Imaging Properties and Tumor Targeting of 68Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3−4 h post injection (first six patients) and static PET scans 2 and 3−4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8−51.1] 2 h p.i. and 13.2 [range 2.5−53.8] 3−4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.

Immune Activation and Anemia Are Associated with Decreased Quality of Life in Patients with Solid Tumors.

Anemia often coincides with depression and impaired quality of life (QoL) in cancer patients. Sustained immune activation can lead to the development of anemia. Furthermore, it also may go along with changes in tryptophan and phenylalanine metabolism. The aim of our pilot study was to study the relationship between anemia, immune-mediated changes in amino acid metabolism, and the QoL and mood of cancer patients. Questionnaires to measure QoL and depression were completed by 152 patients with solid tumors. Hemoglobin, parameters of immune activation as well as tryptophan and phenylalanine metabolism were determined in the patients' sera. Anemic patients (51.7%) presented with higher inflammatory markers, and a higher tryptophan breakdown with lower tryptophan concentrations. They reported an impaired QoL and had higher depression scores. Patients with an impaired QoL (65.8%) also suffered from more fatigue and impaired physical, emotional, and social functioning. They, furthermore, presented with higher concentrations of inflammatory markers (C-reactive protein (CRP) and neopterin) as well as higher tryptophan degradation (in men) and higher phenylalanine concentrations (in women). Sixty-one patients (40.1%) had (mostly mild) depression. In these patients, a higher degree of Th1 immune activation was found. The results of our study suggest that cancer-related anemia goes along with an impaired QoL, which is also associated with immune-mediated disturbances of tryptophan and phenylalanine metabolism.

Undifferentiated round cell sarcomas with CIC-DUX4 gene fusion: expanding the clinical spectrum.

Round cell sarcomas are a heterogeneous group of mesenchymal neoplasms with overlapping morphology and immunohistochemical profile. Ewing sarcoma is the most well-known tumour in this group characterised by EWSR1/FUS rearrangements with members of the ETS family of transcription factors. Undifferentiated round cell sarcomas lacking these rearrangements, known as 'Ewing-like' sarcomas, usually show atypical clinical presentation and focal CD99 positivity. This group of tumours can be subdivided into: capicua transcriptional repressor (CIC)-rearranged sarcomas, Bcl6 corepressor (BCOR)-rearranged sarcomas, sarcomas with EWSR1 fusion to non-ETS family members and unclassified round cell sarcomas. We describe seven new cases of CIC-DUX4 rearranged sarcomas with their clinicopathological features, two of which presented in unusual locations (skin and lymph node). Patient age ranged between 23 and 54 years, three of whom were female. In five cases, aggressive behaviour was observed with rapid disease progression and lethal outcome within 15 months. One patient achieved a complete response after chemotherapy. The last patient whose tumour was located purely in the dermis demonstrated no residual tumour in the re-resection specimen, was not given any further treatment and showed no sign of disease after 24 months. Immunohistochemically, tumour cells in all cases showed focal membranous CD99 positivity, while WT1 N-/C-terminus were positive in all 5/5 cases (nuclear and/or cytoplasmic). NGS analysis revealed a CIC-DUX4 fusion in all cases. This study expands the spectrum of anatomical locations of CIC-DUX4 rearranged sarcomas, highlighting the inclusion of this rare entity in the differential diagnosis of undifferentiated tumours in various anatomical locations outside of soft tissues.