[68Ga]DOTATOC PET-derived radiomics to predict genetic background of head and neck paragangliomas: a pilot investigation.

PURPOSE: To investigate the [68Ga]DOTATOC PET radiomic profile of head and neck paragangliomas (HNPGLs) and identify radiomic characteristics useful as predictors of succinate dehydrogenase genes (SDHx) pathogenic variants. METHODS: Sporadic and SDHx HNPGL patients, who underwent [68Ga]DOTATOC PET/CT, were retrospectively included. HNPGLs were analyzed using LIFEx software, and extracted features were harmonized to correct for batch effects and confronted testing for multiple comparison. Stepwise discriminant analysis was conducted to remove redundancy and identify best discriminating features. ROC analysis was used to define optimal cut-offs. Multivariate decision-tree analysis was performed using CHAID method. RESULTS: 34 patients harboring 60 HNPGLs (51 SDHx in 25 patients) were included. Three sporadic and nine SDHx HNPGLs were metastatic. At stepwise discriminant analysis, both GLSZM-Zone Size Non-Uniformity (ZSNU, reflecting tumor heterogeneity) and IB-TLSRE (total lesion somatostatin receptor expression) were independent predictors of genetic status, with 96.4% of lesions and 91.6% of patients correctly classified after cross validation (p < 0.001). Among non-metastatic patients, GLSZM-ZSNU and IB-TLSRE were significantly higher in sporadic than SDHx HNPGLs (p < 0.001). No differences were revealed in metastatic patients. Decision-tree analysis highlights multifocality and IB-TLSRE as useful variables, correctly identifying 6/9 sporadic and 24/25 SDHx patients. Model failed to classify one SDHA and three sporadic patients (2 metastatic). CONCLUSION: Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases.

Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.

DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer.

The heat shock protein 27 (Hsp27) has emerged as a principal factor of the castration-resistant prostate cancer (CRPC) progression. Also, an antisense oligonucleotide (ASO) against Hsp27 (OGX-427 or apatorsen) has been assessed in different clinical trials. Here, we illustrate that Hsp27 highly regulates the expression of the human DEAD-box protein 5 (DDX5), and we define DDX5 as a novel therapeutic target for CRPC treatment. DDX5 overexpression is strongly correlated with aggressive tumor features, notably with CRPC. DDX5 downregulation using a specific ASO-based inhibitor that acts on DDX5 mRNAs inhibits cell proliferation in preclinical models, and it particularly restores the treatment sensitivity of CRPC. Interestingly, through the identification and analysis of DDX5 protein interaction networks, we have identified some specific functions of DDX5 in CRPC that could contribute actively to tumor progression and therapeutic resistance. We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH, thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof of concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC.

Accidental parathyroidectomy during total thyroidectomy and hypoparathyroidism in a large series of 766 patients: incidence and consequences in a referral center.

PURPOSE: Transient hypoparathyroidism is the most common complication after total thyroidectomy, and accidental parathyroidectomy (AP) may be a cause. The aim of this study was to investigate the incidence of AP and its impact on postoperative calcemia. MATERIALS AND METHODS: From February 2016 to May 2018, 766 patients undergoing total thyroidectomy were prospectively included. Surgical indications, hormonal status, definitive histology, and postoperative calcium and PTH levels were analyzed. RESULTS: 578/(75.45%) were women and 188/(24.55%) men with mean age of 53.4 years. Parathyroid tissue on the thyroid specimen was observed in 40 (5.2%) patients: 30 APs and 10 parathyroid fragments. Among the 30 APs, 12 glands were intrathyroid and 18 (2.3%) in eutopic location. 97 (12.6%) patients were treated for postoperative hypocalcemia: 90 (11.7%) had transient and 5 (0.6%) definitive hypoparathyroidism; 2 were lost in follow-up. 13/30 (43.3%) with AP had transient hypoparathyroidism. A strong correlation was found (p < 0.0001) between AP and postoperative hypocalcemia. 1/30 (3.3%) patient with APs had definitive hypoparathyroidism. Transient and persistent nerve palsies were found in 10 (1.3%) and 3 (0.4%) patients, respectively. DISCUSSION: A careful examination of the thyroid gland after resection help to identify an AP that could be autotransplanted. Surgeon and hospital activity volume per years seem to reduce the risk of hypoparathyroidism. CONCLUSION: Total thyroidectomy and intrathyroid localization of parathyroid glands are risk factors for the AP. The incidence of AP was 2.3%, and this remains low due to our longstanding experience in thyroid and parathyroid surgery.

