Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

The Influence of COVID-19 on New Lung Cancer Diagnoses, by Stage and Treatment, in Northern Italy.

The COVID-19 pandemic has had a significant impact on new cancer diagnoses. This study aims to evaluate the implications of the lockdown period on new lung cancer diagnoses in northern Italy. We compared 2020 with 2019 cancer registry data, reporting the variations by age, stage, and treatments. In 2020, 303 lung cancer cases were registered, 21 fewer than in 2019. Cases fell in men (-31 patients, 9.6%) but not in women (+10 patients, +3.1%). A significant drop in stage I from 19.8% to 12.9% (p < 0.05) and an increase in stage III (12.7% vs. 19.1%; p < 0.05) was observed. Histological confirmation dropped (70.1% vs. 60.1%; p < 0.05) while cytology increased (12% vs. 20.8%; p < 0.01). Surgery declined (28.7% vs. 21.5%; p < 0.05) but increased in stage III (19.5% vs. 25.9%; p = 0.46), while chemotherapy increased (17.6% vs. 34.3%; p < 0.01) for all stages. During the pandemic, new lung cancer diagnoses dropped only in men. The reorganization of health services has ensured a decrease in surgical interventions (due to the unavailability of operating rooms) counterbalanced by an increase in chemotherapy.

The diagnostic and prognostic role of combined [18F]FDG and [68Ga]-DOTA-peptides PET/CT in primary pulmonary carcinoids: a multicentric experience.

OBJECTIVES: In the present retrospective multicentric study, we combined [68Ga]-DOTA-peptides and [18F]FDG-PET/CT findings aiming to investigate their capability to differentiate typical (TC) and atypical pulmonary carcinoids (AC) and their prognostic role. METHODS: From three centers, 61 patients were retrospectively included. Based on a dual tracer combination we classified PET scans as score 1, [18F]FDG- and [68Ga]-DOTA-peptides negative; score 2, [68Ga]-DOTA-peptides positive and [18F]FDG-negative; score 3, [68Ga]-DOTA-peptides negative and [18F]FDG-positive; score 4, both tracers positive. Moreover, for each patient, the ratios of SUVmax on [68Ga]-DOTA-PET to that on [18F]FDG-PET were calculated (SUVr). RESULTS: Thirty-five patients had a final diagnosis of TC. Twenty-two TC (57%) had positive [68Ga]-DOTA-peptides PET; instead, 21/26 (81%) AC had positive [18F]FDG-PET/CT. On dual-tracer analysis, scores 1, 2, 3 and 4 were 13%, 20%, 43% and 24% for all populations; 17%, 26%, 20% and 37% for TC; 8%, 11%, 73% and 8% for AC. Median SUVr was significantly higher in TC than AC (6.4 vs. 0.4, p = 0.011). The best value of SUVr to predict the final diagnosis was 1.05 (AUC 0.889). Relapse or progression of disease happened in 17 patients (11 affected by AC) and death in 10 cases (7 AC). AC diagnosis, positive [18F]FDG-PET, negative DOTA-PET and dual tracer score were significantly correlated with PFS (p = 0.013, p = 0.033, p = 0.029 and p = 0.019), while only AC diagnosis with OS (p = 0.022). CONCLUSION: PET/CT findings had also a prognostic role in predicting PFS. Dual-tracer PET behavior may be used to predict the nature of pulmonary carcinoids and select the most appropriate management. KEY POINTS: • Combination of [18F]FDG and [68Ga]-DOTA-peptides PET/CT results may help to differentiate between atypical and typical lung carcinoids. • The SUVmax ratio between [18F]FDG and [68Ga]-DOTA-peptides PET may help to differentiate between atypical and typical lung carcinoids. • Histotype and PET/CT features have a prognostic impact on PFS.

Nuclear Medicine and Radiological Imaging of Pancreatic Neuroendocrine Neoplasms: A Multidisciplinary Update.

Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low-intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2-G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.

Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT.

