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Objective: We conducted this propensity score (PS)-matched, nationwide, population-based cohort study to estimate the effects of adjuvant oral or intravenous (IV) fluoropyrimidine in patients with high-risk stage II or III colon adenocarcinoma. Design: Using PS matching, we minimized the confounding effects on adjuvant oral or IV fluoropyrimidine outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. Setting: We selected patients from the Taiwan Cancer Registry database receiving adjuvant fluoropyrimidine monotherapy and divided them into those receiving IV fluoropyrimidine (IV group) and those receiving oral fluoropyrimidine (oral group). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) derived for the oral group was 1.34 (95% CI: 1.19-1.51) compared with the IV group. Moreover, in both univariate and multivariate analyses, aHR derived for significant independent prognostic risk factors for poor overall survival were male sex, age ≥ 60 years old, pathologic stage III, right-sided colon cancer, low income, and high Charlson comorbidity index. However, intergroup differences were not significant among female patients or patients < 60 years old on multivariate analysis, including no difference in overall survival. Conclusions: Adjuvant IV fluoropyrimidine is more suitable than adjuvant oral fluoropyrimidine for patients with stage II colon adenocarcinoma who have high-risk pathologic features or stage III colon adenocarcinoma.

There is currently no system to predict 90-day morality among patients with locally advanced head and neck squamous cell carcinoma (HNSCC) after the completion of concurrent chemoradiotherapy (CCRT).To validate the accuracy of a predictive scoring system for 90-day mortality among patients with locally advanced HNSCC who have completed CCRT.This prognostic study included 16 029 patients with HNSCC who completed CCRT between January 2006 and December 2015. Data were extracted from the Taiwan Cancer Registry Database. A risk scoring system was developed based on significant risk factors and corresponding risk coefficients. Data analysis was conducted from June 2018 to February 2019.Mortality within 90 days of completion of definitive CCRT.The 90-day mortality rate after completion of CCRT and the accuracy of the scoring system, based on a comparison of mortality rates between training and test data sets.Among 16 029 patients with locally advanced HNSCC, 1068 (6.66%; 1016 [95.1%] men; mean [SD] age, 55.11 [11.45] years) died before reaching the 90-day threshold, and 14 961 (93.4%; 14 080 [94.1%] men; mean [SD] age, 52.07 [9.99] years) survived. Multivariable analysis revealed that being aged 50 years or older (adjusted hazard ratio [aHR], 1.263; 95% CI, 1.104-1.445; P .001), being aged 70 years or older (aHR, 2.183; 95% CI, 1.801-2.645; P .001), having pneumonia (aHR, 1.946; 95% CI, 1.636-2.314; P .001), having sepsis (aHR, 3.005; 95% CI, 2.503-3.607; P .001), having hemiplegia (aHR, 1.430; 95% CI, 1.085-1.884; P = .01), having moderate or severe renal disease (aHR, 2.054; 95% CI, 1.643-2.568; P .001), having leukemia (aHR, 4.541; 95% CI, 1.132-8.207; P = .03), and having non-HNSCC metastatic solid cancers (aHR, 1.457; 95% CI, 1.292-1.644; P .001) were significant risk factors for 90-day mortality. Risk scores were categorized as very low risk (score of 0), low risk (score 1-3), moderate risk (score 4-6), and high risk (score ≥7), with 90-day mortality rates of 3.37%, 5.00% to 10.98%, 16.15% to 29.13%, and 33.93% to 37.50%, respectively. Mortality rates for patients with the same risk score in the training and test data sets were similar (score of 0, 3.27% vs 3.66%; score of 6, 27.42% vs 25.00%).In this prognostic study, a 90-day mortality scoring system accurately predicted 90-day mortality among patients with locally advanced HNSCC who completed CCRT.

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.

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.

