Worth a local treatment? - Analysis of modern radiotherapy concepts for oligometastatic prostate cancer.

BACKGROUND: Prostate cancer (PCA) is the most-prevalent non-skin cancer in men worldwide. Nevertheless, the treatment of oligometastatic, especially lymph-node (ln) recurrent, PCA remains elusive. The aim of our study was to provide insights in radiotherapy (RT)-treatment of recurrent PCA exhibiting ln- or osseous (oss)-oligometastases. METHODS: Between April 2012 and April 2017, 27 oligometastatic PCA patients (19 ln and 8 single oss) were treated with RT at our institution. RESULTS: The metastasis-free survival (MFS) was 24.8 m (22.0-36.0 m) and 25.4 m (23.9-28.1 m) for the ln- and oss-subgroup resulting in 1-year MFS of 75.4 and 100% and 2-year MFS of 58.7 and 83.3% for ln- and oss-metastatic patients, respectively. Of notice, none of the recurrences for ln-patients was in the RT-field, constituting a local control of 100%. Within the ln-group, pre-RT median-PSA was 2.6 ng/ml, median post-RT PSA was 0.3 ng/ml, which was significant (p = 0.003). Median biochemical-free survival (bfS) was 12.2 m. PCA that was initially confined to the prostate had a better bfS (p < 0.001) and MFS (p = 0.013). The oss-group had a median PSA of 4.9 ng/ml pre-treatment which dropped to a median value of 0.14 ng/ml (p = 0.004). Toxicities were moderate, with only 1 case of III° toxicity. There were no deaths in the ln-group, thus overall survial was 100% here. CONCLUSION: Our study points out the feasibility of RT as a treatment option in recurrent PCA and demonstrates an excellent local control with a low-toxicity profile.

External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points. Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 µSv/h at 2 h p. i., 1.6 ± 0.6 µSv/h at 24 h, 1.1 ± 0.5 µSv/h at 48 h, and 0.7 ± 0.4 µSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 µSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 µSv when the patient was discharged after 72 h. CONCLUSIONS: In terms of the radiation exposure to the public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In other words, the radiation exposure to the public and the concentration of activity in wastewater must be sub-marginal. Therefore, in certain countries, hospitalization of these patients is mandatory.

Simultaneous PET/MR imaging in a human brain PET/MR system in 50 patients--current state of image quality.

OBJECTIVES: The present work illustrates the current state of image quality and diagnostic accuracy in a new hybrid BrainPET/MR. MATERIALS AND METHODS: 50 patients with intracranial masses, head and upper neck tumors or neurodegenerative diseases were examined with a hybrid BrainPET/MR consisting of a conventional 3T MR system and an MR-compatible PET insert. Directly before PET/MR, all patients underwent a PET/CT examination with either [18F]-FDG, [11C]-methionine or [68Ga]-DOTATOC. In addition to anatomical MR scans, functional sequences were performed including diffusion tensor imaging (DTI), arterial spin labeling (ASL) and proton-spectroscopy. Image quality score of MR imaging was evaluated using a 4-point-scale. PET data quality was assessed by evaluating FDG-uptake and tumor delineation with [11C]-methionine and [68Ga]-DOTATOC. FDG uptake quantification accuracy was evaluated by means of ROI analysis (right and left frontal and temporo-occipital lobes). The asymmetry indices and ratios between frontal and occipital ROIs were compared. RESULTS: In 45/50 patients, PET/MR examination was successful. Visual analysis revealed a diagnostic image quality of anatomical MR imaging (mean quality score T2 FSE: 1.27±0.54; FLAIR: 1.38±0.61). ASL and proton-spectroscopy was possible in all cases. In DTI, dental artifacts lead to one non-diagnostic dataset (mean quality score DTI: 1.32±0.69; ASL: 1.10±0.31). PET datasets of PET/MR and PET/CT offered comparable tumor delineation with [11C]-methionine; additional lesions were found in 2/8 [(68)Ga]-DOTATOC-PET in the PET/MR. Mean asymmetry index revealed a high accordance between PET/MR and PET/CT (1.5±2.2% vs. 0.9±3.6%; mean ratio (frontal/parieto-occipital) 0.93±0.08 vs. 0.96±0.05), respectively. CONCLUSIONS: The hybrid BrainPET/MR allows for molecular, anatomical and functional imaging with uncompromised MR image quality and a high accordance of PET results between PET/MR and PET/CT. These results justify the application of this technique in further clinical studies and may contribute to the transfer into whole-body PET/MR systems.

