Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors.

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. METHODS: A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated tumors, and 76 (73.1%) had well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as histologic grade (G1, G2, or G3, for low-grade [well differentiated], intermediate-grade [moderately differentiated], and high-grade [poorly differentiated], respectively), chromogranin A, and proliferation index (Ki-67). RESULTS: The 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 tumors and lower for G3 tumors (P = 0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different grades (P = 0.38). The Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P = 0.004), without significance differences in 18F-FDG SUVmax Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18F-FDG (P = 0.037) and 68Ga-DOTATATE (P = 0.047). Overall survival declined rapidly with increasing grade (P = 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. CONCLUSION: 18F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax relates to grade and Ki-67 and can be used prognostically.

The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom.

UNLABELLED: (68)Ga-DOTATATE PET/CT scanning is a widely accepted method for imaging of neuroendocrine tumors. This cross-sectional study was performed to review the first 8 y of patient data from a large (68)Ga-DOTATATE PET/CT database in order to establish the impact of the modality on patient treatment and survival. METHODS: Demographic data, clinical outcome, survival, and change in management after (68)Ga-DOTATATE PET/CT were evaluated. RESULTS: Between May 2005 and August 2013, 1,258 (68)Ga-DOTATATE PET/CT scans were obtained in 728 patients with confirmed or suspected neuroendocrine tumors. In most patients, the primary site was located in the midgut (26.4%). Analysis of NET grading in patients with known histopathologic data revealed that 35.7% had NET grade G1, 12.2% G2, and 8.7% G3. The most common indications for (68)Ga-DOTATATE PET/CT were follow-up (24.4%) and initial tumor staging (23.4%). Of the 1,258 (68)Ga-DOTATATE PET/CT scans completed, 75.7% were positive and 24.3% negative; there were 14 false-positive and 29 false-negative scans. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97%, 95.1%, 96.6%, 98.5%, and 90.4%, respectively. In 40.9% of patients, the treatment plan was changed after the scans, owing mainly to new, unexpected findings. Statistically significant differences in survival were shown between patients with G1, G2, and G3 grade tumors (P < 0.0001) and also between patients with bone metastasis versus patients with soft-tissue metastasis (P < 0.0001). CONCLUSION: (68)Ga-DOTATATE PET/CT scanning is safe and influences management in a large proportion of patients. Prognosis was dependent on tumor grade, and the presence of bone metastasis was associated with worse overall survival.

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor.

PURPOSE: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type. EXPERIMENTAL DESIGN: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43). RESULTS: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%). CONCLUSIONS: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival.

Role of interferon-alpha in patients with neuroendocrine tumors: a retrospective study.

BACKGROUND/AIM: Interferon alpha (IFNα) is used sparingly in the management of neuroendocrine tumors (NETs) due to toxicity and perceived limited efficacy. Other medical therapeutic options include somatostatin analogues and molecular-targeted agents, as well as chemotherapy and radionuclide targeted-therapy. The aim of the present study was to perform a retrospective analysis of patients treated with IFNα. PATIENTS AND METHODS: Patients were identified from the NET database. Radiological, biochemical and symptomatic response were assessed. Progression-free survival (PFS), adverse events and toxicities were recorded. RESULTS: Thirty-five patients were treated with IFNα, with a mean age of 60.1 (range=38-85) years; eight patients (23%) withdrew before 3 months, one (3%) had complete response; there was one partial response; 25 patients (71%) had at least three months of stable disease. The median PFS was 25 months. CONCLUSION: IFNα demonstrated efficacy and was reasonably tolerated. IFNα may still have a role in small-volume diffuse disease, in syndromic patients where there is resistance to somatostatin analogue, or as a bridge to other therapies.