Objectives: To analyse the results of gamma knife radiosurgery (GKS) for the trreatment of intracranial meningiomas and to assess possible factors related to the outcome and complications of such treatment. Methods: The authors retrospectively reviewed the clinical and radiological data of 179 patients (194 lesions) treated with GKS for meningiomas between May 1992 and October 2000. The mean follow up duration was 37.3 months (range 6.4 to 86.3 months). The study determined the correlation between radiosurgical outcome including imaging changes after GKS and multiple factors such as tumour location and size, patient characteristics, venous sinus status, pre-GKS degree of oedema, other treatment modalities, and radiosurgical parameters. Results: The radiological control rate was 97.1%. Magnetic resonance imaging (MRI) showed complications after GKS in 35 lesions (25.0%) among the 140 lesions followed up with MRI. Complications were divided into peritumorous imaging changes (33 lesions; 23.6%) and transient cranial nerve dysfunction (two lesions; 1.4%). Radiation induced imaging changes were seen mostly in convexity, parasagittal, and falx meningiomas that were deeply embedded in the cortex. About 60% of these were asymptomatic and the overall rate of symptomatic imaging changes was 9.3%. Neurological deficit related to imaging changes developed in only three patients, and all the symptoms were transient. Conclusion: GKS for intracranial meningiomas seems to be a safe and effective treatment. However, meningiomas of the convexity, parasagittal region, or falx cerebri have a higher incidence of peritumorous imaging changes after GKS than those of the skull base. Therefore, the use of GKS needs to be considered very cautiously in cerebral hemispheric meningiomas, taking into consideration patient age and general condition, tumour size and location, pattern of cortical embedding, relation between the tumour and venous sinuses, presenting symptoms, and patient preference.

Background and Aims Targeting costimulatory receptors with agonistic antibodies is a promising cancer immunotherapy option. We aimed to investigate costimulatory receptor expression, particularly 4‐1BB (CD137 or tumor necrosis factor receptor superfamily member 9), on tumor‐infiltrating CD8+ T cells (CD8+ tumor‐infiltrating lymphocytes [TILs]) and its association with distinct T‐cell activation features among exhausted CD8+ TILs in hepatocellular carcinoma (HCC). Approach and Results Tumor tissues, adjacent nontumor tissues, and peripheral blood were collected from HCC patients undergoing surgical resection (n = 79). Lymphocytes were isolated and used for multicolor flow cytometry, RNA‐sequencing, and in vitro functional restoration assays. Among the examined costimulatory receptors, 4‐1BB was most prominently expressed on CD8+ TILs. 4‐1BB expression was almost exclusively detected on CD8+ T cells in the tumor—especially on programmed death 1 (PD‐1)high cells and not PD‐1int and PD‐1neg cells. Compared to PD‐1int and 4‐1BBnegPD‐1high CD8+ TILs, 4‐1BBposPD‐1high CD8+ TILs exhibited higher levels of tumor reactivity and T‐cell activation markers and significant enrichment for T‐cell activation gene signatures. Per‐patient analysis revealed positive correlations between percentages of 4‐1BBpos cells among CD8+ TILs and levels of parameters of tumor reactivity and T‐cell activation. Among highly exhausted PD‐1high CD8+ TILs, 4‐1BBpos cells harbored higher proportions of cells with proliferative and reinvigoration potential. Our 4‐1BB–related gene signature predicted survival outcomes of HCC patients in the The Cancer Genome Atlas cohort. 4‐1BB agonistic antibodies enhanced the function of CD8+ TILs and further enhanced the anti‐PD‐1–mediated reinvigoration of CD8+ TILs, especially in cases showing high levels of T‐cell activation. Conclusion 4‐1BB expression on CD8+ TILs represents a distinct activation state among highly exhausted CD8+ T cells in HCC. 4‐1BB costimulation with agonistic antibodies may be a promising strategy for treating HCCs exhibiting prominent T‐cell activation.

