Peptide Receptor Radionuclide Therapy or Everolimus in Metastatic Neuroendocrine Tumors: The SeqEveRIV Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.

Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.

Safety and Efficacy of Peptide-Receptor Radionuclide Therapy in Elderly Neuroendocrine Tumor Patients.

Peptide receptor radionuclide therapy (PRRT) is a well-established treatment in somatostatin receptor-expressing neuroendocrine tumours (NETs). The safety and efficacy of PRRT in >79 years old patients (EP) have not been systematically investigated. All patients with inoperable/metastatic/progressive G1/G2 NET, >79 years (EP), treated with PRRT at the University Hospital of Basel between 2006 and 2018, were enrolled in this retrospective matched cohort study. Each patient was manually matched with ≥1 younger patient (YP = 60-70 years). The primary endpoint was toxicity. Toxicity (subacute, long-term) was graded according to the criteria for adverse events (CTCAE) v5.0. All toxicity grades ≥ 3, or whose delta (Δ) to baseline were ≥2, were considered significant. The odds ratio (OR) for developing toxicity was tested for non-inferiority of EP vs. YP. Clinical response to PRRT and overall survival (OS) were assessed as secondary outcome measures. Forty-eight EP and 68 YP were enrolled. Both cohorts were balanced regarding median time since diagnosis, tumour location, grading, treatment scheme, and baseline biochemical parameters, except for eGFR (EP: 61 ± 16 vs. YP: 78 ± 19; mL/min/1.73 m2). Twenty-two grade ≥ 3 or Δ ≥ 2 subacute hematotoxicities occurred in 10 EP (10.3% of cycles) and 37 in 19 YP (11.6% of cycles; p = NS). Long-term grade ≥ 3 renal toxicity occurred in 7 EP and 2 YP (p = NS). The median OS was 3.4 years (EP) vs. 6.0 years (YP), HR: 1.50 [0.75, 2.98], p = NS. PRRT is a valid therapeutic option in elderly NET patients with similar toxicity and non-inferior survival compared to matched younger patients.

Updated Trends in Imaging Practices for Pancreatic Neuroendocrine Tumors (PNETs): A Systematic Review and Meta-Analysis to Pave the Way for Standardization in the New Era of Big Data and Artificial Intelligence.

PURPOSE: Medical imaging plays a central and decisive role in guiding the management of patients with pancreatic neuroendocrine tumors (PNETs). Our aim was to synthesize all recent literature of PNETs, enabling a comparison of all imaging practices. METHODS: based on a systematic review and meta-analysis approach, we collected; using MEDLINE, EMBASE, and Cochrane Library databases; all recent imaging-based studies, published from December 2014 to December 2019. Study quality assessment was performed by QUADAS-2 and MINORS tools. RESULTS: 161 studies consisting of 19852 patients were included. There were 63 'imaging' studies evaluating the accuracy of medical imaging, and 98 'clinical' studies using medical imaging as a tool for response assessment. A wide heterogeneity of practices was demonstrated: imaging modalities were: CT (57.1%, n=92), MR (42.9%, n=69), PET/CT (13.3%, n=31), and SPECT/CT (9.3%, n=15). International imaging guidelines were mentioned in 2.5% (n=4/161) of studies. In clinical studies, imaging protocol was not mentioned in 30.6% (n=30/98) of cases and only mentioned imaging modality without further information in 63.3% (n=62/98), as compared to imaging studies (1.6% (n=1/63) of (p<0.001)). QUADAS-2 and MINORS tools deciphered existing biases in the current literature. CONCLUSION: We provide an overview of the updated current trends in use of medical imaging for diagnosis and response assessment in PNETs. The most commonly used imaging modalities are anatomical (CT and MRI), followed by PET/CT and SPECT/CT. Therefore, standardization and homogenization of PNETs imaging practices is needed to aggregate data and leverage a big data approach for Artificial Intelligence purposes.

Successful and Safe Treatment With 177Lu-DOTATATE (Lutathera) of Progressive Metastatic Pancreatic Neuroendocrine Tumor Under Hemodialysis.

Lu-DOTATATE is an effective treatment for inoperable metastatic well-differentiated pancreatic neuroendocrine tumors. There are no guidelines for patients with terminal renal failure. We present the case of a 74-year-old woman who received different lines of treatment: analogs of somatostatin, chemotherapy, a first series of peptide receptor radionuclide therapy (PRRT), and finally chemoembolization. Because of persistent hepatic progression, a safe and successful administration of 4 cycles of a second series of PRRT under hemodialysis was administered. Patient was in scintigraphic complete remission at 12 months with normal hematological parameters at 12 and 30 months after PRRT.

Diagnosis of an intestinal mucormycosis 'fungus ball' located with PET/CT with [18F] FDG-PET/CT.

