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Purpose: To evaluate the clinical–pathological and prognostic significance of the circulating PD-L1 level in patients with surgically treated NSCLC, by combining data for PD-L1 expression with other immune-related markers and tumor metabolism. Methods: Overall, 40 patients with resected NSCLC (stage Ia–IIIa) who had preoperative blood storage and underwent staging PET/CT were enrolled for the study. In all cases, we determined plasma levels of PD-L1 (pg/ml), immune-reactive areas (IRA%) covered by CD3, CD68, CD20, CD8, PD-1, and PD-L1 in the tumor specimen, and metabolic parameters on PET, i.e., SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Variables were statistically analyzed to establish their association with disease-free survival (DFS). Results: The circulating levels of PD-L1 in the bloodstream could be determined in 38/40 (95%) samples. The mean and median expression levels were 34.86pg/ml and 24.83pg/ml, respectively. We did not find any statistically significant correlation between circulating PD-L1 and tissue expression of PD-L1/PD-1. Some mild degree of positive correlation was determined between tissue PD-L1 and SUVmax (ρ = 0.390; p = 0.0148). Hierarchical clustering combining circulating, tissue, and metabolic parameters identified clusters with high metabolic tumor burden or high expression of plasma PD-L1 levels (Z score ≥ 2) as having a poor DFS (p = 0.033). The multivariate analysis detected stage and metabolism (i.e., SUVmax and SUVpeak) as independent prognostic factors for DFS. Conclusion: Plasma levels of PD-L1 are independent of the expression of PD-1/PD-L1 in NSCLC tumor tissue and, when combined with other clinical–pathological parameters, allow for the identification of clusters with different outcomes.

Background: Positron emission tomography (PET) is a valuable tool for the characterization of brain tumors in vivo. However, few studies have investigated the correlation between carbon-11-methionine (11C-METH) PET metrics and the clinical, radiological, histological, and molecular features of patients affected by lower grade gliomas (LGGs). The present observational study evaluated the relationships between 11C-METH PET metrics and structural magnetic resonance imaging (MRI) findings with the histomolecular biomarkers in patients with LGGs who were candidates for surgery. Methods: We enrolled 96 patients with pathologically proven LGG (51 men, 45 women; age 44.1 ± 13.7 years; 45 with grade II, 51 with grade III), who had been referred from March 2012 to January 2015 for tumor resection and had undergone preoperative 11C-METH PET. The semiquantitative metrics for 11C-METH PET included maximum standardized uptake value (SUVmax), SUV ratio to normal brain, and metabolic tumor burden (MTB). The PET semiquantitative metrics were analyzed and compared with the MRI features, histological diagnosis, isocitrate dehydrogenase-1/2 status, and 1p/19q codeletion. Results: Histological grade was associated with SUVmax (P = 0.002), SUV ratio (P = 0.011), and MTB (P = 0.001), with grade III lesions showing higher values. Among the nonenhancing lesions on MRI, SUVmax (P = 0.001), SUV ratio (P = 0.003) and MTB (P < 0.001) were significantly different statistically for grade II versus grade III. The MRI lesion volume correlated poorly with MTB (r2 = 0.13). The SUVmax and SUV ratio were greater (P < 0.05) in isocitrate dehydrogenase-1/2 wild-type lesions, and the SUV ratio was associated with the presence of the 1p19q codeletion. Conclusions: The 11C-METH PET metrics correlated significantly with histological grade and the molecular profile. Semiquantitative PET metrics can improve the preoperative evaluation of LGGs and thus support clinical decision-making.

Purpose: We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin’s lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. Methods: We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors. Results: Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01). Conclusion: After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

Objectives In-vivo characterization of malignant pleural mesothelioma (MPM) with 11C-methionine PET/computed tomography (MET PET). Methods Between September 2014 and February 2016, 30 consecutive patients with clinical suspicion of MPM were prospectively recruited. The study was approved and registered at www.clinicaltrials.gov (NCT02519049). Patients were evaluated at baseline with MET PET (experimental) and fluorine-18 fluorodeoxyglucose PET/computed tomography (FDG PET) (standard). Principal parameters analyzed were SUVmax, SUVmean, metabolic tumor volume (MTV), and metabolic tumor burden (MTB = MTV ×SUVmean). The reference standard for diagnostic performance was based on histology. Results The presence of malignancy was confirmed in 29/30 patients: 23 (76.6%) with MPM (20 epithelioid, two biphasic, and one sarcomatoid), five (16.6%) with adenocarcinoma of the lung, and one (3.3%) with an undifferentiated carcinoma. In one case, diagnosis was benign pleural inflammation. All tumors showed increased uptake of 11C-methionine: median SUVmax, SUVmean, MTV, and MTB were, respectively, 5.70 [95% confidence interval (CI): 4.51-6.79], 3.15 (95% CI: 2.71-3.40), 33.85 (95% CI: 14.08-66.64), and 105.25 (95% CI: 41.77-215.25). Pathology data revealed MTV and MTB to be significantly higher in nonepithelioid histology (P < 0.05). The other parameters showed a homogeneous distribution across the tumor types. Overall, MET PET identified 49 lymph nodes, compared with 34 nodes on FDG PET, demonstrating a sensitivity of 91% (95% CI: 80-96%), a positive predictive value of 92% (95% CI: 82- 97%), and an accuracy of 85% (P = 0.0042). Conclusions MET PET is able to characterize MPM lesions regardless of histology. This technique shows higher sensitivity than FDG PET for the identification of secondary lymph nodes.

International audience; This paper follows the immunotherapy symposium held during the European Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis of the immune checkpoint inhibitors and the drugs most frequently used for the treatment of solid tumours are reviewed. The issues of pseudoprogression (frequency, timeline), hyperprogression and immune-related side effects are discussed, as well as their implications for patient management. A review of the recent literature on the use of FDG PET for assessment of immunotherapy is presented, and recommendations are provided for assessing tumour response and reporting immune-related side effects with FDG PET based on published data and experts' experience. Representative clinical cases are also discussed.

The present study investigated the utility of fluorine-18 (18F) fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). 18F-FDG PET/CT shows high diagnostic performance in evaluating BMI in pediatric HL. BMB should be ideally reserved for patients with doubtful 18F-FDG PET/CT BMI findings. Introduction: The present study investigated the utility of fluorine-18 (18F) fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). Patients and Methods: A total of 224 pediatric patients with HL underwent 18F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI. Results: 18F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI. Conclusion: 18F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18F-FDG PET/CT findings for BMI.

To verify the potential role and feasibility of carbidopa premedication in pediatric patients undergoing ¹⁸F-DOPA (Fluorine-18 fluorodihydroxyphenylalanine) PET scanning. MATERIALS AND METHODS: For this limited study, 5 patients (M:F=3:2; mean age 4.8 years) with a positive history for neuroblastoma who had been referred to our institution for instrumental monitoring during clinical follow-up were enrolled. In all cases, two consecutive ¹⁸F-DOPA PET scans, the first without carbidopa and the second with carbidopa premedication, were scheduled: patients received 4 MBq/kg of radiotracer and a dose of 2 mg/kg of carbidopa. Dedicated VOIs were drawn on the basal ganglia, pancreas, liver, and renal cortex. These regions were semiquantitatively analyzed at both the first and at the second ¹⁸F-DOPA scan, and mean SUV(max) values were compared using the t-test. RESULTS: On a visual basis, a clear reduction in the abdominal accumulation of (18)F-DOPA was observed in all cases after carbidopa premedication. This reduction related both to the biliary structures and the excretory system, and was accompanied by a generalized increase in soft tissue uptake. The semiquantitative analysis documented an absolute increase in SUV(max) after carbidopa premedication in the basal ganglia (3.4±1.3 vs. 2.1±0.8) and liver parenchyma (2.2±0.5 vs. 1.5±0.5), whereas SUV(max) decreased in the renal cortex (1.7±0.8 vs. 3.7±1.0) and the pancreas (2.3±0.6 vs. 3.5±0.5). The changes in SUV(max) were statistically significant for the pancreas and liver parenchyma (p=0.022 and 0.045, respectively), but not for the basal ganglia and renal cortex (p=0.143 and 0.15, respectively). CONCLUSIONS: Carbidopa premedication in the pediatric population appears feasible and seems to influence ¹⁸F-DOPA distribution in the liver and pancreas in a manner similar to that reported in adults. Larger series are however needed to properly define the clinical role of carbidopa premedication in children.

