A treatment planning method for sequentially combining radiopharmaceutical therapy and external radiation therapy.

PURPOSE: Effective cancer treatment generally requires combination therapy. The combination of external beam therapy (XRT) with radiopharmaceutical therapy (RPT) requires accurate three-dimensional dose calculations to avoid toxicity and evaluate efficacy. We have developed and tested a treatment planning method, using the patient-specific three-dimensional dosimetry package 3D-RD, for sequentially combined RPT/XRT therapy designed to limit toxicity to organs at risk. METHODS AND MATERIALS: The biologic effective dose (BED) was used to translate voxelized RPT absorbed dose (D(RPT)) values into a normalized total dose (or equivalent 2-Gy-fraction XRT absorbed dose), NTD(RPT) map. The BED was calculated numerically using an algorithmic approach, which enabled a more accurate calculation of BED and NTD(RPT). A treatment plan from the combined Samarium-153 and external beam was designed that would deliver a tumoricidal dose while delivering no more than 50 Gy of NTD(sum) to the spinal cord of a patient with a paraspinal tumor. RESULTS: The average voxel NTD(RPT) to tumor from RPT was 22.6 Gy (range, 1-85 Gy); the maximum spinal cord voxel NTD(RPT) from RPT was 6.8 Gy. The combined therapy NTD(sum) to tumor was 71.5 Gy (range, 40-135 Gy) for a maximum voxel spinal cord NTD(sum) equal to the maximum tolerated dose of 50 Gy. CONCLUSIONS: A method that enables real-time treatment planning of combined RPT-XRT has been developed. By implementing a more generalized conversion between the dose values from the two modalities and an activity-based treatment of partial volume effects, the reliability of combination therapy treatment planning has been expanded.

Childhood epilepsy with neuropsychological regression and continuous spike waves during sleep: epilepsy surgery in a young adult.

We describe the case of a man with a history of complex partial seizures and severe language, cognitive and behavioural regression during early childhood (3.5 years), who underwent epilepsy surgery at the age of 25 years. His early epilepsy had clinical and electroencephalogram features of the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia (Landau-Kleffner syndrome), which we considered initially to be of idiopathic origin. Seizures recurred at 19 years and presurgical investigations at 25 years showed a lateral frontal epileptic focus with spread to Broca's area and the frontal orbital regions. Histopathology revealed a focal cortical dysplasia, not visible on magnetic resonance imaging. The prolonged but reversible early regression and the residual neuropsychological disorders during adulthood were probably the result of an active left frontal epilepsy, which interfered with language and behaviour during development. Our findings raise the question of the role of focal cortical dysplasia as an aetiology in the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia.

Prostate cancer: F-18-fluorocholine PET-CT utility. [Cancer de la prostate : utilité de la TEP-TDM à la 18F-fluorocholine.]

In oncology, positron emission computed tomography (PET/CT) has become an essential tool for initial staging, response evaluation and follow-up of cancer patients. Most of the frequent tumors (lung, breast, esophagus, and lymphomas) are highly avid for (18)F-fluorodeoxyglucose ((18)FDG), but prostate cancer has not demonstrated significant uptake of FDG. The development of new tracers labeled with (18)F such as choline analogs allowed already to obtain interesting results particularly in patients with biological relapse and inconclusive conventional imaging workup. The impact of (18)F-flurocholine PET/CT on patient management needs to be validated in large studies, but many centers use already this examination in order to guide further management, including radiotherapy planning. (C) 2011 Elsevier Masson SAS. All rights reserved.

Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI.

PURPOSE: Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. METHODS: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. RESULTS: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. DISCUSSION: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.

