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Background In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [18F]Fluoro-Methyl Choline ([18F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT). Methods Patients with biochemical recurrence limited up to three lesions revealed by [18F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [18F]FMCH PET/CT was considered as the primary endpoint. Results Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5–68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p Conclusions Based on our findings, [18F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Background. The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to examine the impact of different patterns of GBM failure on patients’ survival and second surgery outcomes.Methods. Overall survival was assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves.Results. Contact with ventricles, a second surgery and meningeal spread had a statistically impact on patient survival after the diagnosis of GBM recurrence (P=0.032, P=0.019 and PConclusions. The local recurrence pattern could be a promising field of interest for patients with recurrent GBM suitable for a second surgery.

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.

Aim: This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG). Patients & methods: The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. Results: We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. Conclusion: The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.

BACKGROUND: Standard up-front therapy of high grade glioma (HGG) is focused on the so called Stupp protocol, that includes surgical resection followed by radiotherapy (RT) combined with concomitant and adjuvant chemotherapy with temozolomide (TMZ). As supported by several international guidelines, disease assessment is performed using magnetic resonance (MR) one month since the end of RT and then every 3 months: in case of tumour progression the administration of temozolomide (the most active agent against glioma) is interrupted and salvage therapy or best supportive care are recommended. The aim of this study is to investigate in a retrospective manner the real value of first MR following RT and its relevance in clinical decision making about up-front therapy. MATERIAL AND METHODS: Between April 2005 and July 2017, data of 78 patients (pts) with a proven diagnosis of HGG and treated with Stupp protocol at the University Hospital of Pisa were collected. Tumor progression was defined according to Mac-Donald’s Criteria. Considering the potential presence of pseudo-progression (PSP) and the evolutionary pattern of the suspected recurrences, lesions suggestive for tumor progression inside the radiotherapy field were investigate with a new MR after 6–8 weeks. Otherwise, the presence of new lesions outside the radiotherapy field was interpreted as disease progression (PD) and patient’s therapy was changed. Presence or absence of symptoms, extent of surgery and MGMT methylation status were recorded. RESULTS: The first MR after RT-CT evidenced infield progression (interpreted as PSP) in 16 pts (20,5%) and outfield progression in 8 (10.2%).Three out of 8 patients with outfield progression were symptomatic for the tumor growth. The second MRI confirmed the presence of PSP in 10 pts out of 16 pts whereas in 6 patients a true progression (PD) was present since the first MR. CONCLUSION: In absence of symptoms, the first MR after radio-chemotherapy influenced clinical decision making (sending the patients to further salvage therapy or BSC) only in 5 out of 78 patients (6.4%). In 72 patients, even in presence of radiological signs suggestive for disease progression inside the RT field, clinical decision making did not change. Further studies involving a higher number of patients are required in order to confirm our findings.

BACKGROUND: Gangliogliomas are rare tumor usually arising in the supratentorial region, WHO grade 1 or 2. In these tumors, BRAF mutation may constitute a driver genetic alteration and a biomarker of response to BRAF inhibitors. Dabrafenib is an oral inhibitor of BRAF and has shown to significantly improve progression-free survival in patients with BRAF mutated metastatic melanoma. MATERIALS AND METHODS: In March 2015, after being diagnosed with left front-temporal enhancing mass, a 31-year-old lady was referred to the University Hospital of Pisa. In the previous two months, the patient had noticed motor aphasia and, due to the persistence of the symptoms, she was sent to the emergency room by the general practitioner. Previous history did not show any co-morbidity. An MRI displayed a fronto-parietal tumor with some contrast enhancement. The patient underwent craniotomy and subtotal tumor resection. Histopathology revealed a WHO grade I ganglioglioma and immunohistochemistry (IHC) documented focal expression of P-53, CD34, and ki-67 proliferation index of 3%. BRAF V600E mutation (Val600Glu(GTG◊GAG)) was detected by polymerase chain reaction. Postoperatively, the patient received radio-chemotherapy with temozolomide (60 Gy in 30 fractions), but 10 months later the patient experienced disease progression. A second surgery was performed without any neurological impairment. The disease monitoring with MRI revealed a partial tumor removal and the pathology confirmed the previous diagnosis. After second surgery, considering the Karnofsky Performance Status Score of 100, the young age and, the presence of BRAF mutation, our multidisciplinary team (in agreement with colleagues of the Neuro-Oncology Unit of the University of Turin) decided to administer the selective BRAF inhibitor Dabrafenib (75 mg twice per day for the first 21 days, then 150 mg twice per day). Since the beginning of the salvage systemic therapy, the patient did not experience treatment-related adverse events. Magnetic resonance performed two months after the start of Dabrafenib and then every three months showed a major response. After 15 months due to the persistent disease response and MRI, we decided to stop the administration of Dabrafenib. Three months after interruption of dabrafenib a new MRI detected a second disease progression being the patient asymptomatic, and we decided to restart the administration of Dabrafenib, which is ongoing. CONCLUSION: Despite the lack of literature on the use of Dabrafenib in Central Nervous System tumors, this case report provides evidence that Dabrafenib can be active in patients with ganglioglioma with BRAF mutation and confirms the safety related to this agent.