Peptide receptor radionuclide therapy (PRRT) is an effective therapeutic option in patients with metastatic neuroendocrine tumor (NET). However, PRRT fails in about 15-30% of cases. Identification of biomarkers predicting the response to PRRT is essential for treatment tailoring. We aimed to evaluate the predictive and prognostic role of semiquantitative and volumetric parameters obtained from the 68Ga-DOTATOC PET/CT before therapy (bPET) and after two cycles of PRRT (iPET). A total of 46 patients were included in this retrospective analysis. The primary tumor was 78% gastroenteropancreatic (GEP), 13% broncho-pulmonary and 9% of unknown origin. 35 patients (76.1%) with stable disease or partial response after PRRT were classified as responders and 11 (23.9%) as non-responders. Logistic regression analysis identified that baseline total volume (bTV) was associated with therapy outcome (OR 1.17; 95%CI 1.02-1.32; p = 0.02). No significant association with PRRT response was observed for other variables. High bTV was confirmed as the only variable independently associated with OS (HR 12.76, 95%CI 1.53-107, p = 0.01). In conclusion, high bTV is a negative predictor for PRRT response and is associated with worse OS rates. Early iPET during PRRT apparently does not provide information useful to change the management of NET patients.

Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors.

Importance: Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. Objective: To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). Design, Setting, and Participants: This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. Exposures: Upfront PRRT or upfront chemotherapy or targeted therapy. Main Outcomes and Measures: The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. Results: Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95% CI, 0.4-1.0 years]; HR, 0.37 [95% CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95% CI, 10.7-14.1 years] vs 11.6 years [95% CI, 9.1-13.4 years]; HR, 0.81 [95% CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95% CI, 9.2-17.9 years]; HR, 0.83 [95% CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95% CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95% CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95% CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95% CI, 0.12-0.34]; grade 2: aHR, 0.52 [95% CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95% CI, 0.24-0.61]; intestinal: aHR, 0.19 [95% CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95% CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95% CI, 0.29-1.43; P = .31). Conclusions and Relevance: In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors.

Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

68Ga-DOTATOC PET/CT in Pleural Solitary Fibrous Tumors.

ABSTRACT: Solitary fibrous tumor of the pleura (SFTP) is a rare mesenchymal neoplasm. Preoperative diagnosis is usually difficult and based on radiological findings only. We report the imaging results observed in 5 patients with SFTP (2 malignant) obtained by 68Ga-DOTATOC PET/CT. At qualitative analysis, all tumors showed uptake of 68Ga-DOTATOC. Mean tumor SUVmax was 9.9 ± 5.7. The expression of SST2 (somatostatin receptors subtype 2) was confirmed by immunohistochemistry in 2 tumor samples, and by gene amplification of SST2 mRNA in all cases. These data suggest a diagnostic role of radioreceptor PET/CT in SFTP, and open novel potential treatment options in unresectable/metastatic disease.

Sequencing radium 223 and other life-prolonging agents in castration-resistant prostate cancer patients.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.

Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer patients sequentially treated with abiraterone acetate and RADIUM-223.

PURPOSE: To evaluate the fracture risk and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) who received sequentially abiraterone acetate (AA) and radium 223 [223Ra]RaCl2 in the daily clinical practice. MATERIALS: We retrospectively reviewed the records of mCRPC patients who received [223Ra]RaCl2 immediately after progressing during an AA treatment line in everyday clinical practice. RESULTS: We reviewed data of a consecutive series of 94 mCRPC patients. Most of the patients (85.1%) received [223Ra]RaCl2 as second- or third-line treatment. [223Ra]RaCl2 treatment was well-tolerated; there were only four cases of grade 3 anaemia, two cases of grade 3 leukopenia and one case of grade 3 neutropenia. The overall fracture rate is 2.1%; one fracture was recorded during the course of [223Ra]RaCl2 treatment, and one was recorded 1 month after its end. The fractures both occurred at metastatic sites. Median OS from [223Ra]RaCl2 start was more than 14 months regardless of the treatment line when [223Ra]RaCl2 was administered. CONCLUSION: The findings of this study show that the treatment with [223Ra]RaCl2 immediately after AA was active and safe with a very low risk of a fracture. Thus, the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including [223Ra]RaCl2 in the therapeutic algorithm.

Radiotherapy Planning and Molecular Imaging in Lung Cancer.

INTRODUCTION: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. MATERIALS AND METHODS: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually "in vitro" studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. RESULTS: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. CONCLUSION: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

18F-fluorodeoxyglucose positron emission tomography in malignant pleural mesothelioma: diagnostic and prognostic performance and its correlation to pathological results.

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher's exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.

Treatment With 90Y/177Lu-DOTATOC in Patients With Metastatic Adrenocortical Carcinoma Expressing Somatostatin Receptors.

