The impact of surgical volume on outcomes in newly diagnosed colorectal cancer patients receiving definitive surgeries.

Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20-105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume.

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

Severity of Complications and Duration of Type 2 Diabetes and the Risk of Cancer: A Population-Based Study.

BACKGROUND: The literature on the association between diabetes severity and cancer risk is limited and inconclusive. The study aimed to evaluate the association between the adapted Diabetes Complications Severity Index (aDCSI) and the duration of type 2 diabetes and cancer risk. METHODS: Patients ages 20 years or older with newly diagnosed type 2 diabetes between January 1, 2007, and December 31, 2011, were identified from Taiwan National Health Insurance claims data. Standardized incidence ratios (SIR) were calculated to compare cancer incidence in people with diabetes with that in the general population. Poisson regression was used to examine whether SIRs differed by age, sex, aDSCI, and duration of diabetes. RESULTS: A total of 756,547 patients were included, with a median follow-up of 8.8 years. Excluding the first year after diagnosis, the SIR for overall cancer was 1.18 [95% confidence interval (CI) 1.17-1.19]. Higher aDCSI was associated with increased SIRs for overall [SIR ratio 1.03 (1.02-1.03) per point increase], head and neck (1.03; 1.01-1.04), liver (1.04; 1.03-1.05), pancreas (1.03; 1.00-1.05), kidney (1.13; 1.10-1.15), and leukemia (1.09; 1.06-1.13). There was no association between aDCSI and colorectal, extrahepatic biliary tract, uterus and thyroid cancer, and a negative association with breast cancer (0.97; 0.95-0.98). Type 2 diabetes duration was associated with increased SIRs for overall [1.01 (1.00-1.02) per year increase], head and neck (1.03; 1.01-1.05), and liver cancer (1.04; 1.02-1.05). CONCLUSIONS: The heterogeneity in the association between diabetes severity and diabetes-related cancers suggests diverse underlying connections. IMPACT: Adopting distinct approaches in further research and prevention strategies for different kinds of diabetes-related cancers is important.

Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity.

BACKGROUND: Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. METHODS: We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. RESULTS: The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. CONCLUSIONS: This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.

Association of radiation dose to cardiac substructures with major ischaemic events following breast cancer radiotherapy.

BACKGROUND AND AIMS: Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined. METHODS AND RESULTS: This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors. CONCLUSION: Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted.

A retrospective cohort study on the cardiotoxicity incidence rates of immune checkpoint inhibitors for oncology patients.

BACKGROUND: This present study investigated the incidence rates of cardiotoxicity among cancer patients treated with immune checkpoint inhibitors (ICIs) plus other anticancer drugs. METHODS: This was a retrospective hospital-based cohort study using the medical records and the Cancer Registry records from the Taipei Veterans General Hospital. We enrolled patients diagnosed with cancer between 2011 and 2017, who were over 20 years old and had received ICI therapy, including pembrolizumab, nivolumab, atezolizumab, and ipilimumab. Cardiotoxicity was defined by the diagnosis of myocarditis, pericarditis, arrhythmia, heart failure, and Takotsubo syndrome. RESULTS: We identified 407 patients who were eligible to participate in this study. We defined the three treatment groups as follows: ICI therapy, ICI combined with chemotherapy, and ICI combined with targeted therapy. Using ICI therapy as a reference group, the cardiotoxicity risk was not significantly higher compared to the ICI combined with chemotherapy group (adjusted hazard ratio 2.1, 95% confidence interval 0.2-21.1, p = 0.528] or to the ICI combined with targeted therapy group (adjusted hazard ratio 1.2, 95% confidence interval 0.1-9.2, p = 0.883). The total incidence rate of cardiotoxicity was 3.6 of 100 person-years, indicating an average incidence time of 1.0 ± 1.3 years (median: 0.5 years; range: 0.1-4.7 years) for 18 cardiotoxicity patients. CONCLUSION: The incidence rate of ICI-related cardiotoxicity is low. Combination of ICI with either chemotherapy or targeted therapy might not significantly increase the risk of cardiotoxicities among cancer patients. Nevertheless, it is recommend being careful in patients treated high-risk cardiotoxicity medications to avoid drug-related cardiotoxicity with a combination of ICI therapy.

