PET/CT: Role in staging, in follow-up and in the evaluation of disease recurrence in gynecologic cancer.

18F-FDG PET/CT may facilitate improved diagnosis and treatment in gynecological fields. This method provides pretreatment prognostic information concerning the aggressiveness of tumors which may contribute to optimizing and individualizing patient therapy. Although 18F-FDG PET/CT has a limited role for local staging of primary cancer, it has an important role in staging, as it aids particularly in identifying the involvement of lymph nodes and distant metastases throughout the whole body in a single examination in patients with advanced-stage disease and also in restaging after therapy. Another major indication of the modality is the evaluation of disease recurrence, especially in clinically equivocal patients or in patients in which tumor markers are rising, and conventional imaging studies show negative or equivocal findings.

FOLFIRINOX: from the ACCORD study to 2014.

In the field of treatment of pancreatic cancer, there has been significant progress lately. After the ACCORD/PRODIGE-4 study, 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) became the standard combination for first-line chemotherapy. This led also to its use in the neoadjuvant setting in borderline resectable tumors, or locally advanced unresectable disease, improving the resectability and survival. The major disadvantage of this therapy is increased toxicity, limiting its use to young patients with no comorbidities. This arises the need to make dose reductions in clinical practice, with a possible drawback in effectiveness. The authors summarize three Abstracts (#256, #275, #305) presented at the 2014 ASCO Gastrointestinal Cancers Symposium which were focused in the use of modified forms of FOLFIRINOX, their toxicity profile and effectiveness. Reduced toxicity was observed, without affecting the effectiveness of the combination.

(18)F-FDG-PET/CT, (123)I-MIBG and (99m)Tc-MDP whole-body scans, in detecting recurrence of an adult adrenal neuroblastoma.

Neuroblastoma is the most common extracranial solid malignancy in children, but is rare in adults. We report the case of a 33 year old man with recurrence of neuroblastoma, 2 years after the excision of the primary tumor in the right adrenal gland. The iodine-123-radioiodinated metaiodobenzylguanidine ((123)I-MIBG) and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans and the fluorine-18-fluorodeoxyglucose-positron computed tomography ((18)F-FDG PET/CT) findings in this patient are presented. First, we applied (123)I-MIBG scintigraphy that detected increased uptake at the right adrenal gland region and probably at liver lesions and in several bones. Then, the (99m)Tc-MDP bone scan revealed also increased uptake of the radiopharmaceutical in bones, but there was a discrepancy between these two studies concerning the number and location of the lesions. Then, (18)F-FDG PET/CT scan was performed, which showed increased uptake of (18)F-FDG at the right adrenal gland region with extension to the liver and also in multiple bones. Additionally, an aortocaval lymph node was detected. In conclusion, this case indicated that (18)F-FDG PET/CT has defined the extent of the recurrence of neuroblastoma in a better way than (123)I-MIBG and (99m)Tc-MDP together.

A robust method, based on a novel source, for performance and diagnostic capabilities assessment of the positron emission tomography system.

The aim of our work was to provide a robust method for evaluating imaging performance of positron emission tomography (PET) systems and particularly to estimate the modulation transfer function (MTF) using the line spread function (LSF) method. A novel plane source was prepared using thin layer chromatography (TLC) of a fluorine-18-fluorodeoxyglucose ((18)F-FDG) solution. The source was placed within a phantom, and imaged using the whole body (WB) two dimensional (2D) and three dimensional (3D) standard imaging protocols in a GE Discovery ST hybrid PET/CT scanner. Modulation transfer function was evaluated by determining the LSF, for various reconstruction methods and filters. The proposed MTF measurement method was validated against the conventional method, based on point spread function (PSF). Higher MTF values were obtained with 3D scanning protocol and 3D iterative reconstruction algorithm. All MTF obtained using 3D reconstruction algorithms showed better preservation of higher frequencies than the 2D algorithms. They also exhibited better contrast and resolution. MTF derived from LSF were more precise compared with those obtained from PSF since their reproducibility was better in all cases, providing a mean standard deviation of 0.0043, in contrary to the PSF method which gave 0.0405. In conclusion, the proposed method is novel and easy to implement for characterization of the signal transfer properties and image quality of PET/computed tomography (CT) systems. It provides an easy way to evaluate the frequency response of each kernel available. The proposed method requires cheap and easily accessible materials, available to the medical physicist in the nuclear medicine department. Furthermore, it is robust to aliasing and since this method is based on the LSF, is more resilient to noise due to greater data averaging than conventional PSF-integration techniques.