Background 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. Materials and Methods We selected study participants from the National Health Insurance Research Database from January 2000 to December 2008. Patients in the non‐RAS cohort were matched to case study patients at a 1:1 ratio through frequency matching. All participants were followed up for at least 5 years, and those who received cancer diagnoses during follow‐up were identified. Results Among 52 307 patients with and 52 304 patients without RAS, the combined hazard ratio (HR) of all subsequent cancer cases was 1.3 (95% confidence interval [CI]: 1.25‐1.35, P = 0). RAS diagnosis was associated with risk for cancers of the head and neck (aHR = 2, 95% CI: 1.8‐2.3), colon (aHR = 1.2, 95% CI: 1.1‐1.4), liver (aHR = 1.1, 95% CI: 1‐1.3), pancreas (aHR = 1.4, 95% CI: 1.1‐1.7), skin (aHR = 1.4, 95% CI: 1.2‐1.7), breast (aHR = 1.2, 95% CI: 1.1‐1.4), and prostate (aHR = 1.5, 95% CI: 1.3‐1.8), as well as hematologic cancers (aHR = 1.6, 95% CI: 1.3‐1.9). A higher risk was observed for male patients (aHR = 1.35, 95% CI: 1.28‐1.42) than for female patients (aHR = 1.25, 95% CI: 1.18‐1.31) with RAS. Conclusions RAS was associated with specific cancers. Susceptible RAS patients should be screened for specific cancers.

BACKGROUND 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). METHODS The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

Background: Here, we compared the toxicity profiles of contemporary stereotactic radiosurgery (SRS), modern fractionated radiotherapy (FRT), and transsphenoidal surgery used to treat nonfunctioning pituitary macroadenomas. Methods: We included the data of patients with nonfunctioning pituitary macroadenomas. To compare treatment outcomes, the patients were categorized groups 1 (those receiving modern FRT), 2 (those receiving contemporary SRS), and 3 (those receiving transsphenoidal surgery). The multivariable Cox proportional hazards regression analysis was performed to yielded adjusted hazard ratios (aHRs) and their 95% CIs for local recurrence in groups 2 and 3 compared with group 1. Results: We included the data of 248 patients with nonfunctioning pituitary macroadenomas. The analytical results revealed no significant differences in second primary brain or head and neck cancer, hypopituitarism, or optic nerve injury between the three cohorts. The multivariable Cox proportional hazards regression analysis revealed that compared with group 1, the aHRs (95% CIs) for stroke risk in groups 2 and 3 were 0.37 (0.14&ndash, 0.99) and 0.51 (0.31&ndash, 0.84), respectively. Conclusion: Contemporary SRS and transsphenoidal surgery for nonfunctioning pituitary macroadenoma treatment have equivalent toxicity profiles. However, modern FRT for nonfunctioning pituitary macroadenoma treatment might considerably increase stroke risk.

Background: To date, intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) and CCRT with standard fractionation three-dimensional conformal radiation therapy (3D-CRT) have not been compared. In this study, the outcomes of IMRT-based concurrent CCRT and those of 3D-CRT-based CCRT were compared in patients with thoracic esophageal squamous cell carcinoma (TESCC). Methods: We enrolled 2062 patients with TESCC who had received CCRT and categorized them into two groups on the basis of their treatment modality: Group 1 (3D-CRT-based CCRT) and Group 2 (IMRT-based CCRT). Results: Multivariate Cox regression analysis indicated that the American Joint Committee on Cancer advanced stages (&ge, IIIA) and 3D-CRT were significant independent predictors of poor outcomes in patients with TESCC who received definitive CCRT. Moreover, receiving IMRT-based CCRT (adjusted hazard ratio [aHR]: 0.88, 95% confidence interval [CI]: 0.78&ndash, 0.98) was a significant independent prognostic factor for overall survival (p = 0.0223). In Group 2, aHRs (95% CIs) for overall mortality at early (IA&ndash, IIB) and advanced clinical stages were 0.91 (0.67&ndash, 1.25, p = 0.5746) and 0.88 (0.77&ndash, 0.99, p = 0.0368), respectively. Conclusion: IMRT-based CCRT resulted in higher survival rates in patients with advanced clinical stages of TESCC (i.e., IIIA&ndash, IIIC), namely, clinical T3, clinical T4, or lymph node involvement.

