Development and use of non-FDG PET radiopharmaceuticals at the Masaryk Memorial Cancer Institute.

The existence of the cyclotron & PET centre of UJV Rez, a.s., at Masaryk Memorial Cancer Institute allows the Masaryk Memorial Cancer Institute and RECAMO researchers to engage in the research, development and application of new radiopharmaceuticals including compounds labelled by short-living positron emitters (especially [11C]). Currently, a [11C]-labelled tracer, L-[methyl-11C]methionine, is entering phase I clinical evaluation, and scans with PET radiopharmaceuticals other than fluorodeoxyglucose are performed at the Department of Nuclear Medicine. Continued cooperation will bring new possibilities for PET in the Czech Republic in the future.

Genetic testing and prevention of hereditary cancer at the MMCI--over 10 years of experience.

Hereditary cancer syndromes are frequently seen in young cancer patients and patients with a positive family history. Genetic testing is important for the identification of high-risk individuals, and for the early introduction of specialized preventive care or prophylactic surgeries. High-risk tumour suppressor genes (BRCA1 and BRCA2) and DNA repair genes (MLH1, MSH2 and MSH6) are responsible for a substantial part of hereditary breast, ovarian and colorectal cancer. Other hereditary cancers are seen less frequently, but genetic testing has increased for many other site-specific cancers and complex syndromes. Genetic centres and molecular genetic laboratories are located mostly within university or regional hospitals. Some genetic centres are private. It is highly recommended (Czech Society for Medical Genetics) that all laboratories are accredited according to ISO 15,189 and that genetic testing of hereditary cancer syndromes is indicated by medical geneticists. The indication criteria and prevention strategies were published in Supplement 22 of Clinical Oncology 2009 (in Czech). Preventive care for high-risk individuals is organized by thirteen Oncology Centres, which provide most of the oncology care in the Czech Republic. Genetic testing and preventive care for high-risk individuals and mutation carriers is covered by health insurance. The molecular genetic laboratory at the MMCI provides molecular genetic testing of BRCA1, BRCA2, CHEK2 for hereditary breast/ovarian cancer, MLH1, MSH2, MSH6 for Lynch syndrome,TP53 for Li-Fraumeni syndrome, CDKN2A for familial malignant melanoma syndrome and CDH1 gene for hereditary diffuse gastric cancer. Other syndromes are tested in specialized laboratories elsewhere.The use of genetic testing is increasing because of more frequent referrals from oncologists and other specialists and the increasing variety of genes tested. However, in some patients the testing is not recommended and other family members are dying because of the late diagnosis of hereditary syndrome. Greater awareness of the importance of genetic testing in oncology is needed.

[New radiopharmaceuticals and positron-emission tomography applications at the Masaryk Memorial Cancer Institute in Brno]. / Nová radiofarmaka a aplikace pozitronové emisní tomografie na masarykov onkologickém ustavu v Brne.

The construction and launch of the cyclotron & PET centre at the Masaryk Memorial Cancer Institute, which is run in cooperation with the Nuclear Research Institute Praha-Rez, allows the Masaryk Memorial Cancer Institute to engage in the research, development and application of new radiopharmaceuticals including compounds labelled by short-living positron emitters (especially 11C). For the immediate future, new projects are planned, e.g. using the proliferation marker 18F-fluoro-L-thymidine, or neuro-oncological studies using the proteosynthesis and amino acid transport marker 11C-methionine, and eventually also other compounds applicable outside of oncology. The existence of the PET centre at the Masaryk Memorial Cancer Institute therefore offers a wide range of possibilities to both patients and physicians in the Brno region and beyond.

[Interdigitating dendritic cell sarcoma of lower extremities resistant to high dose chemotherapy BEAM with peripheral blood stem cell transplantation]. / Sarkom z interdigitujících dendritických bunek dolní koncetiny rezistentní k vysokodávkované chemoterapii BEAM s autologní transplantací kmenových krvetvorných bunek--popis prípadu a prehled literatury.

