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PurposeTo assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.MethodsIn 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.ResultsSignificantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 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.Conclusions177Lu-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.

Background: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is a recognized option for treating neuroendocrine tumors and has few toxicities, except for the kidneys and bone marrow. The bone marrow dose is generally derived from a SPECT/CT image-based method with four timepoints or from a blood-based method with up to 9 timepoints, but there is still no reference method. This retrospective single-center study on the same cohort of patients compared the calculated bone marrow dose administered with both methods using mono, bi- or tri-exponential models. For the image-based method, the dose was estimated using Planetdose© software. Pearson correlation coefficients were calculated. We also studied the impact of late timepoints for both methods. Results: The bone marrow dose was calculated for 131 treatments with the blood-based method and for 17 with the image-based method. In the former, the median absorbed dose was 15.3, 20.5 and 28.3 mGy/GBq with the mono-, bi- and tri-exponential model, respectively. With the image-based method, the median absorbed dose was 63.9, 41.9 and 60.8 with the mono-, bi- and tri-exponential model, respectively. Blood samples after 24h post-injection did not evidence any change in the absorbed bone marrow dose with the bi-exponential model. On the contrary, the 6-day post-injection timepoint was more informative with the image-based model. Conclusion: This study confirms that the estimated bone marrow dose is significantly lower with the blood-based method than with the image-based method. The blood-based method with a bi-exponential model proved particularly useful, without the need for blood samples after 24h post-injection. Nevertheless, this blood-based method is based on an assumption that needs to be more validated. The important difference between the two methods does not allow to determine the optimal one to estimate the true absorbed dose and further studies are necessary to compare with biological effects. [ABSTRACT FROM AUTHOR]

Salivary gland cancers are rare tumors comprising a large group of heterogeneous tumors with variable prognosis. Their therapeutic management at a metastatic stage is challenging due to the lack of therapeutic lines and the toxicity of treatments. [177Lu]Lu-PSMA-617 (prostate-specific membrane antigen) is a vectored radioligand therapy (RLT) initially developed to treat castration-resistant metastatic prostate cancer with encouraging results in terms of efficacy and toxicity. Many malignant cells could be treated with [177Lu]Lu-PSMA-617 as long as they express PSMA as a consequence of androgenic pathway activation. RLT may be used when anti-androgen hormonal treatment has failed, particularly in prostate cancer. [177Lu]Lu-PSMA-617 has been proposed in certain salivary gland cancers, though the expression of PSMA is demonstrated by a significant uptake using [68Ga]Ga-PSMA-11 PET scan. This theranostic approach could be a new therapeutic option, warranting prospective investigation in a larger cohort. We review the literature on this subject and offer a clinical illustration of compassionate use in France as a perspective for administering [177Lu]Lu-PSMA-617 in salivary gland cancer. [ABSTRACT FROM AUTHOR]

Purpose: NETTER-R aimed to determine the efficacy, safety and tolerability of 177Lu-DOTATATE in patients with progressive, advanced pancreatic neuroendocrine tumours (panNETs) using retrospective real-world data from multiple sites. Methods: This international study retrospectively included patients with panNETs treated with 177Lu-DOTATATE. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included overall survival (OS), safety and tumour response. Results: In total, 110 patients with panNETs were studied; 65.5% received a cumulative dose of 177Lu-DOTATATE 29.6 GBq ± 10% (median: 7.4 GBq). In 62 patients with available RECIST v1.1 tumour response, the median PFS was 24.8 months (95% confidence interval [CI]: 17.5–34.5), and the objective response rate was 40.3% (95% CI: 28.1–53.6); all responses were partial. With a median follow up of 24.5 months (range: 2.0–123.4 months) after the first cycle of 177Lu-DOTATATE, the median OS in the full analysis set (n = 110) was 41.4 months (95% CI: 28.6–50.2). PFS (hazard ratio [HR]: 3.672; p = 0.0009) and OS (HR: 3.360; p < 0.0001) were longer in patients who received no chemotherapy prior to 177Lu-DOTATATE than those who did. No treatment-emergent adverse events (TEAEs) led to treatment discontinuation. Grade 3 anaemia, lymphopenia and thrombocytopenia occurred in 0.9%, 5.4% and 0.9% of patients, respectively. No acute leukaemia or myelodysplastic syndrome was reported. Six patients (5.5%) had renal TEAEs. All renal grade ≥ 3 events were transient and did not lead to treatment modification. Conclusions: These results reinforce the role of 177Lu-DOTATATE for the treatment of patients with advanced, somatostatin receptor-positive panNETs. [ABSTRACT FROM AUTHOR]