Sexual dysfunction among males and females with bipolar disorder and healthy subjects: The burden of illness severity.

OBJECTIVES: Sexual dysfunction has wide-ranging impacts on the person's functioning and quality of life, being associated with higher severity of psychiatric illnesses and poor therapeutic response. Given the paucity of data on this topic in bipolar disorder (BD), we investigated sexual functioning among males and females with BD and healthy controls (HCs) as well as whether illness severity markers and subthreshold mood symptoms were associated with sexual dysfunctions in BD patients. METHODS: The study included 80 BD outpatients and 70 HCs. Sexual functioning was evaluated using the validated, gender-specific Changes in Sexual Functioning Questionnaire (CSFQ-14). RESULTS: BD patients had a significantly poorer sexual functioning than HCs (p < 0.00001). The odds of sexual dysfunction doubled given a one-unit increase in the number of suicide attempts (adjusted OR = 2.01, 95% CI:1.23-3.55; p < 0.01) and increased by 60% for every additional hospitalization (p < 0.05). Greater illness duration was associated with arousal/orgasmic (p < 0.05) and overall sexual dysfunctions (p < 0.01). BD patients with more mixed or (hypo)manic episodes had a lower likelihood of libido loss and arousal/orgasmic disturbances (p < 0.01), respectively. Higher levels of subthreshold depressive symptoms increased by 20% the odds of sexual interest/frequency dysfunctions (p < 0.05), and up to 60% regarding orgasmic disturbances (p < 0.01). CONCLUSIONS: Sexual functioning may be a useful proxy of illness severity as well as a relevant dimension to more deeply characterize BD patients. Further studies are warranted to replicate our findings, to evaluate temporal associations between sexual dysfunctions and illness severity across the BD mood and treatment spectrums and to explore neurobiological underpinnings of these associations.

Molecular imaging of endocrine neoplasms with emphasis on 18F-DOPA PET: a practical approach for well-tailored imaging protocols.

6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-DOPA) PET/CT can be a useful tool for the detection of different neuroendocrine tumors (NETs). The main determinants of 18F-DOPA uptake and retention by NETs are related to expression of LAT1/LAT2 transporters, expression and activity of AADC and biochemical phenotype, all being intimately inter-connected to their embryological origin. In order to improve sensitivity of 18F-DOPA PET, it is of main importance to perform indivisualized imaging protocols across primaries. This review provides a practical approach for performing well-tailored imaging protocols and describes the clinical value of the recommended radiopharmaceuticals.

Sporadic Primary Pheochromocytoma: A Prospective Intraindividual Comparison of Six Imaging Tests (CT, MRI, and PET/CT Using 68Ga-DOTATATE, FDG, 18F-FDOPA, and 18F-FDA).