HIS-Based Support of Follow-Up Documentation - Concept and Implementation for Clinical Studies.

OBJECTIVE: Follow-up data must be collected according to the protocol of each clinical study, i.e. at certain time points. Missing follow-up information is a critical problem and may impede or bias the analysis of study data and result in delays. Moreover, additional patient recruitment may be necessary due to incomplete follow-up data. Current electronic data capture (EDC) systems in clinical studies are usually separated from hospital information systems (HIS) and therefore can provide limited functionality to support clinical workflow. In two case studies, we assessed the feasibility of HIS-based support of follow-up documentation. METHODS: We have developed a data model and a HIS-based workflow to provide follow-up forms according to clinical study protocols. If a follow-up form was due, a database procedure created a follow-up event which was translated by a communication server into an HL7 message and transferred to the import interface of the clinical information system (CIS). This procedure generated the required follow-up form and enqueued a link to it in a work list of the relating study nurses and study physicians, respectively. RESULTS: A HIS-based follow-up system automatically generated follow-up forms as defined by a clinical study protocol. These forms were scheduled into work lists of study nurses and study physicians. This system was integrated into the clinical workflow of two clinical studies. In a study from nuclear medicine, each scenario from the test concept according to the protocol of the single photon emission computer tomography/computer tomography (SPECT/CT) study was simulated and each scenario passed the test. For a study in psychiatry, 128 follow-up forms were automatically generated within 27 weeks, on average five forms per week (maximum 12, minimum 1 form per week). CONCLUSION: HIS-based support of follow-up documentation in clinical studies is technically feasible and can support compliance with study protocols.

PET surveillance of patients with Ewing sarcomas of the trunk: Must the lower legs be included?

AIM: FDG-PET(/CT) is frequently used in surveillance of Ewing sarcoma (ES) patients. Since ES and PNET (primitive neuroectodermal tumours) may cause peripheral metastases some centers routinely recommend whole body PET acquisition from head to toe what may necessitate repositioning of the patient and thus extending examination time. It is not clear yet whether inclusion of lower leg adds to the diagnostic accuracy of PET scanning, especially in primary tumors of the trunk. PATIENTS, METHOD: 40 patients with ES and PNET of the trunk who were referred for surveillance after primary therapy with complete remission, were evaluated retrospectively: 27 men, 13 women; mean age at diagnosis 16.3 (3-35) years. At the time of diagnosis 28 patients had localized and 12 metastatic disease. Almost all of the patients had undergone a combined chemotherapy with surgery or/and radiotherapy. 156 follow-up PET scans of the legs of these patients were evaluated retrospectively. RESULTS: only in three (1.9%) of 156 scans a pathologic FDG accumulation was attributed to metastatic disease of the lower extremities. In these cases the observation of metastatic disease in the legs did not alter therapy, since in all three cases a multifocal disease progression was observed. CONCLUSION: scanning of the lower legs may be omitted during follow-up in patients in whom the primary tumor was located in the trunk and in whom no clinical signs pointing to metastases in the lower legs are present. This provides a sufficient diagnostic power and a shorter examination time, thus increasing patient comfort and scanner availability.

Concept and Implementation of a Single Source Information System in Nuclear Medicine for Myocardial Scintigraphy (SPECT-CT data).