Interdigitating dendritic cell sarcoma is a rare neoplasm forming part of the group of malignancies derived from histocytic cell line. This nosological unit can be detected only by special immunohistochemical exams. A young man aged 25 found a tumorous swelling in the proximal part of his left crus. The pathological process affected proximal tibial epiphysis and adjacent soft tissues. The first FDG-PET examination performed in the process of determining the clinical stage of the disease showed a high activity in the site of primary tumour (SUV 7.71) and in the site of regional inguinal node (SUV 4.25). Histological examination of a diagnostic excision specimen of the tumour in the tibia and the extirpated enlarged regional nodes in the left groin led to the diagnosis of interdigitating dendritic cell sarcoma. The diagnosis was confirmed pathologically by another two centres in the Czech Republic and, due to the unusual nature of the diagnosis, also in Regensburg, Germany. Treatment started with chemotherapy, applied to patients with aggressive lymphomas in the framework of clinical studies, i.e. a combination of MegaCHOP. After 4 cycles, however, there was no visible response on the site of primary tumour. MegaCHOP therapy was therefore discontinued after the 4 cycles. Subsequently, we referred the patient for a high-dose chemotherapy with autologous bone marrow transplantation, similarly to aggressive lymphomas. The collection of blood producing stem cells from peripheral blood was successfully performed after ESHAP chemotherapy. A verificatoin FDG-PET examination was performed before high-dose chemotherapy. Increased activity was detected only in left proximal crus, with an SUV of 4.6. One month after ESHAP chemotherapy, BEAM high-dose chemotherapy with autologous transplantation of blood forming tissue was performed. High-dose chemotherapy was followed up by radiotherapy targeted on the primary tumour in the crus (70 Gy). The third verification FDG-PET examination was performed 3 months after radiotherapy. The examination showed a continuing higher activity in the region of the primary tumour (SUV 2.69) and a new centre of activity was detected in the left inguinal nodes region (SUV4.09). The activity corresponded to the presence of viable tumour tissue in the primary nidus and new metastases in inguinal nodes, without proofs of further proliferation at the time. Nodes of the left groin were removed. Histological examination showed affection of the node by the same type of tumour, i.e. a continuing activity of the disease despite chemotherapy. Due to suspected continuation of viable tumour in the crus judging by the intensity of accumulation of FDG-PET and the proof of a new affection of regional nodes, surgical treatment was preferred after the failure of chemotherapy. After the removal of inguinal nodes, left knee joint exarticulation was performed. This was followed by regional inguinal node region radiotherapy (56 Gy). The last fourth PET-CT examination carried out 4 months after the radiation therapy of the inguinal region showed massive dissemination into the region ofileac and paraaortic nodes (lymphadenopathy up to 6 cm in diameter) with an activity of 5.9 to 6.73 SUV units. Currently, we test the sensitiveness of the disease to 2-chlordeoxyadenosin and look for additional therapeutic options. To our knowledge, the above description is the first documented case of interdigitating dendritic cell sarcoma located in the tibia and crus soft tissue. We have not found any description of high-dose therapy supported by autologous transplantation of blood-forming tissue for this type of tumour in relevant literature. In this case, we record chemoresistance to high-dose chemotherapy and certain radiosensitivty of the tumour at the same time.

[The role of PET in the diagnosis and prediction of the treatment response in patients with cervical carcinoma treated with radiotherapy--results of pilot study]. / Význam PET v diagnostice a predikci lécebné odpovedi karcinomu cervixu u pacientek lécených radioterapií--výsledky pilotní studie.