Spirometric gating devices (SGDs) can measure the respiratory signal with high temporal resolution and accuracy. The primary objective of this study was to assess the feasibility and tolerance of a gated lung PET/CT acquisition using an SGD. The secondary objective was to compare the technical quality, accuracy, and interoperability of the SGD with that of a standard respiratory gating device, Real-Time Position Management (RPM), based on measurement of vertical thoracoabdominal displacement. Methods: A prospective phase I monocentric clinical study was performed on patients undergoing 18F-FDG PET/CT for assessment of a solitary lung nodule, staging of lung malignancy, or planning of radiotherapy. After whole-body PET/CT, a centered gated acquisition of both PET and CT was simultaneously obtained with the SGD and RPM during normal breathing. Results: Of the 46 patients who were included, 6 were prematurely excluded (1 because of hyperglycemia and 5 because of distant metastases revealed by whole-body PET/CT, leading to an unjustified extra gated acquisition). No serious adverse events were observed. Of the 40 remaining patients, the gated acquisition was prematurely stopped in 1 patient because of mask discomfort (2.5%; confidence interval [CI], 0.1%-13.2%). This event was considered patient tolerance failure. The SGD generated accurately gated PET/CT images, with more than 95% of the breathing cycle detected and high temporal resolution, in 34 of the 39 patients (87.2%; 95% CI, 60.0%-100.0%) and failed to generate a biologic tumor volume in 1 of 21 patients with increased 18F-FDG uptake (4.8%; 95% CI, 0.1%-26.5%). The quality and accuracy of respiratory signal detection and synchronization were significantly better than those obtained with RPM (P < 0.05). Conclusion: This trial supports the use of an SGD for gated lung PET/CT because of its high patient tolerance and accuracy. Although this technique seems to technically outperform RPM for gated PET/CT, further assessment of its superiority and the clinical benefit is warranted. We believe that this technique could be used as a gold standard to develop innovative approaches to eliminate respiration-induced blurring artifacts. [ABSTRACT FROM AUTHOR]

Background and Objective: 177Lu-Dotatate is a radio-labeled analog of somatostatin used in the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. In order to prevent nephrotoxic effects of 177Lu-Dotatate a co-infusion of amino acids (AA) is administered, resulting in a decrease in tubular renal reabsorption of 177Lu-Dotatate. This study aimed to quantify the impact of AA co-infusion on the pharmacokinetics of 177Lu-Dotatate in cancer patients and to evaluate its relationship with toxicity during the first treatment cycle (C1).Methods: 7.4 GBq of 177Lu-Dotatate was administered to 42 patients over a 30-min intravenous infusion. Infusion of AA started 2 h before and continued for 6 h after the infusion of 177Lu-Dotatate. Radioactivity-time data (n = 346) were analyzed using NONMEM® (version 7.2.0).Results: 177Lu-Dotatate pharmacokinetics was best described by a three-compartment model with first-order elimination. AA co-infusion had a significant effect ('fixed effect') on 177Lu-Dotatate pharmacokinetics, with a mean value of 1.5-fold (95% confidence interval 1.03-1.97) increase in the elimination rate constant (k10) from 0.204 to 0.306 h-1, but this AA co-infusion effect was associated with a large inter-individual variability (IIV) of 104%. The individual k10 values increased during concomitant AA infusion by a factor ranging from 1.01 to 21.3 for 27 patients, whereas the opposite effect was observed in 15 patients (range 0.36-0.99) of whom seven had a k10 value lower than 0.85. This variability in AA effect contributed to the variability in 177Lu-Dotatate plasma exposure (area under the concentration-time curve from time zero to Day 15 for C1 [AUCDay15]) that correlated with lymphopenia observed at Day 15 (p = 0.004).Conclusions: A substantial effect of AA co-infusion on 177Lu-Dotatate pharmacokinetics was shown but was associated with high IIV, contributing to IIV in hematological toxicity. [ABSTRACT FROM AUTHOR]

Aim: To prospectively evaluate the clinical impact and the diagnostic performance of FCH-PET/CT in patients with occult biochemical recurrence of prostate cancer (PCa). Materials and methods: Results of 179 patients (mean PSA = 7.5ng/mL) with negative/inconclusive results of pelvic-MRI and of bone-scintigraphy were analysed. To determine the impact of FCH-PET/CT on diagnostic thinking and on patient management, the referring physicians prospectively filled-in a 1st and 2nd questionnaire related to patient’s planned management before and after FCH-PET/CT. Based on data from a 6-month follow-up after FCH-PET/CT, an independent assessor blinded to results of FCH-PET/CT determined the adequacy of management changes motivated by FCH-PET/CT. Results: FCH-PET/CT localised foci evocative of recurrent PCa in 59% (105/179) of patients. Results of FCH-PET/CT motivated a change in scheduled patient management in 56% (100/179) of patients; which was considered as adequate in 89% (89/100) of patients. FCH-PET/CT also led to the detection of lung cancer in two patients. Conclusion: FCH PET/CT is a powerful tool to localise the sites of occult biochemical recurrence of PCa, leading to an adequate management change in half of patients. [ABSTRACT FROM AUTHOR]