The utility of 68Gallium-DOTATATE PET/CT in the detection of von Hippel-Lindau disease associated tumors

PURPOSE: Patients with von Hippel-Lindau (VHL) disease may develop various tumors, including neuroendocrine tumors of the pancreas (PNETs) and adrenal, central nervous system hemangioblastomas, kidney tumors and more. (68)Ga-DOTATATE positron emission tomography (PET)/computerized tomography (CT) has been shown to be highly accurate for tumors with somatostatin receptors. We aimed to assess the performance of (68)Ga-DOTATATE PET/CT in patients with VHL disease. METHODS: Patients with a diagnosis of VHL were enrolled in a prospective study and underwent surveillance imaging for pancreatic lesions (n=301). The current analysis includes 73 evaluations with multiple imaging modalities of 36 patients (2.1±0.8 evaluations/patient, range 1–4) for a head-to-head comparison of (68)Ga-DOTATATE PET/CT, CT and/or MRI. In this post-hoc analysis we compared the detection rates of various imaging modalities for pancreatic NET (PNETs) and for any extrapancreatic tumors located within the scan field of CT/MRI abdomen. RESULTS: (68)Ga-DOTATATE PET/CT detected a total of 206 lesions, CT detected 208 lesions and MRI detected 94 lesions in 66, 31 and 66 scans, respectively. (68)Ga-DOTATATE PET/CT (3.4±0.1 per scan) was superior than CT (3.2±0.1 per scan, p=0.02) with a similar trend when comparing with MRI (2.8±0.1 per scan, p=0.03) in detecting lesions in any anatomic locations. CONCLUSIONS: (68)Ga-DOTATATE PET/CT had a significantly higher detection rate when compared with anatomic imaging for all lesions, and comparable detection rate for pancreatic lesions in VHL patients. Hence, given the higher accuracy and lower radiation exposure associated with (68)Ga-DOTATATE PET/CT, its potential role in the surveillance of VHL-associated lesions should be further studied

Pediatric patients with pheochromocytoma and paraganglioma should have routine preoperative genetic testing for common susceptibility genes in addition to imaging to detect extra-adrenal and metastatic tumors

Pediatric pheochromocytomas and paragangliomas are rare with limited data on the optimal management approach. The aim of this study was to determine the role of genetic testing and imaging to detect extra-adrenal and/or metastatic tumors in pediatric pheochromocytomas and paragangliomas

SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma

A staging/prognostic system has long been desired to better categorize pheochromocytoma/paraganglioma which can be very aggressive in the setting of SDHB mutations

Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple Negative Breast Cancer.

The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer. A TNBC metastasis was resected for TIL generation and whole-exome sequencing. Tandem minigenes or long 25-mer peptides encoding selected mutations were electroporated or pulsed onto autologous antigen-presenting cells, and reactivity of TIL was screened by upregulation of CD137 and IFNγ ELISPOT. The nature of the T-cell response against a unique nonsynonymous mutation was characterized. We identified 72 nonsynonymous mutations from the tumor of a patient with TNBC. CD4 and HLA-DRB1*1501-restricted TILs isolated from this tumor recognized a single mutation in (recombination signal binding protein for immunoglobulin kappa J region). Analysis of 16 metastatic sites revealed that the mutation was ubiquitously present in all samples. Breast cancers can express naturally processed and presented unique nonsynonymous mutations that are recognized by a patient's immune system. TILs recognizing these immunogenic mutations can be isolated from a patient's tumor, suggesting that adoptive cell transfer of mutation-reactive TILs could be a viable treatment option for patients with breast cancer.