CONTEXT: We investigated the role of Gallium 68 dodecanetetraacetic acid Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/computed tomography (PET/CT) in detecting somatostatin receptors (SSTRs) in 19 patients with metastatic adrenocortical carcinoma (ACC) and explored the activity of yttrium-90/lutetium-177 (90Y/177Lu-DOTATOC) peptide receptor radionuclide therapy (PRRT). CASE DESCRIPTION AND METHODS: 68Ga uptake in metastatic sites was scored in terms of intensity and anatomical uptake distribution of standard uptake value (SUV). Tissue expression of SSTR2A and SSTR5 was also evaluated by immunohistochemistry (IHC) on primary tumors. Eight (42%) patients displayed radiometabolic uptake of any-grade intensity with focal and limited distribution. Two (11%) patients displayed strong uptake in multiple lesions and were treated with PRRT. Both obtained an overall disease control lasting 4 and 12 months, respectively. CONCLUSIONS: ACC can express SSTRs as detected by IHC and 68Ga-DOTATOC PET. SSTRs-based PRRT may represent a potential treatment opportunity for a minority of patients with advanced ACC. This treatment modality deserves further investigation.

Diagnostic performances of 68Ga-DOTATOC versus 18Fluorodeoxyglucose positron emission tomography in pulmonary carcinoid tumours and interrelationship with histological features.

Few data are available about radio-receptorial positron emission tomography (PET) results by the use of 68Ga-DOTA-peptides in pulmonary carcinoid tumours. In this study, we retrospectively analysed 68Ga-DOTATOC/PET and 18Fluorodeoxyglucose (FDG) PET diagnostic performances in 62 pulmonary carcinoids (occurring in 57 patients) and interrelationship with histological features. All patients underwent at least 1 PET/computed tomography: 26 patients received 68Ga-DOTATOC, 52 patients had 18F-FDG and 20 patients received both techniques. There were 55 typical carcinoids and 7 atypical carcinoids. 68Ga-DOTATOC/PET recorded an 88.4% overall detection rate (DR) (meanSUVmax: 15.5); 18F-FDG/PET a DR of 53.8% (meanSUVmax: 3.2). When adopted a maximum standardized uptake value-threshold of 1.5, DRs of 68Ga-DOTATOC and 18F-FDG/PET increased to 100% and 80.8%, respectively. Moreover, DRs in both techniques vary considerably according to histology with 68Ga-DOTATOC/PET having better performances in typical carcinoids than in atypical carcinoids (DR: 91.7% vs 50.0%, P = 0.076). We also observed a significant correlation between a low number of mitoses (<2/10 high-power field) and 68Ga-DOTATOC/PET-positivity (P = 0.004), and an association trend (P = 0.076) between necrosis and 68Ga-DOTATOC/PET-negativity. In conclusion, 68Ga-DOTATOC had better diagnostic performances than 18F-FDG/PET in detecting pulmonary carcinoids. DRs of both techniques remarkably varied according to histology with 68Ga-DOTATOC/PET performing at its best in typical carcinoids, whereas 18F-FDG/PET did the same in atypical carcinoids.68Ga-DOTATOC/PET results were presumably associated with the number of mitoses and the presence of necrosis.

18F-FDG and 68Ga-somatostatin analogs PET/CT in patients with Merkel cell carcinoma: a comparison study.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients. RESULTS: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site. CONCLUSIONS: Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of "personalized medicine."

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with 177Lu or 90Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of 177Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code. The similarity analysis demonstrated the superiority of the deformable registrations (p < .001). Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [-19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [-67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL. Image based 3D dosimetry for 177Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.

Diagnostic performances of [18F]fluorocholine positron emission tomography in brain tumors.

BACKGROUND: Brain tumors characterization by molecular imaging that allows the depiction of brain lesions metabolic pattern is crucial. Our study aimed to: 1) to evaluate the diagnostic performances of [18F]fluoroethylcholine positron emission tomography/computed tomography ([18F]FECH PET/CT), and 2) correlate PET imaging derived parameters of [18F]FECH to survival in brain tumors. METHODS: From 2009 to 2012, we enrolled 30 patients who underwent [18F]FECH PET/CT. Final diagnosis was established by clinical and radiological follow-up. RESULTS: Final diagnosis was consistent with tumor disease in 27/30 cases. In 3/30 cases tumor disease was ruled out. [18F]FECH PET/CT resulted true positive and negative in 21/30 and 9/30 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of [18F]FECH PET/CT were 78%, 100%, 100%, 33%, and 80%, respectively. Mean and maximum standardized uptake value (SUVmean and SUVmax) resulted statistically correlated to histology (P=0.0255 and P=0.0222, respectively). Using a SUVmax cut-off of 2.0 or 3.2, we distinguished between low- and high-grade gliomas with a good specificity (70% and 80%, respectively). SUVmax and histology resulted correlated to overall survival and disease related survival at multivariate analysis. CONCLUSIONS: Our results, worthy of further investigations, show high diagnostic performances of [18F]FECH PET/CT, and a correlation between PET imaging derived parameters and survival.