Immunociblage des tumeurs: situation et perspectives en 2000

Following 15 years of experimental studies, tumor immunotargeting using monoclonal antibodies directed against tumor associated antigens shows now important monoclonal antibodies directed against tumor associated antigens shows now important clinical developments. This is mainly due to encouraging therapeutic results which have obtained using humanized antibodies such as the anti-CD20 rituximab in follicular B lymphomas and the anti-DrbB2 herceptin in breast carcinomas. Thanks to genetic engineering it is possible to graft variable or hypervariable regions from murine antibodies to human IgG, and even to obtain fully human antibodies by using either transgenic mice containing a large part of the human repertoire of human IgG, or selection of human antibody fragments expressed by phages. Radiolabeling of antibodies played a major role to demonstrate the tumor immunotargeting specificity and remains attractive for the diagnosis by immunoscintigraphy as well as for the treatment by radioimmunotherapy of some cancers. In this review, the current results and the prospects of diagnostic and therapeutic uses of anti-tumor antibodies and their fragments will be described. Concerning diagnosis, 123-iodine or 99m-technetium labeled Fab fragments allowed very demonstrative tumor images but this technique has a limited effect upon the therapeutic attitude. Immuno-PET (positron emission tomography) could enhance the sensitivity of this imaging method. Radio-immunoguided surgery and immunophotodetection are attractive techniques still under evaluation. Concerning therapy, 131-iodine labeled anti-CD20 antibodies gave spectacular results in non-Hodgkin's B lymphomas. In solid tumors which as less radiosensitive, radioimmunotherapy could concern small tumors and need the use of two-steps targeting and/or alpha emitters radioisotopes. Some other strategies will be described such as bispecific antibodies directed against tumors and immune effector cells, some antibody fragments expressed on T cells called T-bodies or some biological studies using intrabodies. Published data and works in progress demonstrate that immunotargeting of tumors will have a growing place in the treatments of cancer patients.

L'immunoscintigraphie par les anticorps monoclonaux radiomarqués. Evolution d'une méthode de diagnostic du cancer et espoir d'une nouvelle forme de thérapie [Immunoscintigraphy using radio-labeled monoclonal antibodies. Development of a method of cancer diagnosis and hopes for a new form of therapy].

Personal results are presented to illustrate the development of immunoscintigraphy for the detection of cancer over the last 12 years, from the early experimental results in nude mice grafted with human colon carcinoma to the most modern form of immunoscintigraphy applied to patients, using I123 labeled Fab fragments from monoclonal anti-CEA antibodies detected by single photon emission computerized tomography (SPECT). The first generation of immunoscintigraphy used I131 labeled, immunoadsorbent purified, polyclonal anti-CEA antibodies and planar scintigraphy, as the detection system. The second generation used I131 labeled monoclonal anti-CEA antibodies and SPECT, while the third generation employed I123 labeled fragments of monoclonal antibodies and SPECT. The improvement in the precision of tumor images with the most recent forms of immunoscintigraphy is obvious. However, we think the usefulness of immunoscintigraphy for routine cancer management has not yet been entirely demonstrated. Further prospective trials are still necessary to determine the precise clinical role of immunoscintigraphy. A case report is presented on a patient with two liver metastases from a sigmoid carcinoma, who received through the hepatic artery a therapeutic dose (100 mCi) of I131 coupled to 40 mg of a mixture of two high affinity anti-CEA monoclonal antibodies. Excellent localisation in the metastases of the I131 labeled antibodies was demonstrated by SPECT and the treatment was well tolerated. The irradiation dose to the tumor, however, was too low at 4300 rads (with 1075 rads to the normal liver and 88 rads to the bone marrow), and no evidence of tumor regression was obtained. Different approaches for increasing the irradiation dose delivered to the tumor by the antibodies are considered.

How to Prepare a Patient for Transarterial Radioembolization? A Practical Guide.

Transarterial radioembolization consist in delivering small particles loaded with Yttrium90, a pure beta emitter, in order to treat primary and secondary liver tumors. This treatment needs precaution since inadequate delivery of these beads can lead to severe complications. Moreover, a precise radiation dosing is crucial to achieve a good clinical success and to avoid complications such as radioembolization-induced liver disease. This review describes all the precautions and highlights clinical and technical considerations that need to be taken to avoid complications.