BACKGROUND: Positron emission tomography (PET) is used to distinguish between benign and malign tumours, to diagnose relapse or post-therapeutic changes and recentlyto predict treatment response. PET is also a complementary method to determine target volumes in radiotherapy. Using the PET in routine oncology practice can change disease management and improve treatment outcomes of cancer patients. We performed a pilot study to validate the role of PET in staging and in radiotherapy treatment planning of cervical carcinoma. PATIENTS AND METHODS: Between March 2005 and May 2007, 51 patients with cervical carcinoma were treated with combination of external beam radiotherapy and HDR brachytherapy, with or without concomitant cisplatin. The lymphatic nodes treatment field size was determined by PET/CT fusion. Treatment results were evaluated by PET 3 and 9 months after completion of radiotherapy. RESULTS: The difference in the results of PET and CT was evaluated in this study. In 32 cases (62.75%) the results of initial PET and CT were identical, in 14 cases (27.45%) the nodal involvement was more extensive according to PET, in 5 cases (9.8%) the nodal involvement was more extensive according to CT. Comparing the results of PET done before and 3 months after the treatment, we found stable disease in 3 cases (5.88%), progression of disease in 4 cases (7.84%), partial regression in 3 cases (5.88 %) and in 35 cases (68.63 %) both PET scans were negative. There should not occur any false positive results caused by inflammatory reaction persisting 3 months after radiotherapy, as was confirmed by repeating PET 9 months after the treatment. CONCLUSION: The results of this study confirmed the important role of PET in diagnosis and treatment of cervical carcinoma and for determination of target volumes in radiotherapy. The predictive value of PET has not yet been validated in our study. PET was integrated into the standard staging of cervical carcinoma in Masaryk Memorial Cancer Institute.

[The impact of PET in radiotherapy of the cervical carcinoma--results of pilot study]. / Význam PET v radioterapii karcinomu delozního hrdla--výsledky pilotní studie.

OBJECTIVE: Positron emission tomography (PET) is a complementary method to determine target volumes in radiotherapy. Daily using of PET in the oncology praxis can change treatment strategy and improve its outcome. Results of this pilot study show the role of PET in staging of cervical carcinoma and in the radiotherapeutic planning. METHODS: Between March 2005 and May 2007, 51 patients with cervical carcinoma were treated with combination of external beam radiotherapy and HDR brachytherapy, with or without concomitant cisplatin. The lymphatic nodes treatment field size was determined by PET/CT fusion. RESULTS: The difference in the results of PET and CT was evaluated in this study. In 32 cases (62.75%) the results of PET and CT were identical, in 14 cases (27.45%) the nodal involvement was more extensive according to PET, in 5 cases (9.8%) the nodal involvement was more extensive according to CT. PET results 3 months after treatment were as follows: in 3 cases (5.88%) stable disease, in 35 cases (68.63%) negative, in 4 cases (7.84%), progression of disease, in 3 cases (5.88%) partial regression. CONCLUSION: The results of this study confirmed the important role of PET in diagnosis and treatment of cervical carcinoma and in determination of target volumes in radiotherapy. PET was found to be a standard staging examination of cervical carcinoma in Masaryk Memorial Cancer Institute.

The impact of PET with 18FDG in radiotherapy treatment planning and in the prediction in patients with cervix carcinoma: results of pilot study.

Positron emission tomography (PET) is used to distinguish between benign and malign tumors, to diagnose relapse or post-therapeutic changes. Lately, PET is used to predict the treatment response. and also a complementary method to determine target volumes in radiotherapy. Daily using of PET in the oncology praxis can change treatment strategy and improve its outcome. Results of this pilot study show the role of PET with 8-F-fluorodeoxyglucose ((18)FDG) for staging of cervical carcinoma and in the radiotherapeutic planning. Between March 2005 and May 2007, 51 patients with cervical carcinoma were treated with combination of external beam radiotherapy and HDR brachytherapy, with or without concomitant cisplatin. The lymphatic nodes treatment field size was determined by PET/CT fusion. Treatment results were evaluated by PET 3 and 9 months after treatment. The differences in the results of PET and CT were evaluated in this study. In 32 cases (62.75%) the results of PET and CT were identical, in 14 cases (27.45%) the nodal involvement was more extensive according to PET, in 5 cases (9.8%) the nodal involvement was more extensive according to CT. PET results 3 months after treatment were as follows: in 3 cases (5.88%) stable disease, in 35 cases (68.63 %) negative, in 4 cases (7.84%), progression of disease, in 3 cases (5.88 %) partial regression. There were no false positive results caused by inflammatory reaction persisting 3 months after radiotherapy, as was confirmed by repeating PET 9 months after treatment. The results of this study confirmed the important role of PET in diagnosis and treatment of cervical carcinoma and in determination of target volumes in radiotherapy. PET was found to be a standard staging examination of cervical carcinoma in Masaryk Memorial Cancer Institute. The predictive value of PET has not yet been validated.