Lymphocytopenia and survival after whole-brain radiotherapy in patients with small-cell lung cancer.

BACKGROUND: To investigate whether whole-brain radiotherapy (WBRT) decreases lymphocyte counts and evaluate the impact of treatment-related lymphopenia on survival in patients with brain metastasis. METHODS: Medical records from 60 small-cell lung cancer patients treated with WBRT from January 2010 to December 2018 were included in the study. Total lymphocyte count (TLC) was obtained pre and post treatment (within 1 month). We performed linear and logistic regression analyses to identify predictors of lymphopenia. The association between lymphopenia and survival was analyzed using Cox regression analysis. RESULTS: Thirty-nine patients (65%) developed treatment-related lymphopenia. The median TLC decrease was -374 cells/µL (interquartile range -50 to -722, p < 0.001). Baseline lymphocyte count was a significant predictor of TLC difference and percentage change in TLC. Logistic regression analysis found male sex (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.00-0.79, p = 0.033) and higher baseline lymphocyte count (OR 0.91, 95% CI 0.82-0.99, p = 0.005) were associated with a lower risk of developing ≥grade 2 treatment-related lymphopenia. Cox regression analysis showed that age at brain metastasis (hazard ratio [HR] 1.03, 95% CI 1.01-1.05, p = 0.013), ≥grade 2 treatment-related lymphopenia, and percentage change in TLC (per 10%, HR 0.94, 95% CI 0.89-0.99, p = 0.032) were prognostic factors of survival. CONCLUSIONS: WBRT decreases TLC and the magnitude of treatment-related lymphopenia is an independent predictor of survival in small-cell lung cancer patients.

Adapted Diabetes Complications Severity Index and Charlson Comorbidity Index in predicting all-cause and cause-specific mortality among patients with type 2 diabetes.

INTRODUCTION: Adapted Diabetes Complications Severity Index (aDCSI) is a commonly used severity measure based on the number and severity of diabetes complications using diagnosis codes. The validity of aDCSI in predicting cause-specific mortality has yet to be verified. Additionally, the performance of aDCSI in predicting patient outcomes compared with Charlson Comorbidity Index (CCI) remains unknown. RESEARCH DESIGN AND METHODS: Patients aged 20 years or older with type 2 diabetes prior to January 1, 2008 were identified from the Taiwan National Health Insurance claims data and were followed up until December 15, 2018. Complications for aDCSI including cardiovascular, cerebrovascular and peripheral vascular disease, metabolic disease, nephropathy, retinopathy and neuropathy, along with comorbidities for CCI, were collected. HRs of death were estimated using Cox regression. Model performance was evaluated by concordance index and Akaike information criterion. RESULTS: 1,002,589 patients with type 2 diabetes were enrolled, with a median follow-up of 11.0 years. After adjusting for age and sex, aDCSI (HR 1.21, 95% CI 1.20 to 1.21) and CCI (HR 1.18, 1.17 to 1.18) were associated with all-cause mortality. The HRs of aDCSI for cancer, cardiovascular disease (CVD) and diabetes mortality were 1.04 (1.04 to 1.05), 1.27 (1.27 to 1.28) and 1.28 (1.28 to 1.29), respectively, and the HRs of CCI were 1.10 (1.09 to 1.10), 1.16 (1.16 to 1.17) and 1.17 (1.16 to 1.17), respectively. The model with aDCSI had a better fit for all-cause, CVD and diabetes mortality with C-index of 0.760, 0.794 and 0.781, respectively. Models incorporating both scores had even better performance, but the HR of aDCSI for cancer (0.98, 0.97 to 0.98) and the HRs of CCI for CVD (1.03, 1.02 to 1.03) and diabetes mortality (1.02, 1.02 to 1.03) became neutral. When aDCSI and CCI were considered time-varying scores, the association with mortality was stronger. aDCSI had a strong correlation with mortality even after 8 years (HR 1.18, 1.17 to 1.18). CONCLUSIONS: The aDCSI predicts all-cause, CVD and diabetes deaths but not cancer deaths better than the CCI. aDCSI is also a good predictor for long-term mortality.

