Translating the theranostic concept to neuro-oncology: disrupting barriers.

Theranostics integrate molecular imaging and targeted radionuclide therapy for personalised cancer therapy. Theranostic treatments have shown meaningful efficacy in randomised clinical trials and are approved for clinical use in prostate cancer and neuroendocrine tumours. Brain tumours represent an unmet clinical need and theranostics might offer effective treatment options, although specific issues need to be considered for clinical development. In this Policy Review, we discuss opportunities and challenges of developing targeted radionuclide therapies for the treatment of brain tumours including glioma, meningioma, and brain metastasis. The rational choice of molecular treatment targets is highlighted, including the potential relevance of different types of targeted radionuclide therapeutics, and the role of the blood-brain barrier and blood-tumour barrier. Furthermore, we discuss considerations for effective clinical trial design and conduct, as well as logistical and regulatory challenges for implementation of radionuclide therapies into neuro-oncological practice. Rational development will foster successful translation of the theranostic concept to brain tumours.

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.

Predictive value of perilesional edema volume in melanoma brain metastasis response to stereotactic radiosurgery.

BACKGROUND AND AIM: Stereotactic radiotherapy (SRT) is an established treatment for melanoma brain metastases (MBM). Recent evidence suggests that perilesional edema volume (PEV) might compromise the delivery and efficacy of radiotherapy to treat BM. This study investigated the association between SRT efficacy and PEV extent in MBM. MATERIALS AND METHODS: This retrospective study reviewed medical records from January 2020 to September 2023. Patients with up to 5 measurable MBMs, intracranial disease per RANO/iRANO criteria, and on low-dose corticosteroids were included. MRI scans assessed baseline neuroimaging, with PEV analyzed using 3D Slicer. SRT plans were based on MRI-CT fusion, delivering 18-32.5 Gy in 1-5 fractions. Outcomes included intracranial objective response rate (iORR) and survival measures (L-iPFS and OS). Statistical analysis involved decision tree analysis and multivariable logistic regression, adjusting for clinical and treatment variables. RESULTS: Seventy-two patients with 101 MBM were analyzed, with a mean age of 68.83 years. The iORR was 61.4%, with Complete Response (CR) in 21.8% and Partial Response (PR) in 39.6% of the treated lesions. PEV correlated with KPS, BRAF status, and treatment response. Decision tree analysis identified a PEV cutoff at 0.5 cc, with lower PEVs predicting better responses (AUC = 0.82 sensitivity: 86.7%, specificity:74.4%,). Patients with PEV ≥ 0.5 cc had lower response rates (iORR 44.7% vs. 63.8%, p < 0.001). Median OS was 9.4 months, with L-iPFS of 27 months. PEV significantly impacted survival outcomes. CONCLUSIONS: A more extensive PEV was associated with a less favorable outcome to SRT in MBM.

The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study.

PURPOSE: Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and chemotherapy even if only a few retrospective studies assessed the impact on overall survival (OS) of these approaches. METHODS: We carried out an Italian multicentric retrospective study of adult patients with H3K27-altered DMG to assess the effective role of systemic therapy in the treatment landscape of this rare tumor type. RESULTS: We evaluated 49 patients from 6 Institutions. The median age was 37.3 years (range 20.1-68.3). Most patients received biopsy as primary approach (n = 30, 61.2%) and radiation therapy after surgery (n = 39, 79.6%). 25 (51.0%) of patients received concurrent chemotherapy and 26 (53.1%) patients received adjuvant temozolomide. In univariate analysis, concurrent chemotherapy did not result in OS improvement while adjuvant temozolomide was associated with longer OS (21.2 vs. 9.0 months, HR 0.14, 0.05-0.41, p < 0.001). Multivariate analysis confirmed the role of adjuvant chemotherapy (HR 0.1, 95%CI: 0.03-0.34, p = 0.003). In patients who progressed after radiation and/or chemotherapy the administration of a second-line systemic treatment had a significantly favorable impact on survival (8.0 vs. 3.2 months, HR 0.2, 95%CI 0.1-0.65, p = 0.004). CONCLUSION: In our series, adjuvant treatment after radiotherapy can be useful in improving OS of patients with H3K27-altered DMG. When feasible another systemic treatment after treatment progression could be proposed.