Second-line therapy in pancreatic cancer.

At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgical resection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).

Preclinical research in treatment of pancreatic cancer.

Pancreatic adenocarcinoma is an aggressive type of malignancy and remains a treatment-refractory cancer. Because of the few treatment options, understanding of the molecular mechanisms is necessary, for new drugs be developed against molecular targets. Two of the novel, promising regimens against molecular targets, NVP-BEZ235 and MSK-777, were examined in three preclinical studies performed in human pancreatic cell lines and mouse models and presented in the 2013 ASCO Annual Meeting. Two of the studies evaluated the role of NVP-BEZ235, an oral phosphatidylinositol-3-kinase (PI3K) inhibitor, in pancreatic cancer treatment, alone and in combination with nab-paclitaxel (Abstract #e15007) or gemcitabine (Abstract #e15070). The third study presents the effectiveness of the novel cell division cycle 7 (Cdc7) kinase inhibitor, MSK-777 (Abstract #e15059). All studies demonstrated promising results and further investigation is ongoing.

Lymphogranuloma Venereum Mimicking Lymphoma on FDG PET/CT.

ABSTRACT: A 42-year-old man presented with painless, left inguinal lymphadenopathy, which was suspicious of malignant lymphoma. Multiple left-sided foci of markedly increased metabolic activity were observed on PET/CT (SUVmax up to 22.3), located at the inguinal, iliac, and para-aortic lymph nodes along with small-sized right inguinal lymphadenopathy. Laboratory tests revealed increased inflammation markers and neutrophilic leukocytosis. Pathological examination from dissected inguinal lymph node was consistent with granulomatous disease. Infection by chlamydia trachomatis was made serologically establishing the diagnosis of lymphogranuloma venereum.

Can the Ratio SUVmax of the Lesion/SUVmax of Mediastinal Tissues Guide the Choice of Surgical Access for the Resection of Thymic Epithelial Tumors?

Background: There are studies showing the utility of the 18-fluorodeoxyglucose positron emission tomography (18FDG PET) scan in the management of patients with thymic epithelial tumors. It seems to be a correlation between the standard uptake value (SUVmax) of thymic epithelial tumors and the histological type and the stage. This study aims to use the ratio of the SUVmax of the lesion to the SUVmax of the adjacent mediastinal tissues in order to guide the choice of the surgical access. Methods: All patients who presented an anterior mediastinal lesion with a high suspicion of being of thymic origin were included in a prospective database. A ratio inferior to 1 could predict a benign nature and less aggressive behavior, and a minimally invasive approach was performed. A ratio superior to 1 suggested a malignant and aggressive behavior, and a median sternotomy (or a thoracotomy) was performed. Results: There were 15 male (mean age 44.6 ± 16.26 years, range 25-73) and 15 female patients (mean age 50.1 ± 16.94 years, range 25-76). When the ratio is inferior to 1, it predicts benign disease in 80% of cases. When it is superior to 1, it predicts in half of cases advanced histological types (high risk thymomas and thymic carcinomas). On the contrary, it can quite accurately predict advanced Masaoka-Koga stages. Conclusions: The protocol of this study is in accordance with the current literature showing the utility of 18FDG PET scan in the treatment of thymic epithelial tumors. This study goes one step further since the choice of surgical access is based on the SUVmax values. The ratio SUVmax of the lesion/SUVmax of the mediastinal tissues could be a new marker, more pertinent than absolute SUVmax values.

[The use of 18F-fluorothymidine and 18F-fluorocholine in imaging with positron emission tomography].

Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) has proven useful for diagnosis, staging, restaging and therapy monitoring in a variety of tumors. Nevertheless there are some limitations. (18)F-FDG is not tumor selective and shows accumulation in inflammatory cells such as macrophages and fibroblasts that require glucose as their substrate for energy production. Furthermore, tissues with high background, such as brain may cause difficulties in image interpretation. Moreover, there are some tumors that are not avid for (18)F-FDG such as prostate cancer, hepatocellular carcinoma and some slow-growing tumors. This limitations motivated efforts to develop new oncologic tracers for PET imaging. Recently, (18)F-fluorothymidine ((18)F-FLT), a radiolabeled analog of thymidine, has been synthesized for imaging tumor cell proliferation. Another tracer that has been synthesized is (18)F-fluorocholine ((18)F-FCH) that can incorporate into tumor cell membranes by metabolic trapping. The purpose of this article is to report the role of these two new radiopharmaceuticals for PET imaging, (18)F-FLT and (18)F-FCH in the management of various malignancies.

The impact of Ga-68 DOTATATE PET/CT imaging on management of patients with paragangliomas.

OBJECTIVE: Paragangliomas are rare tumours of neural crest origin that express high levels of somatostatin receptor. Ga-68 DOTATATE PET/CT is a widely accepted method for imaging of neuroendocrine tumours. This study was performed to review a Ga-68 DOTATATE PET/CT patient database and to establish the impact of the modality on patient treatment. METHODS: Demographic data, imaging data and change in management after Ga-68 DOTATATE PET/CT were evaluated. RESULTS: Ga-68 DOTATATE PET/CT scans were performed in 21 patients in whom paragangliomas had been confirmed after biopsy or surgery and in one patient with suspected paraganglioma. In most patients, the primary site was the organ of Zuckerkandl (12/22). Of the 22 Ga-68 DOTATATE PET/CT scans completed, 19 (86.4%) were positive and three (13.6%) negative. In 12 of 14 recurrent cases (90.9%), the treatment plan was changed after the Ga-68 DOTATATE PET/CT scan owing to new, unexpected findings, while it remained unchanged in two (9.1%). Regarding the change in treatment plan, in most instances the new treatment comprised peptide receptor radionuclide therapy (PRRT). CONCLUSION: Ga-68 DOTATATE PET/CT findings led to a change in the scheduled treatment plan in 90.9% of patients with suspected recurrence. The most frequent change consisted in initiation of PRRT due to disease recurrence or progression or detection of multiple metastases.

A Case Series of BCOR Sarcomas With a New Splice Variant of BCOR/CCNB3 Fusion Gene.

BACKGROUND/AIM: Undifferentiated round cell sarcomas are a heterogeneous group of sarcomas. Identification of BCOR alterations, such as BCOR/CCNB3 and BCOR/MAML3 fusion genes and BCOR ITD has recently contributed in the precise diagnosis of these neoplasms, defining a new entity of the current classification of soft tissue and bone sarcomas. BCOR sarcomas share both morphological and genetic characteristics distinct from Ewing sarcomas. The scope of our study was to retrospectively identify BCOR sarcomas and find the correlations with the clinical outcome of these patients. PATIENTS AND METHODS: Histopathology and immunohistochemistry of pediatric tumor samples were combined with molecular testing (PCR) and fluorescent in situ hybridization to find BCOR sarcomas. RESULTS: We, herein, present our experience with BCOR sarcomas in a referral center of Greece. Moreover, we report in one case the detection of a variant BCOR/CCNB3 fusion not previously described. CONCLUSION: We are the first to report a splice variant of BCOR/CCNB3 which reveals the central position of BCOR in the oncogenesis of these tumors, furthermore we highlight the importance of molecular diagnostics in Ewing-like sarcomas and discuss the current treatment options for this rare entity.

A case of fever of unknown origin: (18)F-FDG-PET/CT findings in Takayasu's arteritis.