OBJECTIVE: Data for clinical documentation and medical research are usually managed in separate systems. We developed, implemented and assessed a documentation system for myocardial scintigraphy (SPECT/CT-data) in order to integrate clinical and research documentation. This paper presents concept, implementation and evaluation of this single source system including methods to improve data quality by plausibility checks. METHODS: We analyzed the documentation process for myocardial scintigraphy, especially for collecting medical history, symptoms and medication as well as stress and rest injection protocols. Corresponding electronic forms were implemented in our hospital information system (HIS) including plausibility checks to support correctness and completeness of data entry. Research data can be extracted from routine data by dedicated HIS reports. RESULTS: A single source system based on HIS-electronic documentation merges clinical and scientific documentation and thus avoids multiple documentation. Within nine months 495 patients were documented with our system by 8 physicians and 6 radiographers (466 medical history protocols, 466 stress and 414 rest injection protocols). Documentation consists of 295 attributes, three quarters are conditional items. Data quality improved substantially compared to previous paper-based documentation. CONCLUSION: A single source system to collect routine and research data for myocardial scintigraphy is feasible in a real-world setting and can generate high-quality data through online plausibility checks.

EANM/ESC guidelines for radionuclide imaging of cardiac function.

Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus". The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

Chemotherapy in metastatic malignant triton tumor: report on two cases.

Malignant triton tumor (MTT) is a rare, highly malignant nerve sheath tumor with rhabdomyoblastic differentiation. Initial debulking surgery followed by adjuvant therapy is the current treatment of choice, but has very limited efficacy when optimal cytoreduction is not achieved by surgical procedure. Neoadjuvant therapy for MTT, to potentially facilitate subsequent surgery, eradicate micrometastatic lesions and, therefore, improve the therapeutical outcome, has never before been presented in literature. Here, we report on the multimodal management of two cases of advanced and metastatic MTT. Treatment modalities involved neoadjuvant and adjuvant chemotherapy, surgical resection, and radiation. In both cases, integrated Positron Emission Tomography/Computed Tomography (PET/CT) emerged as an important diagnostic tool for the reliable assessment of MTT response and metabolic remission.

Tumor staging using whole-body high-resolution 16-channel PET-CT: does additional low-dose chest CT in inspiration improve the detection of solitary pulmonary nodules?

For optimal image fusion between CT and F-18-FDG-PET, the acquisition of CT images is performed in mild expiratory suspension, which might compromise the detection of lung metastases. This study aimed at evaluating the influence of expiration on the detection of solitary pulmonary nodules (SPN) and at assessing if additional inspiratory low-dose CT (I-LDCT) of the chest can improve the detection of potential lung metastases performing whole-body 16-channel PET-CT. Sixty-six patients with malignant tumors underwent PET-CT: contrast-enhanced CT was acquired during mild expiration and was used for fusion with PET images; additionally, chest I-LDCT was performed at deep inspiration. Two radiologists reported all SPN detected at I-LDCT and the expiratory CT scan independently. Overall, 53% of 128 SPN (mean: 3.8+/-0.2 mm) were detected at both respiratory states: 51 SPN only at I-LDCT, and 9 nodules only at expiratory CT. Of the SPN, 117/128 were classified as certain; 45 of those were additionally detected at I-LDCT, and 6 nodules at expiratory CT. A 100% detection rate was reached in SPN >4 mm at I-LDCT versus >8 mm at expiratory CT (all P<0.001). Additional I-LDCT of the chest significantly improves the detection of SPN at whole-body F-18-FDG-PET-CT and thus is recommended as part of the standard protocol for oncological patients.

Correlation between respiration-induced thoracic expansion and a shift of central structures.

The fusion of computed tomography (CT) and positron emission tomography (PET) may improve diagnostic accuracy, but is limited by different breathing protocols. This study aimed at quantifying respiration-induced alignment errors. PET-CT was acquired in 24 patients. Contrast-enhanced whole-body CT was obtained in a single breath hold in the expiratory state of a normal breathing cycle. An inspiratory low-dose CT of the thorax was acquired in the same session, and comparison of the two CT scans was used to assess the potential mismatch of PET and CT fusion. The largest craniocaudal expansion was found in the area of the diaphragm. A considerable sagittal expansion was found in the anterior parts of the lungs. Central tracheo-bronchial structures were displaced during inspiration mainly in the anterior and caudal directions. The craniocaudal shift of central structures showed a linear correlation with the diaphragmatic expansion, whereas the sagittal shift correlated with the sagittal pleural expansion. There was, however, no correlation between craniocaudal and sagittal respiratory motion. Alignment errors are most severe in the base of the lung, but central structures are affected, too. Understanding of the main vectors of respiratory motion may help in image interpretation when PET and CT are acquired separately.