ASL, DSC, DCE perfusion MRI and 18F-DOPA PET/CT in differentiating glioma recurrence from post-treatment changes.

OBJECTIVES: To discriminate between post-treatment changes and tumor recurrence in patients affected by glioma undergoing surgery and chemoradiation with a new enhancing lesion is challenging. We aimed to evaluate the role of ASL, DSC, DCE perfusion MRI, and 18F-DOPA PET/CT in distinguishing tumor recurrence from post-treatment changes in patients with glioma. MATERIALS AND METHODS: We prospectively enrolled patients with treated glioma (surgery plus chemoradiation) and a new enhancing lesion doubtful for recurrence or post-treatment changes. Each patient underwent a 1.5T MRI examination, including ASL, DSC, and DCE PWI, and an 18F-DOPA PET/CT examination. For each lesion, we measured ASL-derived CBF and normalized CBF, DSC-derived rCBV, DCE-derived Ktrans, Vp, Ve, Kep, and PET/CT-derived SUV maximum. Clinical and radiological follow-up determined the diagnosis of tumor recurrence or post-treatment changes. RESULTS: We evaluated 29 lesions (5 low-grade gliomas and 24 high-grade gliomas); 14 were malignancies, and 15 were post-treatment changes. CBF ASL, nCBF ASL, rCBV DSC, and PET SUVmax were associated with tumor recurrence from post-treatment changes in patients with glioma through an univariable logistic regression. Whereas the multivariable logistic regression results showed only nCBF ASL (p = 0.008) was associated with tumor recurrence from post-treatment changes in patients with glioma with OR = 22.85, CI95%: (2.28-228.77). CONCLUSION: In our study, ASL was the best technique, among the other two MRI PWI and the 18F-DOPA PET/CT PET, in distinguishing disease recurrence from post-treatment changes in treated glioma.

The evolving role of reirradiation in the management of recurrent brain tumors.

Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging.Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue.We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed.

Low expression of Ki-67/MIB-1 labeling index in IDH wild type glioblastoma predicts prolonged survival independently by MGMT methylation status.

PURPOSE: The Ki-67/MIB-1 labeling index (LI) is clinically used to differentiate between high and low-grade gliomas, while its prognostic value remains questionable. Glioblastoma (GBM) expressing wild-type isocitrate dehydrogenase IDHwt, a relatively common malignant brain tumor in adults, is characterized by a dismal prognosis. Herein, we have retrospectively investigated the prognostic role of Ki-67/MIB-1-LI in a large group of IDHwt GBM. METHODS: One hundred nineteen IDHwt GBM patients treated with surgery followed by Stupp's protocol in our Institution between January 2016 and December 2021 were selected. A cut-off value for Ki-67/MIB-1-LI was used with minimal p-value based approach. RESULTS: A multivariate analysis showed that Ki-67/MIB-1-LI expression < 15% significantly correlated with a longer overall survival (OS), independently from the age of the patients, Karnofsky performance status scale, extent of surgery and O6-methylguanine (O6-MeG)-DNA methyltransferase promoter methylation status. CONCLUSIONS: Among other studies focused on Ki-67/MIB-1-LI, this is the first observational study showing a positive correlation between OS of IDHwt GBM patients and Ki-67/MIB-1-LI that we propose as a new predictive marker in this subtype of GBM.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma.

PURPOSE: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. METHODS: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis. RESULTS: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01). CONCLUSIONS: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Machine learning in neuro-oncology: toward novel development fields.

PURPOSE: Artificial Intelligence (AI) involves several and different techniques able to elaborate a large amount of data responding to a specific planned outcome. There are several possible applications of this technology in neuro-oncology. METHODS: We reviewed, according to PRISMA guidelines, available studies adopting AI in different fields of neuro-oncology including neuro-radiology, pathology, surgery, radiation therapy, and systemic treatments. RESULTS: Neuro-radiology presented the major number of studies assessing AI. However, this technology is being successfully tested also in other operative settings including surgery and radiation therapy. In this context, AI shows to significantly reduce resources and costs maintaining an elevated qualitative standard. Pathological diagnosis and development of novel systemic treatments are other two fields in which AI showed promising preliminary data. CONCLUSION: It is likely that AI will be quickly included in some aspects of daily clinical practice. Possible applications of these techniques are impressive and cover all aspects of neuro-oncology.