The present handbook is a concise and Comprehensive compendium for students illustrating synthetically the principals of Nuclear Medicine discipline. It provides the reader with a balanced overview of the techinical aspects and main indications of Nuclear Medicine procedures in clinical practice. The text is addressed primarily to the degreecourses for technologists, but can be a useful tool for medical students and a pratical guide for other professionals and training courses.

PURPOSE: Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome. PATIENTS AND METHODS: A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non-small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months. RESULTS: All patients showed a moderately to highly increased uptake of Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9-8.3) and mean SUVratio of 4.4 (range, 1.6-6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm (range, 2.5-453.7 cm) and 301 (4.2-1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ≤4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02). CONCLUSIONS: In our cohort, the definition of optimal semiquantitative and quantitative parameters on Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.

PURPOSE: We present findings concerning (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) at end-treatment evaluation in follicular lymphoma (FL) in order to establish possible predictive factors for progression-free survival (PFS) and patient outcome. METHODS: We retrospectively analysed data from 91 consecutive FL patients (M:F = 51:40, mean age 61) referred to our PET Unit at therapy completion: 38 with an indolent form (grade 1-2) and 53 with an aggressive FL (grade 3a and b) according to the World Health Organization (WHO) classification. A total of 148 FDG PET/CT scans were analysed and findings reported as positive or negative for disease. The overall response to treatment was assessed according to the revised International Workshop Criteria (IWC). The final outcome was defined as remission or disease by taking clinical, instrumental and histological data as standards of reference, with a mean follow-up period of 3 years (range 1-8). A statistical analysis was performed with respect to PFS and patient outcome for FDG PET result, tumour grading, Follicular Lymphoma International Prognostic Index (FLIPI), disease stage and number of relapses, on uni- and multivariate analyses, with p < 0.05 considered as significant. RESULTS: Overall patients presented a mean PFS of 35 months (range 3-86), with a relapse rate of 42%. At final outcome, remission was achieved in 67 of 91 patients (74%). Of the different predictive factors, only FDG PET result significantly correlated with patient outcome (p = 0.0002). PET/CT performance at the end of treatment was as follows: 100% sensitivity, 99% specificity, 89% positive predictive value and 100% negative predictive value. The Kaplan-Meier analysis demonstrated a statistically significant correlation with PFS for FDG PET (p < 0.0001), FLIPI score (0-1 versus ≥ 2) (p = 0.0451) and number of relapses (none versus ≥ 1) (p = 0.0058). These findings were confirmed at the univariate analysis, whereas at the multivariate analysis only FDG PET (p = 0.0006892) and number of relapses (p = 0.01947) were independent predictive factors for PFS. CONCLUSION: End-treatment PET/CT in FL has high accuracy and appears to be a good predictor of PFS and patient outcome, irrespective of grading. As expected, patients facing more than one relapse seem to have significantly shorter PFS in the presence of a positive FDG PET.