Background: To compare the effects of contemporary stereotactic radiosurgery (SRS), modern fractionated radiotherapy (FRT), and transsphenoidal surgery on nonfunctioning pituitary macroadenoma. Methods: We enrolled patients with nonfunctioning pituitary macroadenoma. To compare treatment outcomes, the patients were categorized into three groups according to the treatment modality: group 1, patients receiving modern FRT, group 2, patients receiving contemporary SRS, and group 3, patients receiving transsphenoidal surgery. Results: In total, 548 patients with nonfunctioning pituitary macroadenoma were selected for our study. Univariate and multivariate Cox regression analysis results indicated that the treatment modalities were significant independent prognostic factors. In multivariable Cox proportional hazard regression analysis, the adjusted hazard ratios (aHR, 95% confidence interval (CI)) of local recurrence were 0.27 (0.10&ndash, 0.91) and 1.95 (1.25&ndash, 2.37) for the SRS and transsphenoidal surgery cohorts, respectively, in comparison with the FRT cohort. The aHR (95% CI) of all-cause mortality was 1.03 (0.68&ndash, 1.56) for the transsphenoidal surgery cohort in comparison with the FRT cohort, without statistical significance. However, the aHR (95% CI) of all-cause mortality was 0.36 (0.15&ndash, 0.85) for the SRS cohort in comparison with the FRT cohort. Conclusion: Contemporary SRS has optimal effects on local recurrence and survival compared with modern FRT and transsphenoidal surgery. Modern FRT is associated with more favorable local control and equal survival compared with transsphenoidal surgery.

BACKGROUND 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. METHODS The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. CONCLUSIONS Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043–2053. © 2017 American Cancer Society.

We examined the overall survival rates of a national cohort to determine optimal treatments and prognostic factors for patients with metachronous second primary head and neck squamous cell carcinomas (mspHNSCCs) at different stages and sites. We analyzed data of mspHNSCC patients collected from the Taiwan Cancer Registry database. The patients were categorized into four groups based on the treatment modality: Group 1 (control arm; chemotherapy [CT] alone), Group 2 (reirradiation [re‐RT] alone with intensity‐modulated radiotherapy [IMRT]), Group 3 (concurrent chemoradiotherapy alone [irradiation with IMRT]), and Group 4 (salvage surgery with or without RT or CT). We enrolled 1741 mspHNSCC patients without distant metastasis. Multivariate Cox regression analyses revealed that Charlson comorbidity index (CCI) ≥6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of

// Ju-Chi Liu 1, 4, * , Wen-Rui Hao 1, * , Yi-Ping Hsu 1 , Li-Chin Sung 1, 4 , Pai-Feng Kao 1, 4 , Chao-Feng Lin 1 , Alexander T.H. Wu 6 , Kevin Sheng-Po Yuan 7 , Szu-Yuan Wu 2, 3, 4, 5 1 Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan 2 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 3 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 Department of Biotechnology, Hungkuang University, Taichung, Taiwan 6 Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 7 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Szu-Yuan Wu, email: szuyuanwu5399@gmail.com Keywords: statins, chronic obstructive pulmonary disease, colon cancer Received: March 22, 2016 Accepted: June 27, 2016 Published: August 12, 2016 ABSTRACT 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 [ 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.

