Durable complete response to PET-CT driven stereotactic radiation therapy plus pembrolizumab for pleomorphic Pancoast cancer: Case report and literature review.

PET-driven SBRT plus pembrolizumab as first-line therapy against pleomorphic Pancoast cancer appears beneficial, probably due to high equivalent doses of SBRT on photopenic necrotic core and synergic immune system stimulation of immunoradiotherapy.

[The role of oropharyngoesophageal scintigraphy in the assessment of dysphagia in neurological patients.] / Ruolo dello studio scintigrafico del transito orofaringoesofageo nella valutazione della disfagia nei pazienti affetti da patologia neurologica.

PURPOSE: The aim of this study was to assess the role of oropharingoesophageal scintigraphy (OPES) in the management of neurological patients, investigating the clinical value of semiquantitative analysis. MATERIALS AND METHODS: We enrolled 39 neurological patients clinically evaluated and scored according to the Dysphagia Outcome Severity Scale (DOSS) scale who underwent fibrolaryngoscopic swallowing examination (FEES) and OPES using a 99mTc-nanocolloid-radioblabelled semiliquid bolus. We calculated the following semiquantitative parameters: Oral Transit Time (OTT), Pharyngeal Transit Time (PTT), Esophageal Transit Time (ETT), Retention Index (RI), and Esophageal Emptying Rate (EER10s). Differences in OPES semiquantitative parameters between patients classified according to the DOSS scale were performed using the nonparametric Mann-Whitney U test. Optimal semiquantitative parameters cut-off values that correlated with DOSS classification were investigated with ROC curves. The agreement between OPES, FEES and DOSS results was measured using Cohen's Kappa test (K). RESULTS: A significantly higher OTT (p=0.028), PTT (p=0.011) and ETT (p=0.030) and lower EER10s (p=0.016) values were identified. Moderate agreement resulted between OPES and DOSS results (k=0.429, 95%CI: 0.143-0.715, p=0.002). CONCLUSIONS: Our study revealed a significant correlation between clinical dysphagia graded using DOSS scale and semiquantitative parameters obtained by OPES evaluation. Despite reliable and reproducible OPES results, allowing an adequate study also of the esophageal phase, nowadays scintigraphic study remains an underestimated method to be considered in the diagnosis of dysphagia and related complications.

Safety culture to improve accidental event reporting in radiotherapy.

BACKGROUND AND PURPOSE: The potential for unintended and adverse radiation exposure in radiotherapy (RT) is real and should be studied because RT is a highly complex, multistep process, which requires input from numerous individuals from different areas and steps of the RT workflow. The 'Incident' (I) is an event the consequence of which is not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event that is highly likely to happen but did not occur. The purpose of this work is to show that through systematic reporting and analysis of these adverse events, their occurrence can be reduced. MATERIALS AND METHODS: Staff were trained to report every type of unintended and adverse radiation exposure and to provide a full description of it. RESULTS: By 2018, 110 worksheets had been collected, with an average of 6.1 adverse events per year (with 780 patients treated per year, meaning an average incident rate of 0.78%). In 2001-2009, 37 events were registered (13 I and 24 NM), the majority of them were in the decision phase (12/37), while in 2010-2013, there were 42 (1 I and 41 NM) in both the dose-calculation and transfer phase (19/42). In 2014-2018, 31 events (1 I and 30 NM) were equally distributed across the phases of the RT process. In 9/15 cases of I, some checkpoint was introduced. CONCLUSION: The complexity of the RT workflow is prone to errors, and this must be taken into account by encouraging a safety culture. The aim of this paper is to present the collected incidents and near misses and to show how organization and practice were modified by the acquired knowledge.

Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview.

Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.

Heterogeneous Response to Immunotherapy in a Patient with Tonsillar Squamous Cell Carcinoma Assessed by 18F-FDG PET/CT.

