Visual enhancement pattern during the delayed phase of enhanced CT as an independent prognostic factor in stage IV pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has substantial heterogeneity in biophysical features and in outcomes of patients. Identifying reliable pretreatment imaging biomarkers for PDAC with distant metastases (stage IV) is a key imperative. Our objective was to determine whether visual tumor enhancement pattern on enhanced computed tomography (CT) can be used as a prognostic factor in stage IV PDAC treated with chemotherapy. METHODS: This is a retrospective cohort study of 133 patients with stage IV PDAC who underwent multiphasic enhanced CT before systemic chemotherapy. The enhancement pattern of PDAC was qualitatively categorized as hypoattenuation, isoattenuation, or hyperattenuation on each of the pancreatic, portal venous, and delayed phases. The effects of clinical prognostic factors and the visual tumor enhancement pattern on progression-free survival (PFS) and overall survival (OS) were assessed in univariate and multivariate analyses using Cox proportional hazards models. RESULTS: On univariate analysis, the number of metastatic organs and the visual tumor enhancement pattern during the delayed phase were significantly associated with PFS (p = 0.003 and < 0.001, respectively) and OS (p = 0.005 and < 0.001, respectively). Multivariate analysis identified the number of metastatic organs (PFS, p = 0.021; OS, p = 0.041) and visual tumor enhancement pattern during the delayed phase (PFS, p < 0.001; OS, p < 0.001) as independent predictors of PFS and OS. CONCLUSION: Visual enhancement pattern of PDAC on delayed phase enhanced CT appears to be associated with outcomes and could be a useful prognostic factor in stage IV PDAC, despite the need to add the delayed phase to CT protocol for pancreatic disease.

Extracellular volume fraction determined by equilibrium contrast-enhanced dual-energy CT as a prognostic factor in patients with stage IV pancreatic ductal adenocarcinoma.

OBJECTIVES: To evaluate the feasibility of equilibrium contrast-enhanced dual-energy CT (DECT), as compared with single-energy CT (SECT) and to calculate extracellular volume (ECV) fraction to predict the survival outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with distant metastases (stage IV) treated with chemotherapy. METHODS: The study cohort included a total of 66 patients with stage IV PDAC who underwent DECT before systemic chemotherapy between July 2014 and March 2017. Unenhanced and 120-kVp equivalent images during the equilibrium phase were used to calculate tumor SECT-derived ECV fractions, and iodine density images were obtained from equilibrium-phase DECT for DECT-derived ECV fractions. Correlations between SECT- and DECT-derived ECV fractions were identified using the Pearson correlation coefficient and Bland-Altman analysis. The effects of clinical prognostic factors and tumor SECT- and DECT-derived ECV fractions on progression-free survival (PFS) and overall survival (OS) were assessed by univariate and multivariate analyses using Cox proportional hazards models. RESULTS: The correlation between SECT- and DECT-derived ECV fractions was strong (r = 0.965; p < 0.001). The Bland-Altman plot between SECT- and DECT-derived ECV fractions showed a small bias (- 3.4%). Increasing tumor SECT- and DECT-derived ECV fractions were associated with a positive effect on PFS (SECT, p = 0.002; DECT, p = 0.007) and OS (DECT, p = 0.014; DECT, p = 0.015). Only tumor DECT-derived ECV fraction was an independent predictor of PFS (p = 0.018) and OS (p = 0.022) in patients with stage IV PDAC treated with chemotherapy on multivariate analysis. CONCLUSIONS: The ECV fraction determined by equilibrium contrast-enhanced DECT can potentially predict the survival of patients with stage IV PDAC treated with chemotherapy. KEY POINTS: • Extracellular volume fraction of stage IV pancreatic ductal adenocarcinoma determined by dual-energy CT was strongly correlated to that with single-energy CT (r = 0.965, p < 0.001). • Tumor extracellular volume fraction was an independent predictor of progression-free survival (p = 0.018) and overall survival (p = 0.022). • Extracellular volume fraction determined by dual-energy CT could be a useful imaging biomarker to predict the survival of patients with stage IV pancreatic ductal adenocarcinoma treated with chemotherapy.

Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy.

OBJECTIVES: To assess whether extracellular volume (ECV) fraction with equilibrium contrast-enhanced multidetector computed tomography (MDCT) predicts outcomes for unresectable pancreatic adenocarcinoma patients treated with chemotherapy METHODS: Sixty-seven patients (42 men, 25 women; mean age, 67.5 years; range, 45-83 years) with histologically confirmed surgically unresectable pancreatic adenocarcinoma underwent contrast-enhanced MDCT before systemic chemotherapy. Tumour contrast enhancement (CE) and ECV fraction were calculated using region-of-interest measurement within the pancreatic adenocarcinoma and aorta on unenhanced and equilibrium phase-enhanced CT. The effect on survival variables including age, sex, tumour location, tumour size, TNM stage, carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), tumour CE and tumour ECV fraction was determined on univariate and multivariate analyses using Cox proportional hazards regression model. RESULTS: Median overall survival was 10.5 months. On univariate analysis, elevated serum CA19-9 (hazard ratio (HR), 1.00; p = 0.006) and CEA (HR, 1.02; p = 0.011) levels were found to be associated with a negative effect on overall survival. Increasing tumour CE (HR, 0.98; p < 0.001) and ECV fraction (HR, 0.97; p = 0.001) were associated with a positive effect. Multivariate analysis revealed that only tumour ECV fraction was an independent predictor of overall survival (HR, 0.97; p = 0.012). CONCLUSIONS: ECV fraction with equilibrium contrast-enhanced MDCT could be a useful imaging biomarker for predicting patient survival after chemotherapy for unresectable pancreatic adenocarcinoma. KEY POINTS: • Tumour aggressiveness and response to therapy are influenced by the extravascular extracellular space. • Extracellular volume (ECV) fraction can be quantified with equilibrium contrast-enhanced CT. • Patients with higher tumour ECV fraction had better prognosis after chemotherapy.

Tumor bleeding requiring intervention and the correlation with anemia in uterine cervical cancer for definitive radiotherapy.

BACKGROUND: The prognostic impact of tumor bleeding requiring intervention and the correlation with anemia on the survival outcome of cervical cancer radiotherapy is unclear. METHODS: One hundred and ninety-six patients requiring hemostatic intervention between January 2006 and March 2014 were retrospectively investigated. The correlation between anemia and bleeding during radiotherapy, the prognostic impact of genital bleeding during radiotherapy and the influence of blood transfusion were estimated. RESULTS: None of the patients had incomplete or prolonged treatment exceeding 1 week due to bleeding. All tumor bleeding could be controlled by gauze packing, and no patients suffered from fatal genital bleeding. Bleeding significantly correlated with progression-free survival (P = 0.015) and overall survival (P = 0.048). Regarding the risk factors of anemia: age (P = 0.043), FIGO stage (P < 0.001), tumor diameter (P < 0.001), and bleeding (P = 0.002) were significant. Multivariate analysis revealed FIGO stage (Odds Ratio: 2.360; 95% CI = 1.202-4.633; P = 0.013), tumor diameter (Odds Ratio: 2.089; 95% CI = 1.048-4.162; P = 0.036) and Bleeding (Odds Ratio: 2.226; 95% CI = 1.052-4.709; P = 0.036) were independent to anemia. Anemia (Hazard Ratio = 1.894; 95% CI = 1.082-3.318; P = 0.025) was only independently correlated with progression free survival, while bleeding (Hazard Ratio = 1.156; 95% CI = 0.556-2.406; P = 0.698) had no independent correlation. Blood transfusion did not improve progression-free survival in patients with anemia or genital bleeding (P = 0.742). CONCLUSION: We have proved that genital bleeding requiring intervention during cervical cancer radiotherapy is a negligible prognostic factor and is the independent factor for causing anemia. Easily bleeding tumors are potential prognostic markers, which are not effectively treated using existing radiotherapy.