Object Whole-brain radiation therapy (WBRT), open resection, and stereotactic radiosurgery (SRS) are widely used for treatment of metastatic brain lesions, and many physicians recommend WBRT for multiple brain metastases. However, WBRT can be performed only once per patient, with rare exceptions. Some patients may require SRS for multiple metastatic brain lesions, particularly those patients harboring more than 10 lesions. In this paper, treatment results of SRS for brain metastasis were analyzed, and an attempt was made to determine whether SRS is effective, even in cases involving multiple metastatic brain lesions. Methods The authors evaluated the cases of 323 patients who underwent SRS between October 2005 and October 2008 for the treatment of metastatic brain lesions. Treatment was performed using the Gamma Knife model C or Perfexion. The patients were divided into 4 groups according to the number of lesions visible on MR images: Group 1, 1–5 lesions; Group 2, 6–10 lesions: Group 3, 11–15 lesions; and Group 4, > 15 lesions. Patient survival and progression-free survival times, taking into account both local and distant tumor recurrences, were analyzed. Results The patients consisted of 172 men and 151 women with a mean age at SRS of 59 years (range 30–89 years). The overall median survival time after SRS was 10 months (range 8.7–11.4 months). The median survival time of each group was as follows: Group 1, 10 months; Group 2, 10 months; Group 3, 13 months; and Group 4, 8 months. There was no statistical difference between survival times after SRS (log-rank test, p = 0.554), although the probability of development of new lesions in the brain was greater in Group 4 (p = 0.014). Local tumor control rates were not statistically different among the groups (log-rank test, p = 0.989); however, remote disease progression was more frequent in Group 4 (log-rank test, p = 0.014). Conclusions In this study, patients harboring more than 15 metastatic brain lesions were found to have faster development of new lesions in the brain. This may be due to the biological properties of the patients' primary lesions, for example, having a greater tendency to disseminate hematogenously, especially to the brain, or a higher probability of missed or invisible lesions (microscopic metastases) to treat on stereotactic MR images at the time of radiosurgery. However, the mean survival times after SRS were not statistically different between groups. According to the aforementioned results, SRS may be a good treatment option for local control of metastatic lesions and for improved survival in patients with multiple metastatic brain lesions, even those patients who harbor more than 15 metastatic brain lesions, who, after SRS, may have early and easily detectable new metastatic lesions.

Brain metastases from colorectal carcinoma (CRC) are rare. The objectives of this study are to assess the natural history, outcome, and possible prognostic factors in CRC patients with brain metastases. Between 1995 and 2008, 8,732 patients with CRC were treated at Yonsei University Health System. Brain metastases were found in 1.4% of these patients. Retrospective review and statistical analysis of these 126 patients were performed. Median time from diagnosis of metastatic CRC (mCRC) to brain metastases was 9.0 months (range 0-85 months), and 14 patients (11.1%) had brain involvement as their initial presentation. Among the 126 patients, 91.3% had other systemic metastases; the most common extracranial metastatic site was lung (72.2%). Median follow-up duration was 6.1 months (range 0.1-90.3 months), and median survival after diagnosis of brain metastases was 5.4 months [95% confidence interval (CI) 3.9-6.9 months]. Median survival time after diagnosis of brain metastases was 1.5 months for patients who received only steroids (15.9%), 4.0 months for those who received whole-brain radiation therapy (37.5%), 9.5 months for those who received gamma-knife surgery (GKS) (32.5%), and 11.5 months for those who underwent surgery (20%) (P < 0.001). On multivariate analysis, recursive partitioning analysis (RPA) class and amount of chemotherapy before brain metastasis were independent prognostic factors for survival. Overall prognosis of patients with brain metastases from CRC is poor. Nevertheless, patients with low RPA class, or those with previous less chemotherapy showed good prognosis, indicating that proper treatment may result in improved survival time.