Tonsillar carcinoma is the second most common malignancy of the head and neck region, with Squamous Cell Carcinoma (TSCC) as the most common histological type (>90%). For the advanced stage of TSCC, radiotherapy with or without platinum-based chemotherapy is the only therapeutic option. Immuno-checkpoint inhibitors (ICIs), in particular Nivolumab, considerably improves clinical management of these patients, but the response can be unpredictable. Difficulties can be encountered in evaluating response to immunotherapy, especially with morphological imaging, which can show an atypical response, such as pseudo-progression, leading to a premature discontinuation. Conversely, metabolic imaging can guide a more properly therapeutic decision. We present a case of a 71-year-old man affected by TSCC, treated with chemotherapy, radiotherapy, and Nivolumab as the last line of treatment. Pre- and post-immunotherapy 18F-FDG PET/CT showed an impressive response, avoiding early drug discontinuation and ensuring better management of this patient.

Usefulness of 18F-FDG PET/CT in Patients with Cardiac Implantable Electronic Device Suspected of Late Infection.

The presence of a cardiovascular implantable electronic device (CIED) can be burdened by complications such as late infections that are associated with significant morbidity and mortality and require immediate and effective treatment. The aim of this study was to evaluate the role of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected CIED infection. Fifteen patients who performed a 18F-FDG PET/CT for suspicion of CIED infection were retrospectively analyzed; 15 patients, with CIED, that underwent 18F-FDG PET/CT for oncological reasons, were also evaluated. Visual qualitative analysis and semi-quantitative analysis were performed. All patients underwent standard clinical management regardless 18F-FDG PET/CT results. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) resulted as 90.91%, 75%, 86.67%, 90.91% and 75% respectively. Maximum standardized uptake values (SUVmax) and semi-quantitative ratio (SQR) were collected and showed differences statistically significant between CIED infected patients and those who were not. Exploratory cut-off values were derived from receiver operating characteristic (ROC) curves for SUVmax (2.56) and SQR (4.15). This study suggests the clinical usefulness of 18F-FDG PET/CT in patients with CIED infection due to its high sensitivity, repeatability and non-invasiveness. It can help the clinicians in decision making, especially in patients with doubtful clinical presentation. Future large-scale and multicentric studies should be conducted to establish precise protocols about 18F-FDG PET/CT performance.

Comparison of the Diagnostic Value of MRI and Whole Body 18F-FDG PET/CT in Diagnosis of Spondylodiscitis.

Spondylodiscitis is a spine infection for which a diagnosis by a magnetic resonance imaging (MRI) is considered the most appropriate imaging technique. The aim of this study was to compare the role of an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and an MRI in this field. For 56 patients with suspected spondylodiscitis for whom MRI and 18F-FDG PET/CT were performed, we retrospectively analyzed the results. Cohen's was applied to evaluate the agreement between the two techniques in all patients and in subgroups with a different number of spinal districts analyzed by the MRI. Sensitivity, specificity, and accuracy were also evaluated. The agreements of the 18F-FDG PET/CT and MRI in the evaluation of the entire population, whole-spine MRI, and two-districts MRI were moderate ( = 0.456, = 0.432, and = 0.429, respectively). In patients for whom one-district MRI was performed, 18F-FDG PET/CT and MRI were both positive and completely concordant ( = 1). We also separately evaluated patients with suspected spondylodiscitis caused by Mycobacterium tuberculosis for whom the MRI and 18F-FDG PET/CT were always concordant excepting in 2 of the 18 (11%) patients. Sensitivity, specificity, and accuracy of the MRI and 18F-FDG PET/CT were 100%, 60%, 97%, and 92%, 100%, and 94%, respectively. Our results confirmed the 18F-FDG PET/CT diagnostic value in the diagnosis of spondylodiscitis is comparable to that of MRI for the entire spine evaluation. This could be considered a complementary technique or a valid alternative to MRI.

Heterogeneous response to target therapy in metastatic papillary renal cell carcinoma evaluated by morphologic and metabolic multimodality imaging: A case report.