Lei Qin,1,* Yi-Wei Kao,2,* Yueh-Lung Lin,3 Bou-Yue Peng,4 Win-Ping Deng,5 Tsung-Ming Chen,6 Kuan-Chou Lin,7 Kevin Sheng-Po Yuan,8 Alexander TH Wu,9 Ben-Chang Shia,10 Szu-Yuan Wu11–14 1School of Statistics, University of International Business and Economics, Beijing, China; 2Graduate Institute of Business Administration, Fu Jen Catholic University, Taipei, Taiwan; 3School of Mathematical Sciences, University of Nottingham, Ningbo, China; 4Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 5Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan; 6Department of Otorhinolaryngology, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Oral and Maxillofacial Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 8Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 9PhD Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan; 10College of Management, Taipei Medical University, Taipei, Taiwan; 11Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China; 12Department of Radiation Oncology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 13Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 14Epidemiology and Bioinformatics Center, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Background: Few studies have evaluated the risk of oral cavity cancer (OC) in patients with recurrent oral aphthae (ROA) and dry eye syndrome (DES). This study assessed the risk of OC in patients who had received diagnoses of ROA and DES in Taiwan.Methods: A population-based frequency-matched case–control study was conducted in which data were analyzed from the National Health Insurance Research Database of Taiwan. Patients with ROA and DES were identified as the case cohort. Patients and controls without ROA and DES were frequency matched (1:4) on the basis of age, sex, monthly income, geographical location, and urbanization level. Chi-squared tests were conducted to compare demographic factor distributions between the patients and controls. Cox proportional hazards models were used to calculate the adjusted hazard ratios (aHRs) and 95% CI of OC diagnoses among the patients and controls. Risk consistency between the two cohorts was determined using subgroup analysis.Results: A total of 7,110 patients with ROA and DES and 28,388 controls were identified. The OC risk was significantly higher for female patients than controls (aHR=3.41, 95%CI=1.69–6.86). Furthermore, women aged 50–69 years exhibited a higher risk of OC than those in the other age groups. Female patients aged 50–59 years exhibited the highest aHR for OC (aHR=5.56, 95%CI=1.70–18.25), followed by those aged 60–69 years (aHR=4.34, 95%CI=1.26–15.99).Conclusion: ROA and DES may be associated with a high risk of OC in elderly women. Keywords: risk factor, oral cavity cancer, recurrent oral aphthae, dry eye syndrome, women

In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively. Moreover, fucoidan reduced the luciferase activity of 3'-untranslated region reporter; treatment of cells with the miR-29c mimic or miR-17-5p inhibitor also produced similar results. These effects of fucoidan inhibited the epithelial-mesenchymal transition in breast cancer cells, as evidenced by an increase in E-cadherin and a drop in N-cadherin, and inhibited breast cancer cell survival, as evidenced by the activation of the phosphoinositide 3-kinase/Akt pathway. Taken together, these findings demonstrate that fucoidan inhibits breast cancer progression by regulating the miR-29c/ADAM12 and miR-17-5p/PTEN axes. Fucoidan is a potential chemopreventive/chemotherapeutic agent for breast cancer.

Purpose In the era of intensity-modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of IMRT exclusively, such as concurrent chemoradiotherapy (CCRT), sequential induction chemotherapy followed by radiotherapy (CT-RT), and systemic chemotherapy (CT) alone, for treating unresectable pancreatic adenocarcinomas (PAs) without metastasis. Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of various treatments on unresectable PAs. Patients and methods We minimized the confounding effects of various treatment outcomes in patients with unresectable PAs from the Taiwan Cancer Registry database by dividing them as follows: group 1, CCRT; group 2, sequential CT-RT; group 3, nontreatment; and group 4, CT alone. Results The matching process yielded a final cohort of 2960 patients (740 patients each in groups 1, 2, 3, and 4). In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (95% confidence interval) derived for the definitive CCRT and sequential CT-RT groups compared with the CT alone group were 0.443 (0.397–0.495) and 0.633 (0.568–0.705), respectively. Conclusions A combination of IMRT and systemic CT for the treatment of unresectable PAs might increase survival compared with CT alone.

The risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy (CT) and radiotherapy (RT) is yet to be investigated in a large-scale randomized controlled trial with an adequate sample size of young and old women with breast cancer. To compare the occurrence of major heart events (heart failure and coronary artery disease) in patients with breast cancer, 3489 women who underwent surgical resection of the breast tumor were retrospectively selected from the Taiwan National Health Insurance Research Database. The patients were categorized into the following groups based on their treatment modalities: group 1 (n = 1113), no treatment; group 2 (n = 646), adjuvant RT alone; group 3 (n = 705), adjuvant anthracycline-based CT alone; and group 4 (n = 1025), combined adjuvant RT and anthracycline-based CT. The mean patient age was 50.35 years. Subsequent coronary artery disease and heart failure were identified in 244 (7.0%) and 206 (5.9%) patients, respectively. All three adjuvant therapies were significant independent prognostic factors of major heart events (adjusted hazard ratio [95% confidence interval]: 1.47 [1.24–1.73]; 1.48 [1.25–1.75], and 1.92 [1.65–2.23] in groups 2, 3, and 4, respectively). In patients aged ≥50 years with breast cancer who underwent surgery, the log-rank p values of groups 2 and 3 after adjustment were 0.537 and 0.001, respectively. Adjuvant RT can increase cardiotoxicity in patients with breast cancer, particularly when used in combination with anthracycline-based CT. Therefore, it should be offered with optimal heart-sparing techniques, particularly in younger patients with good prognosis and long life expectancy.

