68Ga-DOTANOC PET/CT detection of multiple extracranial localizations in a patient with anaplastic meningioma / Uso de 68Ga-DOTANOC PET/TC en la detección de localizaciones extracraneales múltiples en un paciente con meningioma anaplásico

We report herein a case of a 65-year-old male with intracranial recurrence of atypical meningioma initially treated with a combination of surgical resection and gamma knife radiotherapy. Afterwards, he underwent a 68Ga-DOTANOC PET/CT scan in order to evaluate the feasibility of peptide receptor radionuclide therapy (PRRT). The scan identified multiple pulmonary, pleural and lymph node localizations. Histological diagnosis was consistent with intracranial atypical meningioma with diffuse metastatic spread. In our case, we have shown that meningioma with extracranial locations may present high uptake of somatostatin receptor analogues. Among other radionuclides, we believe that 68Ga-DOTANOC PET/CT may be particularly useful for staging, detection of recurrence, evaluation of disease extension and alternative therapeutic approaches (AU)

Presentamos el caso de un varón de 65 años de edad, con recurrencia intracraneal de meningioma atípico tratada inicialmente con una combinación de resección quirúrgica y radioterapia bisturí de rayos gamma. Después se sometió a una exploración 68Ga-DOTANOC PET/TC con el fin de evaluar la viabilidad de la terapia metabólica con el receptor del péptido (PRRT). Se identificaron múltiples localizaciones en pulmón, pleura y ganglios linfáticos. El diagnóstico histológico fue compatible con meningioma atípico intracraneal y diseminación metastásica difusa. Se ha demostrado con nuestro caso que meningioma con localizaciones extracraneales puede presentar alta captación de análogos de los receptores de somatostatina. Entre otros radiotrazadores creemos que 68Ga-DOTANOC PET/TC puede ser particularmente útil en la estadificación, detección de la recurrencia, la evaluación de la extensión de la enfermedad y los enfoques terapéuticos alternativos (AU)

(68)Ga-DOTANOC PET/CT detection of multiple extracranial localizations in a patient with anaplastic meningioma.

We report herein a case of a 65-year-old male with intracranial recurrence of atypical meningioma initially treated with a combination of surgical resection and gamma knife radiotherapy. Afterwards, he underwent a (68)Ga-DOTANOC PET/CT scan in order to evaluate the feasibility of peptide receptor radionuclide therapy (PRRT). The scan identified multiple pulmonary, pleural and lymph node localizations. Histological diagnosis was consistent with intracranial atypical meningioma with diffuse metastatic spread. In our case, we have shown that meningioma with extracranial locations may present high uptake of somatostatin receptor analogues. Among other radionuclides, we believe that (68)Ga-DOTANOC PET/CT may be particularly useful for staging, detection of recurrence, evaluation of disease extension and alternative therapeutic approaches.

Feasibility of a multdisciplinary lung cancer videoconference between a peripheral hospital and a comprehensive cancer centre.

OBJECTIVE: Treatment of lung cancer patients is changing rapidly and new treatment options have emerged in recent years. In 2007, to guarantee the best treatment procedure for lung cancer patients being treated in our peripheral hospital, we decided to introduce an interdisciplinary tumour videoconference between the Haemato-Oncological Day Hospital in Merano and the Comprehensive Cancer Centre Innsbruck. This retrospective analysis aims to describe the feasibility of such a conference. PATIENTS AND METHODS: Two hundred and three patients with lung cancer treated at the peripheral hospital of Merano between May 2003 until May 2011 were retrospectively analysed. After introduction of the tumour videoconference in 2007, 54% (n = 110) of the patients in this cohort were discussed in the conference. RESULTS: One hundred and four videoconferences were performed. Videoconference was feasible for 110 patients. Radiotherapeutic treatments were prescribed more frequently in patients from the conference group. Overall, major and minor treatment changes were undertaken in 7% (n = 8) and 18% (n = 20), respectively. CONCLUSION: Interdisciplinary tumour videoconference is feasible between a peripheral hospital and a comprehensive cancer centre. Radiotherapeutic treatment was prescribed more frequently, suggesting that such a conference facilitates the access to cancer-centre-specific treatment modalities. Accordingly, tumour videoconference between a peripheral hospital and a cancer centre is to be recommend.