RATIONALE: Papillary renal cell carcinoma (PRCC) accounts for about 15% to 20% of renal cell carcinoma and is histologically distinguished in type I and type II. The last one is associated with poorer prognosis.Treatment options for PRCC patients are surgery, immunotherapy, revolutionized by Nivolumab, and other target-therapy with an improvement in overall survival. Heterogenous response and a pseudo-progression may be observed in the initial phase of biological treatment that could induce premature discontinuation. PATIENT CONCERNS: We present the case of a 44-year-old woman with left cervical palpable mass increased in size and without concomitant disease or previous surgery. DIAGNOSIS: Neck ultrasonography, contrast-enhanced Computed Tomography, and 18F-FDG PET/CT were performed with the detection of lymph nodes involvement and a left renal lesion. INTERVENTIONS: The patients underwent left radical nephrectomy and homolateral cervical and para-aortic lymphadenectomy, with histological diagnosis of PRCC, type II. After disease relapse, the inter-aortocaval lymph node was laparoscopically removed. Following the detection of further disease relapse in several lymph nodes and the lung, several lines of target-therapy were started; then disease progression and worsening of clinical and hematological status led us to start Nivolumab as last-line therapy. OUTCOMES: A heterogeneous response to therapies was documented with morphological and nuclear medicine imaging, however the concomitant deterioration of performance status and liver function led to discontinuation of Nivolumab; then the patient died, 30 months after diagnosis. LESSONS: Here we describe the clinical case and radiological and nuclear medicine imaging investigations performed by our patient, highlighting that 18F-FDG PET/CT shows greater adequacy in assessing the response to therapy, avoiding premature drug discontinuation, and ensuring better management of a patient with advanced PRCC.

How often suspected pulmonary embolism is diagnosed and its main diagnostic characteristics, in an emergency nuclear medicine service? Four years experience.

OBJECTIVE: Acute pulmonary embolism (APE) is an emergency condition and its treatment must be immediate. Nevertheless, the diagnosis of APE is diffcult because its symptoms and risk factors are not specific. We present our 4 years experience on this subject. SUBJECTS AND METHODS: We retrospectively studied 2178 lung perfusion scintigraphies (LPS). Of them 1846 were performed to patients suspected for APE admitted to the emergency departments of the University Polyclinic of Bari and examined immediately by our Nuclear Medicine Department. Contingency tables and odds ratio (OR) were used to estimate the relation between symptoms, risk factors, D-dimers dosage, other imaging diagnostic tools and LPS results. RESULTS: Lung perfusion scintigraphy was positive for APE in 309/1846 (16.7%) patients which then were treated successfully. In 89.5% of these, 309 patients D-dimer dosage was previously examined and was increased in 97.7% of them, but was not predictive of APE (OR=1.04, P=1). Among all symptoms, a low diagnostic capacity was found for cough (OR=1.25, P=0.066) and for chest pain (OR=0.95, P=649). On the contrary, dyspnea was a significant symptom correlated with positive LPS (OR=1.78, P<0.001). The presence of risk factors was predictive of positive LPS and positively correlated with the number of positive 2 oglin lesions in LPS. x2loglin=6.472, P=0.011). Lung perfusion scintigraphy positive for APE were significantly associated with computed tomography pulmonary angiography and/or chest X-ray results (x =9.618, P=0.022). CONCLUSION: Lung perfusion scintigraphy could early diagnose APE in 16.7% of the cases (referred to our Nuclear Medicine Emergency Service) and exclude APE in 83.3% of these cases. Immediate treatment or release of these patients from the emergency department was thus possible. LPS has a key role in the early diagnosis but even more in exclusion of APE, optimizing the management of patients who do not require admission to intensive care. Our four-year and large-scale experience, based on clinical and resource optimization, support the need of Nuclear Medicine Units to perform LPS as emergency in on-call 24 hrs service.

[Role of 18F-FDG PET/CT in comparison with CECT for whole-body assessment of patients with esophageal cancer.] / Il ruolo della 18F-FDG PET/CT nella stadiazione dei pazienti con carcinoma esofageo.

