Showing papers by "Giuseppe Minniti published in 2016"

EANO guidelines for the diagnosis and treatment of meningiomas

Abstract: Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis

Abstract: Purpose To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, a propensity score analysis was used. Results The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group ( P =.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS ( P =.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis ( P =.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% ( P =.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.

Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

Abstract: Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

Target delineation and optimal radiosurgical dose for pituitary tumors

Abstract: Stereotactic radiosurgery (SRS) delivered as either single-fraction or multi-fraction SRS (2–5 fractions) is frequently employed in patients with residual or recurrent pituitary adenoma. The most common delivery systems used for SRS include the cobalt-60 system Gamma Knife, the CyberKnife (CK) robotic radiosurgery system, or a modified conventional radiotherapy machine (linear accelerator, LINAC). Tumor control and normalization of hormone hypersecretion have been reported in 75–100 % and 25–80 % of patients, respectively. Hypopituitarism is the most commonly reported late complication of radiation treatment, whereas other toxicities occur less frequently. We have provided an overview of the recent available literature on SRS in patients with a pituitary adenoma. Critical aspects of pituitary irradiation, including target delineation and doses to organs at risk, optimal radiation dose, as well as the long-term efficacy and toxicity of SRS for either nonfunctioning or secreting pituitary adenomas are discussed. Single-fraction SRS represents an effective treatment for patients with a pituitary adenoma; however, caution should be used for lesions > 2.5–3 cm in size and/or involving the anterior optic pathway. Future studies will be necessary to optimize target doses and critical organ dose constrains in order to reduce the long-term toxicity of treatments while maintaining high efficacy.

Repeated stereotactic radiosurgery for patients with progressive brain metastases

Abstract: In the present study we have evaluated the efficacy and toxicity of repeated stereotactic radiosurgery (SRS) in patients with recurrent/progressive brain metastases. Between March 2006 and October 2014, 43 patients (21 men and 22 women) with 47 lesions received a second course of SRS given in three daily fractions of 7-8 Gy. With a follow-up study of 19 months, the 1- and 2-year survival rates from repeated SRS were 37 and 20%, respectively, and the 1- and 2-year local control rates were 70 and 60%, respectively. Actuarial local control was significantly better for breast and lung metastases as compared with melanoma metastases; specifically, 1-year local control rates were 38% for melanoma, 78% for breast carcinoma and 73% for non-small cell lung cancer (NSCLC) metastases (p = 0.01). The cause of death was progressive systemic disease in 25 patients and progressive brain disease in 11 patients. Stable extracranial disease (p = 0.01) and Karnofsky performance status (KPS; p = 0.03) were predictive of longer survival. Radiologic changes suggestive of brain radionecrosis were observed in 9 (19%) out of 47 lesions, with an actuarial risk of 34% at 12 months. Neurological deficits (RTOG Grade 2 or 3) associated with brain necrosis occurred in 14% of patients. In conclusion, a second course of SRS given in three daily fractions is a feasible treatment for selected patients with recurrent/progressive brain metastases. Further studies are needed to explore the efficacy and safety of different dose-fractionation schedules, especially in patients with melanoma or large metastases.

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

Abstract: Purpose F-18-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-18-DOPA uptake.Patients and Methods We examined 215 patients with F-18-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans.Results Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands.Conclusions F-18-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

Multiparametric evaluation of low grade gliomas at follow-up: comparison between diffusion and perfusion MR with (18)F-FDOPA PET.

Abstract: Objective:To compare MRI using perfusion and diffusion techniques with 6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET) in the follow-up of low-grade gliomas (LGGs) and to identify the best imaging parameter to differentiate patients with different prognosis.Methods:Between 2010 and 2015, 12 patients with a pathology-proven diagnosis of LGG and MR (with perfusion and diffusion sequences) and a PET study during their follow-up were retrospectively included in our study. Cerebral blood volume (CBV) and apparent diffusion coefficient (ADC) maps on MR studies and PET images were evaluated using a region of interest-based method. All patients were categorized as stable or as having progressive disease at 1-year follow-up. Statistical analysis was performed using Pearson's correlation test and multivariate analysis of variance (p < 0.05).Results:No significant correlations were found between PET parameters [maximum tumour-to-controlateral normal brain ratio (T/Nmax) and...

Comment on Hatzoglou et al: Dynamic contrast-enhanced MRI perfusion versus 18FDG PET/CT in differentiating brain tumor progression from radiation injury.

