Purpose of review: This review aims to cover current MRI techniques for assessing treatment response in brain tumors, with a focus on radio-induced lesions. Recent findings: Pseudoprogression and radionecrosis are common radiological entities after brain tumor irradiation and are difficult to distinguish from real progression, with major consequences on daily patient care. To date, shortcomings of conventional MRI have been largely recognized but morphological sequences are still used in official response assessment criteria. Several complementary advanced techniques have been proposed but none of them have been validated, hampering their clinical use. Among advanced MRI, brain perfusion measures increase diagnostic accuracy, especially when added with spectroscopy and susceptibility-weighted imaging. However, lack of reproducibility, because of several hard-to-control variables, is still a major limitation for their standardization in routine protocols. Amide Proton Transfer is an emerging molecular imaging technique that promises to offer new metrics by indirectly quantifying intracellular mobile proteins and peptide concentration. Preliminary studies suggest that this noncontrast sequence may add key biomarkers in tumor evaluation, especially in posttherapeutic settings. Summary: Benefits and pitfalls of conventional and advanced imaging on posttreatment assessment are discussed and the potential added value of APT in this clinicoradiological evolving scenario is introduced.

The 2021 WHO classification of the CNS Tumors identifies as “Peripheral nerve sheath tumors” (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.

PURPOSE: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3 ^IDHmt/Codel ) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. METHODS: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3 ^IDHmt/Codel . We included patients with histologically proven O3 ^IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathologic review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. RESULTS: 305 newly diagnosed patients with O3 ^IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). CONCLUSION: In patients with newly diagnosed O3 ^IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

Background: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. Methods: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. Results: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor’s aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. Conclusions: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities.

Background: Differentiating brain radionecrosis (RN) from tumor progression (TP) is a persistent clinical difficulty. Here, we compared the diagnostic accuracy of leakage-corrected relative cerebral blood volume (rCBV) and fluid-suppressed amide proton transfer-weighted (APTw) imaging in distinguishing between RN and TP in metastases. Methods: Subjects with enlarging lesions after stereotactic radiosurgery were prospectively examined at 3T. APTw data were acquired with a 3D snapshot-gradient echo sequence. B0 and B1 inhomogeneities were corrected using the WASAB1 protocol. rCBV was calculated according to established guidelines. Image analysis was performed using Olea Sphere 3.0 software. ΔAPTw and ΔrCBV were calculated as the average signal within the lesion normalized against the average signal in the contralateral white matter. A diagnosis of TP or RN was assessed by histology or imaging at follow-up. Independent samples t-tests of ΔAPTw and ΔrCBV and the areas under the curve (AUCs) were computed. Results: Twenty-one metastases (10 RN, 11 TP) were evaluated. APTw differentiated between RN and TP (U = 120, p < 0.001), in contrast to rCBV (U = 71, p = 0.174). The AUC was 0.991 (95% CI = 0.962–1.020) for ΔAPTw, and 0.636 (95% CI = 0.352–0.921) for ΔrCBV. The optimal cutoff points were 0.4 and 2.1 for ΔAPTw and ΔrCBV, respectively. The sensitivity and specificity for RN-TP were 100% and 90% for ΔAPTw and 63.6% and 36.4% for ΔrCBV. Conclusions: Fluid-suppressed APTw metrics enabled more accurate diagnostic performances than leakage-corrected rCBV metrics in distinguishing between RN and TP. These promising results suggest that APTw imaging could valuably complement current multiparametric MRI protocols in brain metastases follow-ups.

Amide proton transfer-weighted (APTw) imaging is a non-invasive molecular MRI technique with a wide range of applications in neuroradiology and particularly neuro-oncology imaging. More than 15 years of pre-clinical experiments and clinical studies have demonstrated that APTw metrics are reproducible and reliable, leading to large-scale clinical acceptance. At present, major vendors of MRI scanners provide APTw sequences upon request. However, most neuroradiologists are unfamiliar with this advanced MRI contrast, its related metrics, and its established added value to patient care. In this manuscript, we present the APTw contrast and illustrate its clinical potential for glioma patients, before and after tumor therapy. We also show common artifacts of APTw imaging and discuss potential limitations and future refinements. Our goal is to suggest how this emerging technique can aid in diffuse gliomas work-up.