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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5033-5033
    Abstract: 5033 Background: Intra-patient inter-metastatic heterogeneity (IIH) has been demonstrated in metastatic castration resistant prostate cancer (mCRPC) patients based on genomic and imaging studies, most often after several lines of therapies. IIH is of utmost importance for PSMA radioligand therapy (RLT) eligibility, biopsy-based precision medicine and/or treatment intensification decision-making. The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study (NCT04000776) is a prospective multicenter PET imaging study that was designed to determine the prevalence of IIH in mCRPC patients and to determine candidacy for RLT. Methods: 3TMPO is a PET-imaging trial including mCRPC patients showing at least 3 metastases on conventional imaging with evidence of biochemical or radiographic progression, at least 3 months after initiation of the last systemic therapy. 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans were performed within 10 days and analyzed quantitatively. A third scan with 68 Ga-Octreotate was done when a PSMA-/FDG+ lesion was found. For all tracers, positivity of a lesion was defined as its SUV peak being 1.5 times higher than the SUV mean of the liver. Lesions smaller than 1 cc and likely benign foci of uptake were excluded. IIH prevalence was the primary outcome, defined as the percentage of patients having at least two lesions with discordant features on PET imaging. Results: We included 98 patients in the final analysis. Patients had a mean age of 69 years and a median PSA of 51.1 ng/mL. Number of metastases were 〈 5 in 46.9% and ≥10 in 33.7% of patients and 10.2, 20.4, 18.4 and 51.0% had received 0, 1, 2 or 〉 2 lines of systemic therapies for mCRPC, respectively. Prevalence of IIH was 83.7% based on pre-specified PET criteria. Overall, seven different combinations of lesion phenotypes were found among patients based on FDG and PSMA PETs, and at least one PSMA-/FDG+ lesion was found in 46 patients (46.9%). Of the 44 patients who underwent Octreotate PET, six (13.6%) had at least one Octreotate-positive lesion. In this FDG/PSMA/Octreotate-imaged subgroup, 11 different combinations of phenotypes were observed between metastases of individual patients. Overall, 52.0% (IC95: 41.7-62.2) of patients were found to be candidate for PSMA RLT, but none for Octreotate RLT. Conclusions: The majority of mCRPC patients showed IIH. Based on a multi-tracer approach, up to 11 lesion phenotype combinations were found amongst patients. Correlation of these imaging phenotypes with genomics and treatment response will be highly relevant for optimized precision medicine, especially with respect to PSMA-RLT. Clinical trial information: NCT04000776 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Canadian Journal of Anaesthesia, Springer Science and Business Media LLC, Vol. 41, No. 3 ( 1994-3), p. 267-267
    Type of Medium: Online Resource
    ISSN: 0832-610X , 1496-8975
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1994
    detail.hit.zdb_id: 2050416-0
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  • 3
    Online Resource
    Online Resource
    American Chemical Society (ACS) ; 2012
    In:  Organic Letters Vol. 14, No. 21 ( 2012-11-02), p. 5428-5431
    In: Organic Letters, American Chemical Society (ACS), Vol. 14, No. 21 ( 2012-11-02), p. 5428-5431
    Type of Medium: Online Resource
    ISSN: 1523-7060 , 1523-7052
    RVK:
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2012
    detail.hit.zdb_id: 1501522-1
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  • 4
    In: ChemInform, Wiley, Vol. 43, No. 46 ( 2012-11-13), p. no-no
    Type of Medium: Online Resource
    ISSN: 0931-7597
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2110203-X
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  • 5
    In: Medical Physics, Wiley, Vol. 34, No. 5 ( 2007-05), p. 1819-1827
    Abstract: Megavoltage cone‐beam CT (MVCBCT), the recent addition to the family of in‐room CT imaging systems for image‐guided radiation therapy (IGRT), uses a conventional treatment unit equipped with a flat panel detector to obtain a three‐dimensional representation of the patient in treatment position. MVCBCT has been used for more than two years in our clinic for anatomy verification and to improve patient alignment prior to dose delivery. The objective of this research is to evaluate the image acquisition dose delivered to patients for MVCBCT and to develop a simple method to reduce the additional dose resulting from routine MVCBCT imaging. Conventional CT scans of phantoms and patients were imported into a commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc treatment mimicking the MVCBCT acquisition process was generated to compute the delivered acquisition dose. To validate the dose obtained from the TPS, a simple water‐equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber