Age-independent benefits of postoperative rehabilitation during chemoradiotherapy on functional outcomes and survival in patients with glioblastoma.

PURPOSE: To investigate the impact of early and continuous postoperative inpatient rehabilitation during chemoradiotherapy on functional outcomes and overall survival (OS) in patients with glioblastoma (GBM), particularly in different age groups. METHODS: This retrospective cohort study at a university hospital (2011-2016) included 75 of 119 consecutive patients newly diagnosed with GBM who underwent standardized treatment and postoperative rehabilitation. Patients were divided into older (≥ 65 years, n = 45) and younger (< 65 years, n = 30) groups, engaging in a 50-day rehabilitation program. We assessed rehabilitation progress, Barthel Index (BI), Brunnstrom Recovery Stage (BRS), adverse events, and OS. BI at discharge and survival were analyzed using multivariate and Cox regression models, respectively. RESULTS: The mean age was 72.5 ± 6.3 and 52.4 ± 7.8 years in the older and younger groups, respectively. Both groups demonstrated significant improvements in BI and BRS. Despite more adverse events in the older group, no significant difference existed in median OS (older group: 18.7 months vs. younger group: 18.3 months, p = 0.87). Early walking training, reduced fatigue during chemoradiotherapy, and high Karnofsky Performance Status at admission significantly impacted the BI at discharge. Cox regression analysis identified the BI at discharge as a significant predictor of survival (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.97-0.99, p = 0.008). CONCLUSION: Integrated rehabilitation improves functional outcomes, and enhanced ADL at discharge is associated with improved survival outcomes in patients with GBM, regardless of age. This highlights the need for personalized rehabilitation in treatment protocols. Further prospective studies are warranted to confirm these findings.

Three-year follow-up analysis of phase 1/2 study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma.

Background: The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up. Methods: Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions. Results: Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment. Conclusions: The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained.