Nomograms containing body dose parameters for predicting survival in patients with nasopharyngeal carcinoma.

PURPOSE: To assess the impact of body dose on survival outcomes in nasopharyngeal carcinoma (NPC) patients and to create novel nomograms incorporating body dose parameters for predicting survival. METHODS: 594 of non-metastasis NPC patients (training group, 396; validation group, 198) received intensity-modulated radiation therapy at our institution from January 2012 to December 2016. Patient characteristics, body dose parameters in dose-volume histogram (DVH) and hematology profiles were collected for predicting overall survival (OS) and progression-free survival (PFS). Nomograms for OS and PFS were developed using the selected predictors. Each nomogram was evaluated based on its C-index and calibration curve. RESULTS: Body dose-based risk score for OS (RSOS), N stage, age, and induction chemotherapy were independent predictors for OS, with a C-index of 0.784 (95% CI 0.749-0.819) in the training group and 0.763 (95% CI 0.715-0.810) in the validation group for the nomogram. As for PFS, the most important predictors were the body dose-based risk score for PFS (RSPFS), N stage, and induction chemotherapy. C-index of PFS nomogram was 0.706 (95% CI 0.681-0.720) in the training group and 0.691 (95% CI 0.662-0.711) in the validation group. The two models outperformed the TNM staging system in predicting outcomes. CONCLUSIONS: Body dose coverage is a useful predictor of prognosis in clinical routine patients. The novel nomograms integrating body dose parameters can precisely predict OS and PFS in NPC patients.

AntiPD-L1 antibody conjugated Au-SPIOs nanoplatform for enhancing radiosensitivity and triggering anti-tumor immune response.

To improve radiotherapy effect by inducing more toxicity for tumors and less for normal tissue and switching immunosuppressive microenvironment caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive microenvironment, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles and superparamagnetic iron oxide nanoparticles (antiPD-L1-SPIOs@PLGA@Au). In vivo T2-weighted images, the best contrast effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au. The tumor control caused by irradiation combined with antiPD-L1-SPIOs@PLGA@Au was better than that by radiotherapy alone in clone formation assay and B16F10 subcutaneous tumor model. Radiosensitivity enhancement induced by the addition of antiPD-L1-SPIOs@PLGA@Au was achieved by increasing ROS production and attenuating DNA damage repair. AntiPD-L1-SPIOs@PLGA@Au could promote the polarization of tumor-associated macrophages (TAMs) to M1 and reverse the immunosuppression caused by TAMs. By increasing the expression of CRT in tumor and blocking the PD-L1/PD pathway, antiPD-L1-SPIOs@PLGA@Au with radiation activated the anti-tumor immune response. In conclusion, antiPD-L1-SPIOs@PLGA@Au could be used as a radiosensitizer and a MRI contrast targeting PD-L1, with the functions of blocking the PD-L1/PD-1 immune checkpoint pathway and reversing the immunosuppression caused by TAMs.

Postoperative Chemoradiotherapy versus Radiotherapy Alone in Major Salivary Gland Cancers: A Stratified Study Based on the External Validation of the Distant Metastasis Risk Score Model.

BACKGROUND: The role of additional chemoradiotherapy (CRT) for distant metastasis (DM) on the resected malignancy of the major salivary gland (SGM) remained unknown. We conducted this study to externally validate a recently reported DM risk score model and compare the survival outcome between adjuvant CRT and RT alone. MATERIALS: We retrospectively reviewed the patients with SGM following postoperative radiotherapy (PORT). The cumulative incidence of DM was assessed using a competing risk method. Multivariate analysis was performed with Cox proportional-hazards regression to identify significant predictors for DM. Patients were classified as high- and low-risk subgroups with the cutoff value of the DM risk score model. The inverse probability of treatment weighting (IPTW) was conducted to minimize the bias of the groups. RESULTS: A total of 586 eligible patients were analyzed and 67 cases underwent adjuvant CRT. The 5-year incidence of DM was 19.5% (95% CI 16.0-23.0%). The model reasonably discriminated the DM risk between the high- and low-risk subgroup in our cohort, and the c-index was 0.75. No survival benefit was observed for the CRT group compared with RT alone in the entire cohort after IPTW (p = 0.095). After subgroup analysis, increased mortality was identified with the administration of CRT in the low-risk subset (p = 0.002) while no significant difference in OS was illustrated in the high-risk subgroup (p = 0.98). CONCLUSIONS: This external validation provides further exploration of the DM risk score model in major SGM. Our results demonstrated no support for the utility of additional chemotherapy to PORT in the major SGM, especially in the low-risk subgroup of patients with DM.

Revealing the crosstalk between nasopharyngeal carcinoma and immune cells in the tumor microenvironment.

Nasopharyngeal carcinoma (NPC) arises from the epithelial cells located in the nasopharynx and has a distinct geographic distribution. Chronic Epstein-Barr virus (EBV) infection, as its most common causative agents, can be detected in 100% of NPC types. In-depth studies of the cellular and molecular events leading to immunosuppression in NPC have revealed new therapeutic targets and diverse combinations that promise to benefit patients with highly refractory, advanced and metastatic NPC. This paper reviews the mechanisms by which NPC cells to circumvent immune surveillance and approaches being attempted to restore immunity. We integrate existing insights into anti-NPC immunity and molecular signaling pathways as well as targeting therapies in anticipation of broader applicability and effectiveness in advanced metastatic NPC.

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis.

PURPOSE: To evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors. METHODS: A total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed. RESULTS: The median follow-up time for the whole group was 31.5 months (range 5-138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/µl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS. CONCLUSION: Taxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.