Comparison of proton beam radiotherapy and hyper-fractionated accelerated chemoradiotherapy for locally advanced pancreatic cancer.

OBJECTIVES: We compared the clinical outcomes of proton beam radiotherapy (PBRT) and those of conventional chemoradiotherapy via hyper-fractionated acceleration radiotherapy (HART) after induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC). METHODS: Twenty-five consecutive patients with LAPC received induction chemotherapy comprising gemcitabine and S-1 before radiotherapy. Of these, 15 and 10 were enrolled in the HART and PBRT groups, respectively. RESULTS: Moderate hematological toxicities were observed only in the HART group, whereas two patients in the PBRT group developed duodenal ulcers. All patients underwent scheduled radiotherapy, with overall disease control rates of 93% and 80% in the HART and PBRT groups, respectively. Local progression was observed in 60% and 40% of patients in the HART and PBRT groups, respectively. However, there was no statistical significance between the two groups regarding the median time to progression (15.4 months in both) and the median overall survival (23.4 v.s. 22.3 months). CONCLUSIONS: PBRT was feasible and tolerable, and scheduled protocols could be completed with careful attention to gastrointestinal ulcers. Despite the lower incidence of local recurrence, PBRT did not yield obvious progression control and survival benefits relative to conventional chemoradiotherapy.

Comparison of ferucarbotran-enhanced fluid-attenuated inversion-recovery echo-planar, T2-weighted turbo spin-echo, T2*-weighted gradient-echo, and diffusion-weighted echo-planar imaging for detection of malignant liver lesions.

PURPOSE: To compare the diagnostic accuracy of superparamagnetic iron oxide (SPIO)-enhanced fluid-attenuated inversion-recovery echo-planar imaging (FLAIR EPI) for malignant liver tumors with that of T2-weighted turbo spin-echo (TSE), T2*-weighted gradient-echo (GRE), and diffusion-weighted echo-planar imaging (DW EPI). MATERIALS AND METHODS: SPIO-enhanced magnetic resonance imaging (MRI) that included FLAIR EPI, T2-weighted TSE, T2*-weighted GRE, and DW EPI sequences was performed using a 3 T system in 54 consecutive patients who underwent surgical exploration with intraoperative ultrasonography. A total of 88 malignant liver tumors were evaluated. Images were reviewed independently by two blinded observers who used a 5-point confidence scale to identify lesions. Results were correlated with results of histopathologic findings and surgical exploration with intraoperative ultrasonography. The accuracy of each MRI sequence was measured with jackknife alternative free-response receiver operating characteristic analysis. The sensitivity of each observer with each MRI sequence was compared with McNemar's test. RESULTS: Accuracy values were significantly higher with FLAIR EPI sequence (0.93) than with T2*-weighted GRE (0.80) or DW EPI sequences (0.80) (P < 0.05). Sensitivity was significantly higher with the FLAIR EPI sequence than with any of the other sequences. CONCLUSION: SPIO-enhanced FLAIR EPI sequence was more accurate in the diagnosis of malignant liver tumors than T2*-weighted GRE and DW EPI sequences. SPIO-enhanced FLAIR EPI sequence is helpful for the detection of malignant liver tumors.

Pancreatic adenocarcinoma: a comparison of automatic bolus tracking and empirical scan delay.