PET/CT and choline: diagnosis and staging.

As prostate cancer is the most prevalent form of cancer in men and constitutes the third most common cause of cancer associated deaths, early diagnosis of primary prostate cancer and accurate staging influencing the appropriate choice of therapy is crucial. PET and PET/CT using [11C]- and [18F]-labelled choline derivates are increasingly being used for imaging primary and recurrent prostate cancer. The value of [11C]- and [18F]choline PET and PET/CT in patients with biochemical recurrence of prostate cancer has been evaluated in many studies and shows an increasing importance. Morphological imaging techniques such as TRUS, CT and MRI (including functional imaging tools) have shown only limited accuracy for the diagnosis of primary prostate cancer. Molecular imaging techniques such as PET and PET/CT may improve the detection rate and localization of primary prostate cancer. The potential of PET/CT using [11C]- and [18F]-labelled choline derivates for the diagnosis of primary prostate cancer has been assessed in a lot of studies with partly controversial results. [11C]- and [18F]choline PET and PET/CT demonstrated moderate sensitivity for the detection of primary prostate cancer, which depends on the tumour configuration. Furthermore the detection rate is limited by a considerable number of microcarcinomas that can often not be visualized due to partial volume effects. Therefore small and in part rind-like tumours can often not be detected. Additionally, specificity of [11C]- and [18F]choline PET and PET/CT is limited as differentiation between benign prostatic changes like prostatitis, prostatic hyperplasia and high-grade intraepithelial neoplasia (HGPIN) is not always possible. At the present time, the routine use of PET/CT with [11C]- and [18F]-labelled choline derivates can not be recommended as a first-line screening procedure for primary prostate cancer in men at risk. However, choline PET and PET/CT may be useful in preparation of a focused re-biopsy in patients suffering from clinically suspected prostate cancer with repeatedly negative prostate biopsies. In the future [11C]- and [18F]choline PET and PET/CT may also be helpful in patient stratification with respect to primary surgery and radiation therapy.

Positron-emission tomography in imaging and staging prostate cancer.

With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.

Molecular imaging suggests efficacy of bevacizumab beyond the second line in advanced colorectal cancer patients.

We report the clinical history of a female affected by advanced colorectal cancer (CRC). The patient was treated with five subsequent therapeutic schedules (FOLFIRI, FOLFOXIRI, FOLFIRI, FOLFOX4, FOLFOX4 plus cetuximab) because of the progression of the disease. The sixth treatment was bevacizumab in combination with 5-fluorouracil and irinotecan (FOLFIRI). The CT scan and the FDG-PET/CT performed 3 months after the beginning of the treatment showed that some, even if not all, lesions had a reduction of both size and metabolic activity. After the second revaluation the disease progressed. This short report suggests that the response of CRC to antiangiogenetic therapy may also occur after several unsuccessful antineoplastic treatments. Different biological features may explain the nonhomogeneous objective response of the metastatic lesions. Molecular imaging techniques seem to be mandatory in the era of tailored therapy since it is useful to have an in vivo 'biological picture' of the neoplastic disease.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients.

BACKGROUND: A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS: The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION: This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

PET in genitourinary tract cancers.

