PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0): a report of the RANO group.

Response Assessment in Neuro-Oncology (RANO) response criteria have been established and were updated in 2023 for MRI-based response evaluation of diffuse gliomas in clinical trials. In addition, PET-based imaging with amino acid tracers is increasingly considered for disease monitoring in both clinical practice and clinical trials. So far, a standardised framework defining timepoints for baseline and follow-up investigations and response evaluation criteria for PET imaging of diffuse gliomas has not been established. Therefore, in this Policy Review, we propose a set of criteria for response assessment based on amino acid PET imaging in clinical trials enrolling participants with diffuse gliomas as defined in the 2021 WHO classification of tumours of the central nervous system. These proposed PET RANO criteria provide a conceptual framework that facilitates the structured implementation of PET imaging into clinical research and, ultimately, clinical routine. To this end, the PET RANO 1.0 criteria are intended to encourage specific investigations of amino acid PET imaging of gliomas.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

Background: The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. Methods: An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. Results: The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). Conclusion: The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.

Cilengitide: an RGD pentapeptide ανß3 and ανß5 integrin inhibitor in development for glioblastoma and other malignancies.

Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks ανß3 and ανß5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial [CENTRIC]) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology.

Computer-based assessment of cognitive functions in brain tumor patients.

NeuroCogFX is a short yet comprehensive computer-based neuropsychological battery of tests developed to investigate neurological patients for cognitive dysfunction after potentially neurotoxic therapy. NeuroCogFX had been standardized in a group of 242 healthy controls (Fliessbach et al., Fortschr Neurol Psychiatr 74:643-650, 2006). The present study was conducted to assess the practicability, reliability, and validity of NeuroCogFX in brain tumor patients without active disease after tumor-directed therapy. To evaluate its validity, neuropsychological testing with NeuroCogFX was completed parallel to a battery of established neuropsychological tests in 54 patients with different types of brain tumors and without active disease for at least 6 months. Retest reliability was assessed in a different sample of 49 patients with gliomas. Results showed good practicability with a median test duration of 28 min (range 16-51 min). Most subtests showed medium-sized retest reliability in healthy controls and tumor patients, with the exception of the 2-back test and reaction time measures in tumor patients. Convergent validity was confirmed for the domains psychomotor speed, verbal memory, and verbal short-term memory. NeuroCogFX enables serial scientific neuropsychological assessment of brain tumor patients. It can be carried out within a short period of time by non-academic personnel and is therefore applicable to large cohorts, e.g., within clinical trials.