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).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 CCRT60Gy with IMRT, and group 2, who received CCRT≥60Gy with IMRT. Group 1 was used as the control for investigating posttreatment mortality risk.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 (P0.0001). After adjustment for confounders, the aHRs (95% CIs) for overall mortality at all clinical stages were 0.75 (0.68-0.83, P0.0001) 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, P0.0001), respectively.Compared with standard-dose IMRT-based CCRT, high-dose IMRT-based CCRT yields more favorable survival outcomes in patients with advanced-stage TESCC.

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).The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment.In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3.Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

Purpose: To determine the optimal adjuvant chemotherapy regimen for patients with high-risk stage II or III colon adenocarcinoma, we conducted this propensity score-matched, nationwide, population-based cohort study to estimate the effects of adjuvant treatments in high-risk stage II or III colon adenocarcinoma. Patients and Methods: Using propensity score matching, we minimized the confounding effects of sex, age, pathologic stage, tumor location, total chemotherapy cycles, and Charlson comorbidity index scores on adjuvant treatment outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. We selected the patients from the Taiwan Cancer Registry database and divided them into four groups: Group 1, comprising patients who received surgery alone, group 2, comprising those who received adjuvant fluoropyrimidine alone, group 3, comprising those who received adjuvant oxaliplatin-fluoropyrimidine-leucovorin (FOLFOX), and group 4, comprising those who received adjuvant folinic acid-fluorouracil-irinotecan (FOLFIRI). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs, as well as the 95% confidence intervals (Cis)) for mortality observed for groups 1, 2, and 4 relative to group 3 were 1.55 (1.32 to 1.82), 1.22 (1.05 to 1.43), and 2.97 (2.43 to 3.63), respectively. After a stratified subgroup analysis for high-risk stage II colon adenocarcinoma, we noted that the aHR (95% CI) for mortality for group 2 relative to group 3 was 0.52 (0.30 to 0.89). Conclusions: Adjuvant fluoropyrimidine alone is the most optimal regimen for patients with high-risk stage II colon adenocarcinoma compared with the other adjuvant chemotherapy regimens. Adjuvant FOLFOX can serve as an optimal regimen for patients with pathologic stage III colon adenocarcinoma, regardless of age, sex, or tumor location.

Background To compare the toxicity profiles of contemporary stereotactic radiosurgery (SRS), fractionated radiotherapy (FRT) with modern techniques, or transsphenoidal surgery on nonfunctioning pituitary macroadenoma. Methods We enrolled patients with nonfunctioning pituitary macroadenoma and categorized them into three groups according to treatment modality to compare treatment outcomes: group 1, those receiving modern FRT; group 2, those receiving contemporary SRS; and group 3, that receiving transsphenoidal surgery. Results 248 patients in total with nonfunctioning pituitary macroadenoma were selected in our study. In multivariable Cox proportional hazards regression analysis, adjusted HRs (aHRs; 95% confidence interval [CI]) of local recurrence were derived for the SRS and transsphenoidal surgery cohorts compared with the FRT cohort was no significant difference in secondary primary brain or head and neck cancers, hypopituitarism, and optic nerve injury between three treatment cohorts. In multivariable Cox proportional hazards regression analysis, adjusted HRs (aHRs; 95% confidence interval [CI]) of stroke risk were derived for the SRS and transsphenoidal surgery cohorts compared with the FRT cohort were 0.37 (0.14-0.99) and 0.51 (0.31-0.84), respectively. Conclusions Contemporary SRS and transsphenoidal surgery in treatment of nonfunctioning pituitary macroadenoma would bring in equal toxicity profiles. Modern FRT might increase risk of stroke in treatment of nonfunctioning pituitary macroadenoma significantly. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

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.The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment.In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease.Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society.