PURPOSE: (18)F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on (18)F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of (18)F-dopa PET/CT in NB and compare its diagnostic value with that of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3-4 NB. METHODS: We prospectively evaluated 28 paired (123)I-MIBG and (18)F-dopa PET/CT scans in 19 patients: 4 at the time of the NB diagnosis and 15 when NB relapse was suspected. For both imaging modalities we performed a scan-based and a lesion-based analysis and calculated sensitivity, specificity and accuracy. The standard of reference was based on clinical, imaging and histological data. RESULTS: NB localizations were confirmed in 17 of 19 patients. (18)F-Dopa PET/CT and (123)I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while (123)I-MIBG scanning showed a sensitivity and accuracy of 68 and 64%, respectively (p < 0.05). No significant difference in terms of specificity was found. In 9 of 28 paired scans (32%) PET/CT results influenced the patient management. We identified 156 NB localizations, 141 of which were correctly detected by (18)F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas (123)I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found. CONCLUSION: In our NB population (18)F-dopa PET/CT displayed higher overall accuracy than (123)I-MIBG scintigraphy. Consequently, we suggest (18)F-dopa PET/CT as a new opportunity for NB assessment.

Background: The aim of this study is the 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)–positron emission tomography (PET) evaluation following radioimmunotherapy (RIT) with ibritumomab tiuxetan Y 90 in patients with non-Hodgkin’s follicular lymphoma (FL). Materials and methods: We retrospectively analyzed data from 59 relapsed or refractory FL patients treated with ibritumomab tiuxetan Y 90 in four different PET centers who had a PET scan carried out before and after RIT. Possible predictive factors of progression-free survival (PFS) were studied through univariate and multivariate analysis. Results: The post-RIT PET documented 45.8% complete responders (CR), 25.4% partial responders (PR) and 28.8% nonresponders [stable disease + progressive disease], with an overall survival of 71.2% (range 59.5%–90.9%). With a median follow-up period of 23 months, the univariate analysis documented a statistically significant relation between disease extent before RIT and response to treatment with respect to PFS (P = 0.015), while all the other prognostic factors showed no significant correlation. When carrying out the multivariate analysis, post-RIT PET resulted as the lonely independent predictor of PFS (P < 0.00001). Conclusions: RIT is an effective therapy in FL patients, as confirmed in our study too. Disease extension before treatment and response to RIT, as assessed by FDG–PET, result as main predictors of PFS, with the post-RIT PET result being the only independent predictive factor.

This study reports on our experience with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric patients affected by Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). We studied 20 pediatric subjects (12 males, 8 females; mean age, 10 years; range, 6 months to 14 years) with malignant lymphoma (9 HD, 11 NHL) for a 4-year period of time. Overall, 45 PET scans were performed: 7 at disease presentation and 38 for evaluation of response to therapy or follow-up study. All PET results were compared with conventional imaging (CI), mainly computed tomography (CT) and/or magnetic resonance imaging (MRI), and supported by clinical follow-up and/or histologic data. In 18 of 20 patients, PET findings correctly identified the status of disease. Two (2) subjects (respectively, 1 HD and 1 NHL, both at follow-up) resulted falsely positive: 1 due to prominent thymic uptake, and the other due to nonspecific inflammation. Of 45 scans, PET findings were consistent with clinical follow-up and other CI data in 43 cases (16 true-positive and 27 true-negative results) and resulted falsely positive in the remaining 2 scans. On a lesion-by-lesion basis (overall, 153 lesions: 84 nodal and 69 extranodal), we found a concordance between CI and PET findings in 25 nodal (29.8%) and in 22 extranodal sites (32%). PET was more accurate than CI, as it identified active disease in 1 patient negative at CI and excluded relapse in 6 patients with inconclusive CI and in 2 patients with a falsely positive CI. Overall, PET sensitivity and specificity was 100% and 93% versus 94% sensitivity and 72.4% specificity for CI. This comparative study shows FDG PET to be more accurate than CI in evaluating children with lymphoma. Our data also confirms that (18)F-FDG PET may show false-positive findings.

