Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

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.

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.

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.

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.

PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids.

Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.

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).

Comparison of different positron emission tomography tracers in patients with recurrent medullary thyroid carcinoma: our experience and a review of the literature.

Several morphological and functional imaging techniques are usually used to detect residual/recurrent medullary thyroid carcinoma (MTC) with variable results; currently, there is growing interest in positron emission tomography (PET) methodology. Herein, we report our experience of and a literature review about the comparison of different positron emission tomography (PET) tracers in patients with residual/recurrent MTC. (18)F-DOPA PET/CT seems to be the most useful imaging method to detect recurrent MTC lesions, performing better than (18)F-FDG and (68)Ga-somatostatin analogs PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with aggressive tumors. (68)Ga-somatostatin analogs PET/CT may be useful to select patients who could benefit from radioreceptor therapy. The information provided by the various PET tracers reflects different metabolic pathways, and may help to select the most appropriate treatment.

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.

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma.

PURPOSE: To retrospectively evaluate and compare (18)F-FDG, (18)F-DOPA and (68)Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. METHODS: Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. RESULTS: At least one focus of abnormal uptake was observed on PET/CT in 13 patients with (18)F-DOPA (72.2% sensitivity), in 6 patients with (68)Ga-somatostatin analogues (33.3%) and in 3 patients with (18)F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between (18)F-DOPA and (18)F-FDG PET/CT (p < 0.01) and between (18)F-DOPA and (68)Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. (18)F-DOPA PET/CT detected 85% of lesions (61 of 72), (68)Ga-somatostatin analogue PET/CT 20% (14 of 72) and (18)F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by (18)F-DOPA PET/CT and (18)F-FDG PET/CT (p < 0.01 for all the analyses) and by (18)F-DOPA PET/CT and (68)Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). CONCLUSION: (18)F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than (18)F-FDG and (68)Ga-somatostatin analogue PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with an aggressive tumour.

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.

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.

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.

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.

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.

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.