Mini-craniotomy for intra-axial brain tumors: a comparison with conventional craniotomy in 306 patients harboring non-dural based lesions.

The use of a mini-craniotomy approach involving linear skin incision and a bone flap of about 3 cm has been reported for several neurosurgical diseases, such as aneurysms or cranial base tumors. More superficial lesions, including intra-axial tumors, may occasionally raise concerns due to insufficient control of the tumor boundaries. The convenience of a minimally invasive approach to intrinsic brain tumors was evaluated by comparing 161 patients who underwent mini-craniotomy (MC) for intra-axial brain tumors with a group of 145 patients operated on by the same surgical team through a conventional craniotomy (CC). Groups were propensity-matched for age, preoperative condition, size and location of the tumor, and pathological diagnosis. Results were analyzed focusing on operative time, the extent of resection, clinical outcome, hospitalization time, and time to start adjuvant therapy. Mini-craniotomy was equally effective in terms of extent of resection (GTR: 70.9% in the MC group vs 70.5% in the CC group) but had shorter operative time (average: 165 min in the MC group vs 205 min in the CC group p < 0.001) and lower rate of postoperative complications both superficial (1.03% vs 6.5% in the CC group p = 0.009) and deep (4% in the MC group vs 5.5% in the CC group p = 0,47). No relationship was found between the size or location of the tumor and resection rate. The MC group had reduced hospitalization time (average: 5.8 days vs 7.6 in CC group p < 0.001) and faster access to adjuvant therapies. 92.5% of the MC patients, which were scheduled for treatment, started radiotherapy within 8 weeks after surgery as opposed to 84.1% in the CC group (p = 0.04). These findings support the increasing use of mini-craniotomy for intra-axial brain tumors.

Radiation therapy for atypical and anaplastic meningiomas: an overview of current results and controversial issues.

Meningiomas are the most common intracranial tumors. Most meningiomas are WHO grade 1 tumors whereas less than one-quarter of all meningiomas are classified as atypical (WHO grade 2) and anaplastic (WHO grade 3) tumors, based on local invasiveness and cellular features of atypia. Surgical resection remains the cornerstone of meningioma therapy and represents the definitive treatment for the majority of patients; however, grade 2 and grade 3 meningiomas display more aggressive behavior and are difficult to treat. Several retrospective series have shown the efficacy and safety of postoperative adjuvant external beam radiation therapy (RT) for patients with atypical and anaplastic meningiomas. More recently, two phase II prospective trials by the Radiation Therapy Oncology Group (RTOG 0539) and the European Organisation for Research and Treatment of Cancer (EORTC 2042) have confirmed the potential benefits of fractionated RT for patients with intermediate and high-risk meningiomas; however, several issues remain a matter of debate. Controversial topics include the timing of radiation treatment in patients with totally resected atypical meningiomas, the optimal radiation technique, dose and fractionation, and treatment planning/target delineation. Ongoing randomized trials are evaluating the efficacy of early adjuvant RT over observation in patients undergoing gross total resection.

Surgical redo versus transseptal or transapical transcatheter mitral valve-in-valve implantation for failed mitral valve bioprosthesis.