Radiomic features derived from pretherapeutic MRI predict chemoradiation response in locally advanced rectal cancer.

BACKGROUND: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant concurrent chemoradiotherapy (CRT) followed by surgical excision. Current evidence suggests a favorable prognosis for those with pathological complete response (pCR), and surgery may be spared for them. We trained and validated regression models for CRT response prediction with selected radiomic features extracted from pretreatment magnetic resonance (MR) images to recruit potential candidates for this watch-and-wait strategy. METHODS: We retrospectively enrolled patients with LARC who underwent pre-CRT MR imaging between 2010 and 2019. Pathological complete response in surgical specimens after CRT was defined as the ground truth. Quantitative features derived from both unfiltered and filtered images were extracted from manually segmented region of interests on T2-weighted images and selected using variance threshold, univariate statistical tests, and cross-validation least absolute shrinkage and selection operator (Lasso) regression. Finally, a regression model using selected features with high coefficients was optimized and evaluated. Model performance was measured by classification accuracies and area under the receiver operating characteristic (AUROC). RESULTS: We extracted 1223 radiomic features from each MRI study of 133 enrolled patients. After tumor excision, 34 (26 %) of 133 patients had pCR in resected specimens. When 25 image-derived features were selected from univariate analysis, classification AUROC was 0.86 and 0.79 with the addition of six clinical features on the hold-out internal validation dataset. When 11 image-derived features were used, the optimized linear regression model had an AUROC value of 0.79 and 0.65 with the addition of six clinical features on the hold-out dataset. Among the radiomic features, texture features including gray level variance, strength, and cluster prominence had the highest coefficient by Lasso regression. CONCLUSION: Radiomic features derived from pretreatment MR images demonstrated promising efficacy in predicting pCR after CRT. However, radiomic features combined with clinical features did not result in remarkable improvement in model performance.

Comprehensive analysis of CDK5 as a novel biomarker for progression in esophageal cancer.

BACKGROUND: Cyclin-dependent kinase 5 (CDK5) is a member of the cyclin-dependent kinase family, and unlike the rest of the members of the family, its kinase activity is independent of cyclins. Accumulating evidence has shown that CDK5 plays a significant role in the progress of tumorigenesis except in nervous system. In particular, the expression of CDK5 and its function in esophageal cancer (ESCA) remain unknown. METHODS: With TCGA and GEO databases, CDK5 was analyzed with the expression, predicted value, clinical relationship, functional enrichment, immune cell infiltration and immune molecules in ESCA. In addition, we explored the CDK5 expression with local datasets and the influence of CDK5 on proliferation, migration and invasion behaviors of the esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo experiments. RESULTS: CDK5 expression was upregulated in ESCA, and this regulation has been verified in cell lines of ESCC. Further analysis has found that the expression of CDK5 was correlated with race, weight, BMI, histological type and tumor central location in ESCA. KEGG analysis revealed that CDK5 was involved in the progress of cancers, innate immune system and PI3K-Akt signaling pathway. CDK5 was closely related to immune cells and immune molecules in ESCA. Functional experiments confirmed CDK5 was an oncogene in ESCC by in vivo and in vitro models. CONCLUSIONS: This study shows that CDK5 is a risk factor to promote tumor progression, and Roscovitine could be one of the effective tools in the therapy of ESCA.