Genitourinary (GU) tract cancers comprise a variety of tumors, which includes some of the most common malignancies in men and women. As a result of the importance of GU neoplasms and the success of positron emission tomography (PET) in imaging and staging cancer, PET with fluorodeoxyglucose (FDG) has been used to depict and stage ovarian, cervical and testicular cancers. The early success of FDG PET in imaging GU tumors is tempered by the fact that some neoplasms of GU origin do not accumulate sufficient FDG for successful imaging. As a result, alternative agents, such as [11C]choline and [11C]acetate, have been used to image prostate cancer and may have utility in bladder cancer, while other PET agents are currently under active evaluation for this and other GU neoplasms. In this paper, we review the current literature and our experience in role of PET in imaging cancers of the GU tract.

18F-FDG PET/CT in the assessment of carcinoma of unknown primary origin.

PURPOSE: Metastatic cancers of unknown primary origin are characterised by a poor prognosis, with a survival rate from diagnosis of approximately 12 months. Conventional radiological imaging allows detection of 20%-27% of primary cancers, whereas the detection rate with positron emission tomography (PET) is 24%-40%. The aim of this study was to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in the identification of occult primary cancers. MATERIALS AND METHODS: The study population consisted of 38 consecutive patients with histologically proven metastatic disease and negative or nonconclusive conventional diagnostic procedures. All patients were studied by 18F-FDG PET performed according to the standard procedure (6 h of fasting, intravenous injection of 370 MBq 18F-FDG, and image acquisition with a PET/CT scanner for 4 min per bed position). RESULTS: 18F-FDG-PET/CT detected the occult primary cancer in 20 cases (53%), showing higher sensitivity than that reported for any other imaging modality, including PET. CONCLUSIONS: The encouraging results, if validated by larger series, support the use of PET/CT in patients with carcinoma of unknown primary origin and negative conventional imaging results.

18F-FDG PET/CT fusion imaging in paediatric solid extracranial tumours.

This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.

11C-choline positron emission tomography/computerized tomography for tumor localization of primary prostate cancer in comparison with 12-core biopsy.

PURPOSE: (11)C-choline positron emission tomography is an innovative imaging technique for prostate cancer. We assessed the sensitivity of positron emission tomography used together with computerized tomography for intraprostatic localization of primary prostate cancer on a nodule-by-nodule basis, and compared its performance with 12-core transrectal biopsy. MATERIALS AND METHODS: In 43 patients with known prostate cancer who had received positron emission tomography/computerized tomography before initial biopsy, we assessed sensitivity of positron emission tomography/computerized tomography for localization of nodules 5 mm or greater (those theoretically large enough for visualization) using radical prostatectomy histopathology as the reference standard. Comparison with transrectal ultrasound guided biopsy was based on sextant assessment of all cancer foci following sextant-by-sextant matching and reconstruction. Sensitivity/specificity of positron emission tomography/computerized tomography and magnetic resonance imaging for prediction of extraprostatic extension was also assessed. RESULTS: Positron emission tomography/computerized tomography showed 83% sensitivity for localization of nodules 5 mm or greater. At logistic regression analysis only nodule size appeared to influence sensitivity. At sextant assessment positron emission tomography/computerized tomography had slightly better sensitivity than transrectal ultrasound guided biopsy (66% vs 61%, p = 0.434) but was less specific (84% vs 97%, p = 0.008). For assessment of extraprostatic extension, sensitivity of PET/CT was low in comparison with magnetic resonance imaging (22% vs 63%, p <0.001). CONCLUSIONS: Positron emission tomography/computerized tomography has good sensitivity for intraprostatic localization of primary prostate cancer nodules 5 mm or greater. Positron emission tomography/computerized tomography and transrectal ultrasound guided biopsy show similar sensitivity for localization of any cancer focus. Positron emission tomography/computerized tomography does not seem to have any role in extraprostatic extension detection. Studies of diagnostic accuracy (as opposed to tumor localization) are needed in patients with suspected prostate cancer to see whether positron emission tomography/computerized tomography could have a role in not selected patients.

Supra-clavicular lymph node metastatic spread in patients with ovarian cancer disclosed at 18F-FDG-PET/CT: an unusual finding.

