Prognostic value of CT myocardial perfusion imaging and CT-derived fractional flow reserve for major adverse cardiac events in patients with coronary artery disease.

OBJECTIVES: The purpose of this study was to analyze the prognostic value of dynamic CT perfusion imaging (CTP) and CT derived fractional flow reserve (CT-FFR) for major adverse cardiac events (MACE). METHODS: 81 patients from 4 institutions underwent coronary computed tomography angiography (CCTA) with dynamic CTP imaging and CT-FFR analysis. Patients were followed-up at 6, 12, and 18 months after imaging. MACE were defined as cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or revascularization. CT-FFR was computed for each major coronary artery using an artificial intelligence-based application. CTP studies were analyzed per vessel territory using an index myocardial blood flow, the ratio between territory and global MBF. The prognostic value of CCTA, CT-FFR, and CTP was investigated with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 243 vessels in 81 patients were interrogated by CCTA with CT-FFR and 243 vessel territories (1296 segments) were evaluated with dynamic CTP imaging. Of the 81 patients, 25 (31%) experienced MACE during follow-up. In univariate analysis, a positive index-MBF resulted in the largest risk for MACE (HR 11.4) compared to CCTA (HR 2.6) and CT-FFR (HR 4.6). In multivariate analysis, including clinical factors, CCTA, CT-FFR, and index-MBF, only index-MBF significantly contributed to the risk of MACE (HR 10.1), unlike CCTA (HR 1.2) and CT-FFR (HR 2.2). CONCLUSION: Our study provides initial evidence that dynamic CTP alone has the highest prognostic value for MACE compared to CCTA and CT-FFR individually or a combination of the three, independent of clinical risk factors.

Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma.

BACKGROUND: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. EXPERIMENTAL DESIGN: Treatment consisted of cetuximab load at 400 mg/m(2) followed by cetuximab 250 mg/m(2) weekly and gemcitabine 50 mg/m(2) twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. RESULTS: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. CONCLUSIONS: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.

Fractionated stereotactic radiotherapy boost and weekly paclitaxel in malignant gliomas clinical and pharmacokinetics results.

Management of Malignant Gliomas continues to be a challenge. We prospectively studied the role of adding weekly Paclitaxel to Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of Malignant Gliomas. Twenty-three Glioblastoma Multiforme and two Anaplastic Astrocytoma were studied. Patients received 46 Gy at 2 Gy/fraction followed by a boost utilizing FSRT at a fraction of 2.5 Gy for 8 fractions. Paclitaxel is delivered concomitantly at 150 mg/m(2) weekly for six cycles. Eighteen patients had pharmacokinetic assays of Paclitaxel levels. All patients were followed until death or for a maximum of 36 months. The overall survival of the whole group was 14 months. The median survival for RPA prognostic classes III, IV, V, and VI were 20, 14, 12, and 11 months. Higher survival (14 months) was noted in the subtherapeutic phenytoin level group compared to 10 months in the therapeutic group (P=0.271). No grade 4 CTCAE (version 3.0) toxicities were observed. Enhanced survival was demonstrated with gross tumor resection (20.8 months), KPS > or =80 (18.7 months) and age < or =60 years (27 months) as compared to subtotal resection or biopsy (12.1 months, P< 0.005), KPS < or =70 (10.8 months, P=0. 005) and older age > 60 (10.46 months, P=0.006), respectively. Our study suggests that: i) the use of weekly Paclitaxel and FSRT in Gliomas is well tolerated with a survival of 14 months; ii) the regimen resulted in improvement of survival of RPA classes IV, V, VI; and iii) the use of FSRT boost may be studied with other chemotherapeutic agents to see if superior results can be attained.

Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer.

PURPOSE: To determine prospectively the maximal tolerated dose and potential antitumor activity of weekly paclitaxel with concurrent hyperfractionated radiotherapy in patients with locally advanced and/or unresectable pancreatic cancer. METHODS AND MATERIALS: We embarked on Phase I-II study of hyperfractionated radiotherapy using a concomitant in-field boost to a total dose of 63.80 Gy in 6 weeks at 1.1 Gy/fraction. Paclitaxel was administered weekly on Days 1, 8, 15, 22, 29, and 36 as a 3-h infusion. Paclitaxel doses were escalated from 20 mg/m(2)/wk to 70 mg/m(2)/wk. Twenty patients were studied, 14 women and 6 men (mean age 64 years). Some patients presented with one or more symptoms. Obstructive jaundice was the main presenting symptom in 10 patients and epigastric pain in 14. All patients had unresectable histologically proven adenocarcinoma of the pancreas (15 head, 4 body, and 1 tail). Reasons for unresectability were involvement of the portal vein, and/or superior mesenteric artery (n = 14), paraaortic nodes (n = 8), and medically inoperable (n = 1). Fourteen patients underwent a biliary bypass procedure before treatment (four endoscopic stenting, five choledochojejunostomy, and five cholecystojejunostomy). The follow-up period ranged from 14 to 66 months (median 44). RESULTS: The dose-limiting toxicity was observed at 70 mg/m(2)/wk. Grade IV Radiation Therapy Oncology Group late GI toxicity was seen in 1 patient in the form of duodenal stricture and hemorrhage. Grade II gastrointestinal adverse effects occurred in 13 patients and Grade 3 in 1 patient. No neurologic morbidity was encountered. Eight patients required cytokine support for Grade 2 and 3 neutropenia. The treatment course was delivered within the planned time in 80% of the patients. Complete relief of pain occurred in 10 of 14 patients. The CA 19-9 level was either stable or decreasing in 12 of 15 patients. Of 17 assessable patients, stable disease was seen in 10, regression in 2, a partial response in 3, and a complete response in 2. CONCLUSION: The use of hyperfractionated radiotherapy to a dose of 63.80 Gy with concomitant weekly paclitaxel is tolerated. The maximal tolerated dose of paclitaxel for this study was 60 mg/m(2)/wk. The preliminary objective responses denote activity of the regimen. We recommend testing this regimen in larger scale studies.

Patient satisfaction with primary health care services in two districts in Lower and Upper Egypt.

This study compares patient satisfaction with primary health care services and identifies factors associated with patient satisfaction in two health districts in Egypt where a project for upgrading primary health care services had been running for three years. An exit interview was conducted for 1108 patients using a structured questionnaire. The results revealed that most clients using primary health care services were females. Patient satisfaction was high for accessibility, waiting area conditions and performance of doctors and nurses. The main complaints centred on the availability of prescribed drugs and laboratory investigations. Additionally, level of privacy in the consultation room was described as unsatisfactory by 33% of patients. There was no association between overall patient satisfaction and age, gender, education level or type of service received.

Patient satisfaction with primary health care services in two districts in Lower and Upper Egypt

This study compares patient satisfaction with primary health care services and identifies factors associated with patient satisfaction in two health districts in Egypt where a project for upgrading primary health care services had been running for three years. An exit interview was conducted for 1108 patients using a structured questionnaire. The results revealed that most clients using primary health care services were females. Patient satisfaction was high for accessibility, waiting area conditions and performance of doctors and nurses. The main complaints centred on the availability of prescribed drugs and laboratory investigations. Additionally, level of privacy in the consultation room was described as unsatisfactory by 33% of patients. There was no association between overall patient satisfaction and age, gender, education level or type of service received