Fluorodeoxyglucose positron emission tomography in multiple myeloma, solitary plasmocytoma and monoclonal gammapathy of unknown significance.

The aim of our study was to evaluate the role of fluorine-18 fluorodeoxyglucose positron emission tomography (FDGPET) in 49 patients with plasma cell malignancies. FDG-PET results were verified by conventional imaging methods, including plain radiographs, magnetic resonance imaging (MRI) and computer tomography (CT). Focally increased FDG uptake was observed in three (23 %) of 11 newly diagnosed myeloma patients with negative bone radiographs. Focally increased tracer uptake was found in five of 26 patients with MM in remission but with suspected relapse. Of the 20 patients who had negative FDG-PET scans, only one relapsed 12 months after FDG-PET examination.. FDG-PET was positive in two of six patients with MGUS and with suspected progression to MM or with suspected other malignancy. In one case a thyroid carcinoma was later detected, in the other an intestinal tumor was found. We conclude that FDG PET might contribute to initial staging of MM patients with negative bone radiographs and is useful for the follow-up of patients in remission especially in non-secretory MM and in patients with large plasmocytoma (>5 cm) after radiochemotherapy.

[Systemic and paraneoplastic manifestations of malignant diseases]. / Systémové a paraneoplastické projevy maligních onemocnení.

Timely diagnosis of malignant diseases largely depends on attention being given to early symptoms and on timely start of an extensive diagnostic process. Only this way can a tumour be diagnosed in its initial stage, and better effect of therapy can be achieved. The following overview provides a list of systemic (paraneoplastic - distant) manifestations of a tumour, and of symptoms related to local tumour expansion. The objective of the overview is to draw attention to all early symptoms of malignant diseases in patients, and to contribute to timely diagnosis and treatment.

[18F-FDG PET in the diagnosis of large vessel vasculitis]. / 18F-FDG PET v diagnostice vaskulitid velkých cév.

