BackgroundSynovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions.MethodsPatients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo bio-distribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy.ResultsFrom January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient.ConclusionsRadioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index.Trial registrationThe study was registered on the NCT01469975 website with a registration code NCT01469975 on November the third, 2011.
Objective: Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-D-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci. Design and methods: This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hü rthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (. 10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination. Results: Results were interpreted in terms of assumed presence of tumoral tissue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n ¼ 16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 mg/l (P , 0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients. Conclusions: nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.
Background The optimal management of spinal cord astrocytomas remains to be defined, as aggressive surgery and radiotherapy are associated with a high risk of morbidity. The value of chemotherapy has not been assessed. Procedure The patient in the present report harbored an infiltrating spinal cord tumor causing paraplegia. A limited biopsy showed a grade II astrocytoma. Following biopsy, the patient received sequential chemotherapy with vincristine and carboplatin. Results Full neurological recovery and complete radiologically‐confirmed remission were achieved after eight months of treatment. Chemotherapy was discontinued after eleven months due to carboplatin hypersensitivity. No adjuvant radiotherapy was given, and the patient remains in complete remission fourteen months after completion of treatment. Conclusions Chemotherapy demonstrates a promising activity and could change the standard practice if its efficacy is confirmed in larger studies. It could be used alone or combined with radiotherapy when post‐operative treatment is recommended. Med. Pediatr. Oncol. 29:560–562, 1997. © 1997 Wiley‐Liss, Inc.
The aim of this work was to study and compare the usefulness of dynamic contrast-enhanced spin-echo MR imaging with high temporal resolution hydroxymethylene diphosphonate technetium-99 m skeletal angioscintigraphy in predicting the osteosarcoma histological response to neoadjuvant chemotherapy. Twelve patients with resectable osteosarcoma were prospectively monitored with dynamic MR imaging and skeletal scintigraphy before start of neoadjuvant chemotherapy, after two cycles of therapy and before surgery. Neoplasm signal intensity and activity intensity were plotted against time, and slopes were calculated for percentage increase over baseline values in the first minute. Stability and increase in slope values during or after chemotherapy were defined as a "radiological non-response". Changes in slopes were compared with the "histological response" (Huvos grading). At midpoint of the chemotherapy, these two imaging modalities failed in predicting final histological response. After the completion of the chemotherapy, these imaging modalities allowed the prediction of histological response with the same accuracy (91 %). In this series, dynamic MR imaging and technetium skeletal scintigraphy provide similar results regarding the prediction of final histological response during neoadjuvant chemotherapy; these results cannot be used to modify the therapeutic protocol at midpoint of chemotherapy; these imaging tools predict accurately the histological response at the end of chemotherapy. These latter results may permit anticipation of the adjuvant chemotherapy strategy during decalcification procedures in resected osteosarcoma and thus to monitor chemotherapy in non-surgical osteosarcoma.
Late relapse should be considered, even after several decades, on occurrence of a second intracranial tumor in this context. Our observation validates the clinical interest of preoperative metabolic imaging for brain tumors with distinctive pattern.
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