Szu Yuan Wu

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated‐RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses.

Dose escalation intensity-modulated radiotherapy-based concurrent chemoradiotherapy is effective for advanced-stage thoracic esophageal squamous cell carcinoma

PURPOSE No studies have investigated the effects of irradiation-dose escalation intensity-modulated radiotherapy (IMRT)-based concurrent chemoradiotherapy (CCRT) in patients with thoracic esophageal squamous cell carcinoma (TESCC). PATIENTS AND METHODS We analyzed data from patients with TESCC who were enrolled in the Taiwan Cancer Registry database. To compare treatment outcomes, the patients were categorized into two groups according to their radiotherapy doses: group 1, who received CCRT<60Gy with IMRT, and group 2, who received CCRT≥60Gy with IMRT. Group 1 was used as the control for investigating posttreatment mortality risk. RESULTS We enrolled 2061 patients with TESCC without distant metastasis who received CCRT with IMRT. Multivariate Cox regression analysis indicated that advanced clinical American Joint Committee on Cancer (AJCC) stage (≥IIIA), alcohol consumption, and cigarette smoking were significant, poor independent predictors in patients with TESCC receiving IMRT-based CCRT. IMRT-based CCRT (≥60Gy; adjusted hazard ratio [aHR]: 0.75; 95% confidence interval [CI]: 0.63-0.83) was a significant independent prognostic factor for overall survival (P<0.0001). After adjustment for confounders, the aHRs (95% CIs) for overall mortality at all clinical stages were 0.75 (0.68-0.83, P<0.0001) in group 2. In group 2, the aHRs (95% CIs) for overall mortality at early (IA-IIB) and advanced (IIIA-IIIC) AJCC clinical stages were 0.89 (0.70-1.04, P=0.1905) and 0.75 (0.67-0.83, P<0.0001), respectively. CONCLUSION Compared with standard-dose IMRT-based CCRT, high-dose IMRT-based CCRT yields more favorable survival outcomes in patients with advanced-stage TESCC.

High‐dose or low‐dose cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer

No randomized studies have compared low‐dose or high‐dose concurrent chemoradiotherapy (CRT).

Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma

Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC).

Statins dose-dependently exert a significant chemopreventive effect on colon cancer in patients with chronic obstructive pulmonary disease: A population-based cohort study.

Purpose We evaluated the chemopreventive effect of statins on colon cancer in patients with chronic obstructive pulmonary disease (COPD) and identified the statin exerting the strongest chemopreventive effect. Methods Using the National Health Insurance Research Database, we identified patients who received a COPD diagnosis in Taiwan between January 1, 2001, and December 31, 2012, and included them in the study cohort. Each patient was followed to assess the colon cancer risk and protective factors. A propensity score was derived using a logistic regression model to estimate the effect of statins by accounting for covariates predicted during the intervention (statins). To examine the dose–response relationship, we categorized statin doses into four groups in each cohort [<28, 28–90, 91–365, and >365 cumulative defined daily dose]. Results Compared with the statin nonusers, the adjusted hazard ratio (aHR) for colon cancer decreased in the statin users (aHR = 0.52, 95% confidence interval = 0.44, 0.62). Hydrophilic statins exerted a stronger preventive effect against colon cancer. Regarding the statin type, lovastatin, pravastatin, and fluvastatin nonsignificantly reduced the colon cancer risk in the patients with COPD. Compared with the statin nonusers, the aHRs for colon cancer decreased in the individual statin users (rosuvastatin, simvastatin, and atorvastatin: aHRs = 0.28, 0.64, and 0.65, respectively). In the sensitivity analysis, statins dose-dependently reduced the colon cancer risk. Conclusions Statins dose-dependently exert significant chemopreventive effects on colon cancer in patients with COPD, with rosuvastatin exerting the largest chemopreventive effect.

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo. An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.