BACKGROUND. Recent professional society guidelines for radionuclide imaging of sporadic pheochromocytoma (PHEO) recommend 18F-fluorodihydroxyphenylala-nine (18F-FDOPA) as the radiotracer of choice, deeming 68Ga-DOTATATE and FDG to be second- and third-line agents, respectively. An additional agent, 18F-fluorodopamine (18F-FDA), remains experimental for PHEO detection. A paucity of research has performed head-to-head comparison among these agents. OBJECTIVE. The purpose of this study was to perform an intraindividual comparison of 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, CT, and MRI in visualization of sporadic primary PHEO. METHODS. This prospective study enrolled patients referred with clinical suspicion for sporadic PHEO. Patients were scheduled for 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, whole-body staging CT (portal venous phase), and MRI within a 3-month period. PET/CT examinations were reviewed by two nuclear medicine physicians, and CT and MRI were reviewed by two radiologists; differences were resolved by consensus. Readers scored lesions in terms of confidence in diagnosis of PHEO (1-5 scale; 4-5 considered positive for PHEO). Lesion-to-liver SUVmax was computed using both readers' measurements. Interreader agreement was assessed using intraclass correlation coefficients (ICCs) for SUVmax. Analysis included only patients with histologically confirmed PHEO on resection. RESULTS. The analysis included 14 patients (eight women, six men; mean age, 52.4 ± 16.8 [SD] years) with PHEO. Both 68Ga-DOTATATE PET/CT and FDG PET/CT were completed in all 14 patients, 18F-FDOPA PET/CT in 11, 18F-FDA PET/CT in 7, CT in 12, and MRI in 12. Mean conspicuity score for PHEO was 5.0 ± 0.0 for 18F-FDOPA PET/CT, 4.7 ± 0.5 for MRI, 4.6 ± 0.8 for 18F-FDA PET/CT, 4.4 ± 1.0 for 68Ga-DOTATATE PET/CT, 4.3 ± 1.0 for CT, and 4.1 ± 1.5 for FDG PET/CT. The positivity rate for PHEO was 100.0% (11/11) for 18F-FDOPA PET/CT, 100.0% (12/12) for MRI, 85.7% (6/7) for 18F-FDA PET/CT, 78.6% (11/14) for FDG PET/CT, 78.6% (11/14) for 68Ga-DOTATATE PET/CT, and 66.7% (8/12) for CT. Lesion-to-liver SUVmax was 10.5 for 18F-FDOPA versus 3.0-4.2 for the other tracers. Interreader agreement across modalities ranged from 85.7% to 100.0% for lesion positivity with ICCs of 0.55-1.00 for SUVmax measurements. CONCLUSION. Findings from this small intraindividual comparative study support 18F-FDOPA PET/CT as a preferred first-line imaging modality in evaluation of sporadic PHEO. CLINICAL IMPACT. This study provides data supporting current guidelines for imaging evaluation of suspected PHEO. TRIAL REGISTRATION. ClinicalTrials.gov NCT00004847.

Diagnostic Rechallenge with 18F-FCH PET/CT Often Allows Minimally Invasive Parathyroidectomy While Maintaining Exceptional Cure Rates.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has gained acceptance as the preferred surgical procedure for management of primary hyperparathyroidism (pHPT). Appropriate selection of patients for a MIP is a crucial step in its utilization. The aim of the study was to evaluate the role of 18F-FCH PET/CT as second-line imaging for accurately directing MIP. METHODS: This is a retrospective single-center study. Seventy-two patients with biochemical evidence of pHPT and a non-conclusive or negative first-line imaging (ultrasound and dual isotope subtraction scintigraphy) received 18F-FCH PET/CT between January 2018 and February 2020. All imaging studies were performed at our institution. Assessment of therapeutic changes and outcomes was performed. RESULTS: of the 72 patients imaged with 18F-FCH PET/CT, 54 subsequently underwent parathyroidectomy. When considering the ability of 18F-FCH PET/CT alone to predict a uniglandular disease, the sensitivity, specificity, PPV and NPV were 92.7% (95%CI: 80.1-98.5), 46.2% (19.2-74.9), PPV 87.3% (80.5-92) and NPV 61.2% (31.4-84.5), respectively. When we combined the data provided by 18F-FCH PET/CT with the data already collected from 1st line imaging we were able to complete a minimally invasive surgery in 38 of the 41 (92%) patients with a uniglandular disease. Thirteen patients (24%) had a multiglandular disease, all of them except one underwent bilateral neck exploration based on the data collected by all imaging modalities combined. Overall, cure was achieved in 53 (98%) patients. CONCLUSION: 18F-FCH PET/CT, interpreted along with first-line imaging results in selected patients, can better facilitate utilization of MIS while maintaining exceptional cure rates.

Intraindividual comparison of 18 F-FDOPA and 68 Ga-DOTATOC PET/CT detection rate for metastatic assessment in patients with ileal neuroendocrine tumours.

INTRODUCTION: In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of 68 Ga-DOTA-peptides and 18 F-fluorodihydroxyphenylalanine (18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68 Ga-DOTATOC and 18 F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs. METHODS: All patients with ileal NETs who underwent both 18 F-FDOPA and 68 Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses. RESULTS: Forty one patients with ileal NETs were evaluated. 18 F-FDOPA and 68 Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for 18 F-FDOPA vs 88% for 68 Ga-DOTATOC, P = .35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18 F-FDOPA PET/CT, and 25 (4%) by 68 Ga-DOTATOC PET/CT only. In a per-lesion analysis, 18 F-FDOPA PET/CT performed better than 68 Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P < .001). 18 F-FDOPA PET/CT detected significantly more metastases than 68 Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes. CONCLUSION: 18 F-FDOPA PET/CT seems not inferior than 68 Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18 F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68 Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.

Risk stratification of adrenal masses by [18 F]FDG PET/CT: Changing tactics.

CONTEXT: [18 F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy. OBJECTIVES: To assess the performance of Tumour standardized uptake value (SUV)max :Liver SUVmax for malignancy-risk and to build and evaluate a prediction model. DESIGN/METHODS: The cohort consisted of consecutive patients with adrenal masses evaluated by [18 F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in nonoperated cases. The performance of the previously reported cut-off for Tumour SUVmax :Liver SUVmax (>1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study). RESULTS: Sixty-four patients were evaluated; 28% of them had a Cushing's syndrome. Fifty-four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [18 F]FDG uptake. CT-derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUVmax :Liver SUVmax  > 1.5 showed a good diagnostic performance: Se = 90.0%/Sp = 92.6%/PPV = 69.2%/NPV = 98.0% and accuracy = 92.2%. A predictive model based on tumour size and tumour-to-liver uptake SUVmax ratio for malignancy-risk was validated and provides a complementary approach to the ratio. CONCLUSIONS: Tumour SUVmax :Liver SUVmax uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision-making process.

Pheochromocytoma surgery without systematic preoperative pharmacological preparation: insights from a referral tertiary center experience.

BACKGROUND: Despite significant advances in imaging and genetics, as well as surgical and anesthetic innovations, morbidity in pheochromocytoma surgery remains significant. The aim of this study was to identify the predictive factors of global and cardiovascular morbidity following unilateral laparoscopic adrenalectomy for pheochromocytoma. METHODS: We conducted a retrospective study from a unicentric cohort. All patients who underwent non-converted laparoscopic unilateral adrenalectomy for pheochromocytoma between 2000 and 2017 were included. Our patients did not systematically benefit from preoperative pharmacological preparation. It is to be noted that they never received alpha-blockers. Preoperative, intraoperative, and postoperative data during follow-ups were collected. Univariate and multivariate analyses by logistic regression were performed. RESULTS: A total of 134 patients were included. Fifty-three percent of patients did not receive preoperative pharmacological preparation (PPP) and 33% neither preoperative antihypertensives nor PPP before surgery. There was no postoperative mortality. The global morbidity was 13.4%, while cardiovascular morbidity was 4.5%. The main factors associated with global morbidity were preoperative diuretics, a medical history of stroke, and the need for pressor amines postoperatively. The main factor associated with cardiovascular morbidity was the need for pressor amines postoperatively. Predictive factors of postoperative need for pressor amines for hypotension were the tumor size, preoperative beta-blockers, and/or diuretics. CONCLUSION: In this large cohort of patients, our data revealed no mortality and low global and cardiovascular morbidity rates, showing that pheochromocytoma surgery without systematic PPP and even without preoperative antihypertensives is feasible and safe for selected patients. Our data also highlight the need for a good preoperative evaluation of the patient and the tumor, in order to optimize treatments and to help the detection of high-risk patients. This also allows us to better prevent and anticipate their possible complications.

