A novel dosimetric metrics-based risk model to predict local recurrence in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.

BACKGROUND: To develop a risk model based on dosimetric metrics to predict local recurrence in nasopharyngeal carcinoma (NPC) patients treated with intensive modulated radiation therapy (IMRT). METHODS: 493 consecutive patients were included, among whom 44 were with local recurrence. One-to-two propensity score matching (PSM) was used to balance variables between recurrent and non-recurrent groups. Dosimetric metrics were extracted, and critical dosimetric predictors of local recurrence were identified by Cox regression model. Moreover, recurrent sites and patterns were examined by transferring the recurrent tumor to the pretreatment planning computed tomography. RESULTS: After PSM, 44 recurrent and 88 non-recurrent patients were used for dosimetric analysis. The univariate analysis showed that eight dosimetric metrics and homogeneity index were significantly associated with local recurrence. The risk model integrating D5 and D95 achieved a C-index of 0.706 for predicting 3-year local recurrence free survival (LRFS). By grouping patients using median value of risk score, patients with risk score ˃ 0.885 had significantly lower 3-year LRFS (66.2% vs. 86.4%, p = 0.023). As for recurrent features, the proportion of relapse in nasopharynx cavity, clivus, and pterygopalatine fossa was 61.4%, 52.3%, and 40.9%, respectively; and in field, marginal, and outside field recurrence constituted 68.2%, 20.5% and 11.3% of total recurrence, respectively. CONCLUSIONS: The current study developed a novel risk model that could effectively predict the LRFS in NPC patients. Additionally, nasopharynx cavity, clivus, and pterygopalatine fossa were common recurrent sites and in field recurrence remained the major failure pattern of NPC in the IMRT era.

Cost-Effectiveness of Ribociclib for Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer.

PURPOSE: Ribociclib has provided significant improvements in progression-free survival (PFS) and overall survival (OS) of postmenopausal patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). However, given the high cost of ribociclib, its value must be evaluated based on cost-effectiveness. Thus, we aimed to explore the cost-effectiveness of ribociclib for postmenopausal patients with HR-positive and HER2-negative ABC. METHODS: A comprehensive Markov model was developed to estimate the cost-effectiveness of ribociclib plus fulvestrant versus placebo plus fulvestrant as first-line treatment for HR-positive, HER2-negative ABC. Variables were estimated based on data from the randomized Phase III MONALEESA-3 trial. Ten-year values were estimated for quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Direct treatment costs were estimated from the perspective of a United States payer. One-way and probabilistic sensitivity analyses were conducted to confirm the model's robustness. RESULTS: Ribociclib plus fulvestrant increased the treatment cost by $382,172 and provided 0.47 QALYs, relative to fulvestrant alone, which corresponded to an ICER of $813,132 per QALY. Sensitivity analyses revealed that ribociclib was unlikely to be cost-effective even under the most favorable assumptions. When the cost of ribociclib was <$1,384, there was a >50% chance of cost-effectiveness at a willingness-to-pay threshold of $150,000/QALY. Subgroup analyses also confirmed that ribociclib was not cost-effective. CONCLUSION: At current drug prices in the United States, ribociclib is unlikely to be cost-effective for treating postmenopausal patients with HR-positive HER2-negative ABC. Despite the clinical benefits of ribociclib, its cost would need to decrease to provide more favorable economic outcomes.

A novel immune checkpoint-related seven-gene signature for predicting prognosis and immunotherapy response in melanoma.

