BackgroundThe programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.MethodsWe reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein–Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan–Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.ResultsOf the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression (r = − 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01).ConclusionsPD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.
Abstract. In recent years, asparaginase-based chemotherapy regimens have produced excellent short-term efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL). However, few long-term outcomes have been reported to date. A phase II clinical trial evaluating the efficacy and safety of a combination of gemcitabine, oxaliplatin and asparaginase (GELOX), followed by radiotherapy (RT) in the treatment of localized ENKTL, was reported by this group in 2012. By the time of the present analysis, detailed information had been collected for all 27 patients in the phase II trial, over an extended follow-up period. The median follow-up time was 63.15 months. The 5-year overall survival and progression-free survival were 85.0 and 74.0%, respectively. Recurrence within the RT field was observed in three patients, and the planning target-volume control rate at 5 years was 88.9%. One patient with confirmed lung invasion who did not respond to autologus stem cell transplantation (ASCT) was successfully treated by salvage therapy with lenalidomide monotherapy, and the EBV DNA load in this individual reflected disease progression and treatment response. No clinically significant late toxicities were identified during follow-up visits. In conclusion, this updated analysis confirmed the long-term benefit of the GELOX regimen followed by RT, and demonstrated a good safety profile for this treatment. This strategy may be one of the most suitable options for the treatment of early stage ENKTL.
The link between circulating lymphocyte-to-monocyte ratio (LMR) and newly diagnosed metastatic non-small cell lung cancer (NSCLC) is not fully defined. The study was conducted to evaluate the prognostic impact of LMR on survival outcomes in previously untreated metastatic NSCLC patients receiving platinum-based doublet. Chemotherapy-naive metastatic NSCLC patients undergoing platinum-based doublet were retrospectively enrolled. Clinical features regarding gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, histology, absolute lymphocyte count (ALC), absolute monocyte count (AMC) and LMR were collected to determinate their prognostic impact on progression-free survival (PFS) and overall survival (OS). Up to 370 patients were eligible for the study. By univariate analysis, ECOG performance status, histology, ALC, AMC and LMR were showed to be significantly associated with PFS and OS. In subsequent Cox multivariate analysis, non-squamous cell carcinoma, ALC ≥ 2.45 × 10(9)/L, AMC <0.45 × 10(9)/L and LMR ≥ 4.56 were demonstrated to be independently correlated with better PFS. In addition, independent favorable prognostic factors for OS were only limited to LMR ≥ 4.56 and non-squamous cell carcinoma, whereas ECOG performance status of 2 and AMC ≥ 0.45 × 10(9)/L remained as independently inferior prognostic indicators for OS. Our findings implicate that circulating AMC and LMR are regarded as independent prognostic factors for PFS and OS in previously untreated metastatic NSCLC patients receiving platinum-based doublet.
In order to implement more effective policies for cancer pain management, a better understanding of current practices is needed. Physicians managing cancer pain and patients experiencing cancer pain were randomly surveyed across 10 Asian countries to assess attitudes and perceptions toward cancer pain management. A total of 463 physicians (77.3% oncologists) with a median experience of 13 years were included. Medical school training on opioid use was considered inadequate by 30.5% of physicians and 55.9% indicated ≤10 h of continuing medical education (CME). Of the 1190 patients included, 1026 reported moderate-to-severe pain (median duration, 12 months). Discordance was observed between physician and patient outcomes on pain assessment with 88.3% of physicians reporting pain quantification, while 49.5% of patients claimed that no scale was used. Inadequate assessment of pain was recognized as a barrier to therapy optimization by 49.7% of physicians. Additional barriers identified were patients’ reluctance owing to fear of addiction (67.2%) and adverse events (65.0%), patients’ reluctance to report pain (52.5%), excessive regulations (48.0%) and reluctance to prescribe opioids (42.8%). Opioid use was confirmed only in 53.2% (286/538) of patients remembering their medication. Pain affected the activities of daily living for 81.3% of patients. These findings highlight the need for better training and CME opportunities for cancer pain management in Asia. Collaborative efforts between physicians, patients, policy makers, and related parties may assist in overcoming the barriers identified. Addressing the opioid stigma and enhancing awareness is vital to improving current standards of patient care.
The prognostic significance of tumor-associated macrophages (TAMs) in multiple myeloma (MM) in the era of novel drugs remains unclear. CD163 expression was detected by immunohistochemistry to determine the number of TAMs in 198 MM patients receiving bortezomib-based regimens and the data were used to evaluate its relevance with clinical characteristics, treatment response, and prognosis. Patients with high levels of infiltrated CD163+ TAMs (>55/HPF) at diagnosis tended to have more adverse clinical characteristics. Patients with high CD163+ TAM content (>55/HPF) at diagnosis had worse progression-free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001),and achieved lower complete remission (CR)/near-CR rate (P<0.001), than patients with low CD163+ TAM levels. Multivariate analysis revealed that CD163+ TAM content was an independent adverse prognostic factor for PFS and OS. Our data indicated that CD163+ TAM content at diagnosis is a powerful predictor of prognosis for MM in the era of novel drugs, and this discovery offers new insight into potential therapeutic strategies.
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