Tumoral dissemination of ovarian cancer most commonly occurs through the intra-peritoneal route; nevertheless, although it is rare, ovarian cancer may also metastasise through the lymphatic channels. Lymphatic diffusion of ovarian cancer usually involves pelvic and retro-peritoneal lymph nodes. Extra-abdominal lymph nodes are rarely involved and their detection may represent a challenge for the oncologist. We describe here two patients studied for ovarian cancer by [18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT): one case during pre-operative staging, the other for restaging after surgery. In both cases PET examination identified extraabdominal lymph node tumoral spread in the left supra-clavicular space; biopsy led to a final diagnosis of recurrent ovarian cancer. Previous reports in the literature on tumoral spread of ovarian cancer to the supra-clavicular nodes are rare, however this possible site of metastatic involvement has to be kept in mind by oncologists and our data show that the 18F-FDG PET/CT may be useful to disclose this unusual supra-diaphragmatic lymphatic diffusion of metastatic lymphatic ovarian cancer.

Artefacts of PET/CT images.

Positron emission tomography (PET) is a non-invasive imaging modality, which is clinically widely used both for diagnosis and accessing therapy response in oncology, cardiology and neurology.Fusing PET and CT images in a single dataset would be useful for physicians who could read the functional and the anatomical aspects of a disease in a single shot.The use of fusion software has been replaced in the last few years by integrated PET/CT systems, which combine a PET and a CT scanner in the same gantry. CT images have the double function to correct PET images for attenuation and can fuse with PET for a better visualization and localization of lesions. The use of CT for attenuation correction yields several advantages in terms of accuracy and patient comfort, but can also introduce several artefacts on PET-corrected images.PET/CT image artefacts are due primarily to metallic implants, respiratory motion, use of contrast media and image truncation. This paper reviews different types artefacts and their correction methods.PET/CT improves image quality and image accuracy. However, to avoid possible pitfalls the simultaneous display of both Computed Tomography Attenuation Corrected (CTAC) and non corrected PET images, side by side with CT images is strongly recommended.

(18)F-FDG PET/CT in the evaluation of recurrent ovarian cancer: a prospective study on forty-one patients.

AIM: Many patients with ovarian cancer are at high risk of recurrence especially in the 2 years following first-line therapy. CA125 serum levels measurement associated to computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) are currently used during follow-up to detect recurrent disease. Unfortunately, in a relevant percentage of cases all of these traditional imaging techniques provide a significant number of doubtful/equivocal results or turn out negative even in presence of elevated Ca125 levels. Aim of our study was to evaluate sensitivity, specificity and accuracy of (18)F-FDG PET/CT in a group of patients with suspicion of ovarian cancer recurrence. METHODS: We prospectively evaluated 41 patients with a mean age of 59.4 years who had been previously treated for ovarian cancer with surgery and radio-chemotherapy or radio-chemotherapy alone. Following the performance of traditional radiologic imaging (US, CT, MRI) and Ca125 measurement, all patients underwent additional (18)F-FDG PET/CT. PET/CT results were compared with histologic findings or clinical, laboratory and repeated traditional imaging techniques during subsequent follow-up data. RESULTS: Of 41 patients 32 had a positive PET-CT (30 true positive, two false positive) whereas nine a negative PET/CT (five true negative, four false negative). Overall, in our experience (18)F-FDG PET/CT provided a good sensitivity (88.2%), specificity (71.4%) and accuracy (85.4%), superior to that reported in literature for traditional radiologic imaging. CONCLUSIONS: It can be concluded that (18)F-FDG PET/CT appears to be a useful and accurate tool in disclosing early recurrent ovarian cancer.

Role of 18F-FDG PET-CT imaging for the detection of an unknown primary tumour: preliminary results in 21 patients.