Predicting risk factors of postoperative hypocalcemia after total thyroidectomy: is safe discharge without supplementation possible? A large cohort study.

PURPOSE: With increasing economic pressures to shorten the length of hospital stay, there has been much recent interest in studying risk factors for the development of postoperative hypocalcemia after total thyroidectomy. The aim of this study was to investigate whether serum calcium and/or PTH levels can predict post-thyroidectomy hypoparathyroidism. METHODS: From January to December 2014, 477 consecutive patients undergoing total thyroidectomy were included. Corrected calcemia and PTH were systematically performed on postoperative day 1/(POD1). Symptomatic patients were treated on POD1 or POD2 with calcium and vitamin D. RESULTS: Sixty-eight patients (14.25%) were treated for postoperative hypocalcemia. No patients with calcemia ≥ 2.16 mmol/l and PTH ≥ 1.9 pmol/l were supplemented and therefore were safely discharged on POD1 (specificity = 100%). All patients with calcemia ≤ 1.89 mmol/l were treated regardless the PTH values (n = 10) (specificity = 100%). For calcium value between 1.9 and 2.16 mmol/l with a PTH > 4.7 pmol/l, nobody was treated. With a calcemia between 1.9 and 2.16 mmol/l and a PTH > 1.9 pmol/l, 44 patients did not develop any symptom. ROC curve analysis showed that combination of Cac = 2.16 mmol/l and iPTH = 4.7 pmol/l provided a sensitivity of 97.06% and a specificity of 76.53% (p < 0.0001). We therefore propose an algorithm that would allow to 70% of patients could have been discharged on POD1 without risk of hypocalcemia or overtreatment. CONCLUSION: Combination of corrected calcemia and PTH on POD1 can efficiently predict hypocalcemia and be integrated into clinical practice for personalizing lengths of hospitalization and appropriate treatment. TRIAL REGISTRATION: ClinicalTrials.gov PRS. Unique Identifying number or registration ID: NCT04372225.

Long intergenic noncoding RNA profiles of pheochromocytoma and paraganglioma: A novel prognostic biomarker.

Many long intergenic noncoding RNAs (lincRNAs) serve as cancer biomarkers for diagnosis or prognostication. To understand the role of lincRNAs in the rare neuroendocrine tumors pheochromocytoma and paraganglioma (PCPG), we performed first time in-depth characterization of lincRNA expression profiles and correlated findings to clinical outcomes of the disease. RNA-Seq data from patients with PCPGs and 17 other tumor types from The Cancer Genome Atlas and other published sources were obtained. Differential expression analysis and a machine-learning model were used to identify transcripts specific to PCPGs, as well as established PCPG molecular subtypes. Similarly, lincRNAs specific to aggressive PCPGs were identified, and univariate and multivariate analysis was performed for metastasis-free survival. The results were validated in independent samples using RT-PCR. From a pan-cancer context, PCPGs had a specific and unique lincRNA profile. Among PCPGs, five different molecular subtypes were identified corresponding to the established molecular classification. Upregulation of 13 lincRNAs was found to be associated with aggressive/metastatic PCPGs. RT-PCR validation confirmed the overexpression of four lincRNAs in metastatic compared to non-metastatic PCPGs. Kaplan-Meier analysis identified five lincRNAs as prognostic markers for metastasis-free survival of patients in three subtypes of PCPGs. Stratification of PCPG patients with a risk-score formulated using multivariate analysis of lincRNA expression profiles, presence of key driver mutations, tumor location, and hormone secretion profiles showed significant differences in metastasis-free survival. PCPGs thus exhibit a specific lincRNA expression profile that also corresponds to the established molecular subgroups and can be potential marker for the aggressive/metastatic PCPGs.