Verifique sus conocimientos sobre tomografía computarizada (TC)

La presente entrega de la serie de Nursing sobre las pruebas complementarias está dedicada a la tomografía computarizada (TC). La TC fue pensada inicialmente para explorar el encéfalo en profundidad, pero su capacidad diagnóstica ha caracterizado su evolución desde sus inicios a principios de la década de los setenta, cuando el ingeniero británico Sir Godfrey Newbold Hounsfield ideó el primer prototipo de TC. En la actualidad se utiliza para la exploración y estudio de prácticamente la totalidad de órganos y tejidos. La TC se caracteriza por tener una elevada capacidad de discriminación en las estructuras anatómicas en función de su densidad. Esto permite diferenciar órganos, tejidos y sus lesiones, ofreciendo la posibilidad de obtener más información de la que mostraba la imagen radiológica convencional, que se caracterizaba por la obtención de una imagen general de la estructura a estudiar. En el caso de la TC, uno de los aspectos más destacados es la adquisición axial de la imagen, que permite estudiar porciones de anatomía. La capacidad de visión multiplanar de los nuevos equipos multicoronas, junto con la capacidad de diferenciar densidades, la convierten en una poderosa herramienta diagnóstica. Desde el punto de vista de atención al paciente, la enfermera explica e informa sobre la dinámica de las exploraciones que, dadas las características de la TC, hacen imprescindible el conocimiento de las preparaciones y los cuidados durante y después de la técnica para que se resuelvan de manera eficaz y sin molestias para el paciente.

Verifique sus conocimientos sobre tomografía computarizada (TC)

La presente entrega de la serie de Nursing sobre las pruebas complementarias está dedicada a la tomografía computarizada (TC). La TC fue pensada inicialmente para explorar el encéfalo en profundidad, pero su capacidad diagnóstica ha caracterizado su evolución desde sus inicios a principios de la década de los setenta, cuando el ingeniero británico Sir Godfrey Newbold Hounsfield ideó el primer prototipo de TC. En la actualidad se utiliza para la exploración y estudio de prácticamente la totalidad de órganos y tejidos. La TC se caracteriza por tener una elevada capacidad de discriminación en las estructuras anatómicas en función de su densidad. Esto permite diferenciar órganos, tejidos y sus lesiones, ofreciendo la posibilidad de obtener más información de la que mostraba la imagen radiológica convencional, que se caracterizaba por la obtención de una imagen general de la estructura a estudiar. En el caso de la TC, uno de los aspectos más destacados es la adquisición axial de la imagen, que permite estudiar porciones de anatomía. La capacidad de visión multiplanar de los nuevos equipos multicoronas, junto con la capacidad de diferenciar densidades, la convierten en una poderosa herramienta diagnóstica. Desde el punto de vista de atención al paciente, la enfermera explica e informa sobre la dinámica de las exploraciones que, dadas las características de la TC, hacen imprescindible el conocimiento de las preparaciones y los cuidados durante y después de la técnica para que se resuelvan de manera eficaz y sin molestias para el paciente.

Successful minimally invasive surgery for primary hyperparathyroidism: influence of preoperative imaging and intraoperative parathyroid hormone levels.

