Eric Frampas

FDG-positron-emission tomography for staging and therapeutic assessment in patients with plasmacytoma

Plasmacytoma can be confined to bone (solitary bone plasmacytoma) or occur in extramedullary sites (extramedullary plasmacytoma).[1][1]–[4][2] Diagnostic criteria are a biopsy-proven lesion of bone or soft tissue with evidence of clonal plasma cells, normal bone marrow with no evidence of clonal

Radioimmunoconjugates for the treatment of cancer.

Radioimmunotherapy (RIT) has been developed for more than 30 years. Two products targeting the CD20 antigen are approved in the treatment of non-Hodgkin B-cell lymphoma (NHBL): iodine 131-tositumomab and yttrium 90-ibritumomab tiuxetan. RIT can be integrated in clinical practice for the treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy. High-dose treatment, RIT in first-line treatment, fractionated RIT, and use of new humanized monoclonal antibodies (MAbs), in particular targeting CD22, showed promising results in NHBL. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiation and less accessible to large molecules such as MAbs, clinical efficacy remains limited. However, pretargeting methods have shown clinical efficacy. Finally, new beta emitters such as lutetium 177, with better physical properties will further improve the safety of RIT and alpha emitters, such as bismuth 213 or astatine 211, offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the consolidation setting. Personalized treatments, based on quantitative positron emission tomography (PET), pre-therapeutic imaging, and dosimetry procedures, also could be applied to adapt injected activity to each patient.

Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma

Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti‐carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine‐131 in medullary thyroid cancer (MTC)‐bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells.

Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study

Purpose Magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) are important imaging techniques in multiple myeloma (MM). We conducted a prospective trial in patients with MM aimed at comparing MRI and PET-CT with respect to the detection of bone lesions at diagnosis and the prognostic value of the techniques. Patients and Methods One hundred thirty-four patients received a combination of lenalidomide, bortezomib, and dexamethasone (RVD) with or without autologous stem-cell transplantation, followed by lenalidomide maintenance. PET-CT and MRI were performed at diagnosis, after three cycles of RVD, and before maintenance therapy. The primary end point was the detection of bone lesions at diagnosis by MRI versus PET-CT. Secondary end points included the prognostic impact of MRI and PET-CT regarding progression-free (PFS) and overall survival (OS). Results At diagnosis, MRI results were positive in 127 of 134 patients (95%), and PET-CT results were positive in 122 of 134 patients (91%; P = .33). Normalization of MRI after three cycles of RVD and before maintenance was not predictive of PFS or OS. PET-CT became normal after three cycles of RVD in 32% of the patients with a positive evaluation at baseline, and PFS was improved in this group (30-month PFS, 78.7% v 56.8%, respectively). PET-CT normalization before maintenance was described in 62% of the patients who were positive at baseline. This was associated with better PFS and OS. Extramedullary disease at diagnosis was an independent prognostic factor for PFS and OS, whereas PET-CT normalization before maintenance was an independent prognostic factor for PFS. Conclusion There is no difference in the detection of bone lesions at diagnosis when comparing PET-CT and MRI. PET-CT is a powerful tool to evaluate the prognosis of de novo myeloma.

Tumor Immunotargeting Using Innovative Radionuclides

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

Clinical impact of fluorodeoxyglucose-positron emission tomography scan/computed tomography in comparison with computed tomography on the detection of colorectal cancer recurrence.

Background and aims Early detection is an essential prognostic factor in colorectal cancer (CRC) recurrence. Our aim was to evaluate diagnostic performances of 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)/computed tomography (CT) as compared with CT in the detection of CRC recurrence. Methods Data of patients with suspected CRC recurrence and in whom both FDG-PET/CT and CT were performed were analyzed. All detected lesions were characterized according to their number, size, and localization. Positive histological or radiological follow-up was considered as the ‘gold standard’. Diagnostic performances of FDG-PET/CT and CT were calculated by lesion, globally and with respect to the site of recurrence. Results One hundred and seventy-six true-positive lesions were identified in 71 patients. CT scan was positive in 58 (82%) patients and FDG-PET/CT in 70 (98%) patients. In per lesion analysis, the global accuracy of FDG-PET/CT in detection of lesions was of 88% (sensitivity=95%, specificity=54%), which was higher than that of CT (53%, sensitivity=55%, specificity=43%), particularly in case of lymph nodes metastases (100 vs. 35%) and locoregional lesions (100 vs. 39%) (P<0.0001). FDG-PET/CT modified the clinical management in 31 patients. Conclusions FDG-PET/CT is more sensitive than CT for diagnosis of CRC recurrence and can modify the management in 40% of patients.