Hypoxia is a pathological condition arising in living tissues when oxygen supply does not adequately cover the cellular metabolic demand. Detection of this phenomenon in tumors is of the utmost clinical relevance because tumor aggressiveness, metastatic spread, failure to achieve tumor control, increased rate of recurrence, and ultimate poor outcome are all associated with hypoxia. Consequently, in recent decades there has been increasing interest in developing methods for measurement of oxygen levels in tumors. Among the image-based modalities for hypoxia assessment, positron emission tomography (PET) is one of the most extensively investigated based on the various advantages it offers, i.e., broad range of radiopharmaceuticals, good intrinsic resolution, three-dimensional tumor representation, possibility of semiquantification/quantification of the amount of hypoxic tumor burden, overall patient friendliness, and ease of repetition. Compared with the other non-invasive techniques, the biggest advantage of PET imaging is that it offers the highest specificity for detection of hypoxic tissue. Starting with the 2-nitroimidazole family of compounds in the early 1980s, a great number of PET tracers have been developed for the identification of hypoxia in living tissue and solid tumors. This paper provides an overview of the principal PET tracers applied in cancer imaging of hypoxia and discusses in detail their advantages and pitfalls.

PURPOSE: The aim of this study was to investigate the relationship between (123)I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new (18)F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS). METHODS: We analysed 24 NB patients who had undergone (123)I-MIBG and (18)F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of (123)I-MIBG and (18)F-DOPA PET/CT scans. RESULTS: The (123)I-MIBG and (18)F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p 3 (3rd tertile) and an even higher risk (HR:37.2, 95% CI 2.4-574) in those with (18)F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for (123)I-MIBG and (18)F-DOPA WBMB, respectively). CONCLUSION: Our results confirm the good agreement between (18)F-DOPA PET/CT and (123)I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, (123)I-MIBG scan and (18)F-DOPA PET/CT scores were independently and significantly associated with disease progression.

AIMS: Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) is a hypoxia-avid, positron emitter radiotracer. The primary aim of this study is to assess the efficacy of pretherapy Cu-ATSM PET/CT as a prognostic factor of response to therapy. The secondary aims are to investigate if there is a difference between early and late PET/CT scans and if there is a difference between the biologic tumor volume (BTV) in radiotherapy treatment planning calculated between Cu-ATSM and F-FDG, and to assess if Cu-ATSM is a prognostic marker of disease progression. METHODS: Eleven patients with head and neck cancer treated with chemoradiotherapy were enrolled prospectively; both Cu-ATSM and F-FDG PET/CT scans before and after treatment were obtained. The Cu-ATSM scans were performed after 1 hour (early) and 16 hours (late). RESULTS: All patients had stage III or IV squamous cell head and neck cancer; 7 of 11 patients had nodal metastasis, and 22 cancer foci were detected with Cu-ATSM. SUVmax was 16.2 ± 7.9, and there was no significant SUVmax difference between early and late imaging. F-FDG SUVmax before therapy was 15.6 ± 9.4, whereas F-FDG SUVmax after therapy was 1.5 ± 1.2. Sensitivity and specificity values of Cu-ATSM calculated with receiver operating characteristic curves were 100% and 50% considering the SUVmax and 100% and 33% considering the volume, respectively. No difference has been found between the BTV contoured with Cu-ATSM and F-FDG. CONCLUSIONS: The Cu-ATSM scans showed high sensitivity but low specificity in predicting neoadjuvant chemoradiotherapy response. No difference was noted between early and late scans. F-FDG and Cu-ATSM provided similar results about delineation of BTV.

Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.

AIM: Role of 18F-DOPA PET/CT in neuroblastoma (NB) compared with CT/MR. MATERIALS AND METHODS: In all, 21 patients (M:F = 14:7; mean age, 7.4 years) affected by advanced stage NB (III-IV) were prospectively enrolled. Overall, 37 paired 18F-DOPA PET and CT/MR scans were performed, and for each, we identified site and number of lesions. Standard of reference was based on a multidisciplinary assessment, including 123I-MIBG, selective biopsy, and clinical-instrumental monitoring. Both scan-based and a lesion-based analysis was performed, and for each modality, we calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: On the scan-based analysis, 18F-DOPA PET and CT/MR showed the following rates: sensitivity, specificity, NPV, PPV, and accuracy were 100%, 92.3%, 100%, 96%, and 97.3% versus 91.7%, 61.5%, 80%, 81.5%, and 81.1%, respectively (P = 0.014). Overall 179 findings were reported at imaging, of which 139 (77.7%) resulted true sites of disease at final outcome. On the lesion-based analysis, the 2 imaging modalities showed the following sensitivity, specificity, NPV, PPV, and accuracy rates: 90.6%, 90%, 73.5%, 96.9%, and 90.5% versus 47.5%, 27.5%, 13.1%, 69.5%, and 43% (P < 0.00001). CONCLUSIONS: In our study, 18F-DOPA PET/CT results more accurate than CT/MR in advanced stage NB therefore should be taken into consideration for the diagnostic workup of these patients.