PURPOSE: Adenoma is the main parathyroid disorder leading to primary hyperparathyroidism (PHP). Minimally invasive parathyroidectomy (MIP) is recognized as a valid procedure for adenoma-related PHP. It requires precise preoperative localization combining Tc-99m-MIBI (methoxy-isobutyl-isonitrile) scintigraphy and single-photon emission computed tomography (SPECT) with x-ray computed tomography (CT) and intraoperative confirmation of successful excision by change in intact parathormone (iPTH) levels. The study aim was to assess the surgery success in relation to these two parameters. METHODS: All patients operated on for PHP from 2005 to mid-2014 at our institution were retrospectively reviewed. MIP was performed in case of precise preoperative adenoma localization on scintigraphy, absence of past cervical surgery, and absence of concomitant thyroid resection necessity. In these patients, iPTH levels were monitored intraoperatively. Confirmation criteria for iPTH values were a return to normal level or a decrease >50 % of basal iPTH level. RESULTS: There were 197 PHP operations during the study period: 118 MIP and 79 bilateral neck explorations (BNEs). The MIP success rate was 95 % (112/118) with a preoperative MIBI scan ± CT accurate in 94 % (111/118) of the patients and with correct iPTH in 90 % (106/118) of the cases. Among the 12 iPTH levels that did not meet the confirmation criteria, 10 returned to normal range by postoperative day 2. Treatment failure appeared in three patients (one BNE, two MIPs). CONCLUSIONS: Tc-99m-MIBI dual-phase scintigraphy with SPECT/CT is the key examination for functional and morphological parathyroid adenoma localization. If preoperative scintigraphy is obvious and intraoperative assessment is clear, one could possibly safely omit iPTH, as it may lead to unnecessary BNE in primary PHP.

Brain SPECT imaging in Sydenham's chorea

The objective of the present study was to determine whether brain single-photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males, 8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of 740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the remaining four were normal. The six patients with abnormal results were females and their data were not correlated with severity of symptoms. Patients with abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days) compared to those with normal SPECT (mean of 85 days) but this difference did not reach statistical significance. Brain SPECT can be a helpful method to determine abnormalities of the basal ganglia in SC patients but further studies on a larger number of patients are needed in order to detect the phase of the disease during which the examination is more sensitive.

Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multipinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target’s radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals.

A clinical gamma camera-based pinhole collimated system for high resolution small animal SPECT imaging

The main objective of the present study was to upgrade a clinical gamma camera to obtain high resolution tomographic images of small animal organs. The system is based on a clinical gamma camera to which we have adapted a special-purpose pinhole collimator and a device for positioning and rotating the target based on a computer-controlled step motor. We developed a software tool to reconstruct the target’s three-dimensional distribution of emission from a set of planar projections, based on the maximum likelihood algorithm. We present details on the hardware and software implementation. We imaged phantoms and heart and kidneys of rats. When using pinhole collimators, the spatial resolution and sensitivity of the imaging system depend on parameters such as the detector-to-collimator and detector-to-target distances and pinhole diameter. In this study, we reached an object voxel size of 0.6 mm and spatial resolution better than 2.4 and 1.7 mm full width at half maximum when 1.5- and 1.0-mm diameter pinholes were used, respectively. Appropriate sensitivity to study the target of interest was attained in both cases. Additionally, we show that as few as 12 projections are sufficient to attain good quality reconstructions, a result that implies a significant reduction of acquisition time and opens the possibility for radiotracer dynamic studies. In conclusion, a high resolution single photon emission computed tomography (SPECT) system was developed using a commercial clinical gamma camera, allowing the acquisition of detailed volumetric images of small animal organs. This type of system has important implications for research areas such as Cardiology, Neurology or Oncology.

Apport de nouvelles techniques dans l’évaluation de patients candidats à une chirurgie d’épilepsie : résonance magnétique à haut champ, spectroscopie proche infrarouge et magnétoencéphalographie