INTRODUCTION: Positron emission tomography (PET) is a non-invasive diagnostic method which shows the bio-distribution of positron emitter labelled radiopharmaceuticals in the body. Due to the fact that not only timorous, but in certain conditions also some inflammatory cells may exhibit increased accumulation of 18F-FDG, 18F-FDG PET can be used in the diagnosis of both tumours and certain types of inflammations. OBJECTIVE: The objective of the study is to asses the benefits of 18F-FDG PET in the patients examined for symptoms of fever of uncertain origin whose results suggested the possibility of large vessel vasculitis. SAMPLE AND METHODS: In the years 2003 and 2004, the positron emission tomography centre at Masaryk Oncological Institute in Brno examined 35 patients in order to establish the cause of febrilia using 18F-FDG PET. The suspicion of large vessel vasculitis was based on the detection of high accumulation of radiopharmaceuticals in large vessels walls (in the aorta and the larger outgoing branches). The patients underwent a further standard imaging test to diagnose large vessel vasculitis as follows: CT angiography (CTA) in 4 patients, MR angiography (MRA) in 3 patients and duplex ultrasonography (USG) in 7 patients. A definitive diagnosis of primary autoimmunity of large vessel vasculitis was counter checked histologically or based on a therapeutic test by means of the effect of corticotherapy in immunosuppressive doses. RESULTS: Positive PET findings were recorded in 23 out of 35 patients (65.7%). 11 out of 23 PET positive patients (47.8% of PET positive persons and 31.4% of all patients with febrilia) were suspected to have active large vessel vasculitis based on PET examination. In 10 of the 11 patients, it was possible to perform additional examinations necessary to confirm the diagnosis: a histological test of arteria temporalis in one case, and a therapeutic test using corticotherapy in all 10 cases. Large vessel vasculitis was confirmed in all 10 individuals (2 men and 8 women aged 53-66, median age of 62 years). None of the CTA, MRA or USG examinations in any of the cases detected direct or clear signs ofvasculitis, but 3 CTA and 1 MRA examinations could be considered abnormal. The detection of temporal (giant cell) arteritis based on excision of arteria temporalis superficialis points to the limits of PET examination which is unable to assess veins with a diameter of less than 5 mm. On the other hand, it documents the possibility of extra-cranial damage being proved in this diagnosis with the use PET. In seven of the ten cases, a control PET scan was done during corticotherapy. It showed a drop in the accumulation of radiopharmaceuticals, and therefore a drop in the inflammatory metabolic activity on the walls of the large vessels, which was in line with the drop in the laboratory parameters of the inflammation (FW, CRP). CONCLUSION: Positron emission tomography using 18F-FDG can be used to detect active large vessel vasculitis in patients examined for symptoms of fever of uncertain origin. Apparently, PET can detect cases of large vessel vasculitis where other imaging methods have failed and can be also used to follow the development of vasculitis activity during therapy.

[The value of fluorodeoxyglucose positron emission tomography in multiple myeloma]. / Prínos fluorodeoxyglukózové pozitronové emisní tomografie (FDG-PET) u mnohocetného myelomu.

UNLABELLED: The aim of this study was investigate the appearance of multiple myeloma on flurorine--18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient's management were evaluated. METHODS: Altogether 50 patients, 13 patients with newly diagnosed multiple myeloma with negative radiographs, 4 patients with solitary plasmocytoma, 27 patients in remission with suspected relapse and 6 patients with monoclonal gammopathy of unknown significance (MGUS) with suspicion for multiple myeloma or other malignancy underwent FDG-PET examination. The results of routinely performed radiographs, and MR or CT imaging modalities as well as the clinical course were used for verification of the FDG-PET results. RESULTS: Focally increased tracer uptake was observed in 3 (23 %) of newly diagnosed myeloma patients with negative radiographs and was verified with CT or MR with followed indication for therapy. The FDG-PET was negative in two cases of newly diagnosed multiple myeloma with negative radiographs, no focal infiltration on MR imagination, but with anemia, high monoclonal imunoglobulin and bone marrow infiltration, which was indication for therapy. In all other cases FDG-PET negativity in asymptomatic myeloma had good prognostic significance; these patients are without progression after with a median follow up 14 (7-20) months. Focally increased tracer uptake was found in 5 of the 27 patients in remission. In 4 cases of them it was due to multiple myeloma relapse, in one case due to ovarial carcinoma. Only in 1 patient the PET-FDP failed to recognize extraosseal progression on the scull. 21 patients had true negative FDG-PET imagination, in 1 case disease relapsed 12 months after FDG-PET examination; the other 20 patients are still without progress of this disease with median follow up 15 (7-20) months. FDG-PET was positive in 2 from the 6 patients with MGUS. In one of them carcinoma of thyreoidea was detected, in second the FDG-PET activity was localized in gut, tumor was verified with CT and colonoscopy. CONCLUSION: In conclusion, FDG PET might contribute to initial staging of radiographs negative multiple myeloma and might be useful for follow up of patients in remission, especially in consecratory multiple myeloma, or in patients with large plasmocelular tumor (> 5 cm) after concomitant radiochemotherapy.