Update to the RANO working group and EANO recommendations for the clinical use of PET imaging in gliomas.

This Policy Review provides recommendations for the use of PET imaging in patients with gliomas and represents a joint effort of the Response Assessment in Neuro-Oncology (RANO) working group for PET and the European Association for Neuro-Oncology. The initial guideline was published in 2016, and summarised the previously established clinical benefit of PET with radiolabelled glucose and amino acid tracers in patients with gliomas. Since then, numerous additional studies have been published on this topic, focusing on differential diagnosis, prediction of molecular information, and prognostication.

PSMA radioligand uptake correlates with PSMA expression in high-grade glioma and brain metastasis: insights from a prospective PET-MRI guided multiregional biopsy study.

Purpose: Prostate-specific membrane antigen (PSMA) is a potential target for radioligand therapy (RLT) in neuro-oncology. This study investigates the direct relation between [Ga]Ga-PSMA-11 uptake on PET and PSMA expression in the tumour micro-environment of high-grade glioma (HGG) and brain metastasis (BM).

Methods: Twelve patients with HGG (glioblastoma n = 6, oligodendroglioma n = 1), or BM (lung- n = 4, breast cancer n = 1), underwent PET-MRI after intravenous [Ga]Ga-PSMA-11 injection (1.

The Complexity of Malignant Glioma Treatment.

Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role.

FAPI PET in the Management of Lung Tumors.

Fibroblast activation protein (FAP), selectively expressed on activated fibroblasts in proliferating tissues, is emerging as a promising target in oncology. In lung cancer, the leading cause of cancer-related deaths worldwide, [F]FDG PET/CT has set the bar high and earned widespread recognition in clinical guidelines for its essential role in staging and follow-up. Yet, FAP-targeted imaging agents like FAPI PET/CT have demonstrated significant potential due to their high tumor specificity, rapid tracer uptake, and low background activity.

Treatment-related survival patterns in diffuse intrinsic pontine glioma using a historical cohort: A report from the European Society for Pediatric Oncology DIPG/DMG Registry.

Background: Our aim is to investigate the association of treatment with survival in patients with diffuse intrinsic pontine glioma (DIPG) by examining 6 historical treatment paths.

Methods: We retrospectively analyzed data from 409 patients with radiologically centrally reviewed DIPG, sourced from the German Society of Pediatric Oncology and Hematology HIT-HGG trial database and the SIOPE-DIPG/DMG Registry. Survival outcomes were estimated using the Kaplan-Meier method, and univariable and multivariable Cox proportional hazard models were estimated to study treatment effects.

Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in atypical teratoid/rhabdoid tumors.

Atypical teratoid/rhabdoid tumors (ATRTs) are highly malignant embryonal tumors of the central nervous system with a dismal prognosis. Using a newly developed and validated patient-derived ATRT culture and xenograft model, alongside a panel of primary ATRT models, we found that ATRTs are selectively sensitive to the nucleoside analog gemcitabine. Gene expression and protein analyses indicate that gemcitabine treatment causes the degradation of sirtuin 1 (SIRT1), resulting in cell death through activation of nuclear factor κB (NF-κB) and p53.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established.

Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.

Results: Median overall survival (OS) was 15.

[F]FET PET/MRI: An Accurate Technique for Detection of Small Functional Pituitary Tumors.

Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain.

International consensus on the initial diagnostic workup of cancer of unknown primary.

Background: Although the incidence of Cancer of Unknown Primary (CUP) is estimated to be 1-2 % of all cancers worldwide, no international standards for diagnostic workup are yet established. Such an international guideline would facilitate international comparison, provide adequate incidence and survival rates, and ultimately improve care of patients with CUP.

Methods: Participants for a four round modified Delphi study were selected via a CUP literature search in PubMed and an international network of cancer researchers.

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances.

Introduction: There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer "FAPI" has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells.

Methods: We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512).

Pediatric high-grade gliomas and the WHO CNS Tumor Classification-Perspectives of pediatric neuro-oncologists and neuropathologists in light of recent updates.

Background: The WHO Classification of Tumors of the Central Nervous System has undergone major restructuring. Molecularly defined diagnostic criteria were introduced in 2016 (revised 4th edition) and expanded in 2021 (5th edition) to incorporate further essential diagnostic molecular parameters. We investigated potential differences between specialists in perception of these molecularly defined subtypes for pediatric high-grade gliomas (pedHGG).

Noninvasive differentiation of molecular subtypes of adult nonenhancing glioma using MRI perfusion and diffusion parameters.

Background: Nonenhancing glioma typically have a favorable outcome, but approximately 19-44% have a highly aggressive course due to a glioblastoma genetic profile. The aim of this retrospective study is to use physiological MRI parameters of both perfusion and diffusion to distinguish the molecular profiles of glioma without enhancement at presentation.

Methods: Ninety-nine patients with nonenhancing glioma were included, in whom molecular status (including 1p/19q codeletion status and IDH mutation) and preoperative MRI (T2w/FLAIR, dynamic susceptibility-weighted, and diffusion-weighted imaging) were available.

Transitioning to molecular diagnostics in pediatric high-grade glioma: experiences with the 2016 WHO classification of CNS tumors.

Background: Pediatric neuro-oncology was profoundly changed in the wake of the 2016 revision of the WHO Classification of Tumors of the Central Nervous System. Practitioners were challenged to quickly adapt to a system of tumor classification redefined by molecular diagnostics.

Methods: We designed a 22-question survey studying the impact of the revised WHO classification on pediatric high-grade glioma.

The neurovascular unit in diffuse intrinsic pontine gliomas.

Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a median overall survival of eleven months. Lack of chemotherapy efficacy may be related to an intact blood-brain barrier (BBB). In this study we aim to investigate the neurovascular unit (NVU) in DIPG patients.

A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma.

Introduction: This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG).

Methods: Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year.

Complementary and alternative medicine in children with diffuse intrinsic pontine glioma-A SIOPE DIPG Network and Registry study.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is a rare and aggressive childhood brainstem malignancy with a 2-year survival rate of <10%. This international survey study aims to evaluate the use of complementary and alternative medicine (CAM) in this patient population.

Methods: Parents and physicians of patients with DIPG were asked to participate in a retrospective online survey regarding CAM use during time of illness.

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors.

This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood-brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy.

Correction to: A suggestion to introduce the diagnosis of "diffuse midline glioma of the pons, H3 K27 wildtype (WHO grade IV)".

The citation of the original publication in PubMed contains an error. The seventh author name is wrongly cited.