Treatment of advanced nasopharyngeal cancer using low- or high-dose concurrent chemoradiotherapy with intensity-modulated radiotherapy: A propensity score-matched, nationwide, population-based cohort study

BACKGROUND No large-scale, head-to-head, phase III, randomized, controlled trial with an adequate sample size has investigated the effect of concurrent low-dose (LD) or high-dose (HD) cisplatin with radiotherapy on nasopharyngeal cancer (NPC). Thus, we conducted a propensity-score-matched, nationwide, population-based cohort study in Taiwan to investigate the outcomes of LD-concurrent chemoradiotherapy (CCRT) or HD-CCRT with intensity-modulated radiotherapy (IMRT) in patients with advanced NPC. METHODS In this study, patients were categorized into 2 groups according to their chemotherapy regimen: HD-CCRT and LD-CCRT groups. RESULTS We enrolled 1968 patients (328 and 1640 in the LD-CCRT and HD-CCRT groups, respectively) who had received CCRT with IMRT. According to both univariate and multivariate Cox regression analyses, a hazard ratio (95% confidence interval) of 0.75 (0.54-1.06, P = .103) was derived for the HD-CCRT group. CONCLUSION LD-CCRT or HD-CCRT with IMRT can be a standard treatment that can prolong the survival of patients with advanced NPC.

Efficacy of thoracic radiotherapy in patients with stage IIIB–IV epidermal growth factor receptor-mutant lung adenocarcinomas who received and responded to tyrosine kinase inhibitor treatment

PURPOSE Large-scale, prospective, randomized studies of the efficacy of thoracic radiotherapy (RT) in patients with unresectable stage IIIB-IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinomas who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment are not currently available. Therefore, we designed a propensity score-matched, nationwide, population-based, cohort study for estimating the effects of thoracic RT on patients with EGFR-mutant lung adenocarcinomas. PATIENTS AND METHODS We analyzed patients with unresectable stage IIIB-IV EGFR mutant lung adenocarcinomas and categorized them into two groups according to treatment modality and compared their outcomes; groups 1 and 2 consisted of patients who received EGFR TKI treatment alone until tumor progression and those who received and responded to EGFR TKI treatment and subsequently received thoracic RT for lung tumors, respectively. The patients in groups 2 and 1 were matched at a ratio of 1:4. RESULTS The matching process yielded a final cohort of 1475 patients (1180 and 295 patients in groups 1 and 2, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) derived for thoracic RT for lung tumor after EGFR TKI use and tumor response (group 2) compared with EGFR TKI treatment alone (group 1) was 0.72 (0.60-0.85). CONCLUSIONS Thoracic RT might be associated with overall survival in patients with unresectable stage IIIB-IV EGFR-mutant lung adenocarcinomas who received and responded to EGFR TKI treatment.

Recurrent aphthous stomatitis may be a precursor or risk factor for specific cancers: A case-control frequency-matched study

Recurrent aphthous stomatitis (RAS) is considered a prophase symptom in patients with specific cancers. This study assessed the association between RAS and subsequent onset of cancer based on a nationwide population‐based database in Taiwan.

Influenza vaccination might reduce the risk of ischemic stroke in patients with atrial fibrillation: A population-based cohort study

Purpose Atrial fibrillation (AF) is associated with the risk of ischemic stroke, regardless of the administration of appropriate antithrombotic prophylaxis. This study investigated whether influenza vaccination is associated with the risk of ischemic stroke, to determine a solution to reduce this risk in patients with AF. Methods We used data from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients diagnosed as having AF (n = 14 454) before January 1, 2005; these patients were followed until December 31, 2012. The index date was January 1, 2005. A propensity score was derived using a logistic regression model to estimate the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A Cox proportional hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in vaccinated and unvaccinated patients with AF. Results We included 6570 patients (2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001, respectively). Conclusions Influenza vaccination might exert a dose-response effect against ischemic stroke in patients with AF who have risk factors for ischemic stroke by reducing the incidence of ischemic stroke, particularly in those aged 65–74 and ≥75 y.