tumor Surgery.

BACKGROUND: A head-up display (HUD) in which navigational information is projected into the microscope view may enable surgeons to perform operations more efficiently. Projecting depictions of both tumor and important intracranial structures on the HUD may facilitate safe surgery. OBJECTIVE: To investigate accuracy and errors regarding important intracranial structures, errors due to brain shifts, and preservation rates for important intracranial structures. METHODS: A total of 184 surgeries in 172 patients were performed using this operation system. Postoperatively, we determined accuracy and errors for actual structures and virtual reality on the HUD and performed statistical analyses. RESULTS: Preresection accuracy for important intracranial structures was highest for the internal carotid artery (ICA; 90.4%) and lowest for the posterior inferior cerebellar artery (53.6%). Differences between pre- and postresection accuracy were greatest, in descending order, for the cortical vein ( P < .0001), V4 segment of vertebral artery ( P < .0001), and anterior inferior cerebellar artery ( P = .00780), whereas differences between pre- and postresection errors were smallest for the cranial nerve V ( P = .500), middle cerebral artery ( P = .0313), and ICA ( P = .0313). Cases of poor preresection accuracy and large differences in pre- to postresection accuracy were seen in the prone position. CONCLUSION: A reliable surgical resection rate was achieved using the HUD, and reliable preservation of important intracranial structures was also possible. Accuracy was concluded to be within an acceptable range.