Old age and EGFR mutation status in inoperable early-stage non-small cell lung cancer patients receiving stereotactic ablative radiotherapy: A single institute experience of 71 patients in Taiwan.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is now the standard of care for patients with inoperable early-stage lung cancer. Many of these patients are elderly. EGFR (epidermal growth factor receptor) mutation is also common in the Asian population. METHODS: To evaluate the effects of old age and EGFR mutation on treatment outcomes and toxicity, we reviewed the medical records of 71 consecutive patients with inoperable early-stage non-small cell lung cancer (NSCLC) who received SABR at Taipei Veterans General Hospital between 2015 and 2021. RESULTS: The study revealed that median age, follow-up, Charlson comorbidity index, and ECOG score were 80 years, 2.48 years, 3, and 1, respectively. Of these patients, 37 (52.1%) were 80 years or older, and 50 (70.4%) and 21 (29.6%) had T1 and T2 diseases, respectively. EGFR mutation status was available for 33 (46.5%) patients, of whom 16 (51.5%) had a mutation. The overall survival rates at 1, 3, and 5 years were 97.2, 74.9, and 58.3%, respectively. The local control rate at 1, 3, and 5 years was 97.1, 92.5, and 92.5%, respectively. Using Cox proportional hazards regression we found that male sex was a risk factor for overall survival (p = 0.036, 95% CI: 1.118-26.188). Two patients had grade 2 pneumonitis, but no other grade 2 or higher toxicity was observed. We did not find any significant differences in treatment outcomes or toxicity between patients aged 80 or older and those with EGFR mutations in this cohort. CONCLUSION: These findings indicate that age and EGFR mutation status do not significantly affect the effectiveness or toxicity of SABR for patients with inoperable early-stage NSCLC.

Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.

Mammalian transducin-like enhancer of split family proteins (TLEs) are homologous to Drosophila Groucho (Gro) and are essential transcriptional repressors. Seven TLE family members, TLE1-7, have been identified to date. These proteins do not bind DNA directly; instead, they bind a set of transcription factors and thereby inhibit target gene expression. Loss of TLEs in mice usually leads to defective early development; however, TLE functions in developmentally mature cells are unclear. Recent studies have revealed that TLEs are dysregulated in certain human cancer types and may function as oncogenes or tumor suppressors in different contexts. TLE levels also affect the efficacy of cancer treatments and the development of drug resistance. In addition, TLEs play critical roles in the development and function of immune cells, including macrophages and lymphocytes. In this review, we provide updates on the expression, function, and mechanism of TLEs; discuss the roles played by TLEs in tumorigenesis and the inflammatory response; and elaborate on several TLE-associated signaling pathways, including the Notch, Wnt, and MAPK pathways. Finally, we discuss potential strategies for targeting TLEs in cancer therapy.

Synthesis of a cerium-based nanomaterial with superior oxidase-like activity for colorimetric determination of glutathione in food samples.

Enzyme-like nanomaterials have received significant attention for their high stability and low cost. However, most nanomaterials require complicated synthesis processes, limiting the range of their potential applications. In this study, a novel cerium-based nanomaterial was fabricated in a facile manner from a mixture of dipicolinic acid (DPA), guanosine 5'-monophosphate (GMP), and cerium acetate under ambient conditions. The obtained nanomaterial, designated as DPA-Ce-GMP, exhibited superior oxidase-like activity owing to the mixed valence (Ce3+/Ce4+) of cerium ions. DPA-Ce-GMP efficiently catalyzed the oxidation of 3,3,5,5-tetramethylbenzidine (TMB), achieving a color reaction without requiring hydrogen peroxide. Thus, DPA-Ce-GMP was incorporated into a simple, rapid, and sensitive colorimetric sensor for glutathione (GSH) detection. Within this sensor, TMB oxidation is inhibited by the reducibility of GSH. The sensor exhibits a linear response over two concentration ranges (0.05-10 and 10-40 µM), and its detection limit is 17.1 nM (3σ/slope). The proposed sensor was successfully applied to GSH quantification in food samples. The developed sensor provides an efficient biomimic oxidase for GSH detection in real samples. Facile approach to prepare cerium-based nanomaterial with superior oxidase-like activity for colorimetric detection of glutathione in food samples.

