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 ( 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

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 ( 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

[18F]FDG positron emission tomography/computed tomography and multidetector computed tomography roles in thymic lesion treatment planning

Rationale: Thymic masses may represent an unsolved diagnostic problem which often require surgical procedures for an accurate staging. A non-invasive way to determine the nature of thymic lesions would help identify the patients which are true candidates for surgery. Our retrospective study aims to assess multidetector computed tomography and 2-[18F]fluoro-2-deoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) capacity to distinguish benign from malignant thymic lesions. Methods: Helical multidetector CT (MDCT) and [18F]FDG-PET/CT of twenty consecutive patients presenting with a thymic mass at our Institute were retrospectively analyzed. MDCT scans were focused on morphologic features and invasiveness characteristics. Qualitative and semi-quantitative analyses by maximum standardized uptake value corrected for body weight (SUVbw max) were performed on [18F]FDG-PET/CT. In all cases, readers were blinded to pathology findings. Both imaging techniques were correlated to final pathology. Student's t-test was performed on SUVbw max stratified for thymic epithelial tumors. Results: In the group of benign lesions MDCT correctly identified well-defined margins of masses in 8 out of 8 patients whereas [18F]FDG-PET/CT was negative in 7 out of 8 patients. Among malignant lesions MDCT revealed mediastinum fat or infiltration of adjacent organs in 10/12 patients. On the other hand [18F]FDG-PET/CT showed increased radiotracer uptake in 12/12 patients. Conclusions: MDCT and [18F]FDG-PET/CT alone are not able to differentiate the nature of thymic lesions. However, they are two non-invasive complementary techniques which can be used to differentiate benign from high-risk malignant thymic lesions. These findings should be taken into account before surgery is performed as a diagnostic procedure. © 2008 Elsevier Ireland Ltd. All rights reserved

Role of [18F]FDG-PET/CT after radiofrequency ablation of liver metastases: Preliminary results

Purpose: Focal metastasis may be treated with radiofrequency ablation (RFA), a low invasive method yet limited by the lack of direct evidence of radicality of treatment. We, hereby, aimed at assessing the role of positron emission tomography-computed tomography (PET/CT) with fluoride radiolabeled deoxy-glucose ([18F]FDG) in RFA treatment success evaluation and early diagnosis of local relapse of liver metastasis after RFA procedure. Methods: RFA was performed in nine patients on 12 liver metastasis, serially imaged through [18F]FDG-PET/CT and multidetector CT (MDCT) at 1, 3, 6, and 9 months after treatment. Eight lesions were also scanned with [ 18F]FDG-PET/CT at 1 week after treatment. Imaging analyses were performed on 47 [18F]FDG-PET/CT and 51 MDCT. Imaging reading outcomes were compared to each other and to biopsy tissue results when available. Results: In one case, [18F]FDG-PET/CT revealed radiotracer uptake at RFA site a week after procedure. Negative concordant outcome was obtained on eight lesions at 1 month after RFA, on eight cases at 3 months, on four at 6 months, and on two cases at 9 months. Extra-liver (peritoneal) disease was detected in one case by both [18F]FDG-PET/CT and MDCT. In seven cases, [18F]FDG-PET/CT revealed the presence of local recurrence earlier than MDCT. In no cases did MDCT detect local relapse earlier than [ 18F]FDG-PET/CT. Conclusion: [18F]FDG-PET/CT may detect RFA treatment failure as well as local relapse after RFA earlier than MDCT. © 2008 Springer-Verlag