This is a case of a 54 years old woman with fever of unknown origin. Physical examination showed nothing remarkable. Chest radiographs, abdominal ultrasound examination (US) and chest-abdominal-pelvic CT, showed segmental thickening of the wall of the aorta. On admission, the C-reactive protein level and the erythrocyte sedimentation rate were elevated. (18)Fluoro-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET/CT) showed increased uptake of the aorta wall and its main branches that could be indicative of arteritis. The temporal artery biopsy was negative for giant-cell arteritis. The patient responded well to prednisolone treatment. A second (18)F-FDG-PET/CT scan showed great improvement. (18)F-FDG-PET/CT scan early indicates arteritis of the great vessels that in this case was considered to be TA and contributes in monitoring disease activity.

[The importance of recombinant human thyroid stimulating hormone in the follow-up and treatment of disseminated thyroid cancer after thyroidectomy].

In patients operated for differentiated thyroid cancer (DTC), before thyroid remnant ablation and treatment of metastatic disease, thyroid hormones are withdrawn four to six weeks in order to induce an increase in serum thyroid stimulating hormone (TSH) of more than 25-30 microU/mL and thus to stimulate thyroid gland uptake and retention of iodine-131 ((131)I), given therapeutically. Secretion of thyroglobulin (Taug) is also increased. However, thyroid hormone withdrawal frequently causes clinical hypothyroidism. Recombinant human TSH (rhTSH) can provide TSH stimulation without withdrawal of thyroid hormones. The primary clinical utility of rhTSH has been for the post-surgical monitoring in patients with DTC but is currently an aid in thyroid remnant ablation and treatment of thyroid tumors with encouraging results. In this review we have briefly described the findings reported during the period 1994-2006 concerning the diagnostic and therapeutic usefulness of rhTSH in patients with DTC after total or near total thyroidectomy.

A case of non-malignant multifocal lesions on the methyl diphosphonate technetium-99m bone scan with enteropathy. SAPHO syndrome.

This is a case of a 24-year-old man with non-malignant multifocal bone lesions on the methyl diphosphonate technetium-99m bone scan, that may represent a variant of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. The patient complained for diffuse osseous pain, focused mainly in the hip joints. X-rays of the hips were normal but X-rays of the shoulders showed hyperostosis of the right clavicle with no erosions. SAPHO is a rare syndrome of unknown aetiology with no more than a hundred cases reported during the last 10 years. Its typical form consists of characteristic painful osteoarticular manifestations and dermatological findings. In a variant of this syndrome, such as in our case, dermatological manifestations may be absent, but hyperostosis with osseous hypertrophy and enteropathy are present. No other malignant or benign disease was diagnosed. All routine laboratory tests for an inflammatory rheumatoid disease were negative. Treatment with non steroid anti-inflammatory agents was successful and after six months, there were no clinical symptoms and lesions on the bone scan faded. Four years later the patient remained free from symptoms. We discuss the scintigraphic, radiological laboratory clinical findings, the therapeutic criterion and the exclusion of any malignant or other benign bone disease that suggest the diagnosis of SAPHO syndrome. In conclusion, although we were unable to perform a bone biopsy, we suggest that no other diagnosis but an enteropathic variant of SAPHO syndrome may better describe the above clinical and laboratory findings. Bone scan findings have a principal diagnostic role in SAPHO syndrome.

Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors.

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. METHODS: A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated tumors, and 76 (73.1%) had well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as histologic grade (G1, G2, or G3, for low-grade [well differentiated], intermediate-grade [moderately differentiated], and high-grade [poorly differentiated], respectively), chromogranin A, and proliferation index (Ki-67). RESULTS: The 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 tumors and lower for G3 tumors (P = 0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different grades (P = 0.38). The Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P = 0.004), without significance differences in 18F-FDG SUVmax Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18F-FDG (P = 0.037) and 68Ga-DOTATATE (P = 0.047). Overall survival declined rapidly with increasing grade (P = 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. CONCLUSION: 18F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax relates to grade and Ki-67 and can be used prognostically.

