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.

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.

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.

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.

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.

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.

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.

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.

68Ga-DOTATATE uptake in pineal gland, a rare physiological variant: case series.

(68)Ga-DOTATATE PET-CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had (68)Ga-DOTATATE PET-CT scans and one underwent (68)Ga-DOTATATE PET-MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of (68)Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.

Adolescent With 68Ga DOTATATE-Avid Vertebral Hemangioma Mimicking Metastasis in PET Imaging.

68Ga DOTATATE PET/CT is a well-established method in the diagnostic workup of neuroendocrine tumors. We report the case of a 15-year-old adolescent boy with histologically proven appendiceal carcinoid tumor referred for 68Ga DOTATATE PET/CT to identify residual or metastatic disease. PET images showed increased tracer uptake in the body of T4 vertebra. This uptake could be misdiagnosed for bone metastasis, but CT characteristic appearance was in keeping with vertebral hemangioma. Both bone metastasis in carcinoid tumor and bone hemangiomas in adolescents are rare conditions, but the combined metabolic and morphological information on PET/CT can lead to the correct diagnosis.

Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients.

BACKGROUND: Although Kirsten rat sarcoma (KRAS) gene mutational testing is essential for the optimal design of therapeutic strategies for colorectal cancer, it is not always feasible or reliable. In this retrospective study, we examined whether (18)F-Fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans can serve as a surrogate examination for KRAS mutational testing. PATIENTS AND METHODS: KRAS codon 12 and 13 mutational status was tested in 44 colorectal primary tumors and was compared with the (18)F-FDG PET/CT maximum standardized uptake value (SUVmax) values of the respective metastatic lesions. Glucose transporter-1 (GLUT1) mRNA levels were also measured in colorectal primary tumors. RESULTS: No statistically significant correlation between (18)F-FDG PET/CT SUVmax values and KRAS mutation status was found (parametric t-test: p=0.4753; non-parametric Kruskal-Wallis test: p=0.51). This result cannot be attributed to the effect of differing GLUT1 mRNA levels, as shown by multivariate analysis. CONCLUSION: Our study failed to promote (18)F-FDG PET/CT uptake as a surrogate examination for KRAS mutation testing.

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.

SPECT and 18F-FDG PET/CT imaging of multiple paragangliomas and a growth hormone-producing pituitary adenoma as phenotypes from a novel succinate dehydrogenase subunit D mutation.

Mutations in the subunits B, C, D, and recently in A of the succinate dehydrogenase have been associated with the development of paragangliomas. We report the case of a 37-year-old man presented with multiple paragangliomas and a growth hormone-producing pituitary adenoma, with a novel succinate dehydrogenase subunit D mutation as the genetic analysis revealed. We present the similarities and the differences of the findings in patient imaging with either methods of SPECT (I-MIBG and In-pentetreotide) or PET/CT with F-FDG. This case revealed that F-FDG PET/CT detected more lesions and was superior compared with the other methods.

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.

Clinical importance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography in the management of patients with bronchoalveolar carcinoma: Role in the detection of recurrence.

[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been reported to have a low sensitivity in the initial diagnosis of bronchoalveolar carcinoma (BAC) due to BAC's low metabolic activity. The aim of this study was to assess the value of [18F]FDG-PET/CT in the detection of BAC recurrence. Between February 2007 and September 2011, the [18F]FDG-PET/CT scans that were performed on patients with known, histologically proven BAC were studied. A total of 24 [18F]FDG-PET/CT scans were performed in 22 patients, including 16 males and 6 females, with a mean age of 65±9 years. Among the scans, 15 were performed to assess for possible recurrence with equivocal findings in conventional imaging methods and 9 for restaging post-therapy. In all cases conventional imaging studies (CT and MRI) were performed 5-30 days prior to PET/CT. Among the 24 [18F]FDG-PET/CT scans, 18 were positive and 6 negative. Among the 15 [18F]FDG-PET/CT scans performed for suspected recurrence, 34 lesions were detected and the mean maximum standardized uptake value (SUVmax) was 6.8±3.26. In nine scans, upstaging was observed, while two were in agreement with the findings of the conventional modalities. A greater number of lesions were detected in two scans and fewer lesions were detected in one, with no change in staging. Only one scan was negative. By contrast, in patients examined for restaging, there were only five lesions with a mean SUVmax of 4.86±3.18. Agreement between the findings of [18F]FDG-PET/CT and the conventional modalities was observed in 8 out of 9 cases. Although [18F]FDG-PET/CT has been reported to have a low sensitivity in the initial diagnosis of BAC, the present results indicate that when there is recurrence, the lesions become [18F]FDG avid. [18F]FDG-PET/CT may provide further information in patients evaluated for recurrence and thus improve patient management.

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).

Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging.

CONTEXT: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and medically challenging malignancy. Even if the extent of initial surgery is deemed adequate, the recurrence rate remains high, up to 50% in most series. Measurement of serum calcitonin is important in the follow-up of patients with MTC, and reliably reflects the existence of the disease. EVIDENCE ACQUISITION: There is no single sensitive diagnostic imaging method to reveal all MTC recurrences or metastases. Conventional morphologic imaging methods (U/S, CT, and MRI) and several methods of nuclear medicine have been used for this purpose with variable accuracy. RESULTS: The main role of nuclear medicine imaging is the detection of residual or recurrent tumor in the postoperative follow-up. In this review we present the radiopharmaceuticals used in the diagnosis of MTC recurrence, and comparison among them. CONCLUSIONS: The most used radiopharmaceuticals labelled with γ emitters are: Metaiodobenzylguanidine (MIBG), labelled with (131)I or (123)I, (111)In-pentetreotide (Octreoscan), 99mTc-pentavalent dimercaptosuccinic acid ((99m)Tc(V)-DMSA), and (99m)Tc-EDDA/HYNIC-Tyr3-Octreotide ( Tektrotyd). The radiopharmaceuticals labelled with a positron-emitting radionuclide (ß+), suitable for positron emission tomography (PET) imaging are: (18)F-fluorodeoxyglucose ((18)F-FDG), (18)F-fluorodihydroxyphenylalanine (18F-DOPA), and 68Ga-labelled somatostatin analogues (68Ga-DOTATATE or DOTATOC).