Mucormycosis is a life-threatening infection with most commonly rhino-orbital-cerebral and pulmonary syndromes that mostly occurs in immunocompromised patients. FDG-PET/CT emerged as a sensitive non-invasive tool to identify systemic mucormycosis. We present a 59-year-old woman for whom a PET/CT with 18F-FDG was performed in search of a primary location of mucormycosis with non-contributive conventional workup. A large left abdominal mass was seen, compatible with a fungus ball, with intense parietal uptake and without any central uptake. The localization of the infection provided a target for surgery and permitted to adapt the therapeutic strategy. After resection, the final diagnosis was consistent with mucormycosis. To our knowledge, this is the first report of a PET/CT image with FDG showing an intestinal fungus ball. PET/CT with 18F-FDG may contribute to the management of patients with fungal infections of unknown origin.

Evaluation of 2 diuretic 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography imaging protocols for intrapelvic cancer.

BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important part in the oncological evaluation of the abdomen and pelvis, but the interpretation and quantification is often hampered by intense physiological urinary activity. We evaluate 2 different diuretic imaging protocols by comparing intensity of urinary activity and we look at the impact of multiple variables on the final urinary activity. METHODS: Comparative analysis of 102 patients (median age: 64) having intrapelvic carcinoma. After full body acquisition, 58 patients were administered 20 mg of furosemide 90 min post injection of FDG (P90). For 44 patients, 20 mg of furosemide was administered 30 min post injection of FDG (P30). Comparisons between groups were performed using the Mann-Whitney Test and χ2. The BMI, creatinine, clearance, age, injected activity, diuretic protocol, gender and glycemia were evaluated with multivariate analysis for their impact on the final urinary activity. RESULTS: Concerning the comparison of the urinary activity we observe a significant difference (P=0.0029) between P90 and P30 for the SUVmax (median 4.3 [range 1.6: 17.7] vs. 6.0 [range 2.9: 15.1]), and for the SUVmean (P<0.001) (median 2.4 [range 1.1; 9.9] vs. 3.8 [range 2.0; 10.1]). For 2 patients of P30, the acquisition was interrupted because the patient needed to void. Multivariate analysis shows that creatinine and creatinine clearance do not have a significant independent impact on the final bladder activity. CONCLUSIONS: By comparing the 2 diuretic imaging protocols, we found a significant lower urinary activity for the P90 protocol and the regression decision tree shows that the P90 protocol is mostly superior. The P30 protocol, which seems to be less well tolerated, is adequate in the group of patients with an injected activity of less than 240 MBq and older than 65 years, if P90 is not feasible. For most patients with injected activity ≥240 MBq or BMI of ≥25 and a glycemia >120 mg/dL, a significant amount of residual urinary activity remains for both protocols.

Oncocytic Adenoma of Thyroid Incidentally Detected by 18F-Fluorocholine PET/CT.

A 58-old-man underwent (18)F-fluorocholine PET/CT for restaging of prostate cancer because of a rising level of prostate-specific antigen.( 18)F-fluorocholine showed no significant tracer uptake at the site of the prostatectomy or the pelvic lymph nodes. Incidental high tracer uptake was observed in a 26 × 23 mm left thyroid nodule. A benign tumor of the thyroid (oncocytic adenoma of thyroid) was diagnosed after left loboisthmectomy.

Comparison of an alternative and existing binning methods to reduce the acquisition duration of 4D PET/CT.

PURPOSE: Respiratory motion is a source of artifacts that reduce image quality in PET. Four dimensional (4D) PET/CT is one approach to overcome this problem. Existing techniques to limiting the effects of respiratory motions are based on prospective phase binning which requires a long acquisition duration (15-25 min). This time is uncomfortable for the patients and limits the clinical exploitation of 4D PET/CT. In this work, the authors evaluated an existing method and an alternative retrospective binning method to reduce the acquisition duration of 4D PET/CT. METHODS: The authors studied an existing mixed-amplitude binning (MAB) method and an alternative binning method by mixed-phases (MPhB). Before implementing MPhB, they analyzed the regularity of the breathing patterns in patients. They studied the breathing signal drift and missing CT slices that could be challenging for implementing MAB. They compared the performance of MAB and MPhB with current binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. RESULTS: MPhB can be implemented depending on an optimal phase (in average, the exhalation peak phase -4.1% of the entire breathing cycle duration). Signal drift of patients was in average 35% relative to the breathing amplitude. Even after correcting this drift, MAB was feasible in 4D CT for only 64% of patients. No significant differences appeared between the different binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. The authors also determined the inaccuracies of MAB and MPhB to measure the maximum amplitude of tumor motion with three bins (less than 3 mm for movement inferior to 12 mm, up to 6.4 mm for a 21 mm movement). CONCLUSIONS: The authors proposed an alternative binning method by mixed-phase binning that halves the acquisition duration of 4D PET/CT. Mixed-amplitude binning was challenging because of signal drift and missing CT slices. They showed that more than three bins were necessary for a more accurate measurement of the maximum amplitude of the tumor motion. However, the current 4D-CT technology limits the increase of the number of bins in 4D PET/CT because of missing CT slices. One can reconstruct 4D PET images with more bins but without attenuation/scatter correction.