AIM: We aimed to evaluate the role of 18F-FDG PET/CT in the TNM staging of esophageal cancer in comparison with contrast-enhancement computed-tomography (CECT). Futhermore we set out to determine the role of semiquantitative PET parameters. METHODS: 55 patients performed 18F-FDG PET/CT and CECT. Values of Sensitivity (Se), specificity (Sp), accuracy and predictability (PPV and NPV) were evaluated. McNemar test was applied for comparison. Cohen's K was calculated to measure the agreement. 18F-FDG PET/CT semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) in relation to site and histotype, were assessed by ANOVA test and post-hoc test. RESULTS: About T parameter, Se, Sp, accuracy, PPV and NPV of CECT and 18F-FDG PET/CT were respectively 82.35%, 94.48%, 85.00%, 93.33% and 76% for both the tecniques; the agreement resulted substantial. There were no statistically significant relationships between 18F-FDG PET/CT parameters and sites; MTV value differs in histotypes. About N parameter, Se, Sp, accuracy, PPV and NPV of CECT were respectively 82.35%, 57.89%, 65.00%, 46.67%, 88%; for 18F-FDG PET/CT were 88.23%, 60.53%, 61%, 50% and 92%; the agreement resulted fair. About M parameter, Se, Sp, accuracy, PPV and NPV PET/CT were equal for both techniques: 76.92%, 52.38%, 58.33%, 33%, 88%; the agreement resulted moderate. No statistical difference was observed in any comparison. CONCLUSION: 18F-FDG PET/CT is a useful tool for whole-body evaluation of patients with esophageal cancer, allowing an effective clinical TNM staging. In particular 18F-FDG PET/CT's ability in detecting distant metastases suggest its routinary performance as a second level of investigation.

Sickle cell diseases: What can nuclear medicine offer?

Sickle cell disease (SCD) is the best known haemoglobinopathy, caused by a mutation substituting valina for glutamic acid at position 6 of the beta-globin chain of adult hemoglobin A, resulting in hemoglobin S (HbS). The homozygous HbS disease (HbSS), an autosomal recessive disorder, is the most common form and the Mediterranean area, along with sub-Saharian African and India, have the highest prevalence (1%-15%). In particular, Sicily with a prevalence of 2%-5%, is among the most interested regions. However, migratory flows have led to a wider diffusion of the disease no longer confined to endemic areas. In Europe, the yearly estimate of affected births are 1,300 but more than 90% of children with SCD survive into adulthood thanks to screening programs and early available care; however, their lifespan remains shortened by two or three decades compared to general population. In Greece, the number of affected births surpassing 100,000 yearly and the total number of newborns carrying two deleterious genes, if no prevention measures are taken, is estimated to be about 120-130/year. Diagnosis of SCD is based on analysis of haemoglobin through protein electrophoresis or chromatography, that are cheap and widely available techniques, even if haemoglobin mass spectrometry and DNA analysis are techniques with high-throughput testing. Prenatal diagnosis is used in many European countries, so the number of affected newborns has significantly decreased during the last 3 years. Over the course of SCD, sickling process may cause acute and chronic abdominal pain due to vaso-occlusive crisis, bone pain often in long bones due to bone marrow infarction, chronic hemolytic anemia, splenic sequestration with rapid enlargement of the spleen, delayed sexual maturation and cholelithiasis, with important inter-indivuidual variability. Sickle hepatopathy reflects liver sickling process within hepatic sinusoids and includes gallstone disease, hepatic sequestration, hepatic sideroris, acute sickle cell hepatic crises (ASHC) and sickle cell intrahepatic cholestasis (SCIC). Clinically, it appears with fever, right upper quadrant pain, jaundice and increased serum liver function tests. These patients are repeatedly esposed to trasfused red cells that contributes to iron overload and may contribute to hepatic haemosiderosis. Increased bone turnover and resorption by osteoclasts and by marrow expansion due to activation of hematopoiesis. The hematopoietic system may expand physiologically. Computed tomography (CT) is an easily reproducible imaging method that allows the morphologic whole-body evaluation although with a high dose of radiation exposure and possible side effects from intravenous contrast media. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique without radiation chosen to image cholangiopathy and may be followed by the execution of endoscopic retrograde cholangiopancreatography (ERCP) in case of gallstone disease. Otherwise it can be helpful in identifying extramedullary hematopoiesis sites. Dual-energy X-rays absorptiometry (DEXA) is performed to evaluate deficit of bone mineral density (BMD), in which reduction of osteoblastic activity, high risk for necrosis may induce to fragility fractures. We recently had the experience of a typical case of a 56 years old Albanian woman with SCD, with jaundice after a long history of recurrent vaso-occlusive crisis. She was submitted to splenectomy and cholecystectomy 5 years before and since then she was treated with hydroxyurea. Hemocromatosis was excluded by genetic analysis. Hepatic biopsy (Pearl's stain) showed sinusoidal dilatation and diffuse iron accumulation in hepatocytes and Kupffer cells. Endo-hepatic jaundice was observed in MRCP images. It was interesting that DEXA examination was within normal range in both right proximal femur. This may probably be due to the presence of sclerotic lesions in the vertebrae, as was seen in the CT images. Technetium-99m-methylen bisphosphonate (99mTc-MDP) skeletal scintigraphy is a higly sensitive whole-body diagnostic nuclear medicine technique able to evaluate early bone metabolic changes. Multimodality SPET/CT allows to correlate scintigraphic findings with anatomical images with higher sensitivity and specificity. The higher uptake of 99mTc-MDP in SCD patients is due to the activation of hematopoetic system and relies on the osteoblastic response to bone resorption as in our patient. The 99mTc-MDP scan may be better than fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to show sclerotic lesions. Technetium-99m nanocolloids bone marrow scintigraphy (BMS) provides information about the assessment of the reticulum-endothelial system (RES), the whole-body distribution of functional red bone marrow and the presence and the extent of extramedullary hematopoiesis, especially in liver, spleen and bone marrow. Fluorine-18-FDG PET/CT completes the whole-body assessment with an integrated multimodal approach with high spatial resolution that evaluates the metabolic activity and the standardized uptake value (SUV) in SCD patients. Modern genetic diagnosis and gene treatment give promise for having fewer cases of SCD in the future.