PURPOSE: Metastatic cancer of unknown primary origin is a syndrome characterised by a poor prognosis, with a typical survival rate from diagnosis of no longer than 1 year. Only 20-27% of primary tumours are identified by conventional radiological imaging. By contrast, it has been reported that 18F-fluorodeoxyglucose positron emission tomography (FDG PET) allows the identification of 24-40% of otherwise unrecognised primary tumours. To our knowledge, the studies on this topic have been conducted using 18F-FDG PET imaging alone. The aim of this study was to evaluate the potential additional diagnostic role of fused 18F-FDG PET-CT imaging for the detection of metastatic occult primary tumours. METHODS: The study population consisted of 21 consecutive patients with biopsy-proven metastatic disease and negative conventional diagnostic procedures. Each patient underwent a PET scan, carried out according to a standard procedure (6 h of fasting, i.v. injection of 370 MBq of 18F-FDG and image acquisition with a dedicated PET-CT scanner for 4 min per bed position). RESULTS: 18F-FDG PET-CT detected the occult primary tumour in 12 patients (57% of cases), providing a detection rate higher than that reported with any other imaging modality, including conventional 18F-FDG PET. CONCLUSION: The favourable results of this study need to be confirmed in larger patient populations with long-term follow-up.

[Insulin-like growth factor (IGF)-II in human hepatocarcinogenesis--a potential therapeutic target?]. / Insulin-like growth factor (IGF)-II in der humanen Hepatokarzinogenese--eine potentielle therapeutische Zielstruktur?

Several studies have examined the expression profiles of human hepatocellular carcinomas (HCCs) using high density microarray technology, but subtyping with potential mechanistic and therapeutic impact has not been achieved so far. Here we have analysed the expression pattern of human HCCs and HCC cell lines in comparison to normal liver. A characteristic of one group of HCCs and all HCC cell lines was overexpression of insulin-like growth factor (IGF)-II. Moreover, IGF-II expression was mutually exclusive to induction of several IFN-related genes. In vitro, treatment of HCC cells with IFNgamma leads to a strong reduction of IGF-II expression. Equally, specific reduction of IGF-II was achieved using RNAinterference in HCC cells. Therefore, IGF-II may represent an excellent target for IFNgamma-treatment and specific siRNA-mediated therapeutic intervention.

Does 18F-FDG PET/CT play a role in the differential diagnosis of parotid masses.

AIM: The aim of the present study was to assess the accuracy of an hybrid PET/CT scanner in the evaluation of newly diagnosed parotid masses, comparing the results with those reported in the literature with using PET scanners only. METHODS: The potential role of 18F-FDG PET/CT in distinguishing benign from malignant parotid masses in 14 consecutive patients was investigated. All patients were preoperatively evaluated by means of ultrasound (US), US-guided fine needle aspiration (FNA) cytology, computed tomography (CT) scan, magnetic resonance imaging (MRI) and 18F-FDG PET/CT. For To interpreting FDG PET findings, the right to left parotid (R/L) SUV max ratio was calculated in a group of 54 patients without evidence of parotideal disease (mean+/-SD = 1+/-0.2; range = 0.8-1.2); considering the R/L SUV max ratio, focal or diffuse uptakes <0.8 or >1.2 were considered as potentially pathological. RESULTS: Imaging data were compared with surgical and histopathological findings. At FDG PET/CT, 9 false positive cases were found (8 Warthin's tumours, 1 pleomorphic adenoma), 1 false negative (acinar cell carcinoma), 4 true negative (1 Warthin's tumour, 1 pleomorphic adenoma, 1 lymph epithelial cyst, 1 parotid inflammation) whereas there was no case of true positive. The global accuracy of FGD PET/CT was rather low = at 29%. CONCLUSIONS: In agreement with other preliminary reports in which the FDG PET without CT fusion imaging was used, in our experience 18F-FDG PET/CT did not prove to play a significant role in differential diagnosis (benign vs malignant) of parotid masses. Further studies collecting larger groups of patients are needed to further elucidate this observation.

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.