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Introduction: In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life., Methods: Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT-30 Gy in 6 fractions) and exclusive chemotherapy (CHT-emozolomide 200 mg/m 2 /day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms-NSS) RESULTS: From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01)., Conclusions: The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment.

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.

The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5-10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5-19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

Fotemustine (FTM) is a common treatment option for glioblastoma patients refractory to temozolomide (TMZ). Although elderly patients represent a large component of glioblastoma population, the feasibility and the efficacy of second-line FTM are not available in those patients.We retrospectively analyzed the records of glioblastoma patients older than 65 years, receiving FTM at a dose of 70-100 mg/m(2) of FTM every week for 3 consecutive weeks (induction phase) and then every 3 weeks (70-100 mg/m(2)), as second-line treatment.Between January 2004 and December 2011, 65 glioblastoma patients (median age, 70 years; range, 65-79 years) were eligible for this analysis. Sixty-five patients received a total of 364 FTM cycles, with a median of 4 cycles for each patient. After induction, we observed 1 complete response (1.5 %), 12 partial responses (18.5 %), 18 stable diseases (27.7 %), and 34 patients' progressions (47.7 %). Disease control rate was 43.1 %. Median survival from the beginning of FTM therapy was 7.1 months, while the median progression-free survival was 4.2 months, and the 6-months progression free survival rate was 35.4 %. The most relevant grade 3-4 toxicity events were thrombocytopenia (15.3 %) and neutropenia (9.2 %). In the univariate and multivariate analysis, time from radiotherapy to FTM, number of TMZ and FTM cycles and disease control resulted independent prognostic factors.This study showed that FTM is a valuable therapeutic option for elderly glioblastoma patients, with a safe toxicity profile.

This review aims to summarize what is currently known about neurocognitive outcome and quality of life in patients with brain tumors treated with radiotherapy. Whether potential tumor-controlling benefits of radiotherapy outweigh its potential toxicity in the natural history of brain tumors is a matter of debate. This review focuses on some of the adult main brain tumors, for which the issue of neurocognitive decline has been thoroughly studied: low-grade gliomas, brain metastases, and primary central nervous system lymphomas. The aims of this review are: (1) the analysis of existing data regarding the relationship between radiotherapy and neurocognitive outcome; (2) the identification of strategies to minimize radiotherapy-related neurotoxicity by reducing the dose or the volume; (3) the evidence-based data concerning radiotherapy withdrawal; and (4) the definition of patients subgroups that could benefit from immediate radiotherapy. For high grade gliomas, the main findings from literature are summarized and some strategies to reduce the neurotoxicity of the treatment are presented. Although further prospective studies with adequate neuropsychological follow-up are needed, this article suggests that cognitive deficits in patients with brain tumor have a multifactorial genesis: radiotherapy may contribute to the neurocognitive deterioration, but the causes of this decline include the tumor itself, disease progression, other treatment modalities and comorbidities. Treatment variables, such as total and fractional dose, target volume, and irradiation technique can dramatically affect the safety of radiotherapy: optimizing radiation parameters could be an excellent approach to improve outcome and to reduce neurotoxicity. At the same time, delayed radiotherapy could be a valid option for highly selected patients.

Background and Aim: Radiotherapy may be used as an adjuvant treatment of pituitary adenomas. The aim of our study was to present our experience of multimodal treatment of pituitary adenomas, consisting in temporary implantation of (192)Ir-labeled wires following transphenoidal surgery., Subjects and Methods: An observational investigation was performed on a series of 80 patients undergoing surgery (S) for pituitary adenomas between 1982 and 2000, some of whom received post-operative external beam radiotherapy (EBRT) (no.=19 between 1982 and 1990), brachytherapy (B) (no.=35, all after 1991), or both irradiation modalities (EBRT+B) (no.=14). The different treatments were compared in terms of hormonal normalization in the subgroup of patients with hypersecreting adenomas, tumor control, and side effects., Results: Hormonal normalization was obtained in 84% of S+B patients and in 61% of S+EBRT patients. Tumor control was obtained in 74.3% of S+B patients and in 63.1% of S+EBRT patients. Anterior pituitary hormones deficits ranged from 8.6-34% in S+B patients and from 15.8-47.4% in S+EBRT patients, after a mean follow-up of 14 yr. The latter group also showed a higher rate of multiple deficits (42.1% vs 22.8%). Diabetes insipidus and other major complications were rare events in all groups., Conclusions: We presented one original experience regarding brachytherapy in the management of pituitary tumors, which turned out to be effective and safe. Additional prospective, and possibly randomized, studies should clarify whether in the era of 3-dimensional conformal radiotherapy and stereotactic radiotherapy this treatment modality may still have a role.