Good clinical practice recommendations for the use of PET/CT in oncology.

Positron emission tomography/computed tomography (PET/CT) is a nuclear medicine functional imaging technique with proven clinical value in oncology. PET/CT indications are continually evolving with fresh advances made through research. French practice on the use of PET in oncology was framed in recommendations based on Standards-Options-Recommendations methodology and coordinated by the French federation of Comprehensive Cancer Centres (FNLCC). The recommendations were originally issued in 2002 followed by an update in 2003, but since then, a huge number of scientific papers have been published and new tracers have been licenced for market release. The aim of this work is to bring the 2003 version recommendations up to date. For this purpose, a focus group was set up in collaboration with the French Society for Nuclear Medicine (SFMN) to work on developing good clinical practice recommendations. These good clinical practice recommendations have been awarded joint French National Heath Authority (HAS) and French Cancer Institute (INCa) label status-the stamp of methodological approval. The present document is the outcome of comprehensive literature review and rigorous appraisal by a panel of experts, organ specialists, clinical oncologists, surgeons and imaging specialists. These data were also used for the EANM referral guidelines.

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

PURPOSE: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: A 18 F-FDOPA PET/CT study in head and neck paragangliomas.

OBJECTIVES: Nuclear imaging findings by virtue of phenotyping disease heavily depend on genetic background, metabolites, cell membrane specific targets and signalling pathways. PPGL related to succinate dehydrogenase subunits mutations (SDHx mutations) are less differentiated than other subgroups and therefore may lack to concentrate 18 F-FDOPA, a precursor of catecholamines biosynthesis. However, this 18 F-FDOPA negative phenotype has been reported mostly in SDHx-PPGL of sympathetic origin, suggesting that both genotype status and location (from sympathetic vs parasympathetic paraganglia; adrenal vs extra-adrenal) could influence 18 F-FDOPA uptake. The aim of this study was to test if SDHx drives 18 F-FDOPA uptake in presence of normal epinephrine/norepinephrine concentrations. DESIGN: Retrospective study PATIENTS: A cohort of 86 head and neck PPGL patients (including three metastatic) with normal metanephrines underwent 18 F-FDOPA PET/CT. The relationships between 18 F-FDOPA uptake and tumour genotype were evaluated. RESULTS: In nonmetastatic HNPGL (50 non-SDHx/33 SDHx), no significant difference was observed between these two groups for SUVmax (P = .256), SUVmean (P = .188), MTV 42% (P = .596) and total lesion uptake (P = .144). Metastatic HNPGL also had high elevated uptake values. CONCLUSIONS: Our results suggest that SDH deficiency or metastatic behaviour have no influence on 18 F-FDOPA uptake in HNPGL probably due to their very-well differentiation status, even at metastatic stage. The potential prognosticator value of 18 F-FDOPA uptake would need to be further explored in the setting of metastatic PPGL of sympathetic origin.

Current experts' views on precision nuclear medicine imaging of phaeochromocytoma and paraganglioma.

The EANM/SNMMI 2019 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma (PPGL) describe the current experts' views on molecular imaging in the era of precision medicine, and contain all of the information needed by nuclear physicians for performing, interpreting, and reporting the results of imaging investigations. This editorial, from a clinician's perspective, describes the first-choice radiopharmaceutical for a particular clinical setting as an important element of the revised guidelines. It also gives new evidence-based data showing the steadily growing role of nuclear imaging in PPGL phenotyping and assessment of their clinical characteristics and outcomes.