The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with (124)I/(131)I- and (86)Y/(90)Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (

The role of (18)F-FDG PET in the management of gynaecologic malignancies remains unclear mainly due to the failure of clinicians to appreciate the significance of this imaging tool. However, this under utilisation is being actively re-addressed with a large number of reviews and studies, particularly in the last few years.PET has been shown to have high sensitivity and specificity in the evaluation of relapse and nodal disease in cervical cancer, while other uses such as staging and monitoring response to therapies being under further investigation. Similarly, promising results have been published in the use of PET in patients affected by endometrial cancer and uterine sarcomas for detecting lymph nodes metastasis and recurrent disease. In ovarian cancer, PET appears to have a great potential in staging and assessment of disease relapse. An important utility of PET in gynaecologic tumours, which is shared with a large number of other malignancies, is its value in positively changing the patients' management.The surge in studies using PET in gynaecological malignancies is in its early stages, and further studies are required to optimise the role of PET in these conditions.

BACKGROUND: The surgical treatment of biliary atresia is still a great challenge for pediatric surgeons. Kasai's operation usually needs a wide, painful, muscle-cutting laparotomies that quite often are followed by pain and peritoneal adhesion. These possible complications may disturb the post-operative course and humper liver transplantation. Advancements in minimally invasive surgery have allowed even the most complex procedures to be approached using these techniques. METHODS: The authors present a case of successful Roux-en-Y laparoscopic portoenterostomy for the treatment of biliary atresia. We report a case of a 3-month-old patient with biliary atresia who weighted Kg 5,300 at the operation. The patient was placed in supine position. The procedure was performed with 4 trocars of 3 mm and 1 of 10 mm. The umbilical site was used for extracorporeal Roux-en-Y enteroenterostomy. CO2 was insufflated at a pressure of 8 mmHg and a flow of 0.5 L/min. A drain was placed through the lower trocar site with the tip near the anastomosis. RESULTS: The procedure was free of neither intraoperative nor post-operative complications. Feeding by nasogastric tube was started after 2 days. Total oral feeding was possible after 8 days. CONCLUSION: Laparoscopic approach to perform Kasai's operation is technically feasible and thanks to a magnified vision, it allows to abtain a good visualization of the portal structures with an adequate retraction of the liver. This procedure can avoid or decrease the post-operative complications such as pain, breathing difficulty, adhesions and resulting in very small scars. Anyway laparoscopic Kasaiportoenterostomy should be done by a surgeon with a good experience in laparoscopic hand-suturing and neonatal experience and with the support of an experienced in neonatal and infantile videosurgery anaesthesiologist.

A 7-year-old girl with indolent left upper extremity edema had axillary, supraclavicular, right retrocaval, paravertebral, mesenteric, and right iliac adenopathy confirmed by ultrasound and CT. Selective axillary biopsy demonstrated epitheliomorphic malignancy with neuroendocrine/neuroectodermic differentiation. Bone scintigraphy demonstrated several thoracic spin lesions. I-123 metaiodobenzylguanidine imaging was negative. Ga-68 DOTA-NOC PET/CT demonstrated multiple lesions in her axilla, thoracic spine, and retroperitoneum. Biopsy of a palpable nodule at her left forearm revealed alveolar rhabdomyosarcoma with neuroendocrine differentiation.