Azienda USL IRCCS Institute of Neurological Science

Bologna, Italy

Azienda USL IRCCS Institute of Neurological Science

Bologna, Italy
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Brandes A.A.,Azienda USL IRCCS Institute of Neurological science | Franceschi E.,Azienda USL IRCCS Institute of Neurological science | Paccapelo A.,Azienda USL IRCCS Institute of Neurological science | Tallini G.,University of Bologna | And 13 more authors.
Oncologist | Year: 2017

Background. MGMT methylation status represents a powerful prognostic factor in newly diagnosed glioblastoma (GBM). Recently, its role in recurrent tumors has also been suggested; however, few data investigating the stability of this biomarker during the clinical course of the disease are available. In this study, we evaluated the rate of change of MGMT methylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM. Methods. We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion. Other eligibility criteria were age >18 years and Eastern Cooperative Oncology Group performance status 0-2.We evaluated the MGMT methylation status by methylation-specific polymerase chain reaction. Results. From our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated. MGMT methylation status at both first and second surgery was available for 108 patients. MGMT was methylated in both surgeries in 38 patients (35.2%), while it was unmethylated in 43 patients (39.8%). We found a significant concordance between the first and the second MGMT methylation assessments (K=0.500, p <.001), MGMT methylation being stable in 75% of the cases. Conclusion. MGMT methylation presents relative stability during the clinical course of GBM. © AlphaMed Press 2017.


Nayak L.,Dana-Farber Cancer Institute | Deangelis L.M.,Sloan Kettering Cancer Center | Brandes A.A.,Azienda USL IRCCS Institute of Neurological Science | Peereboom D.M.,Cleveland Clinic | And 17 more authors.
Neuro-Oncology | Year: 2017

Background. The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria defne 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 specifc 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 quantifable metric of neurologic function evaluable during a routine offce examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, interobserver variability, and feasibility. Results. The NANO scale is a quantifable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine offce visits. The score defnes 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. © 2017 The Author.


Brandes A.A.,Azienda USL IRCCS Institute of Neurological Science | Franceschi E.,Azienda USL IRCCS Institute of Neurological Science
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting | Year: 2014

Few evidence-based guidelines are available for the treatment of adult medulloblastoma, an extremely rare disease. Therapeutic regimens, typically modeled following pediatric protocols, consist of surgical resection followed by radiotherapy with or without adjuvant chemotherapy. Because of the rarity of this disease in adults, any treatment undertaken is based mainly on small and retrospective studies. Unlike pediatric patients, adults with medulloblastoma have been treated according to risk-adapted therapeutic strategies in only a few prospective studies. Overall, approximately 30% of patients experience recurrence and die of disease-related causes. Although the patients could respond to second-line treatments, the prognosis of patients with recurrence remains dismal. An important challenge for the future will be the biologic characterization of medulloblastoma in adults, with the identification of specific genetic patterns of patients with different prognosis and different response to targeted treatments.


Okada H.,University of California at San Francisco | Weller M.,University of Zürich | Huang R.,Brigham and Women's Hospital | Finocchiaro G.,Instituto Neurologico Besta | And 15 more authors.
The Lancet Oncology | Year: 2015

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. © 2015 Elsevier Ltd.


PubMed | University of California at San Francisco, Dana-Farber Cancer Institute, University of Zürich, University of California at Los Angeles and 8 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2015

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.


PubMed | University of Padua, University of Verona, Bellaria Hospital, University of Bologna and 3 more.
Type: Journal Article | Journal: Anticancer research | Year: 2015

Treatment options for glioblastoma (GBM) at recurrence have limited efficacy. Re-surgery has been used for confirmation of recurrent disease and to provide relief of symptoms but the real impact on survival is unknown.A retrospective analysis was performed for GBM patients followed between 01/2005 and 06/2010 at our Institution.Two hundred and thirty-two patients with recurrent GBM were evaluated. One hundred and two patients (44%) were treated with re-surgery followed by chemotherapy and 130 patients (56%) with chemotherapy alone. In multivariate analysis, no significant effect of re-surgery was found, with age (p=0.001), MGMT methylation (p=0.002) and PFS at 6 months (p=0.0001) being significant prognostic factors.Second surgery might have a limited impact in the clinical course of recurrent GBM patients.

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