// Yen-Kuang Lin 1 , Han-Lin Hsu 2,3 , Wei-Cheng Lin 4 , Jer-Hwa Chang 2,3 , Yw-Chun Chang 4 , Chia-Lun Chang 5 , Kevin Sheng-Po Yuan 6 , Alexander T.H. Wu 7 and Szu-Yuan Wu 8,9,10,11* 1 Biostatistics Center and School of Public Health, Taipei Medical University, Taipei, Taiwan 2 Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 3 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Division of Thoracic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 5 Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 6 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 7 Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 8 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 9 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 10 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 11 Department of Biotechnology, Hungkuang University, Taichung, Taiwan Correspondence to: Szu-Yuan Wu, email: // Keywords : lung cancer, pN2, survival, adjuvant radiotherapy Received : August 26, 2016 Accepted : October 28, 2016 Published : November 09, 2016 Abstract Purpose: Few large, prospective, randomized studies have compared the effects of postoperative radiotherapy (PORT) in pathological N2 (pN2) with those of surgical resection alone. in terms of long-term survival in lung adenocarcinoma (adenoCA; wild-type [WT] epidermal growth factor receptor [EGFR]) and squamous cell carcinoma (squCA) settings. This nationwide cohort study clarifies the role of PORT in the survival of pN2 lung adenoCA (WT EGFR) and squCA patients Patients and Methods: We analyzed data of patients with adenoCA (WT EGFR) and squCA collected from the Taiwan Cancer Registry database. The patients were categorized into five groups according to the treatment modality: Group 1 (surgery alone), Group 2 (adjuvant chemotherapy [CT] alone), Group 3 (adjuvant radiotherapy [RT] alone), Group 4 (adjuvant concurrent chemoradiotherapy [CCRT]), and Group 5 (adjuvant sequential CT and intensity-modulated RT [IMRT]). Results: We enrolled 588 lung adenoCA (WT EGFR) and squCA patients without distant metastasis. After adjustments for age at surgery, surgical years, and Charlson comorbidity index scores, the multivariate Cox regression analysis demonstrated that adjusted HRs (aHRs; 95% confidence intervals [CIs]) for the overall mortality of female lung adenoCA (WT EGFR) patients were 0.257 (0.111-0.594), 0.530 (0.226-1.243), 0.192 (0.069-0.534), and 0.399 (0.172-0.928) in Groups 2, 3, 4, and 5, respectively. For male lung squCA patients, the aHRs (95% CIs) for overall mortality were 0.269 (0.160-0.451), 0.802 (0.458-1.327), 0.597 (0.358-0.998), and 0.456 (0.265-0.783) in Groups 2, 3, 4, and 5, respectively. Conclusions: Adjuvant CCRT or sequential CT and IMRT at ≥5000 cGy significantly reduced the mortality rate of female lung adenoCA (WT EGFR) and male squCA pN2 patients.