The new lens dose limit: implication for occupational radiation protection.

AIM AND OBJECTIVES: The aim of this article was to explore the implications of the new Euratom dose limit for occupational radiation protection in the context of medical occupational radiation exposures. The European Directive 2013/59/Euratom takes into account the new recommendations on reduction in the dose limit for the lens of the eye for planned occupational exposures released in 2012 by the International Commission on Radiological Protection (ICRP 118). MATERIALS AND METHODS: Different dose-monitoring procedures and devices were considered. Occupational eye lens doses reported by previous studies were analyzed, mainly considering workers involved in interventional procedures with X-rays. The current status of eye lens radiation protection and the main methods for dose reduction were investigated. RESULTS: The analysis showed that the workers, potentially exceeding the new limit, are clinical staff performing interventional procedures with a relatively high X-ray dose. Regarding radiological protection issues, the considered literature reports that the proper use of personal protective equipment may reduce the eye lens absorbed dose. CONCLUSION: The evaluation of the occupational eye lens dose is essential to establish which method of personal dose monitoring should be preferred. Furthermore, education and training about the right use of personal protective equipment are important for medical staff working with ionizing radiation.

Diagnostic Performance of 18F-FDG PET/CT Semiquantitative Analysis in the Management of Sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown origin characterized by nonspecific clinical symptomatology. 18F-FDG PET/CT can visualize activated inflammatory cells of sarcoidosis and simultaneously provide whole-body images. OBJECTIVE: To evaluate the clinical usefulness of 18F-FDG PET/CT and its semiquantitative parameters for the assessment of treatment efficacy in patients with sarcoidosis. METHODS: Thirty-one consecutive patients who performed 18F-FDG PET/CT for sarcoidosis assessment were selected. All subjects performed 18F-FDG PET/CT before any treatment (PET1) and after 6-12 months (PET2). SUVmax and SUVmean on PET1 and PET2 were collected. SUVs values were employed to evaluate the ratios with the liver (R-LIVERmax, R-LIVERmean) and the blood (R-BLOODmax, R-BLOODmean). The difference between the PET1 and PET2 values was evaluated (ΔSUVmax, ΔSUVmean, ΔR-LIVERmax, ΔR-LIVERmean, ΔR-BLOODmax, ΔR-BLOODmean). Patients were classified as Responders (R), Partial-Responders (PR) and Non- Responders (NR). RESULTS: Seventeen patients (54.8%) had a complete metabolic response (R), 4 (12.9%) were PR while 10 (32.3%) had no Metabolic Response (NR). The chi-square test showed that response groups were related neither to the stage of disease (p=0.59) nor to therapy performed (p<0.079). The comparison between each Δ semiquantitative parameter showed a statistically significant decrease from PET1 to PET2 (0.0001 < p < 0.002). The comparison between Δ mean values in relation to response groups showed to be statistically significant (0.001 < p < 0.005). Conversely, they did not show statistical significance in relation to the clinical stage groups and to the kind of therapy performed (p>0.05). Pearson's coefficient demonstrated a reverse correlation between a number of sites still involved in disease after therapy and each Δ semiquantitative parameters (p≤0.0001). CONCLUSION: 18F-FDG PET/CT should be considered a useful technique for the evaluation of sarcoidosis and semiquantitative parameters. Further studies are needed to determine the long-term impact of 18F-FDG PET/CT on clinical outcomes.