BACKGROUND: Redo surgical mitral valve replacement (SMVR) is the current standard of care for patients with failed bioprosthetic mitral valve (MV). Transcatheter mitral valve-in-valve replacement (TMViV) is arising as an alternative to SMVR in high risk patients. We sought to evaluate procedural safety, early and mid-term outcomes of patients who underwent transseptal TMViV (TS-TMViV), transapical TMViV (TA-TMViV), or redo-SMVR. METHODS: We identified patients with failed bioprosthetic MV who underwent TS-TMViV, TA-TMViV, or SMVR at four Italian Centers. Clinical and echocardiographic data were codified according to Mitral Valve Academic Research Consortium definition (MVARC), except for significant valve stenosis. RESULTS: Between December 2012 and September 27, 2019 patients underwent TS-TMViV, 22 TA-TMViV, and 29 redo-SMVR. TS-TMViV and TA-TMViV patients presented higher mean age and surgical risk scores compared with SMVR group (77.8 ± 12 years, 77.3 ± 7.3 years, 67.8 ± 9.4 years, p < .001; STS PROM 8.5 ± 7.2; 8.9 ± 4.7; 3.6 ± 2.6, p < .001). TS-TMViV procedure was associated with shorter intensive care unit time and total length of stay (LOS) compared with TA-TMViV and SMVR group. There were no differences in MVARC procedural success at 30-days (74.1, 72.7, and 51.7%, p = .15) and one-year all-cause mortality between groups (14.8, 18.2, and 17.2%, p = 1.0). MV mean gradient was similar between TS-TMViV, TA-TMViV, and SMVR groups at 30 days and 12 months. CONCLUSIONS: For the selected patients, TS-TMViV and TA-TMViV are to be considered a valid alternative to redo-SMVR with comparable 1-year survival. TS-TMViV is the less invasive strategy and has the advantage of shortening the LOS compared with TA-TMViV.

Radiotherapy of Parasellar Tumours.

Parasellar tumours represent a wide group of intracranial lesions, both benign and malignant. They may arise from several structures located within the parasellar area or they may infiltrate or metastasize this region. The treatment of the tumours located in these areas is challenging because of their complex anatomical location and their heterogenous histology. It often requires a multimodal approach, including surgery, radiation therapy (RT), and medical therapy. Due to the proximity of critical structures and the risks of side effects related to the procedure, a successful surgical resection is often not achievable. Thus, RT plays a crucial role in the treatment of several parasellar tumours. Conventional fractionated RT and modern radiation techniques, like stereotactic radiosurgery and proton beam RT, have become a standard management option, in particular for cases with residual or recurrent tumours after surgery and for those cases where surgery is contraindicated. This review examines the role of RT in parasellar tumours analysing several techniques, outcomes and side effects.

Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas.

OBJECTIVES: To evaluate the efficacy of a second course of fractionated stereotactic radiotherapy (re-SRT) and temozolomide (TMZ) as salvage treatment option in patients with aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs). PATIENTS AND METHODS: Twenty-one patients with recurrent or progressive APTs (n = 17) and PCs (n = 4) who received combined TMZ and re-SRT, 36 Gy/18fractions or 37.5 Gy/15fractions, were retrospectively evaluated. TMZ was given at a dose of 75 mg/m2 given concurrently to re-SRT, and then 150-200 mg/m2/day for 5 days every 4 weeks or 50 mg/m2 daily for 12 months. Local control (LC) and overall survival (OS) were calculated from the time of re-SRT by Kaplan-Meier method. RESULTS: With a median follow-up of 27 months (range 12-58 months), 2-year and 4-year LC rates were 73% and 65%, respectively; 2-year and 4-year survival rates were 82% and 66%, respectively. A complete response was achieved in 2 and partial response in 11 patients. Six patients recurred with a median time to progression of 14 months. O(6)-Methylguanine-DNA methyltransferase (MGMT) status and tumor volume emerged as prognostic factors. Grade 3 radiation-related toxicities occurred in 3 (14%) patients. Grade 2 or 3 hematologic toxicities during chemotherapy occurred in 8 (38%) patients. CONCLUSION: Re-SRT and TMZ is a safe treatment offering high LC in patients with progressive APTs and PCs. The potential advantages of combined chemoradiation as up-front or salvage treatment need to be explored in prospective trials.

Neurological outcome and memory performance in patients with 10 or more brain metastases treated with frameless linear accelerator (LINAC)-based stereotactic radiosurgery.