Pre-existing chronic kidney disease and hypertension increased the risk of cardiotoxicity among colorectal cancer patients treated with anticancer drugs.

BACKGROUND: This population-based study was to investigate the potential risk factors of cardiotoxicity among colorectal cancer (CRC) patients treated with anticancer drugs. METHODS: This was a retrospective cohort study using the National Health Insurance Research Database to identify the CRC patients receiving chemotherapy (CT) alone or CT combined with targeted therapies between 2000 and 2013. The patients enrolled were those who had the first diagnosis of CRC established ≥20 years and had no cancer history three years before the incident diagnosis of CRC. The outcomes of cardiotoxicity were defined by the diagnosis of acute myocarditis, cardiomyopathy, heart failure, hypertensive heart disease, and so on. RESULTS: A total of 11 819 CRC patients were identified and 3781 were eligible; 556 (14.7%) patients developed cardiotoxicity after receiving anticancer treatment. Patients showed a similar risk of having primary outcome (hazard ratio [HR], 0.7; p = 0.3662) between CT and CT combined with targeted therapy groups, whereas the risk of developing secondary outcome was significantly different between the two groups (HR, 0.7; p = 0.0339). The hazard was found to be increased with age (60-69, HR 2.1, p = 0.0236; 70-79, HR 3.3, p = 0.0003; and ≥80, HR 3.7, p < 0.0001). CRC patients who had a prior history of hypertension exhibited a higher risk than those without hypertension (HR 1.6, p < 0.0001). The hazard of having cardiotoxicity among patients with a prior history of severe chronic kidney disease was 2.4 times than that in those without renal dysfunction, regardless of the stage of cancer (HR 2.4, p < 0.0001). CONCLUSION: CRC patients over 60 years of age run a higher risk of developing cardiotoxicity when treated with anticancer drugs. For CRC patients who have a previous history of hypertension or chronic kidney disease, physicians must be careful in evaluating the risk of anticancer drugs-related cardiotoxicity. Prescribe drugs may prevent cardiotoxicity if necessary.

Hospital volume and physician volume in association with survival in patients with nasopharyngeal cancer after radiation therapy.

BACKGROUND: Cancer patients treated at higher-volume hospitals or by more experienced physicians have better outcomes. However, little is known about the effect of these provider volumes on the prognosis of patients receiving definitive radiotherapy (RT). This study aims to examine the independent association between hospital volume and physician volume in relation to the overall survival (OS) of nasopharyngeal cancer (NPC) patients after RT. METHODS: Patients with newly diagnosed NPC receiving definitive RT between 2001 and 2017 were identified from Taiwan's National Health Insurance Research Database. We collected demographic characteristics of patients, physicians and hospitals, as well as cancer treatment and comorbidities. Patients were categorized into quartiles according to cumulative hospital and physician volumes of their treatment providers. The effects of hospital and physician volumes on OS was examined by the frailty Cox regression model. RESULTS: A total of 16,315 NPC patients treated by 258 physicians in 92 hospitals were identified. When the effects of hospital volume and physician volume on survival were separately examined, both of them were positively associated with OS. In a fully adjusted model considering patient and provider characteristics, hospital volume, physician volume, and clustering effects, it showed that hospital volume significantly predicted OS, while physician volume did not. In patients treated with advanced technique RT, hospital volume was significantly associated with OS. However, volume effect was not observed in 2-D RT subgroup. CONCLUSIONS: NPC patients receiving RT at higher-volume hospitals saw better survival. Treatment for NPC should be centralized to high-volume hospitals rather than high-volume physicians.

Effect of early radiotherapy initiation and high-dose chemotherapy on the prognosis of pediatric atypical teratoid rhabdoid tumors in different age groups.

