Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis.

Importance: The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. Objectives: To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. Data Sources: PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Study Selection: Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data Extraction and Synthesis: Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). Results: A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. Conclusions and Relevance: These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

Exploration and validation of radiomics signature as an independent prognostic biomarker in stage III-IVb nasopharyngeal carcinoma.

There is no consensus on specific prognostic biomarkers potentially improving survival of nasopharyngeal carcinoma (NPC), especially in advanced-stage disease. The prognostic value of MRI-based radiomics signature is unclear. A total of 970 quantitative features were extracted from the tumor of 100 untreated NPC patients (stage III-IVb) (discovery set: n = 70, validation set: n = 30). We then applied least absolute shrinkage and selection operator (lasso) regression to select features that were most associated with progression-free survival (PFS). Candidate prognostic biomarkers included age, gender, overall stage, hemoglobin, platelet counts and radiomics signature. We developed model 1 (without radiomics signature) and model 2 (with radiomics signature) in the discovery set and then tested in the validation set. Multivariable Cox regression analysis was used to yield hazard ratio (HR) of each potential biomarker. We found the radiomics signature stratified patients in the discovery set into a low or high risk group for PFS (HR = 5.14, p < 0.001) and was successfully validated for patients in the validation set (HR = 7.28, p = 0.015). However, the other risk factors showed no significantly prognostic value (all p-values for HR, > 0.05). Accordingly, pretreatment MRI-based radiomics signature is a non-invasive and cost-effective prognostic biomarker in advanced NPC patients, which would improve decision-support in cancer care.

Machine Learning Algorithms for Risk Prediction of Severe Hand-Foot-Mouth Disease in Children.

The identification of indicators for severe HFMD is critical for early prevention and control of the disease. With this goal in mind, 185 severe and 345 mild HFMD cases were assessed. Patient demographics, clinical features, MRI findings, and laboratory test results were collected. Gradient boosting tree (GBT) was then used to determine the relative importance (RI) and interaction effects of the variables. Results indicated that elevated white blood cell (WBC) count > 15 × 109/L (RI: 49.47, p < 0.001) was the top predictor of severe HFMD, followed by spinal cord involvement (RI: 26.62, p < 0.001), spinal nerve roots involvement (RI: 10.34, p < 0.001), hyperglycemia (RI: 3.40, p < 0.001), and brain or spinal meninges involvement (RI: 2.45, p = 0.003). Interactions between elevated WBC count and hyperglycemia (H statistic: 0.231, 95% CI: 0-0.262, p = 0.031), between spinal cord involvement and duration of fever ≥3 days (H statistic: 0.291, 95% CI: 0.035-0.326, p = 0.035), and between brainstem involvement and body temperature (H statistic: 0.313, 95% CI: 0-0.273, p = 0.017) were observed. Therefore, GBT is capable to identify the predictors for severe HFMD and their interaction effects, outperforming conventional regression methods.