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Background: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC)., Methods: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used., Results: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04)., Conclusions: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy., (© 2020 Wiley Periodicals LLC.)

Purpose: Nephroureterectomy with bladder cuff excision may not be sufficient as monotherapy for patients with pT3N0M0 upper tract urothelial carcinoma. The efficacy of postoperative adjuvant chemotherapy in this setting remains controversial. We evaluated the efficacy of adjuvant chemotherapy for patients with pT3N0M0 upper tract urothelial carcinoma in overall, cancer specific and recurrence-free survival., Materials and Methods: We retrospectively reviewed records on 171 consecutive patients with pT3N0M0 upper tract urothelial carcinoma treated with radical nephroureterectomy between 2004 and 2014 at 2 branches of the same institution. Postoperative adjuvant chemotherapy was gemcitabine/cisplatin or cisplatin/fluorouracil/leucovorin. Overall, cancer specific and recurrence-free survival rates were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis., Results: Postoperative adjuvant chemotherapy was administered in 60 patients vs nonadjuvant therapy in 111 patients. Median followup was 35.8 months. Between the adjuvant and nonadjuvant treatment groups there were statistically significant differences in 5-year cancer specific (80.5% vs 57.6%, p = 0.010) and recurrence-free (74.4% vs 52.9%, p = 0.026) survival rates. Although there was no statistically significant difference in overall survival (71.9% vs 49.0%, p = 0.072), there was a trend of better overall survival in the patients who received postoperative chemotherapy. On multivariable analysis age (p = 0.018), tumor location (p = 0.003) and adjuvant chemotherapy (p = 0.001) were predictors of cancer specific survival., Conclusions: Adjuvant chemotherapy improves cancer specific and recurrence-free survival in patients with pT3N0M0 upper tract urothelial carcinoma after radical nephroureterectomy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Most studies on second primary malignancies (SPMs) after primary thyroid cancer were conducted in USA or Europe. The discrepancy between SPMs in these studies could be attributed to geographical and ethnic heterogeneity. Thus, there is a clear need for another large-scale epidemiological study, particularly in Asian countries, to define the incidence and risk of SPMs in thyroid cancer survivors., Design: A population-based study was conducted using the nation-wide database from Taiwan Cancer Registry between 1979 and 2006., Methods: We quantified standardized incidence ratios (SIRs) and cumulative incidence of SPMs among 19,068 individuals (4205 males and 14,863 females) with primary thyroid cancer., Results: A total of 644 cases (3.38%) developed at least a SPM during 134,678 person-years of follow-up. The risk for subsequent SPMs was significantly greater than that of the general population (SIR=1.33, 95% CI 1.23-1.44). There was a greater risk of developing major salivary glands, nasopharyngeal, lung, thymus, breast (females), bladder, and brain cancers, and leukemia and lymphoma. We observed that the risk was highest within the first 5 years of diagnosis of thyroid cancer (SIR=5.29, 1.68, and 0.68 for ≤ 5, 5-10, and >10 respectively) and in the younger patients (SIR=1.81 vs 1.61 for <50 and ≥ 50 respectively). The median overall survival for primary thyroid cancer patients was 23.28 years, but it was only 4.73 years for those who developed SPMs., Conclusion: Thyroid cancer is associated with a 33% risk increment of SPMs, which had a negative impact on survival. There are sites of SPMs in the Asian population that are distinctive from those in the Western population, suggesting that other genetic predisposition or environmental factors may play a role.

Background: Esophageal cancer is 1 of the 10 most common cancers and is a particular devastating form of cancer worldwide. More than 90% patients with esophageal cancer in Taiwan have squamous cell carcinoma (SCC). In the present study, we assessed the factors affecting survival of patients with esophageal cancer using data from Taiwan, a high-incidence area for esophageal SCC., Methods: We performed a retrospective review of 12,482 patients who were newly diagnosed with esophageal cancer from 1998 to 2007. The data were obtained from the National Health Insurance Research Database in Taiwan. Study participants were followed-up until the end of 2008., Results: Of the 12,482 patients, 11,490 (92.1%) were male with a median age of 60 years, and 992 (7.9%) were female with a median age of 71 years at the time of diagnosis. The overall 1-, 2-, 5-, and 10-year survival rates after diagnosis were 40.3, 22.9, 12.8, and 7.6%, respectively. Among parametric models for esophageal cancer prognosis, male sex, no curative treatment (surgery and/or radiotherapy), old age, and low socioeconomic status were significantly associated with shorter survival. Furthermore, curative treatment with surgery improved the survival of esophageal cancer patients more significantly compared with patients who undergo definite radiotherapy., Conclusions: Our data indicated that age, sex, and curative treatment were significant predictors of lifetime survival in patients with esophageal cancer. The overall survival rates of patients with esophageal cancer are relatively low, while survival of patients who undergo surgery is improved significantly.

Objective: The incidence of oral cavity cancers is increasing rapidly in South-East Asia, which may be attributable to tobacco smoking, alcohol and betel-nut chewing. However, the actual incidence and risk of second primary malignancies after oral cavity cancers have not been well established in this region. A population-based study was therefore conducted., Methods: Standardized incidence ratios and cumulative incidences were calculated for second primary cancers using the Taiwan Cancer Registry database for the period 1979-2003, which included 26 166 cases having an initial diagnosis of oral cavity cancers., Results: A 3.11-fold increase in risk for second cancer at all sites was observed after oral cavity cancers compared with the general population (standardized incidence ratio = 3.11, 95% confidence interval: 2.97-3.25). Of nine sites with excess risks of developing a second cancer, the frequency was highest in the oral/pharynx (60%), followed by lung (7.2%) and esophagus (5.5%). Second esophageal and lung cancers had a greater impact on survival compared with other types of second cancer. Notably, the risk excess was more prominent for patients with a follow-up interval of ≤ 1 year and a first primary cancer diagnosed at age of ≤ 40. These patients may justify closer surveillance., Conclusions: This is the largest population-based study with a homogeneous patient population focusing on oral cavity cancers within a high-incidence area. We found that oral cavity cancers are associated with an increased risk of nine second malignancies, which had a negative impact on survival.