18F-fluorodeoxyglucose positron emission tomographic scan in solid-type p-stage-I pulmonary adenocarcinomas: what can produce false-negative results?

Objective: False-negative (FN) uptake of 18F-fluorodeoxyglucose (FDG) can be divided into those cases related to technological limitations of positron emission tomography (PET) and those related to inherent properties of neoplasms. Our goal was to clarify possible factors causing FN PET results in patients with solid-type pulmonary adenocarcinomas (PAs). Methods: From January 2007 to December 2014, of the 255 patients with p-stage-1 non-small-cell lung cancer observed and treated (surgically) in our institution, we retrospectively reviewed the PET/computed tomography (CT) records, the clinical information, the preoperative thin-section CT images, and the pathological features [classified by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) subtyping criteria] of 94 consecutive solid-type p-stage-1 PAs. Univariable and multivariable logistic analyses were used to identify and weigh the independent predictors of the PET findings using the following variables: body weight, blood glucose level, tumour size, tumour location, and histological classification. Results: There were 58 men and 36 women (mean age = 68.7 ± 8.9 years, range 42-85). Considering the maximum standardized uptake value (SUVmax) ≥ 2.5 as a 'PET-positive' result, 77 lesions (81.9%) proved PET positive and 17 lesions (18.1%), PET negative (with SUVmax < 2.5). Overall, the median SUVmax value was 5.7 [interquartile range (IQR) 2.8-10.3]. Higher SUVmax values ( P < 0.001) were observed in those PAs larger than 2 cm in their major axis (median SUVmax = 9.0; IQR 4.6-14.6); in PAs < 2 cm, the median SUVmax was 4.1; IQR 2.2-5.9. When clustering the cohort in two histological classes (class A, colloid/mucinous/lepidic versus class B, micropapillary/solid/acinar/papillary), the radiometabolic patterns were significantly different (median SUVmax = 2.8; IQR 1.7-4.9 in class A vs median = 7.4 IQR 4.5-13.9 in class B, P < 0.001). Significant PET FN rates were reported in (i) PAs measuring < 2 cm in their major axis (27.9%), (ii) lesions located in the lower zones of the lung (31.0%), and (iii) class A tumours (37.5%). In the multivariable logistic analysis, histological type (IASLC/ATS/ERS aggregated clusters) proved to be the only independent relevant factor for determining whether PET results were negative or positive (OR:7.23, 95% CI: 2.05-25.43, P = 0.002). Conclusions: The IASLC/ATS/ERS pattern significantly influences FDG uptake in solid-type p-stage-1 PAs. The fact that colloid/mucinous/lepidic adenocarcinomas have a notable tendency to produce negative findings on PET scans warrants particular attention.

Primary Sarcomatoid Carcinoma of the Lung: Radiometabolic ((18)F-FDG PET/CT) Findings and Correlation with Clinico-Pathological and Survival Results.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a very rare and uninvestigated subtype of non-small cell lung cancer (NSCLC). METHODS: The aims of this study were to define the radiometabolic features (by (18)F-FDG PET/CT) in a bi-centric cohort of 49 PSC patients and to explore their relation with clinico-pathological characteristics and long-term survival results after surgical treatment. RESULTS: There were 40 males and 9 females aged 65.2 ± 10.47 years. Overall long-term survival was 26.7 % at 5 years. Mean and median values of SUVmax were 15.21 and 15, respectively (SD ±5.5). Performing an age-, gender- and staging-matched analysis comparing PSC Stage-I only with a cohort of Stage-I NSCLC (n = 93), we observed significantly higher SUVmax values in PSC group (15.11 vs 7.66, p = 0.001). CONCLUSIONS: No differences in terms of SUVmax were found with regard to tumour dimensions, histology (pure vs mixed, pleomorphic vs others), pathological stage and pattern of recurrence. P-stage, surgical radicality, vascular/lymphatic invasion but not SUVmax affected long-term survival in PSC.