PURPOSE: To assess the neurocognitive function and neurological toxicity of frameless linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in patients with 10 or more brain metastases (BM). PATIENTS AND METHODS: Forty consecutive adult patients who received SRS for ten or more 10 BM < 3 cm in maximum size were evaluated. All plans were generated using a single-isocenter multiple-target (SIMT) SRS technique with doses of 22 Gy for lesions < 2 cm and 16-18 Gy for those ≥ 2 cm in size. Survival analyses were estimated by Kaplan-Meier method from the date of SRS. Neurocognitive function using the Hopkins verbal learning test-revised (HVLT-R) and activity of daily living scale (ADLS) were collected prospectively at baseline and at 3,6 and 12-month follow-up. Toxicity was assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (Version 5.0). RESULTS: With a median follow-up of 10.8 months, 1-year survival and local control rates were 65% and 86%, respectively. Grade 2 or 3 toxicity occurred in eleven patients, being associated with radiological changes suggestive of radiation necrosis in seven patients. Three months after SRS, the mean relative decline was 14.2% for HVLT-R delayed recall, 12.3% for HVLT-R recognition, and 9.8% for HVLT-R total recall. A significant deterioration of HVLT-R scores ranged from 5.5 to 18.7% of patients at different time points. ADLS scores declined over time, but changes were not significant. CONCLUSIONS: SRS is an effective and safe approach for patients with 10 or more BM able to maintain the pretreatment neurocognitive function in the majority of patients.

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

INTRODUCTION: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. METHODS: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months. RESULTS: Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p  ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. CONCLUSION: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

Prediction of survival in patients affected by glioblastoma: histogram analysis of perfusion MRI.

PURPOSE: The identification of prognostic biomarkers plays a pivotal role in the management of glioblastoma. The aim of this study was to assess the role of magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) with histogram analysis in the prognostic evaluation of patients suffering from glioblastoma. MATERIALS AND METHODS: Sixty-eight patients with newly diagnosed pathologically verified GBM were retrospectively evaluated. All patients underwent MRI investigations, including DSC-MRI, surgical procedure and received postoperative focal radiotherapy plus daily temozolomide (TMZ), followed by adjuvant TMZ therapy. Relative cerebral blood volume (rCBV) histograms were generated from a volume of interest covering the solid portions of the tumor and statistically evaluated for kurtosis, skewness, mean, median and maximum value of rCBV. To verify if histogram parameters could predict survival at 1 and 2 years, receiver operating characteristic (ROC) curves were obtained. Kaplan-Meier method was used to calculate patient's overall survival. RESULTS: rCBV kurtosis and rCBV skewness showed significant differences between subjects surviving > 1 and > 2 years, According to ROC analysis, the rCBV kurtosis showed the best statistic performance compared to the other parameters; respectively, values of 1 and 2.45 represented an optimised cut-off point to distinguish subjects surviving over 1 or 2 years. Kaplan-Meier curves showed a significant difference between subjects with rCBV kurtosis values higher or lower than 1 (respectively 1021 and 576 days; Log-rank test: p = 0.007), and between subjects with rCBV kurtosis values higher or lower than 2.45 (respectively 802 and 408 days; Log-rank test: p = 0.001). CONCLUSION: The histogram analysis of perfusion MRI proved to be a valid method to predict survival in patients affected by glioblastoma.

Management of nonfunctioning pituitary tumors: radiotherapy.

External beam radiotherapy (RT) is an essential part of the management of intracranial tumors and has been used in treating pituitary adenomas for more than five decades. It has been demonstrated that conventional RT for postoperative residual or progressive nonfunctioning pituitary adenomas (NFAs) present an excellent long-term local tumor control, although its use has been limited because of the potential late toxicity related to radiation treatments. Recent advances in radiation techniques have led to more accurate treatments, rendering obsolete many commonly held views of the "old" radiotherapy. New techniques include intensity modulated radiotherapy, volumetric-modulated arc therapy, and stereotactic techniques, either stereotactic radiosurgery or fractionated stereotactic radiotherapy. New techniques allow the delivering of higher radiation doses to the target with rapid dose fall-off in the surrounding normal tissues, and potentially limiting the long term toxicity of radiation. In this review, we present a critical analysis of the most recent available literature on the use of radiation in patients with NFAs, focusing particularly on the efficacy and safety of radiation stereotactic techniques.