Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

Utility of transabdominal ultrasound for surveillance of known pancreatic cystic lesions: prospective evaluation with MRI as reference standard.

OBJECTIVES: To prospectively assess the utility of transabdominal ultrasound in surveillance of known pancreatic cystic lesions (PCL) using same day MRI as reference standard. METHODS: In an IRB-approved study with written informed consent, patients with known PCL underwent pancreas US on same day as surveillance MRI. US was performed blinded to same date MRI results. Transverse (TR), antero-posterior (AP), cranio-caudal (CC), and longest any plane diameter, were measured for each PCL at US and MRI. Visualization was correlated with patient (weight, abdominal diameter, thickness of abdominal fat, sex) and cyst (location, size, internal complexity) factors. RESULTS: 252 PCLs evaluated in 57 subjects (39 females; mean age 67 (range 39-86) yrs). Mean maximum PCL diameter 8.5 (range 2-92) mm. US identified 100% (5/5) of cysts ≥3 cm; 92% (12/13) ≥2 and <3 cm; 78% (43/55) ≥1 and <2 cm; 35% (27/78) ≥5 mm and <1 cm; and 16% (16/101) <5 mm. US visualization correlated with PCL location (<0.0001), size (p < 0.0001), patient gender (p = 0.005), participation of attending radiologist (p = 0.03); inversely with patient weight (p = 0.012) and AP abdominal diameter (p = 0.01). CONCLUSION: Many PCLs are visualized and accurately measured at follow-up with transabdominal ultrasound. Visualization correlates with lesion size, location, patient sex, weight, and abdominal diameter.

Clinical and cross-sectional imaging features of spontaneous pancreatic pseudocyst-portal vein fistula.

PURPOSE: To evaluate clinical and imaging features of pancreatic pseudocyst-portal vein fistula (PPVF). METHODS: Patients with evidence of PPVF on CT/MRI were included. Clinical presentation, outcomes, imaging appearance of the portal vein were recorded. RESULTS: 75% of patients developed portal hypertension, 62% cavernous transformation of the portal vein and 25% portal biliopathy. PPVF presented on CT as fluid-attenuated portal vein, and on MRI as T2-weighted hyperintense fluid-filled portal vein. PPVF was misdiagnosed as portal vein thrombosis in all patients who underwent CT as initial examination. CONCLUSIONS: Whenever PPVF is suspected on CT, MRI can be helpful to achieve accurate diagnosis and avoid unnecessary interventions.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition.

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations.

Nemaline myopathy (NM) is the most common of several congenital myopathies that present with skeletal muscle weakness and hypotonia. It is clinically heterogeneous and the diagnosis is confirmed by identification of nemaline bodies in affected muscles. The skeletal muscle alpha-actin gene (ACTA1) is one of five genes for thin filament proteins identified so far as responsible for different forms of NM. We have screened the ACTA1 gene in a cohort of 109 unrelated patients with NM. Here, we describe clinical and pathological features associated with 29 ACTA1 mutations found in 38 individuals from 28 families. Although ACTA1 mutations cause a remarkably heterogeneous range of phenotypes, they were preferentially associated with severe clinical presentations (p < 0.0001). Most pathogenic ACTA1 mutations were missense changes with two instances of single base pair deletions. Most patients with ACTA1 mutations had no prior family history of neuromuscular disease (24/28). One severe case, caused by compound heterozygous recessive ACTA1 mutations, demonstrated increased alpha-cardiac actin expression, suggesting that cardiac actin might partially compensate for ACTA1 abnormalities in the fetal/neonatal period. This cohort also includes the first instance of an ACTA1 mutation manifesting with adult-onset disease and two pedigrees exhibiting potential incomplete penetrance. Overall, ACTA1 mutations are a common cause of NM, accounting for more than half of severe cases and 26% of all NM cases in this series.