was used to measure the MVCBCT image acquisition dose. Absolute dose distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU) on pelvis and head and neck patients, respectively. A compensation factor was introduced to generate composite plans of treatment and MVCBCT imaging dose. The article provides a simple equation to compute the compensation factor. The developed imaging compensation method was tested on routinely used clinical plans for prostate and head and neck patients. The quantitative comparison between the calculated dose by the TPS and measurement points on the cylindrical phantom were all within 3%. The dose percentage difference for the ion chamber placed in the center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to patients forms a small anterior‐posterior gradient ranging from per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver slightly more dose than current portal imaging but render soft tissue information for positioning. Overall, the additional dose from daily MVCBCTs of prostate patients is small compared to the treatment dose . Dose‐volume histograms of compensated plans for pelvis and head and neck patients imaged daily with MVCBCT showed no additional dose to the target and small increases at low doses. The results indicate that the dose delivered for MVCBCT imaging can be precisely calculated in the TPS and therefore included in the treatment plan. This allows simple plan compensations, such as slightly reducing the treatment dose, to minimize the total dose received by critical structures from daily positioning with MVCBCT. The proposed compensation factor reduces the number of MU per treatment beam per fraction. Both the number of fractions and the beam arrangement are kept unchanged. Reducing the imaging volume in the cranio‐caudal direction can further reduce the dose delivered for MVCBCT. This is a useful feature to eliminate the imaging dose to the eyes or to focus on a specific region of interest for alignment.
    Type of Medium: Online Resource
    ISSN: 0094-2405 , 2473-4209
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 1466421-5
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  • 6
    In: Journal of Applied Clinical Medical Physics, Wiley, Vol. 10, No. 1 ( 2009-12), p. 33-42
    Abstract: Megavoltage cone‐beam CT (MVCBCT) is an imaging technology that provides a 3D representation of the patient in treatment position. Because it is a form of x‐ray tomography, MVCBCT images give information about the attenuation coefficients of the imaged tissues, and thus could be used for dose calculation. However, the cupping and missing data artifacts seen on MVCBCT images can cause inaccuracies in dose calculations. To eliminate these inaccuracies, a correction method specific to pelvis imaging and based on phantom measurements has been devised. Pelvis‐shaped water phantoms of three different sizes were designed and imaged with MVCBCT. Three sets of correction factors were created from the artifacts observed in these MVCBCT images by dividing the measured CT number by the predefined CT number for water. Linear interpolation is performed between the sets of correction factors to take into account the varying size of different patients. To compensate for the missing anatomy due to the limited field of view of the MVCBCT system, the MVCBCT image is complemented with the kilovoltage CT (kVCT) image acquired for treatment planning. When the correction method is applied to an anthropomorphic pelvis phantom, the standard deviation between dose calculations performed with kVCT and MVCBCT images is 0.6%, with 98% of the dose points agreeing within . With uncorrected MVCBCT images this percentage falls to 75%. An example of dose calculation performed with a corrected clinical MVCBCT image of a prostate cancer patient shows that changes in anatomy of normal tissues result in variation of the dose distribution received by these tissues. This correction method enables MVCBCT images to be used for the verification of the daily dose distribution for patients treated in the pelvis region. PACS numbers: 87.57.Q‐ Computed tomography, 87.57.cp Artifacts and distortion
    Type of Medium: Online Resource
    ISSN: 1526-9914 , 1526-9914
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2010347-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 35 ( 2009-12-10), p. 5906-5910