18F-FDG PET/CT in therapy response and in predicting responders or non-responders in malignant pleural mesothelioma patients, by using semi-quantitative mRECIST and EORTC criteria.

OBJECTIVE: To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in therapy response assessment according modified response evaluating criteria of solid tumors (mRECIST) and the predictive role of volume-based semi-quantitative parameters in patients with malignant pleural mesothelioma (MPM). Furthermore modified RECIST criteria for MPM mRECIST and the European Organization for Research and Treatment of Cancer (EORTC) criteria were compared and the predictive role of 18F-FDG PET/CT in the post-therapy outcome. SUBJECTS AND METHODS: Thirty five selected patients with MPM underwent 18F-FDG PET/CT scan at baseline (1) and after therapy (2). Semi-quantitative 18F-FDG PET/CT parameters were collected for each scan and also differences (Δ) ΔSUVmax, ΔSUVav, ΔMTV, ΔTLG, response index (RI)max% and RIav% were evaluated. Radiologic response to therapy was assessed by using the mRECIST and EORTC. RESULTS: The correlation between response to therapy assessed by EORTC and mRECIST criteria was moderate (K=0.418; 95%CI:0099-0736). According to mRECIST, statistical differences between responders and non-responders were significant in the analysis of semi-quantitative parameters. According mRECIST criteria, all parameters defined a good area under the curve (AUC) but the better AUC resulted for ΔMTV (cut-off≤11.3, sensitivity=91.3%, specificity=91.7%) and ΔTLG (cut-off≤59.1, sensitivity=82.6%, specificity=100%). Kaplan-Meier curves between responders and non-responders did not show statistically significant differences. CONCLUSION: The semi-quantitative analysis of 18F-FDG PET/CT has an important role in MPM therapy response assessment and has a predictive role in distinguishing responders and non-responders.

Bone Involvement in Hodgkin's Lymphoma: Clinical Features and Outcome.

Hodgkin's lymphoma (HL) is now a highly curable disease, with an improving 5-year survival rate that has now reached 86%. At the time of presentation, HL is usually almost entirely confined to the lymph nodes. We performed a retrospective single-institution study of 384 cases with a median follow-up of 44 months, with the aim of identifying clinical and radiological characteristics and outcomes of patients with bone HL; 32 patients (8%) had primary bone involvement, always with concurrent nodal disease. These included 22 men (69%) and 10 women (31%) with the median age as 41 years. Advanced stages and nodular sclerosis histology prevailed among the subgroup. Radiographic features of bone HL are not specific but indicate a destructive malignant process with osteosclerosis and/or osteolysis. With current chemotherapeutic regimens, the long-term prognosis of patients with osseous HL appears good. The presence of bone lesions in HL should not be interpreted as implying a worse prognosis than without bone involvement.

Tyrosine-Kinase Inhibitors Therapies with Mainly Anti-Angiogenic Activity in Advanced Renal Cell Carcinoma: Value of PET/CT in Response Evaluation.

Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib. As anti-angiogenic agents, TKIs interfere the loop, being able to inhibit tumor proliferation. TKIs are now available treatments for advanced RCC, which demonstrated to improve overall survival and/or progression free survival. Their effects can be detectable early on Positron Emission Tomography/Computed Tomography (PET/CT) by change in 18F-fluoro-2-deoxy-2-d-glucose (18F-FDG) uptake, the main radiotracer used to date, as a strong indicator of biological response. 18F-FDG PET/CT demonstrated an ability to predict and monitor disease progression, allowing an early and reliable identification of responders, and could be used for image-guided optimization and "personalization" of anti-angiogenic regimens. New radiotracers for biometabolic imaging are currently under investigation, which exploit the other pathways involved in the cancer process, including cellular proliferation, aerobic metabolism, cell membrane synthesis, hypoxia and amino acid transport, as well as the angiogenic process, but they require further studies.