Rigid-body transformation of list-mode projection data for respiratory motion correction in cardiac PET.

High-resolution cardiac PET imaging with emphasis on quantification would benefit from eliminating the problem of respiratory movement during data acquisition. Respiratory gating on the basis of list-mode data has been employed previously as one approach to reduce motion effects. However, it results in poor count statistics with degradation of image quality. This work reports on the implementation of a technique to correct for respiratory motion in the area of the heart at no extra cost for count statistics and with the potential to maintain ECG gating, based on rigid-body transformations on list-mode data event-by-event. A motion-corrected data set is obtained by assigning, after pre-correction for detector efficiency and photon attenuation, individual lines-of-response to new detector pairs with consideration of respiratory motion. Parameters of respiratory motion are obtained from a series of gated image sets by means of image registration. Respiration is recorded simultaneously with the list-mode data using an inductive respiration monitor with an elasticized belt at chest level. The accuracy of the technique was assessed with point-source data showing a good correlation between measured and true transformations. The technique was applied on phantom data with simulated respiratory motion, showing successful recovery of tracer distribution and contrast on the motion-corrected images, and on patient data with C15O and 18FDG. Quantitative assessment of preliminary C15O patient data showed improvement in the recovery coefficient at the centre of the left ventricle.

Elastic surface contour detection for the measurement of ejection fraction in myocardial perfusion SPET.

The aim of this study was to investigate the use of an automated three-dimensional myocardial contour detection method using elastic surfaces for the assessment of left ventricular ejection fraction (EF) from electrocardiographically (ECG) triggered myocardial perfusion single-photon emission tomography (SPET). The validity of this method was studied on the basis of both phantom measurements and patient studies. Phantom measurements were performed using an elastic phantom of the left ventricle simulating a beating heart, with a simulated EF ranging from 10% to 78%. The data from 27 patients who had undergone both ECG-triggered myocardial perfusion SPET and planar gated radionuclide ventriculography (RNV) were used to compare the EF derived from the SPET data with the automated contour detection method and the EF derived from the RNV data with standard analysis software. EF values as measured by RNV ranged from 11% to 68%. The overall accuracy of the automated contour detection method proved to be very high. In the phantom study the deviation of the measured EF from the reference values was less than 4% for all of the simulated EFs. The studies on the patient data yielded a correlation coefficient (Pearson) greater than 0.94 as compared with planar RNV. Intra- and inter-observer reproducibility was high, with correlation coefficients exceeding 0.97. It is concluded that the proposed method allows accurate, reproducible and fast measurement of the left ventricular EF on the basis of myocardial perfusion SPET.

Three-dimensional contour detection of left ventricular myocardium using elastic surfaces.

Since the human heart has a complex anatomy, the two-dimensional analysis of myocardial scintigrams obviously is not satisfactory. Three-dimensional display can be more easily read by clinicians and depicts more accurately tracer accumulation defects. In this study we propose a three-dimensional myocardial contour detection approach using elastic surfaces. After manual reorientation into short-axis slices and transformation into heart coordinates, the myocardial mid-wall surface passing through the radial activity mass points is calculated using a second-order partial differential equation as a mathematical model. Special considerations are implemented to demarcate organs close to the heart. In a total of 1102 myocardial scintigrams the three-dimensional contour detection calculated a reasonable shape of the left ventricular myocardium in all cases. Even in areas with severe myocardial infarction, this approach was able to bridge tracer accumulation defects. Inter- and intra-observer variability tests confirmed a high reproducibility and user independence. In conclusion, in this study the proposed three-dimensional contour detection of left ventricular myocardium using elastic surfaces was found to be fast, user-independent and reliable, leading to realistic three-dimensional parametric images of myocardial scintigrams that even clinicians not experienced in nuclear cardiology can easily read.