Next-Generation Sequencing Panel for 1p/19q Codeletion and IDH1-IDH2 Mutational Analysis Uncovers Mistaken Overdiagnoses of 1p/19q Codeletion by FISH.

The 1p/19q codeletion is the result of a translocation between chromosome 1 (Chr1p) and chromosome 19 (Chr19q) with the loss of derivative (1;19)(p10;q10) chromosome. The 1p/19q codeletion has predictive and prognostic significance, and it is essential for the classification of gliomas. In routine practice, the fluorescence in situ hybridization (FISH) diagnosis of 1p/19q codeletion is sometimes unexpected. This study aimed to develop a next-generation sequencing panel for the concurrent definition of the 1p/19q codeletion and IDH1/IDH2 mutation status to resolve these equivocal cases. A total of 65 glioma samples were investigated using a 1p/19q-single-nucleotide polymorphism (SNP)-IDH panel. The panel consists of 192 amplicons, including SNPs mapping to Chr1 and Chr19 and amplicons for IDH1/IDH2 analysis. The 1p/19q SNP-IDH panel consistently identified IDH1/IDH2 mutations. In 49 of 60 cases (81.7%), it provided the same 1p/19q results obtained by FISH. In the remaining 11 cases, the 1p/19q SNP-IDH panel uncovered partial chromosome imbalances as a result of interstitial amplification or deletion of the regions where the FISH probes map, leading to a mistaken overdiagnosis of 1p/19q codeletion by FISH. The 1p/19q SNP-IDH next-generation sequencing panel allows reliable analysis of the 1p/19q codeletion and IDH1/IDH2 mutation at the same time. The panel not only allows resolution of difficult cases but also represents a cost-effective alternative to standard molecular diagnostics procedures.

Association between socioeconomic status and survival in glioblastoma: An Italian single-centre prospective observational study.

BACKGROUND: To date, no prospective study has been conducted to investigate the role of socioeconomic status (SES) on clinical outcome of glioblastoma (GBM) in Italy, where there is a National Health Service that provides universal coverage regardless of the patient's economic status. METHODS: We performed a prospective observational study investigating the association between SES and survival in GBM patients at our institution, a hub centre for brain cancer research and treatment. We included GBM patients who underwent medical treatment or chemo-radiation between April 2017 and December 2017. The SES was measured using the income-brackets, attributed by the Italian Ministry of Finance on the basis of the income of the fiscal family unit, referring to the previous year. RESULTS: One hundred and six patients were included in the study. In multivariate analysis, overall survival (OS) correlated significantly with higher-income (HR = 0.623.95% CI 0.467-0.832; p = 0.001) and MGMT methylation status (HR = 0.158.95% CI 0.082-0.304; P < 0.001). When adjusted for age, performance status and extension of surgery, survival benefit remained superior for higher-income HR = 0.641 (95% CI 0.478-0.858; p = 0.003) and MGMT methylated tumours HR = 0.167 (95% CI 0.084-0.331; p < 0.001). CONCLUSIONS: SES is an important determinant of prognosis in GBM even in the Italian National Health Service, which provides universal, largely free and relatively comprehensive healthcare. Despite aspirations to achieve equality in healthcare, socioeconomic differences exist and may impact the clinical outcome.

Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric high-grade glioma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric high-grade gliomas to various treatments. For areas in which scientific investigation was scarce, consensus was reached through an iterative process. RAPNO response assessment recommendations include the use of MRI of the brain and the spine, assessment of clinical status, and the use of corticosteroids or antiangiogenics. Imaging standards for brain and spine are defined. Compared with the recommendations for the management of adult high-grade glioma, for paediatrics there is inclusion of diffusion-weighted imaging and a higher reliance on T2-weighted fluid-attenuated inversion recovery. Consensus recommendations and response definitions have been established and, similar to other RAPNO recommendations, prospective validation in clinical trials is warranted.

The Risk Assessment in Low-Grade Gliomas: An Analysis of the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) criteria.

Diffuse low-grade gliomas (LGG) are rare tumors that affect young adult patients. The European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) have both developed their own clinical prognostic scores to assist clinicians in treatment decision-making. These criteria have been used to include patients in phase III studies. To date, it is unknown which is the best score to define the prognosis of LGG. Additionally, a pure clinical classification is probably not a sufficiently informative basis for choosing the proper treatment in different situations. A combined score with both clinical and molecular features will likely be indispensable.

Immunotherapy response assessment in neuro-oncology: a report of the RANO working group.

Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.