PURPOSE: The optimal treatment strategy for pediatric atypical teratoid rhabdoid tumor (ATRT) is inconclusive. This study evaluated the prognostic value of early radiotherapy (RT) and high-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) in pediatric ATRT. METHODS: This pooled analysis included ATRT patients treated at our institution and from other studies who were identified by a search of the PubMed electronic database. The effect of patient demographics and treatment profiles on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression. RESULTS: Overall, 34 patients from our institution and 436 patients from 35 published studies were included. In multivariable analysis, patients with gross total resection (GTR), early RT (time to RT interval < 2 months), and HDC/ASCR had both better PFS [hazard ratio (HR) 0.46, p[Formula: see text] 0.001; HR 0.64, p = 0.011; and HR 0.51, p = 0.005, respectively] and OS (HR 0.55, p = 0.002; HR 0.48, p = 0.004; and HR 0.42, p < 0.001, respectively). For patients aged < 3 years, both RT and HDC/ASCR were significant favorable factors for PFS (HR 0.32 and 0.46, respectively) and OS (HR 0.40 and 0.36, respectively), while early RT was not prognostic. For patients aged ≥ 3 years, early RT was significantly associated with better PFS (HR 0.51) and HDC/ASCR did not affect PFS, and neither was related to OS. CONCLUSION: Both early RT initiation and HDC/ASCR were important components in the treatment of pediatric ATRT. However, the optimal treatment strategies might differ by age.

The role of adjuvant radiotherapy in stage I endometrial cancer: A single-institution outcome.

OBJECTIVE: Postoperative radiotherapy for early endometrial cancer has been investigated in several randomized trials. These trials demonstrate that it reduces loco-regional recurrence, but has no impact on overall survival. The aims of this study were to better understand the role of adjuvant radiotherapy and determine predictors for loco-regional recurrence or development of distant metastasis. MATERIALS AND METHODS: A retrospective medical records review was performed on patients with surgical stage I endometrial cancer treated at Taipei Veterans General Hospital between 2006 and 2013. Multivariable analysis was conducted using Cox regression for prognostic predictors. RESULTS: A total of 337 patients were identified. The estimated five-year overall survival and loco-regional recurrence-free survival were 96.3% and 97.9% in the non-radiotherapy group, and 91.6% and 97.1% in the radiotherapy group (p = 0.06 overall survival, p = 0.956 loco-regional recurrence-free survival). Multivariable analysis revealed that elevated preoperative serum Cancer Antigen 125 (CA-125) level (hazard ratio (HR) = 2.54), age older than 60 years old (HR = 3.34), and depth of myometrial invasion > 50% (HR = 3.37) were significant factors in overall survival. Elevated preoperative CA-125 level (HR = 5.37), age older than 60 years (HR = 6.57), positive lymphovascular space invasion (HR = 50.20), and adjuvant radiotherapy (HR = 0.05) were independent predictors of loco-regional recurrence-free survival. For distant metastasis, deep myometrial invasion was a significant risk factor. CONCLUSIONS: Postoperative radiotherapy delivery is an independent predictor for loco-regional recurrence-free survival but has no impact on overall survival in this population. Preoperative CA-125 level is a risk factor for loco-regional recurrence, and deep myometrial invasion was correlated with distant metastasis.

Risk and predictors of subsequent cancers of patients with newly-diagnosed atrial fibrillation - A nationwide population-based study.