    Abstract: Anthracyclines are a component of breast cancer chemotherapy regimens in both adjuvant and metastatic settings. Anthracycline rechallenge for metastatic disease, for those previously exposed to adjuvant anthracyclines, may not be considered because of concerns about efficacy, tolerability, and cumulative cardiotoxicity. Patients and Methods This prospective, multicenter, single-arm, phase II trial examined the efficacy and safety of pegylated liposomal doxorubicin (PLD) 35 mg/m 2 plus cyclophosphamide 600 mg/m 2 as first-line therapy, delivered every 3 weeks, in 70 patients who developed metastatic disease more than 12 months after completion of an adjuvant anthracycline-containing regimen. Seven patients discontinued treatment early and were excluded from the efficacy analysis. Results After a median of six cycles, the objective response rate was 38%. An additional 33% of patients achieved stable disease lasting more than 6 months, for an overall clinical benefit rate of 71%. The estimated median time to progression was 12.2 months. Median overall survival time was 16.5 months. Clinical response was equally robust in patients with and without prior taxane exposure. Treatment was well tolerated. The most common grade 3 to 4 toxicities were palmar-plantar erythrodysesthesia (PPE; 10%), dyspnea (9%), and neutropenia (9%). One (1.4%) of 70 patients discontinued treatment as a result of PPE. One patient (1.4%) experienced an infusion reaction requiring discontinuation. No symptomatic cardiac events were observed. Conclusion PLD plus cyclophosphamide is effective and well tolerated in patients with metastatic breast cancer who have received prior adjuvant anthracycline-containing chemotherapy. The majority of patients experienced a clinical benefit without any significant impact on cardiac function.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Brachytherapy, Elsevier BV, Vol. 9, No. 3 ( 2010-7), p. 266-273
    Type of Medium: Online Resource
    ISSN: 1538-4721
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
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  • 9
    In: Brachytherapy, Elsevier BV, Vol. 5, No. 2 ( 2006-4), p. 85-86
    Type of Medium: Online Resource
    ISSN: 1538-4721
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
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  • 10
    In: Medical Physics, Wiley, Vol. 36, No. 4 ( 2009-04), p. 1421-1432
    Abstract: Megavoltage cone‐beam CT (MVCBCT) is the most recent addition to the in‐room CT systems developed for image‐guided radiation therapy. The first generation MVCBCT system consists of a treatment x‐ray beam produced by a conventional linear accelerator equipped with a flat panel amorphous silicon detector. The objective of this study was to evaluate the physical performance of MVCBCT in order to optimize the system acquisition and reconstruction parameters for image quality. MVCBCT acquisitions were performed with the clinical system but images were reconstructed and analyzed with a separate research workstation. The geometrical stability and the positioning accuracy of the system were evaluated by comparing geometrical calibrations routinely performed over a period of . The beam output and detector intensity stability during MVCBCT acquisition were also evaluated by analyzing in‐air acquisitions acquired at different exposure levels. Several system parameters were varied to quantify their impact on image quality including the exposure (2.7, 4.5, 9.0, 18.0, and ), the craniocaudal imaging length (2, 5, 15, and ), the voxel size (0.5, 1, and ), the slice thickness (1, 3, and ), and the phantom size. For the reconstruction algorithm, the study investigated the effect of binning, averaging and diffusion filtering of raw projections as well as three different projection filters. A head‐sized water cylinder was used to measure and improve the uniformity of MVCBCT images. Inserts of different electron densities were placed in a water cylinder to measure the contrast‐to‐noise ratio (CNR). The spatial resolution was obtained by measuring the point‐spread function of the system using an iterative edge blurring technique. Our results showed that the geometric stability and accuracy of MVCBCT were better than over a period of . Beam intensity variations per projection of up to 35.4% were observed for a MVCBCT acquisition. These variations did not cause noticeable reduction in the image quality. The results on uniformity suggest that the cupping artifact occurring with MVCBCT is mostly due to off‐axis response of the detector and not scattered radiation. Simple uniformity correction methods were developed to nearly eliminate this cupping artifact. The spatial resolution of the baseline MVCBCT reconstruction protocol was approximately . An optimized reconstruction protocol was developed and showed an improvement of 75% in CNR with a penalty of only 8% in spatial resolution. Using this new reconstruction protocol, large adipose and muscular structures were differentiated at an exposure of . A reduction of 36% in CNR was observed on a larger (pelvic‐sized) phantom. This study demonstrates that soft‐tissue visualization with MVCBCT can be substantially improved with proper system settings. Further improvement is expected from the next generation MVCBCT system with an optimized megavoltage imaging beamline.
    Type of Medium: Online Resource
    ISSN: 0094-2405 , 2473-4209
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 1466421-5
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