Imaging in malignant germ cell tumors involving the hypothalamo-neurohypophyseal axis: the evaluation of the posterior pituitary bright spot is essential.

PURPOSE: Malignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI. METHODS: Patients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed. RESULTS: A total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4-33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p < .001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p = .004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p = .005), with an even greater delay in germinoma compared to NGGCT (p = .002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days). CONCLUSION: A loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis.

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer.

BACKGROUND: Somatostatin receptor (SSTR)-targeted PET/CT is used for patients affected with small cell lung cancer (SCLC), but the clinical impact has not been elucidated yet. We aimed to determine whether SSTR PET/CT can trigger relevant therapeutic management changes in patients with SCLC and whether those modifications achieve disease control and are associated with prolonged survival. METHODS: One hundred patients with SCLC received SSTR PET/CT. In a retrospective setting, we evaluated the diagnostic performance of PET versus CT and compared therapies before and after PET/CT to determine the impact of molecular imaging on treatment decision. We also determined the rate of disease control after therapeutic modifications and assessed survival in patients with and without changes in the therapeutic regimen. RESULTS: Relative to CT, SSTR PET alone was superior for assessing bone lesions in 19 of 39 instances (49%). Treatment was modified in 59 of 100 (59%) after SSTR PET/CT. Forty of 59 (74.6%) received systemic treatment after hybrid imaging, with the remaining 15 of 59 (25.4%) scheduled for nonsystemic therapy. In the latter group, 13 of 15 (86.7%) received local radiation therapy or active surveillance (2/15 [13.3%]). Individuals scheduled for systemic treatment after imaging received peptide receptor radionuclide therapy (PRRT) in 28 of 44 (63.6%), followed by chemotherapy in 10 of 44 (22.7%), change in chemotherapy regimen in 3 of 44 (6.8%), and initiation of tyrosine kinase inhibitor in the remaining 3 of 44 (6.8%). Among patients with modified treatment, follow-up was available in 53 subjects, and disease control was achieved in 14 of 53 (26.4%). However, neither change to systemic treatment (155 days; hazard ratio, 0.94; 95% confidence interval, 0.53-1.67) nor change to nonsystemic treatment (210 days; hazard ratio, 0.67; 95% confidence interval, 0.34-1.34) led to a prolonged survival when compared with subjects with no change (171 days, P ≥ 0.22, respectively). CONCLUSIONS: In patients with SCLC, SSTR-targeted hybrid imaging provides complementary information on the disease status. PET/CT led to management changes in 59% (mainly PRRT), achieving disease control in >26%. The high fraction of patients scheduled for PRRT may lay the foundation for combination strategies to achieve synergistic antitumor effects, for example, by combining PRRT plus recently introduced RNA polymerase II inhibitors.

Flt3L, LIF, and IL-10 combination promotes the selective in vitro development of ESAMlow cDC2B from murine bone marrow.

The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAMlow CD103- XCR1- CD172a+ CD11b+ cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL-10 (collectively named as FL10). FL10 promotes common dendritic cell progenitors (CDP) proliferation in the cultures, similar to Flt3L and CDP sorted and cultured in FL10 generate exclusively cDC2. These cDC2 express the transcription factors Irf4, Klf4, and Notch2, and their growth is reduced using BM from Irf4-/- mice, but the expression of Batf3 and Tcf4 is low. Functionally they respond to TLR3, TLR4, and TLR9 signals by upregulation of the surface maturation markers MHC II, CD80, CD86, and CD40, while they poorly secrete proinflammatory cytokines. Peptide presentation to TCR transgenic OT-II cells induced proliferation and IFN-γ production that was similar to GM-CSF-generated BM-DC and higher than Flt3L-generated DC. Together, our data support that FL10 culture of BM cells selectively promotes CDP-derived ESAMlow cDC2 (cDC2B) development and survival in vitro.