BACKGROUND: To evaluate the efficacy of automatic bolus tracking in multidetector row CT (MDCT) for pancreatic adenocarcinoma as compared with standard scan delay using the fixed duration contrast injection technique. MATERIALS AND METHODS: Seventy-nine patients with pancreatic adenocarcinomas underwent three-phase enhanced CT with an individualized scan delay as determined by automatic bolus tracking (protocol 1) or an empiric scan delay (protocol 2). We evaluated enhancement of the aorta, portal vein, hepatic parenchyma, pancreatic parenchyma, and pancreatic adenocarcinoma during each phase. Two radiologists graded the conspicuity of pancreatic adenocarcinoma in the pancreatic parenchymal phase. The results for the different groups were statistically compared. RESULTS: Pancreatic parenchymal enhancement (mean ± standard deviation, 100.2 HU ± 17.6 vs. 88.5 HU ± 22.1; P < 0.05) and tumor-to-pancreas contrast (mean ± standard deviation, 75.3 HU ± 25.0 vs. 63.1 HU ± 24.1; P < 0.05) were significantly greater in protocol 1 than in protocol 2 during pancreatic parenchymal phase. Qualitative results correlated well with quantitative results (reviewer 1: R (s) = 0.78, P < 0.001; reviewer 2: R (s) = 0.66, P < 0.001) CONCLUSION: The use of automatic bolus tracking with MDCT can significantly improve the degree of contrast enhancement in the pancreatic parenchyma and tumor-to-pancreas conspicuity.

Estimation of Extracellular Volume Fraction With Routine Multiphasic Pancreatic Computed Tomography to Predict the Survival of Patients With Stage IV Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study aimed to determine whether extracellular volume (ECV) fraction with routine equilibrium contrast-enhanced computed tomography (CT) can predict outcomes in patients with stage IV pancreatic ductal adenocarcinoma (PDAC) treated with chemotherapy. METHODS: This is a retrospective cohort study of 128 patients with stage IV PDAC who underwent multiphasic pancreatic CT before systemic chemotherapy. Contrast enhancement and ECV fraction of the primary lesion were calculated using region-of-interest measurement within the PDAC and aorta on unenhanced and equilibrium phase-enhanced CT. The effects of clinical prognostic factors and ECV fractions on progression-free survival (PFS) and overall survival (OS) were assessed by univariate and multivariate analyses using Cox proportional hazards models. RESULTS: The number of metastatic organs and tumor ECV fraction were significant for PFS (P = 0.005 and 0.001, respectively) and OS (P = 0.012 and 0.007, respectively). On the multivariate analysis, multiple metastatic organs (PFS, P = 0.046; OS, P = 0.047) and lower tumor ECV fraction (PFS, P = 0.010; OS, P = 0.026) were identified as independent predictors of poor PFS and OS. CONCLUSION: Extracellular volume fraction with routine equilibrium contrast-enhanced CT may potentially predict survival in patients with stage IV PDAC treated with chemotherapy.

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC). METHODS: We reviewed 30 thoracic ESCC patients who underwent neoadjuvant DCF-RT followed by esophagectomy, and evaluated the safety and efficacy of DCF-RT. DCF-RT consisted of 40 Gy radiation with two courses of intravenous DCF (docetaxel, 30 mg/m2/day, day 1; cisplatin, 7 mg/m2/day, day 1; 5-FU, 350 mg/m2/day, days 1-5 and days 8-12) repeated every 2 weeks. Esophagectomy was scheduled 8-10 weeks after completion of DCF-RT. RESULTS: Twenty-nine of thirty patients completed radiotherapy; however, 27 of 30 patients required dose reduction of the second cycle of DCF. Complete response (CR), partial response, and stable disease were observed in 7, 11, and 10 patients, respectively. The number of lymph node metastases after DCF-RT was significantly lower than that before DCF-RT (P < 0.0001). Among the 30 patients, pathological CR (pCR) in the primary tumor was observed in 17 patients, and pCRs in both the primary tumor and lymph nodes were observed in 14 patients. The 3-year overall survival rate was 62.2%, and that of patients who experienced pCR was 84%. CONCLUSIONS: Neoadjuvant DCF-RT was tolerable and yielded a high pCR rate in ESCC. Therefore, neoadjuvant DCF-RT may confer a survival benefit and may be a candidate neoadjuvant therapy regimen for patients with locally advanced thoracic ESCC.

Risk factors for radiation pneumonitis after stereotactic radiation therapy for lung tumours: clinical usefulness of the planning target volume to total lung volume ratio.

OBJECTIVE: To identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic radiation therapy (SRT) for lung tumours. METHODS: We retrospectively evaluated 68 lung tumours in 63 patients treated with SRT between 2011 and 2015. RP was graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. SRT was delivered at 7.0-12.0 Gy per each fraction, once daily, to a total of 48-64 Gy (median, 50 Gy). Univariate analysis was performed to assess patient- and treatment-related factors, including age, sex, smoking index (SI), pulmonary function, tumour location, serum Krebs von den Lungen-6 value (KL-6), dose-volume metrics (V5, V10, V20, V30, V40 and VS5), homogeneity index of the planning target volume (PTV), PTV dose, mean lung dose (MLD), contralateral MLD and V2, PTV volume, lung volume and the PTV/lung volume ratio (PTV/Lung). Performance of PTV/Lung in predicting symptomatic RP was also analysed using receiver operating characteristic (ROC) analysis. RESULTS: The median follow-up period was 21 months. 10 of 63 patients (15.9%) developed symptomatic RP after SRT. On univariate analysis, V10, V20, PTV volume and PTV/Lung were significantly associated with occurrence of RP  ≥Grade 2. ROC curves indicated that symptomatic RP could be predicted using PTV/Lung [area under curve (AUC): 0.88, confidence interval (CI: 0.78-0.95), cut-off value: 1.09, sensitivity: 90.0% and specificity: 72.4%]. CONCLUSION: PTV/Lung is a good predictor of symptomatic RP after SRT. Advances in knowledge: The cases with high PTV/Lung should be carefully monitored with caution for the occurrence of RP after SRT.

Pacemaker malfunction associated with proton beam therapy: a report of two cases and review of literature-does field-to-generator distance matter?

It is well known that radiotherapy causes malfunctions of cardiac implantable electronic devices such as pacemaker (PM) and implantable cardioverter-defibrillator because of incidental neutron production. Here, we report our experience with two cases of PM reset among seven patients with PM who underwent proton beam therapy (PBT) from January 2011 to April 2015 at our centre. Our experience shows PM reset can occur also with abdominal PBT. In both cases, PM reset was not detected by electrocardiogram (ECG) monitoring but was rather discovered by post-treatment programmer analysis. Our cases suggest that PM malfunction may not always be detected by ECG monitoring and emphasize the importance of daily programmer analysis.

Associations between liver (18)F fluoro-2-deoxy-D-glucose accumulation and various clinical parameters in a Japanese population: influence of the metabolic syndrome.

PURPOSE: Liver demonstrates a heterogeneous (18)F fluoro-2-deoxy-D: -glucose ((18)F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver (18)F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data. METHODS: (18)F-FDG positron emission tomography (PET) imaging was performed in 101 consecutive subjects for cancer screening. Multiple stepwise regression analysis was used to define the best predictors of the liver standardized uptake value (SUV) among height, weight, waist circumference, body mass index (BMI), systolic and diastolic blood pressure, BG and other biochemical data, i.e., aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total protein, total bilirubin, and alkaline phosphatase. Furthermore, we evaluated the association between liver (18)F-FDG uptake and the metabolic syndrome. RESULTS: The independent factors for increased liver (18)F-FDG uptake (mean SUV > or = 2) were BMI (P < 0.0001), triglycerides (P = 0.0007), and high-density lipoprotein cholesterol (P = 0.0013). Other factors were not significantly associated with liver (18)F-FDG uptake. In addition, the liver (18)F-FDG uptake of metabolic syndrome subjects was significantly higher than that of a non-metabolic syndrome subjects. CONCLUSIONS: BMI was the strongest determinant of liver (18)F-FDG uptake, and the liver (18)F-FDG uptake of metabolic syndrome subjects was significantly higher than that of non-metabolic syndrome subjects. This result suggests that a subject with a high liver (18)F-FDG uptake should be screened for the metabolic syndrome.