Abstract: We read with great interest the paper by Hatzoglou et al, recently published in Neuro-Oncology,1 concerning the discrimination between progressive disease and radiotherapyinduced changes in brain tumors, which is a clinical challenge of paramount importance. To address this diagnostic problem, the authors compared dynamic contrast enhanced (DCE) MRI and fluorine-18-fluorodeoxyglucose (FDG) PET/CT in a total of 53 patients with primary brain tumors (n = 29) or brain metastases (n = 26). They found that the DCE MRI–derived plasma volume ratio (Vpratio) and transfer coefficient ratio (K trans ratio), as well as the FDG PET–derived standardized uptake value ratio (SUVratio) were useful in distinguishing between progression and radiation injury, both in the overall cohort and in the 2 main subgroups (primary and secondary brain tumors). They concluded, however, that DCE MRI–derived Vpratio was the “most robust” predictor of progression after showing a trend toward higher performances for Vpratio with respect to SUVratio (sensitivity and specificity = 92% and 77% vs 68% and 82%; AUC = 0.87 vs 0.75, P = .061, for Vpratio and SUVratio, respectively). Perfusion-weighted MRI and FDG PET are widely available imaging modalities which have proven to be useful to complement standard MRI in this setting. However, we would like to emphasize that, in the last decade, PET using radiolabeled amino acids has developed as a powerful diagnostic tool in brain tumor diagnostics. Recently, the Response Assessment in Neuro-Oncology (RANO) working group and the European Association for Neuro-Oncology (EANO) have published their recommendations for the clinical use of PET imaging in gliomas in Neuro-Oncology.2 These recommendations clearly favor amino acid PET over FDG PET and claim the superiority of amino acid PET over standard MRI in several clinical scenarios, including the differentiation of glioma recurrence from treatment-induced changes. To the best of our knowledge, no such level of evidence and consensus has been reached with regard to perfusion-weighted MRI in this field. The fact that amino acid PET is widely used in centers that have full access to the spectrum of functional and molecular MRI techniques emphasizes the value of amino acid PET beyond these alternative MRI methods.3 These important aspects are not mentioned in the paper by Hatzoglou et al and should be disclosed to the readers. Fewer data are available on the implementation of amino acid PET in brain metastases and no specific recommendations have been published so far. Nonetheless, the results of a direct comparison between perfusion-weighted MRI and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) PET demonstrated a higher accuracy of amino acid PET in classifying indeterminate enlarging brain metastases after radiation treatment.4 Additionally, further studies have confirmed the high accuracy of different amino acid PET tracers in this setting, although no comparison with advanced MRI techniques was included.5,6 In single centers, combined MRI and amino acid PET criteria are already being clinically used for this problem solving.7 Finally, we would also like to remark that Hatzoglou et al have probably compared DCE MRI with an underpowered FDG PET technique, as a single time point PET has already shown to be less accurate than dual time point acquisitions in the same setting.8 In conclusion, we agree that the results of Hatzoglou et al are valuable, since it is the largest, albeit heterogeneous prospective series providing a comparison between DCE MRI and FDG PET/CT in differentiating brain tumor progression from radiation injury after cranial irradiation. However, the emerging role of amino acid PET imaging in this field is not adequately addressed and needs to be disclosed to the readers.

Radiotherapy and Radiosurgery

Abstract: Surgery is the primary treatment modality for patients with craniopharyngiomas. Complete surgical excision is associated with a 5-year tumor growth control of 70–90 % in either adult or pediatric series [1, 2]. For uncompleted resected craniopharyngiomas, local control can be improved with the use of radiotherapy (RT) [3–5]. A few retrospective studies have demonstrated that partial resection followed by RT may provide outcomes comparable to those achieved with complete resection with lower incidence of toxicity as compared with aggressive surgery [6–9]. Modern RT has seen technical advances in all aspects of treatment with better immobilization, imaging, treatment planning, and dose delivery. In the last two decades, stereotactic radiation techniques, either stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), have been employed in patients with craniopharyngioma with the aim of treating less normal brain and minimizing the long-term consequences of conventional RT while improving its effectiveness. In addition, there is a renewed interest in particle therapy with protons and ions, because of their physical and biological properties.

Radiotherapy, Radiosurgery, and Proton Beam

Abstract: Chordomas of the skull base are rare bone tumors with locally aggressive behavior. Surgery is the primary treatment of skull base chordomas, although long-term observation series have shown its limitation in achieving a complete removal of the lesion due to the critical location and the infiltrative patterns into the bone and neurovascular structures of the skull base.