Kikuchi Disease with Generalized Lymph Node, Spleen and Subcutaneous Involvement Detected by Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Kikuchi-Fujimoto disease, known as Kikuchi disease, is a rare benign and self-limiting disorder that typically affects the regional cervical lymph nodes. Generalized lymphadenopathy and extranodal involvement are rare. We report a rare case of a 19-year-old female with a history of persistent fever, nausea, and debilitating malaise. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multiple hypermetabolic generalized lymph nodes in the cervical, mediastinum, axillary, abdomen and pelvic regions with diffuse spleen, diffuse thyroid gland, and focal parotid involvement, bilaterally. In addition, subcutaneous lesions were noted in the left upper paraspinal and occipital regions. An excisional lymph node biopsy guided by 18F-FDG PET/CT revealed the patient's diagnosis as Kikuchi syndrome.

False-Positive 18F-FDG PET/CT Imaging: Dramatic "Flare Response" After Rituximab Administration.

We report the case of a 45-year-old woman diagnosed with non-Hodgkin lymphoma. Six months after completion of R-CHOP, she relapsed, and 2 cycles of R-ESHAP were given, with a view to allograft transplant. One month later, F-FDG PET/CT revealed disease progression. Biopsy of lymph nodes showed reactive changes, without evidence of lymphoma. Rituximab, a monoclonal antibody, is used for treatment of non-Hodgkin lymphoma, but its addition may result in an extensive inflammatory response. It is important to be aware of the potential for false-positive F-FDG PET/CT imaging after rituximab therapy. Unexpected findings should be confirmed by biopsy.

The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom.

UNLABELLED: (68)Ga-DOTATATE PET/CT scanning is a widely accepted method for imaging of neuroendocrine tumors. This cross-sectional study was performed to review the first 8 y of patient data from a large (68)Ga-DOTATATE PET/CT database in order to establish the impact of the modality on patient treatment and survival. METHODS: Demographic data, clinical outcome, survival, and change in management after (68)Ga-DOTATATE PET/CT were evaluated. RESULTS: Between May 2005 and August 2013, 1,258 (68)Ga-DOTATATE PET/CT scans were obtained in 728 patients with confirmed or suspected neuroendocrine tumors. In most patients, the primary site was located in the midgut (26.4%). Analysis of NET grading in patients with known histopathologic data revealed that 35.7% had NET grade G1, 12.2% G2, and 8.7% G3. The most common indications for (68)Ga-DOTATATE PET/CT were follow-up (24.4%) and initial tumor staging (23.4%). Of the 1,258 (68)Ga-DOTATATE PET/CT scans completed, 75.7% were positive and 24.3% negative; there were 14 false-positive and 29 false-negative scans. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97%, 95.1%, 96.6%, 98.5%, and 90.4%, respectively. In 40.9% of patients, the treatment plan was changed after the scans, owing mainly to new, unexpected findings. Statistically significant differences in survival were shown between patients with G1, G2, and G3 grade tumors (P < 0.0001) and also between patients with bone metastasis versus patients with soft-tissue metastasis (P < 0.0001). CONCLUSION: (68)Ga-DOTATATE PET/CT scanning is safe and influences management in a large proportion of patients. Prognosis was dependent on tumor grade, and the presence of bone metastasis was associated with worse overall survival.

Imaging in tuberculosis.

Early diagnosis of tuberculosis (TB) is necessary for effective treatment. In primary pulmonary TB, chest radiography remains the mainstay for the diagnosis of parenchymal disease, while computed tomography (CT) is more sensitive in detecting lymphadenopathy. In post-primary pulmonary TB, CT is the method of choice to reveal early bronchogenic spread. Concerning characterization of the infection as active or not, CT is more sensitive than radiography, and (18)F-fluorodeoxyglucose positron emission tomography/CT ((18)F-FDG PET/CT) has yielded promising results that need further confirmation. The diagnosis of extrapulmonary TB sometimes remains difficult. Magnetic resonance imaging (MRI) is the preferred modality in the diagnosis and assessment of tuberculous spondylitis, while (18)F-FDG PET shows superior image resolution compared with single-photon-emitting tracers. MRI is considered superior to CT for the detection and assessment of central nervous system TB. Concerning abdominal TB, lymph nodes are best evaluated on CT, and there is no evidence that MRI offers added advantages in diagnosing hepatobiliary disease. As metabolic changes precede morphological ones, the application of (18)F-FDG PET/CT will likely play a major role in the assessment of the response to anti-TB treatment.