Improvement of Radioimmunotherapy Using Pretargeting

During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabeled monoclonal antibodies and receptor binding agents. Conventional radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor, and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics. Pretargeting techniques (pRIT) are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb) from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA, and bispecific antibody-hapten bindings. pRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta, and Auger emitters) with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT.

Complications des gestes interventionnels percutanés sous contrôle radioscopique, échographique ou scanographique

Resume Les objectifs de cet article sont de decrire les complications des gestes interventionnels percutanes les plus courants, diagnostiques et therapeutiques thoraco-abdominaux et osteo-articulaires, guides par radioscopie, echographie ou scanner avec leurs facteurs de risque et de preciser les recommandations pour leur pratique. Avant tout geste interventionnel, il faut s’assurer de l’absence d’anomalie de coagulation, prendre le temps d’expliquer la procedure au patient et respecter les conditions d’asepsie stricte. En effet, les complications hemorragiques et infectieuses sont les principales causes de mortalite et de morbidite quel que soit le geste percutane. Sur un scanner post-biopsie d’un nodule pulmonaire, 30 % de pneumothorax immediats sont identifies. Les complications majeures apres une biopsie hepatique trans-parietale surviennent dans les 3 a 6 heures. Le taux de complication global d’un drainage percutane est inferieur a 10 %. Le taux de mortalite apres thermo-ablation par radiofrequence d’une tumeur maligne est faible (0,5 a 1,4 %). Les arthrites septiques, complications majeures mais rares, des gestes osteo-articulaires sont parmi les causes les plus frequentes de plaintes.

Éventration périnéale après proctectomie : Diagnostic et prise en charge

Postoperative perineal hernia is a rare complication following abdominoperineal excision of the rectum. We report four cases illustrating its clinical presentation and modern management. Surgical technique for rectal excision and perineal closure, making of an epiplooplasty, postoperative infection may contribute to the occurrence of this complication. Mesh repair through an anterior open or laparoscopic abdominal approach is one of the surgical options if not contraindicated by age and/or general condition. Perineal or combined approaches can also be selected to solve this difficult problem.Resume L’eventration perineale (ou hernie perineale postoperatoire) est une complication rare de l’amputation abdominoperineale du rectum. Nous en rapportons 4 cas illustrant la presentation clinique et les modalites de prise en charge de cette pathologie dont l’etiopathogenie reste discutee. Les modalites de l’amputation du rectum et de la technique de fermeture du perinee, la realisation d’une epiplooplastie, l’infection du site operatoire ont ete incriminees dans la survenue de cette complication. Lorsque l’âge et/ou le terrain autorisent une reparation, l’implantation d’une prothese par voie abdominale ouverte ou cœlioscopique represente l’option therapeutique adoptee dans ce travail, mais la voie perineale ou l’association des 2 abords peuvent avoir de l’interet pour corriger ce probleme toujours difficile a resoudre.

The intraportal injection model for liver metastasis: advantages of associated bioluminescence to assess tumor growth and influences on tumor uptake of radiolabeled anti-carcinoembryonic antigen antibody.

BackgroundRadioimmunotherapy is emerging as a new tool for adjuvant therapy of colorectal cancer. The liver remains the main site for metastases, carrying a high mortality rate. Many animal models are available but none associates easy, reliable implantation and in-vivo follow-up for experimental therapeutic studies. The aims of this study were to develop a reliable hepatic metastatic colonic cancer model in mice using the intraportal route for injection, with follow-up by bioluminescence (BLI) and to evaluate the impact of tumor location on tumor antigen direct targeting using radiolabeled anti-CEA (carcinoembryonic antigen) antibodies. MethodsLs-174T Luc+ is a colon carcinoma cell line strongly expressing CEA, transfected with the luciferase gene for BLI. Isolated or aggregated cells (1×106) were injected through the portal vein. The tumor burden was investigated using BLI to assess hepatic implantation and growth kinetics. The biodistribution of the 125I anti-CEA antibody fragment (F6) was studied in this model and was compared with subcutaneous implantation. ResultsThe tumor implantation rate was 100% using aggregated cells compared with 26.6% of isolated cells. Photons emitted by 1×106 cells were detected by BLI immediately after injection and allowed visual confirmation of hepatic distribution. The tumor growth was assessed over time to select homogeneous groups of animals. Radiolabeled anti-CEA antibody biodistributions showed a significantly higher uptake in hepatic than in subcutaneous tumors. ConclusionThe association of hepatic tumor graft through the portal route and BLI provides a reliable animal model and permits sensitive in-vivo detection and follow-up of hepatic metastases. The hepatic model seems to more closely reproduce colon cancer metastases compared with subcutaneous metastasis. The hepatic model is of particular interest for studying radioimmunotherapy.