BACKGROUND: New emergence of immunotherapy has significantly improved clinical outcome of melanoma patients with advanced and metastatic diseases. We aimed to develop a gene signature based on the expression of PD-1/PD-L1 signaling pathway genes to predict prognosis and immunotherapy response in melanoma patients. METHODS: Melanoma samples from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) were used as the training set and external validation sets respectively. Prognostic genes for overall survival (OS) were identified by univariate Cox regression analysis. Then a multi-gene risk signature was established with the Least Absolute Shrinkage and Selector Operation (LASSO) regression and multivariate Cox regression. The predictive and prognostic value of gene signature was evaluated by Kaplan Meier curve, Time-dependent receiver operating characteristic (ROC) curve, and area under curve (AUC). Gene set enrichment analysis (GSEA) was performed to investigate the discrepantly enriched biological processes between low-risk and high-risk group of melanoma patients. RESULTS: A seven-gene risk signature (BATF2, CTLA4, EGFR, HLA-DQB1, IKBKG, PIK3R2, PPP3CA) was constructed. The signature was an independent risk factor for OS (hazard ratio = 1.544, p < 0.001) and it could robustly predict OS in both training and validation sets. Besides, high risk scores indicated advanced clinical stage and no response to immunotherapy for melanoma patients. GSEA demonstrated that high risk score was intimately associated with immune response and immune regulation. In conclusion, the novel seven-gene signature could serve as a robust biomarker for prognosis and a potential indicator of immunotherapy response in melanoma.

Characteristic And Novel Therapeutic Strategies Of Nasopharyngeal Carcinoma With Synchronous Metastasis.

Nasopharyngeal carcinoma (NPC) is rare in Western countries, but its incidence in China and Southeast Asia is notably high. NPC shows a high rate of distant metastasis including metachronous metastasis (mmNPC, metastasis after definitive chemo-radiotherapy) and synchronous metastasis (smNPC, metastasis at initial diagnosis). 4-10% of patients would be diagnosed as smNPC annually, and the survival outcomes of these patients are quite poor. As with few clinical trials exclusively focusing on this population, treatment on smNPC is not unified and many problems remain unsolved. To date, systematic chemotherapy (CT) still remains a fundamental treatment in smNPC. Although no randomized trial has been conducted to compare different CT regimens in smNPC, gemcitabine and taxanes in combination with platinum seem optimal in first-line setting. In second-line CT, there is no consensus: mono-chemotherapy with drugs such as gemcitabine, taxanes or capecitabine could be taken into consideration. Immunotherapy based on checkpoint inhibitors shows promising efficacy both in first-line and in the following lines of therapy. In addition to CT, local therapy in smNPC is also very important. Locoregional radiotherapy (RT) for primary tumor in combination with CT could strikingly increase OS with acceptable toxicities. And local treatment, such as surgery and RT, for metastatic lesions could bring extra survival benefit in patients with solitary or limited metastases. Overall, the present study provides an overview of the literature on the various studies of smNPC.

Protective effects of hydrogen rich water on the intestinal ischemia/reperfusion injury due to intestinal intussusception in a rat model.

This study aimed to investigate the protective effects of hydrogen rich water on the intestinal ischemia/reperfusion (I/R) injury in a rat intestinal intussusception (II) model. Ninety Sprague-Dawley rats were randomly assigned into three groups (n = 30 per group). In sham group, rats received laparotomy, and the intestine was exposed for 15 minutes without II. In I/R + saline group and I/R + hydrogen group, rats received II after laparotomy and then intestine was relocated 8 hours later, followed by immediately intraperitoneal injection of normal saline and hydrogen rich water (HRW) (5 mL/kg), respectively. One hour later, the intestine was collected for hematoxylin-eosin staining and immunohistochemistry for apoptotic cells and 8-oxo-deoxyguanosine, and blood was harvested for detection of tumor necrosis factor-α, malondialdehyde and superoxide dismutase. Hematoxylin-eosin staining showed the intestinal mucosa was significantly damaged in I/R + saline group, which was markedly attenuated after HRW treatment. The serum tumor necrosis factor-α content increased significantly in I/R + saline group, but HRW treatment reduced serum tumor necrosis factor-α content as compared to I/R + saline group (P < 0.05). Serum malondialdehyde content and 8-oxo-deoxyguanosine positive cells in the intestine increased dramatically after II, but HRW significantly reduced them in I/R+hydrogen group (P < 0.05). In addition, superoxide dismutase activity reduced markedly and apoptotic cells increased in I/R + saline group as compared to sham group, but they HRW increased superoxide dismutase activity and reduced apoptotic cells significantly in I/R + hydrogen group (P < 0.05). Our results indicate hydrogen rich water is able to attenuate II induced intestinal I/R injury via inhibiting intestinal inflammation, attenuating intestinal/serum oxidative stress and reducing apoptotic intestinal cells.