AIMS: Patients with atrial fibrillation (AF) may be at higher risk for cancer, possibly due to the presence of coexisting risk factors. In this study, we investigate the magnitude and predictors of this potential risk within a population-based study. METHODS AND RESULTS: The study cohort included 332,555 AF patients aged ≥20 years without past history of cancer. Standardized incidence ratio (SIR) was used as a measure of relative risk, comparing observed cancer incidence among patients with AF with that expected based on cancer incidence in the Taiwanese population. During the observation period, 22,911 incident cancers occurred with an incidence of 1.65%/year. Compared with the general population, AF patients had a significantly higher cancer risk with a SIR of 1.37 (95%CI = 1.36-1.39). Patients with new-onset AF had an elevated cancer risk which was highest within 1 year (SIR = 2.30; 95%CI, 2.25-2.36) and persisted beyond 10 years after AF was diagnosed (SIR = 1.18; 95%CI, 1.11-1.25). Age ≥ 65 years, male gender, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and liver cirrhosis were significantly associated with development of cancers among AF patients. The hazard ratio of cancers increased from 1.40 (95%CI = 1.28-1.53) for patients having 1 risk factor to 5.14 (95%CI = 4.03-6.06) for patients with 6 risk factors, in comparison to those without any risk factors. CONCLUSION: In the nationwide cohort study, we show that AF patients had a higher risk of cancer. Age, male gender, hypertension, diabetes, COPD and liver cirrhosis are important risk factors of cancer among AF patients. Prompt and detailed examinations may be considered for incident AF patients with multiple risk factors to early detect the occult malignancy.

Increased risk of pelvic fracture after radiotherapy in rectal cancer survivors: A propensity matched study.

To determine whether radiotherapy (RT) can increase pelvic fracture risk in rectal cancer survivors. Rectal cancer patients who underwent curative surgery between 1996 and 2011 in Taiwan were retrospectively studied using the National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar, and femoral neck fracture) were defined as pelvic fracture. Propensity scores for RT, age, and sex were used to perform one-to-one matches between the RT and non-RT group. Risks of pelvic and arm fractures were compared by multivariable Cox regression. Of the 32 689 patients, 7807 (23.9%) received RT, and 1616 suffered from a pelvic fracture (incidence rate: 1.17/100 person-years). The median time to pelvic fracture was 2.47 years. After matching, 6952 patients each in the RT and non-RT groups were analyzed. RT was associated with an increased risk of pelvic fractures in the multivariable Cox model (hazard ratio (HR): 1.246, 95% confidence interval (CI): 1.037-1.495, P = 0.019) but not with arm fractures (HR: 1.013, 95% CI: 0.814-1.259, P = 0.911). Subgroup analyses revealed that RT was associated with a higher pelvic fracture rate in women (HR: 1.431, 95% CI: 1.117-1.834) but not in men, and the interaction between sex and RT was significant (P = 0.03). The HR of pelvic fracture increased 2-4 years after RT (HR: 1.707, 95% CI: 1.150-2.534, P = 0.008). An increased risk of pelvic fracture is noted in rectal cancer survivors, especially women, who receive RT.

Role of early and aggressive post-operative radiation therapy in improving outcome for pediatric central nervous system atypical teratoid/rhabdoid tumor.

PURPOSE: The purpose of the study is to evaluate possible prognostic factors and optimal management for pediatric atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS). METHODS: Twenty-eight pediatric patients with CNS AT/RT who were treated with radiation therapy (RT) as part of multimodality treatment regimens at a single institution (1996-2015) were reviewed. Survival outcomes were analyzed in relation to possible prognostic factors. RESULTS: The 28 patients analyzed were followed up for a median 48-month period. Median progression-free survival (PFS) was 11 months, and overall survival (OS) was 57 months. Patients < 3 years old had RT delayed for a longer period after surgery (p = 0.04), and the mean RT dose to tumor bed was lower (p < 0.01) than in patients ≥ 3 years old. In multivariate analysis, a higher primary tumor bed RT dose was identified as a favorable prognostic factor for both PFS (hazard ratio [HR] = 0.85 per gray, p < 0.01) and OS (HR = 0.92 per gray, p = 0.02). In addition, an interval between surgery and RT initiation > 2 months, with disease progression observed before RT, as compared with an interval ≤ 2 months without disease progression prior to RT, was associated with worse PFS (HR = 8.50, p < 0.01) and OS (HR = 5.27, p < 0.01). CONCLUSIONS: Early and aggressive RT after surgery is critical for successful disease control in AT/RT patients. Conversely, a delay in RT until disease progression is observed that leads to unfavorable outcomes.