The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation assay and fluorescence in situ hybridization (FISH) for the assessment of 1p/19q deletion were performed. Expression of PD-L1 in tumour cells and TIIs was found in 37 (32.2%) and 6 (5.2%) patients, respectively. Kaplan-Meier analysis indicated that PD-L1 expression in tumour cells was significantly associated with poor overall survival (OS) (P = 0.017), though multivariate Cox analysis did not confirm this association (hazard ratio 1.204; P = 0.615). PD-L1 expression in TIIs did not correlate with the patient prognosis (P = 0.545). In addition, MGMT methylation and IDH-1 (R132H) expression were associated with a better prognosis (P < 0.001 and P = 0.024, respectively). The expression of PD-L1 was associated with CD3-positive T-cell infiltration (P < 0.001), and IDH-1 wild type status (P = 0.008). A deeper insight into PD-L1 expression could help to ensure the success of future immunotherapy in GBM. Our study suggested that PD-L1 target therapy might be beneficial for PD-L1-expressing GBM patients with a poor prognosis.

PURPOSEThe purpose of this study was to analyze the influence of the platform switching concept on an implant system and peri-implant bone using three-dimensional finite element analysis.MATERIALS AND METHODSTwo three-dimensional finite element models for wide platform and platform switching were created. In the wide platform model, a wide platform abutment was connected to a wide platform implant. In the platform switching model, the wide platform abutment of the wide platform model was replaced by a regular platform abutment. A contact condition was set between the implant components. A vertical load of 300 N was applied to the crown. The maximum von Mises stress values and displacements of the two models were compared to analyze the biomechanical behavior of the models.RESULTSIn the two models, the stress was mainly concentrated at the bottom of the abutment and the top surface of the implant in both models. However, the von Mises stress values were much higher in the platform switching model in most of the components, except for the bone. The highest von Mises values and stress distribution pattern of the bone were similar in the two models. The components of the platform switching model showed greater displacement than those of the wide platform model.CONCLUSIONDue to the stress concentration generated in the implant and the prosthodontic components of the platform switched implant, the mechanical complications might occur when platform switching concept is used.

This prospective study was performed to determine the efficacy, safety, and tolerability of concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy with temozolomide (TMZ) in the treatment of patients with WHO grade III gliomas. Thirty-three adult patients with WHO grade III glioma and aged >17 years were enrolled from three institutions between 2003 and 2008. The median age was 41 years (range, 17-60 years). The pathological diagnoses were anaplastic astrocytomas in 21 patients and anaplastic oligodendrogliomas in 12 patients. The preoperative Karnofsky performance scale score was >60 for all patients. The patients received fractionated focal irradiation in daily fractions of 2 Gy administered five days per week for six weeks, for a total of 60 Gy, in combination with continuous daily TMZ, followed by six cycles of adjuvant TMZ. The median dose of radiotherapy was 59.4 Gy (range, 28.8-61.2 Gy) and the duration of CCRT was 7.0 weeks (range, 3.1-8.3 weeks). A median of 6.2 cycles (range, 2-12 cycles) of TMZ chemotherapy were performed during the period of adjuvant chemotherapy. The response rate was 61% and the tumor-control rate was 82%. Mean progression-free survival (PFS) was 48.7 months (95% CI, 36.0-61.4) and the 12, 24, and 36-month PFS was 74%, 60%, and 50%, respectively. Mean overall survival (OS) was 66.4 months (95% CI, 56.4-76.4) and the 12 and 24-month OS was 97% and 77%, respectively. The extent of surgical resection was a significant prognostic factor for PFS and OS (hazard ratio, 0.24; 95% CI, 0.02-0.73; and hazard ratio, 0.12; 95% CI, 0.01-0.88, respectively; P < 0.001). However, there was no significant difference in the PFS and OS of patients regarding loss of heterozygosity in chromosomes 1p and 19q and methylation of O (6)-methylguanine-DNA methyltransferase promoter, because of the small number of patients available. Only five cases (15%) receiving CCRT with TMZ and three cases (9%) receiving adjuvant chemotherapy had hematological toxicity greater than grade 3. All these patients, however, tolerated the therapy well enough to continue treatment. No opportunistic infections were noted. This protocol for WHO grade III gliomas was relatively safe and tolerable. It showed the possibility of achieving favorable results compared with those of historical controls. A randomized controlled study with a long-term follow-up may be mandatory to evaluate its efficacy.

Programmed death ligand 1 (PD-L1) expression provides significant value to predict prognosis and response following immunotherapy in several types of cancers. However, its clinicopathological and prognostic significance in melanoma remains unclear. PD-L1 and the number of tumor infiltrating lymphocytes (TILs) were investigated in 63 Korean patients with melanoma based on the melanoma scoring system. We also compared the results using the PD-L1 antibodies—22C3 and E1L3N clones. In addition, BRAF gene mutation was detected using anti-BRAF antibody and real-time polymerase chain reaction. Overall, 29 (46.0%), 16 (25.4%), and 18 (28.6%) patients exhibited the acral lentiginous type, nodular type, and other histological subtypes of melanoma, respectively. PD-L1 expression was detected in 37 (58.7%) cases and was closely associated with a CD8+TIL high phenotype ( P < 0.001). Combined survival analysis depending on PD-L1 and CD8+TILs status showed that the PD-L1-/CD8+TIL high group demonstrated the best survival outcome, whereas patients with PD-L1+/CD8+ TIL low showed the worst prognosis ( P = 0.039). However, PD-L1+/CD8+ TIL low was not an independent prognostic factor. The 22C3 and E1L3N clones showed a high concordance rate (kappa value, 0.799). BRAF mutation status was not correlated with PD-L1 expression. We suggest that evaluation of the combined status of PD-L1 and TIL might be useful to predict the survival of patients with melanoma.

AimsThe importance of programmed cell death ligand 1 (PD‐L1) expression has emerged in clinical trials of PD‐L1 target therapy in renal cell carcinoma (RCC). This study compares PD‐L1 assays in RCC.Methods and resultsTwo US Food and Drug Administration‐approved PD‐L1 assays (22C3 and SP142) and one research‐use only antibody (E1L3N) were used in a retrospective cohort of 591 patients with RCC. PD‐L1 positivity on tumour cells (TCs) and immune cells (ICs) and combined positive score (CPS) were evaluated. With the 22C3, SP142 and E1L3N assays, positive PD‐L1 expression on TCs ≥1% was observed in 24 (4.1%), 12 (2.0%) and 16 (2.7%) cases and on ICs ≥1% was observed in 132 (22.3%), 120 (20.3%) and 65 (11.0%) cases, respectively. PD‐L1 expression scores among the three assays showed moderate–high positive correlation (ρ = 0.599–0.835, P < 0.001). Assays appeared similar, although staining in ICs was comparatively less frequent with E1L3N. 22C3 showed frequent positivity in TCs. PD‐L1 expression on TCs was associated with papillary type 2 RCC (P < 0.001). IC infiltration and PD‐L1 expression on ICs were predominantly found in clear cell and papillary type 1 RCC (P < 0.05).ConclusionsProgrammed death 1 (PD‐1)/PD‐L1 target therapy may be beneficial for patients with papillary type 2 RCC, even if they are categorised as a heterogeneous group. PD‐L1 assays should be carefully selected, and accurate histological subtyping of RCC is needed prior to decisions on PD‐L1 testing, because of the different PD‐L1 expression observed among varying RCC subtypes.