Studies conducted in Western countries have reported excess risks for second primary malignancies after breast cancer. However, there is little documentation of ethnic differences in these excess risks. Asian women are characterized by younger age at diagnosis of breast cancer, but very few reports are available on the incidences and risks for second primary cancers in this region. Using population-based data from the Taiwan National Cancer Registry (TNCR) for the period 1979 to 2003, we quantified standardized incidence ratios and cumulative incidence of second cancers among 53,783 women with initial diagnoses of breast cancer. Age-specific incidences showed peaks among women in their 40s, and 1,085 cases (2.02%) developed nonbreast second primary cancers. The risk for second cancers differs significantly according to age at diagnosis of breast cancer. In comparison with women diagnosed when >or=50 years (standardized incidence ratio, 0.96; 95% confidence interval; 0.89-1.04), there were significantly greater risks for bone, corpus uterine, ovarian, thyroid, esophageal, kidney and lung cancers, nonmelanoma skin cancer, and leukemia or lymphoma in women diagnosed when <50 years (standardized incidence ratio, 1.43; 95% confidence interval, 1.29-1.58). The survival probabilities differed between breast cancer patients with and without second cancers (P<0.001). After diagnosis of the second cancer, the median survival time was only 2.87 years. In conclusion, we confirmed that young age at diagnosis of breast cancer predicted a subsequently increased risk for second malignancies, and the second cancers indeed worsen survivorship in patients who survived breast cancer.

Background: This study was undertaken to determine the status of cyclooxygenase-2 (COX-2) in nasopharyngeal cancer (NPC) in Taiwanese patients and its relationship to survival after radiotherapy (RT). In addition, the effect of NS-398, a potent selective COX-2 inhibitor, was tested in vitro alone and in combination with radiation on NPC-BM1 human NPC cells as a prelude to using this drug along with RT in the treatment of patients with NPC., Methods: Thirty-seven patients diagnosed with T4N0-3M0 NPC were enrolled into this study. COX-2 expression was determined by immunohistochemical staining of formalin-fixed, paraffin-embedded tumor tissue. Patient survival was the clinical end point. The effects of COX-2 expression on cell survival and radioresistance was tested in vitro using the selective COX-2 inhibitor NS-398 in conjunction with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) and clonogenic assays., Results: COX-2 immunoreactivity was detected in 62% of NPC tumors, and expression levels were high in 43%. Survival analysis showed the 5-year overall survival rates for patients who had high COX-2 expression was 27% compared with 60% for those with low/absent expression (p = .047). Pattern of failure analysis showed no significant difference between high and low COX-2 expression in locoregional failure (27% vs 25%, p = .91). However, patients with N0 to N1 disease and high COX-2 expression had a significantly higher incidence of distant metastasis compared with patients with stage N0 to N1 disease and low COX-2 expression (83% vs 15%, p = .004). This difference was not observed in patients with N2 to N3 disease. This difference contributed to worse survival of patients whose tumors had high COX-2 expression levels. The selective COX-2 inhibitor NS-398 was directly cytotoxic to NPC-BM1 cells in vitro, as judged in an MTT assay (viable cells decreased from 92% to 76%, 52%, and 22%, with increases of NS-398 from 20 to 40, 60, and 80 microM, respectively). Radiation-induced cell death was also increased by treatment with NS-398. At a 10% survival level, 40 microM NS-398 increased radiation cytotoxicity by a factor of 1.37, whereas 60 microM increased it by a factor of 4.9., Conclusions: COX-2 overexpression is a predictor for poor survival for advanced stage NPC. In vitro, NS-398 radiosensitizes the NPC-BM1 cell line, providing a basis for testing the combination of COX-2 inhibitors with radiation in the treatment of patients with NPC., ((c) 2005 Wiley Periodicals, Inc.)

This retrospective study reports on the treatment outcomes of 45 men with penile cancer and seeks to address the issue concerning the treatment of inguinal lymph nodes (LN). Of these 45 patients, five had verrucous carcinoma and the other 40 had squamous cell carcinoma. Eighteen patients had inguinal lymph nodes (LNs) metastasis and received treatments of inguinal LNs involving bilateral inguinal LN dissection or unilateral inguinal LN dissection with or without postoperative radiotherapy. The median follow-up was 37 months. The ultimate local and regional controls for patients with verrucous carcinoma were 100 and 100%, respectively. Among the 40 patients with squamous cell carcinoma, the overall local control rate was 90%. The 5-year overall survival (OS) and disease-free survival (DFS) rates of patients without or with pathological inguinal LN metastasis were 70 vs. 22% (p=0.01), and 55 vs. 16% (p=0.004), respectively. The regional failure rates after inguinal LN dissection for pathological inguinal LN metastasis were 11% (1/9) and 60% (3/5) in patients with and without adjuvant radiotherapy. This study demonstrates that verrucous carcinoma shows excellent treatment outcomes following surgery alone. Squamous cell carcinoma of the penis is associated with a high incidence of inguinal lymph node metastasis. Elective groin dissection is indicated for all penile cancer patients except those with verrucous carcinoma and pT1 cancer with well-differentiated tumor. For patients with pathologically positive inguinal LN metastasis, adjuvant radiotherapy can increase inguinal control in this study. It warrants further prospective trial to prove the value of adjuvant radiotherapy in patients with pathological documented inguinal LN metastasis in penile cancer.