Wen-Yen Chiou

Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

PURPOSE Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. METHODS AND MATERIALS The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n=1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n=4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. RESULTS Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p=0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio=0.87; 95% CI, 0.56-1.33; p=0.524) after adjusting for other factors. CONCLUSIONS Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

Higher caseload improves cervical cancer survival in patients treated with brachytherapy

ObjectivesIncreased caseload has been associated with better patient outcomes in many areas of health care, including high-risk surgery and cancer treatment. However, such a positive volume vs. outcome relationship has not yet been validated for cervical cancer brachytherapy. The purpose of this study was to examine the relationship between physician caseload and survival rates in cervical cancer treated with brachytherapy using population-based data.MethodsBetween 2005 and 2010, a total of 818 patients were identified using the Taiwan National Health Insurance Research Database. Multivariate analysis using a Cox proportional hazards model and propensity scores was used to assess the relationship between 5-year survival rates and physician caseloads.ResultsAs the caseload of individual physicians increased, unadjusted 5-year survival rates increased (P = 0.005). Using a Cox proportional hazard model, patients treated by high-volume physicians had better survival rates (P = 0.03), after adjusting for comorbidities, hospital type, and treatment modality. When analyzed by propensity score, the adjusted 5-year survival rate differed significantly between patients treated by high/medium-volume physicians vs. patients treated by low/medium-volume physicians (60% vs. 54%, respectively; P = 0.04).ConclusionsProvider caseload affected survival rates in cervical cancer patients treated with brachytherapy. Both Cox proportional hazard model analysis and propensity scores showed association between high/medium volume physicians and improved survival.

High Incidence of Ischemic Stroke Occurrence in Irradiated Lung Cancer Patients: A Population-Based Surgical Cohort Study

Background and Purpose A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients. Methods A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint. Results Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44–12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001). Conclusions A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.

Clinical and Pathologic Factors Affecting Lymph Node Yields in Colorectal Cancer

Objective Lymph node yield is recommended as a benchmark of quality care in colorectal cancer. The objective of this study was to evaluate the impact of various factors upon lymph node yield and to identify independent factors associated with lymph node harvest. Materials and Methods The records of 162 patients with Stage I to Stage III colorectal cancers seen in one institution were reviewed. These patients underwent radical surgery as definitive therapy; high-risk patients then received adjuvant treatment. Pathologic and demographic data were recorded and analyzed. The subgroup analysis of lymph node yields was determined using a t-test and analysis of variants. Linear regression model and multivariable analysis were used to perform potential confounding and predicting variables. Results Five variables had significant association with lymph node yield after adjustment for other factors in a multiple linear regression model. These variables were: tumor size, surgical method, specimen length, and individual surgeon and pathologist. The model with these five significant variables interpreted 44.4% of the variation. Conclusions Patients, tumor characteristics and surgical variables all influence the number of lymph nodes retrieved. Physicians are the main gatekeepers. Adequate training and optimized guidelines could greatly improve the quality of lymph node yields.

Prognosticators and the relationship of depression and quality of life in head and neck cancer.

BACKGROUND AND PURPOSE To evaluate the relationship of emotional status and health-related quality of life (HRQOL) in disease-free head and neck cancer (HNC) patients post treatment and to explore their predictive factors. MATERIALS AND METHODS Seventy-three HNC patients, post treatment at least 1 year, were recruited to complete three questionnaires, EORTC QLQ-C30, EORTC-H&N35 cancer module, and the Beck Depression Inventory-II (BDI-II). RESULTS Patients with depression demonstrated significantly poor global health status/QoL (score 41.7 vs. 71.9, P<0.001) and almost all functioning, except for role functioning. Besides, depressive patients presented statistically significant worse symptoms in all QLQ-C30 items, except constipation and financial problems, and in all QLQ-H&N35 symptoms except for teeth and coughing problems. Depression was significantly negative correlated with all functional scales and global health status/QoL (r = -0.341 to -0.750, all P<0.05), and was significantly positive correlated with symptom scales (r = 0.348 to 0.793, all P<0.05), except for constipation. Stepwise multiple linear regression analyses showed that physical functioning and physical distressful symptoms play an important role in the perception of HRQOL (total 46% explained). Global health status and impaired social functioning could explain depression in addition to emotional functioning (total 64% explained). CONCLUSIONS HNC patients with depression were noted to have poorer HRQOL in almost every functioning symptom. HNC patients may get benefit from early interventions to improve HRQOL, emotional status, or both by a more rapid and friendly questionnaire to earlier identify patients with poor HRQOL or depressive status.

Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo

Radiation therapy (RT) is the current standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Radioresistance is a major contributor to radiotherapy failure. In this study, we used patient-derived cells and a radiation-resistant cell line in vitro and in vivo for two purposes: evaluate the anti-tumor effects and understand the mechanisms in the dual PI3K/mTOR signaling pathway regulation of radiosensitization. Our findings indicate that in OML1-R cells, the radioresistance phenotype is associated with activation of the PI3K/AKT/mTOR signaling pathway. Compared to a combination of PI3K or mTOR inhibitors and radiation, dual blockade of the PI3K and mTOR kinases significantly improved radiation efficacy in oral cancer and patient-derived OSCC cells. Dual PI3K/mTOR inhibition enhanced the effect of radiation by inhibiting AKT/mTOR signaling pathways and caused G1 phase arrest, which is associated with downregulation of cyclin D1/CDK4 activity, leading to growth inhibition. In nude mice xenografted with radioresistant OML1-R cells, the combined treatment was also more effective than RT alone in reducing tumor growth. This treatment was also demonstrated to be dependent on the inhibition of protein kinase-dependent S6 kinase pathway and eIF4E-mediated cap-dependent translation. These findings indicate that activation of the PI3K/AKT/mTOR signaling pathway has a role in radioresistance of OSCC. We determined that a PI3K/mTOR inhibitor combined with radiation exhibits synergistic inhibition of the AKT/mTOR axis and induces cell cycle arrest. Our results show the therapeutic potential of drugs targeting the PI3K/AKT/mTOR signaling pathway should be new candidate drugs for radiosensitization in radiotherapy.

Better Survival with Three-Dimensional Conformal Radiotherapy Than with Conventional Radiotherapy for Cervical Cancer: A Population-Based Study

Three-dimensional conformal radiation therapy (3DCRT) has emerged as a preferred treatment for gynecologic malignancies. Yet its superiority to conventional radiotherapy (2-dimensional radiotherapy (2DRT)) for gynecologic malignancies has not been well established. Data from the 2005 to 2010 National Health Insurance Research Database (NHIRD) provided by the National Research Institutes in Taiwan were analyzed to address this issue. Patients were initially diagnosed as having cervical cancer according to the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 180, and this clinical diagnosis was confirmed histopathologically or cytologically. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the reported data. Between January 2005 and December 2010, there were 776 patients with newly diagnosed cervical cancer without metastasis, local recurrence, or surgical treatment before RT and 132 and 644 patients, respectively, who received 2DRT and 3DCRT. After adjustment for age, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, side effects, urbanization level, geographic region, and enrollee category in the 5-year follow-up period, the HR was 1.82 (95% CI, 1.16–2.85, P = 0.009). The 5-year survival rate in the 2DRT and 3DCRT groups was 73.0% and 82.3%, P = 0.007, respectively. Cervical cancer patients treated with 3DCRT had better overall survival.

The incidence of venous thromboembolism in cervical cancer: a nationwide population-based study

BackgroundVenous thromboembolism (VTE) is a life-threatening condition that occurs as a complication of cervical cancer. The aim of this study was to evaluate the incidence of VTE in cervical cancer patients during a 5-year follow-up.MethodsThe study analyzed data deposited between 2003 and 2008 in the National Health Insurance Research Database (NHIRD), provided by the National Health Research Institutes in Taiwan. Totally, 1013 cervical cancer patients after treatment and 2026 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the VTE risk.ResultsThe 5-year cumulative risk for VTE was significantly higher in the cervical cancer group than in the control group (3.3% vs 0.3%, p < 0.001). The hazard ratio for VTE was 10.14 times higher in the cervical cancer group than in the controls. The combined presence of more comorbidities was associated with a higher risk for VTE. Furthermore, cervical cancer patients without VTE had a significantly higher survival (75.3% vs 30.3%, p < 0.001).ConclusionsThe cumulative risk of VTE was significantly higher in cervical cancer patients, and these patients also had lower survival rates. Strategies to reduce these risks need to be examined.

Factors Affecting Myocardial Infarction in Cervical Cancer Patients: A Population-Based Study

Background Radiotherapy (RT) or concurrent chemoradiation therapy has been suggested to increase the risk of coronary heart disease for cervical cancer patients, but the results of studies have been inconsistent. Therefore, we aimed to investigate the factors which influence the risk of developing myocardial infarction (MI) in cervical cancer patients with a large, nationwide cohort. Methods The study analyzed data from the 1996 to 2010 National Health Insurance Research Database provided by the National Health Research Institutes in Taiwan. The assessed number of patients with cervical cancer with radiotherapy only, surgery with bilateral oophorectomy only, and with appendectomy were 308, 323 and 229, respectively. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of myocardial infarction. Results The adjusted hazard ratio for cervical cancer in patients with MI was 1.97 (95% CI, 0.97 - 3.91; P = 0.05) for the group that received RT alone, and 2.13 (95% CI, 1.11 - 3.75; P = 0.01) for the surgery group when compared with controls. The more risk comorbidities they have, the higher the risk of myocardial infarction would be for the patients. Conclusion The incidence of MI was significantly higher among cervical cancer patients with RT alone or surgery with bilateral oophorectomy alone than among general populations. RT might be as a factor to increase risk as bilateral oophorectomy. Whether RT itself triggers menopause or impairs the ovarian hormone production that increases the risk of MI needs to be further investigated.

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma: A care-compliant case report.

Background:Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed. Case Summary:At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified. Conclusions:SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine.