The VentrAssist (VA) is a novel, continuous flow left ventricular assist device (LVAD). The purpose of this trial was to investigate the safety and efficacy of the VA in elderly patients with ...end-stage heart failure.
In this prospective trial, patients requiring circulatory support either as destination therapy (DT) or as a bridge to transplant (BTT) were implanted with a VA device.
Between June 2003 and August 2006, 9 elderly patients (mean age 65 years) were implanted. The median support time was 454 (range 73 to 977) days for the DT and 35 (range 26 to 508) days for the BTT cohort. All patients survived implantation; 30-day mortality was 22% (n = 2). The adverse event profile was encouraging, with no embolic neurologic events and minimal sepsis. Cumulative trial support time was 7.3 patient-years.
The VentrAssist shows promise as a safe and reliable "third-generation" VAD. Having demonstrated potential as a DT and prolonged BTT device, extended clinical trials are warranted.
The cattle tick Rhipicephalus microplus is widely distributed in tropical and subtropical regions, causing high economic impact on cattle production. The control of tick infestations is regarded ...worldwide as critical and has been based on the use of organophosphates, synthetic pyretroids, amitraz and recently ivermectin and fipronil. The present study reports the analysis by gas chromatography/mass spectrometry of the constituents of leaf extracts of Croton sphaerogynus and results of acaricidal activity against the cattle tick R. microplus. The larval package test using the serial dilutions 0.625%, 1.25%, 2.5%, 5.0%, 10.0% and 20.0% (v/v) gave mortality rates 2.25%, 8.26%, 8.81%, 24.80%, 83.66% and 99.32%, respectively. Relevant constituents identified were abietanes, podocarpenes and clerodane type furano diterpenes. The present work may represent a possibility of attainment of natural substances useful for the control of R. microplus.
Purpose The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an ...individualized treatment planning strategy based on ^sup 99m^Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. Methods We performed retrospective dosimetry of the standard TheraSphere treatment on 52 intermediate (n=17) and advanced (i.e. portal vein thrombosis, n=35) hepatocarcinoma patients with tumour burden<50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on ^sup 99m^Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of ^sup 99m^Tc-MAA and ^sup 90^Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS(TM) by Philips). STRATOS(TM) absorbed dose calculation was validated for ^sup 90^Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BED^sub ave^) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. Results MAA and ^sup 90^Y biodistributions were not different (71 % of cases), different in 23 % and uncertain in 6 %. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p=0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC=0.87 vs 0.80, z=2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50 %) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14 %, p<0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD^sub 50^ wasasymptotically =100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD^sub 15^asymptotically =75 Gy. Conclusion A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.
Purpose
The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an ...individualized treatment planning strategy based on
99m
Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images.
Methods
We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (
n
= 17) and advanced (i.e. portal vein thrombosis,
n
= 35) hepatocarcinoma patients with tumour burden < 50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on
99m
Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of
99m
Tc-MAA and
90
Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for
90
Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BED
ave
) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment.
Results
MAA and
90
Y biodistributions were not different (71 % of cases), different in 23 % and uncertain in 6 %. Response correlated with absorbed dose (Spearman’s
r
from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (
p
= 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80,
z
= 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50 %) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3–5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14 %,
p
< 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD
50
was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD
15
≈ 75 Gy.
Conclusion
A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.
Purpose: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for ...an individualized treatment planning strategy based on super(99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. Methods: We performed retrospective dosimetry of the standard TheraSphere registered treatment on 52 intermediate (n=17) and advanced (i.e. portal vein thrombosis, n=35) hepatocarcinoma patients with tumour burden<50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on super(99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of super(99m)Tc-MAA and super(90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS(TM) by Philips). STRATOS(TM) absorbed dose calculation was validated for super(90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BED sub(ave)) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. Results: MAA and super(90)Y biodistributions were not different (71 % of cases), different in 23 % and uncertain in 6 %. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p=0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC=0.87 vs 0.80, z=2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50 %) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14 %, p<0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD sub(50) was approximately 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD sub(15) approximately 75 Gy. Conclusion: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.
Aims:
BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer.
Methods:
A total of 386 patients were followed ...for 15 months after first-line chemotherapy + bevacizumab start. The rate of bevacizumab interruption for progression or adverse drug reactions (ADRs) constituted the primary endpoint.
Results:
A total of 78.2% of patients interrupted bevacizumab: 56.6% for progression, 7.3% for ADRs, and 36.1% for other reasons. Median treatment duration was 6.7, 2.5, and 4.6 months, respectively. Median progression-free survival was 10.3 months; however, 35.8% of patients were not progressed and were thus censored at the data cutoff of 15 months, while 21.8% were still receiving bevacizumab. Patients discontinuing for progression/ADRs more frequently had metastases in >1 site (p = .0001), and a shorter median progression-free survival (6.9 vs 13.9 months, p < .0001).
Conclusions:
In Italy, first-line bevacizumab is interrupted mainly for progression, only 7.3% due to adverse events, and about one third of cases for other reasons. In clinical practice, the attitude to treat until progression as per guidelines might be implemented.
ClinicalTrials.gov Identifier: NCT01609075
•Croton is a large genus of Euphorbiaceae used medicinally in many tropical countries of the new and old worlds.•Chemical analyses and antiproliferative activity of extracts of Croton sphaerogynus ...were investigated.•Important diterpenes, previously recognized as possessing antitumor activity, were detected.•The results suggest promising use of extracts and substances of C. sphaerogynus in the control of malignant processes.
Several Croton species have been used in traditional medicine and contain substances active against cancer, such as diterpenoids and alkaloids. Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. The main goal of this study was to characterize the main constituents of the leaf extracts of C. sphaerogynus and evaluate their in vitro antiproliferative activity against tumor cell lines. Hexane, dichloromethane and methanol extracts of leaves were analyzed by GC/MS and evaluated for their in vitro antiproliferative activity on the cell lines 786-0 (kidney), HT-29 (colon), K562 (leukemia), NCI-ADR/RES (drug resistant ovary), NCI-H460 (lung), MCF-7 (mammary), PC-3 (prostate), OVCAR-3 (ovary), U251 (glioma) and UACC-62 (melanoma). Relevant constituents in dichloromethane and hexane extracts were abietane, podocarpane and clerodane type furano diterpenes. Dicloromethane and hexane extracts exhibited activity against NCI-H460 (GI50 0.26μg/mL and 0.33μg/mL, respectively) and K562 (GI50 0.60μg/mL and <0.25μg/mL, respectively). Taking into account all cell lines tested, the dichloromethane extract was shown to have higher activity (mean log GI50 0.86) than hexane and methanol extracts (mean log GI50 1.26 and 1.49, respectively). The antiproliferative activity observed in the present work is probably accounted for by the abietane and/or podocarpane diterpenes.
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