L'épilepsie constitue le désordre neurologique le plus fréquent après les maladies cérébrovasculaires. Bien que le contrôle des crises se fasse généralement au moyen d'anticonvulsivants, environ 30 % des patients y sont réfractaires. Pour ceux-ci, la chirurgie de l'épilepsie s'avère une option intéressante, surtout si l’imagerie par résonance magnétique (IRM) cérébrale révèle une lésion épileptogène bien délimitée. Malheureusement, près du quart des épilepsies partielles réfractaires sont dites « non lésionnelles ». Chez ces patients avec une IRM négative, la délimitation de la zone épileptogène doit alors reposer sur la mise en commun des données cliniques, électrophysiologiques (EEG de surface ou intracrânien) et fonctionnelles (tomographie à émission monophotonique ou de positrons). La faible résolution spatiale et/ou temporelle de ces outils de localisation se traduit par un taux de succès chirurgical décevant. Dans le cadre de cette thèse, nous avons exploré le potentiel de trois nouvelles techniques pouvant améliorer la localisation du foyer épileptique chez les patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie d’épilepsie : l’IRM à haut champ, la spectroscopie proche infrarouge (SPIR) et la magnétoencéphalographie (MEG). Dans une première étude, nous avons évalué si l’IRM de haut champ à 3 Tesla (T), présentant théoriquement un rapport signal sur bruit plus élevé que l’IRM conventionnelle à 1,5 T, pouvait permettre la détection des lésions épileptogènes subtiles qui auraient été manquées par cette dernière. Malheureusement, l’IRM 3 T n’a permis de détecter qu’un faible nombre de lésions épileptogènes supplémentaires (5,6 %) d’où la nécessité d’explorer d’autres techniques. Dans les seconde et troisième études, nous avons examiné le potentiel de la SPIR pour localiser le foyer épileptique en analysant le comportement hémodynamique au cours de crises temporales et frontales. Ces études ont montré que les crises sont associées à une augmentation significative de l’hémoglobine oxygénée (HbO) et l’hémoglobine totale au niveau de la région épileptique. Bien qu’une activation contralatérale en image miroir puisse être observée sur la majorité des crises, la latéralisation du foyer était possible dans la plupart des cas. Une augmentation surprenante de l’hémoglobine désoxygénée a parfois pu être observée suggérant qu’une hypoxie puisse survenir même lors de courtes crises focales. Dans la quatrième et dernière étude, nous avons évalué l’apport de la MEG dans l’évaluation des patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie. Il s’est avéré que les localisations de sources des pointes épileptiques interictales par la MEG ont eu un impact majeur sur le plan de traitement chez plus des deux tiers des sujets ainsi que sur le devenir postchirurgical au niveau du contrôle des crises.

La stimulation du nerf vague pour le traitement de la dépression réfractaire : les résultats après un an de suivi

La stimulation du nerf vague (SNV) a reçu l’approbation de Santé Canada en 2001, comme en Europe, pour le traitement de la dépression réfractaire et en 2005 aux États-Unis. Les études européennes et américaines rapportent un taux de réponse de 50% et de rémission de 30% après un an de traitement. La sélection des patients, encadrée par la recherche de marqueurs biologiques et des critères de résistance, pourrait contribuer à améliorer les taux de réponse. Cette étude décrit le suivi des patients ambulatoires souffrant de dépression réfractaire, d’un spectre unipolaire ou bipolaire (n=13) sous SNV. Une révision exhaustive de l’histoire médicale et thérapeutique précède une évaluation clinique intensive. Si un consensus d’équipe est obtenu, une investigation clinique à la recherche des marqueurs biologiques est effectuée. Ceci inclut une tomographie par émission de photons simples (SPECT), une tomographie par émission de positrons (TEP), une formule sanguine complète, un test de suppression à la dexaméthasone (DST), une collecte d’urine 24h (catécholamines et cortisol), une polysomnographie et une évaluation neuropsychologique abrégée. Après 1 an de traitement, 61,5% (8/13) des patients ont atteint le seuil de réponse (diminution de 50% des symptômes), dont 87.5% (7/8) en rémission. Les patients diagnostiqués d’un trouble bipolaire, présentant un DST anormal et/ou avec déficits cognitifs ont répondu au traitement et poursuivent leur rémission après 2 ans. Une sélection minutieuse des patients pour le SNV serait une méthode efficace pour traiter les dépressions réfractaires, notamment pour prévenir les rechutes, amenant un état euthymique durable pour la plupart des patients.