// Jer-Hwa Chang 1,2 , Chia-Che Wu 3 , Kevin Sheng-Po Yuan 3 , Alexander T.H. Wu 4 and Szu-Yuan Wu 5,6,7 1 Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 2 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4 The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan 5 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 6 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 7 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Correspondence to: Szu-Yuan Wu, email: // Keywords : head and neck cancer; recurrence; incidence; survival; prognostic factors Received : June 09, 2016 Accepted : February 15, 2017 Published : March 17, 2017 Abstract Purpose: For locoregionally recurrent head and neck squamous cell carcinoma (HNSCC), appropriate therapeutic decisions remain unclear. We examined the treatment outcomes of a national cohort to determine suitable treatments for and prognostic factors in patients with locoregionally recurrent HNSCCs at different stages and sites. Patients and methods: We analyzed data of >20-year-old patients with HNSCC at American Joint Committee on Cancer clinical stages I–IV without metastasis from Taiwan National Health Insurance and cancer registry databases. The index date was the date of recurrent HNSCC diagnosis. Recurrent HNSCC was defined as the annotation of locoregional recurrence with tissue proof in cancer registry databases. The enrolled patients were categorized into three groups: Group 1 comprised those undergoing chemotherapy (CT) alone; Group 2 comprised those receiving reirradiation (re-RT) alone (total radiation dose ≥ 60 Gy through intensity modulation radiation therapy [IMRT]); Group 3 comprised those receiving concurrent chemoradiotherapy (CCRT) alone (irradiation total dose ≥60 Gy through IMRT); and Group 4 comprised those receiving salvage surgery with or without RT or CT. Results: We enrolled 4,839 and 28,664 HNSCC patients with and without locoregional recurrence, respectively (median follow-up, 3.25 years). Locoregional recurrence rate and incidence were 14.44% and 40.73 per 1,000 person-years, respectively. Age ≥ 65 years, Charlson comorbidity index (CCI) score > 6, advanced clinical stage at first diagnosis, and recurrence-free interval < 1 year were significant independent prognostic risk factors for overall survival as per univariate and multivariate Cox regression analyses. After adjusting for age, sex, CCI scores, clinical stage at first diagnosis, and recurrence-free interval, adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for overall mortality in recurrent clinical stages I and II were 0.63 (0.45–0.89, p = 0.009), 0.65 (0.52–0.83, p < 0.001), and 0.32 (0.26–0.40, p < 0.001) in Groups 2, 3, and 4, respectively, whereas they were 1.23 (0.99–1.52, p = 0.062), 0.69 (0.60–0.79, p < 0.001), and 0.39 (0.34–0.44, p < 0.001) for Groups 2, 3, and 4, respectively, for overall mortality in recurrent clinical stage III and IV. Conclusions: Age, CCI score, clinical stage at first diagnosis, and recurrence-free interval are significant independent prognostic factors for overall survival of recurrent HNSCC patients. Regardless of recurrence stage or site, salvage surgery is the recommended first recurrent HNSCC treatment choice. Re-RT alone and CCRT are more suitable for inoperable recurrent early-stage oral and nonoral cavity recurrent HNSCCs, respectively.

Purpose: To propose a risk classification scheme for locoregionally advanced (Stages III and IV) head and neck squamous cell carcinoma (LA-HNSCC) by using the Wu comorbidity score (WCS) to quantify the risk of curative surgeries, including tumor resection and radical neck dissection. Methods: This study included 55,080 patients with LA-HNSCC receiving curative surgery between 2006 and 2015 who were identified from the Taiwan Cancer Registry database, the patients were classified into two groups, mortality (n = 1287, mortality rate = 2.34%) and survival (n = 53,793, survival rate = 97.66%), according to the event of mortality within 90 days of surgery. Significant risk factors for mortality were identified using a stepwise multivariate Cox proportional hazards model. The WCS was calculated using the relative risk of each risk factor. The accuracy of the WCS was assessed using mortality rates in different risk strata. Results: Fifteen comorbidities significantly increased mortality risk after curative surgery. The patients were divided into low-risk (WCS, 0&ndash, 6, 90-day mortality rate, 0&ndash, 1.57%), intermediate-risk (7&ndash, 11, 2.71&ndash, 9.99%), high-risk (12&ndash, 16, 17.30&ndash, 20.00%), and very-high-risk (17&ndash, 18 and &gt, 18, 46.15&ndash, 50.00%) strata. The 90-day survival rates were 98.97, 95.85, 81.20, and 53.13% in the low-, intermediate-, high-, and very-high-risk patients, respectively (log-rank p &lt, 0.0001). The five-year overall survival rates after surgery were 70.86, 48.62, 22.99, and 18.75% in the low-, intermediate-, high-, and very-high-risk patients, respectively (log-rank p &lt, 0.0001). Conclusion: The WCS is an accurate tool for assessing curative-surgery-related 90-day mortality risk and overall survival in patients with LA-HNSCC.