Multimodality Imaging in Tumor Angiogenesis: Present Status and Perspectives.

Angiogenesis is a complex biological process that plays a central role in progression of tumor growth and metastasis. It led to a search for antiangiogenic molecules, and to design antiangiogenic strategies for cancer treatment. Noninvasive molecular imaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), could be useful for lesion detection, to select patients likely to respond to antiangiogenic therapies, to confirm successful targeting, and dose optimization. Additionally, nuclear imaging techniques could also aid in the development of new angiogenesis-targeted drugs and their validation. Angiogenesis imaging can be categorized as targeted at three major cell types: (I) non-endothelial cell targets, (II) endothelial cell targets, and (III) extracellular matrix proteins and matrix proteases. Even if radiopharmaceuticals studying the metabolism and hypoxia can be also used for the study of angiogenesis, many of the agents used in nuclear imaging for this purpose are yet to be investigated. The purpose of this review is to describe the role of molecular imaging in tumor angiogenesis, highlighting the advances in this field.

Comparison between CT Net enhancement and PET/CT SUV for N staging of gastric cancer: A case series.

BACKGROUND: The therapeutic approach of gastric cancer strictly depends on TNM staging mainly provided by CT and PET/CT. However, the lymph node size criterion as detected by MDCT causes a poor differential diagnosis between reactive and metastatic enlarged lymph nodes with low specificity values. Our study aims to compare 320-row CT Net enhancement and fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (F-FDG PET/CT) SUV for N staging of gastric cancer. MATERIALS AND METHODS: 45 patients with histologically proven gastric cancer underwent CT and F-FDG PET/CT. Two radiologists in consensus evaluated all images and calculated the CT Net enhancement and F-FDG PET/CT SUV for N staging, having the histological findings as the reference standard. CT and F-FDG PET/CT sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (PPV and NPV) were evaluated and compared by using the Mc Nemar test. RESULTS: The histological examination revealed nodal metastases in 29/45 cases (64%). CT Net enhancement obtained sensitivity, specificity, accuracy, PPV and NPV of 90%, 81%, 87%, 90% and 81%, respectively. F-FDG PET/CT SUV obtained sensitivity, specificity, accuracy, PPV and NPV of 66%, 88%, 73%, 90% and 58%, respectively. No statistically significant difference between the two imaging modalities was found (p = 0.1). CONCLUSION: CT Net enhancement represents an accurate tool for N staging of gastric cancer and could be considered as the CT corresponding quantitative parameter of F-FDG PET/CT SUV. It could be applied in the clinical practice for differentiating reactive lymph nodes from metastatic ones improving accuracy and specificity of CT.

Increased and normalized uptake of 18F-FDG in a case of bone periprosthetic infection treated by antibiotics.

We report the case of a 69 years old man with left hip prosthesis, who presented clinical, biochemical and imaging signs of periprosthetic infection treated with linezolid, an antibacterial agent of the oxazolidinone class. Two weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan showed increased uptake in the skeleton and also increased uptake in several focal areas in the spine and near the prosthesis and the surgical wound on the left gluteus medius. Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four weeks of treatment was stopped due to red blood cells and platelets toxicity. Six weeks later, the patient developed high fever again and in order to revaluate the periprosthetic inflammation, he was resubmitted to 18F-FDG PET/CT which showed normal 18F-FDG uptake in the whole skeleton, including the prosthesis and the subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were still detected. In the next 4 weeks the patient was under a "watch and wait" follow-up in a steady state. IN CONCLUSION: In the case we report, since we found no otnt focal areas in the lumbar spine where due to age-related bone deformities including some Schmorl's nodes. The inflammation in the bone prosthesis and the subcutaneous wound responded almost totally to the antibiotic treatment we applied.

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment.

We investigated the prognostic value of interim F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis.Thirty pHL patients (age ≤16) underwent serial F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΔΣSUVmax0-2, ΔΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78).Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method.Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΔΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΔΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005).Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΔΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.