Background/aim In patients with recurrent glioblastoma, the best timing to administer bevacizumab is not well addressed yet. In this study, we reported the results of a monocentric experience comparing the early use of bevacizumab (following the first GBM recurrence) with the delayed administration (following the second or even further GBM recurrences). Materials and methods This analysis included 129 glioblastoma patients with a median follow-up of 22.4 months (range=5.26-192 months). Results The median time lapse from diagnosis of glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated with deferred administration of bevacizumab and 9.9 for patients with early administration (p=0.047). Bevacizumab progression-free survival with early and delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from the start of bevacizumab was 6.18 months in patients with early administration, and 6.47 in the delayed administration one (p=0.318). Conclusion Delayed administration of bevacizumab can be considered in selected patients with less aggressive recurrent glioblastoma.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P

Background/aim In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. Materials and methods Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. Results From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. Conclusion IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.

We propose molecularly imprinted polymers (MIPs) as valid tools for the selective removal from water of these drugs. MIPs are synthesized by copolymerization of cross-linking and function-al monomers in the presence of a target analyte, which acts as a molecular template. Following the polymerization, the template is removed to leave cavities with selectivity for the analyte, allowing the polymer to rebind the analyte with a very high specificity.

Background: Glioblastoma (GBM) accounts for approximately 50% of all glioma and among these tumors, are the most malignant. The current standard of care for patients with newly diagnosed GBM includes temozolomide and radiotherapy. Melanocortins are peptides with well-recognized anti-inflammatory and neuroprotective activity. No data are currently available on MC4R gene polymorphisms and gliomas or their relationship with radiotherapy or chemotherapy. Given the association of MC4R with antiinflammatory activity, neuroprotection, induction of neural stem/progenitor cell proliferation in brain hypoxia, and prevention of astrocyte apoptosis, the aim of this study was to retrospectively evaluate the possible prognostic/predictive role of the MC4R SNPs on GBM therapy. Methods: Sixty-one patients with a proven diagnosis of GBM, ECOG PS 0–2, age greater than18 years, and treated with radiotherapy and temozolomide were enrolled. Blood samples (3 ml) were collected in EDTA tubes and stored at -80°C. Genomic DNA was extracted using QIAamp DNA Blood Mini Kit. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed; the allelic discrimination was performed using an ABI PRISM 7900 SDS and with validated TaqMan® SNP genotyping assays. PCR reactions were carried out according to the manufacturer’s protocol. Kaplan Meier curves were performed for statistical association with genotypes. A P value less than 0.0125 (Bonferroni’s correction) was considered significant. Results: Fifty-six patients were clinically evaluated. The median progression-free survival (PFS) and median overall survival (OS) were 10.8 months and 23 months, respectively. The distribution of genotypes in the 56 patients did not deviate from Hardy-Weinberg equilibrium. A relevant finding of our study was the identification of a MC4R genotype that was significantly associated with PFS. Indeed, with regard to PFS, patients harbouring the rs489693 AA genotype had a median PFS of 3 months whereas patients with AC/CC genotypes had a median PFS of 13.7 months (P=0.0088). Interestingly, the rs489693 AA patients also had a lower median OS, even though the difference was not sta[[Unsupported Character - Codename ­]]tistically significant as compared with the median OS of the AC/CC genotypes (15.6 vs. 24.6 months, respectively, P=0.274). No significant differences in PFS and OS for the other genotypes of the investigated MC4R polymorphisms were found. Conclusion: The rs489693 AA genotype is significantly associated with a shorter PFS in GBM patients treated with radiotherapy and temozolomide schedule. The present pharmacogenetic, retrospective, pilot study may represent the stimulus to prospectively investigate the role of rs489693 MC4R polymorphism as a predictive pharmacogenetic marker of GBM radio-chemotherapy.

Bevacizumab is an anti-VEGF antibody used in the treatment of recurrent glioblastoma (GBM). Despite the available literature, few is known about the best schedule to administer this angiogenesis inhibitor: i) early, at the first recurrence, or ii) later, after a second line of chemotherapy. In this retrospective multicenter study, we reported the results obtained in 51 patients (pts) with recurrent GBM treated with single agent bevacizumab after the failure of a second-line chemotherapy with fotemustine (FTM). In March 2016, at the time of data analysis, 3 patients (5.9%) were still alive with stable disease, whereas 48 patients were dead due to disease progression. Kaplan-Meier estimated median survival from diagnosis of GBM was 28 months (95%CI 22.1-33.9). The median survival measured from the beginning of FTM and bevacizumab therapy were 11.3 (95% CI 8.4-13.6) and 6 (95% CI 3.8-8.1) months, respectively. Six and 12-month PFS rate from the beginning of bevacizumab treatment were 18% and 13%, respectively. Despite the interpretation of this study is limited by the retrospective design, bevacizumab may be a promising approach after failure of second-line FTM therapy.

ObjectiveThe objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer.MethodsThe hospital records of 45 patients with18F-fluorodeoxyglucose (18F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen.ResultsPositron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P= 0.04 andP= 0.03, respectively).ConclusionsStereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.

BACKGROUND: Glioblastoma (GBM) is the most baleful malignant brain tumor in adults. After a diagnosis of relapsed GBM, multimodality salvage treatment are not incisive enough to improve overall survival (OS) beyond a few months, and their best use and the timing is not well established. Bevacizumab (BEV) seems to improve OS. The best timing for BEV administration requires further investigation. We report the results of a monocentric experience comparing the early use of BEV with delayed administration. MATERIAL AND METHODS: Data was collected from September 2008 from pts who met the following criteria:0>18years, a pathologically-confirmed diagnosis of GBM, disease recurrence after up-front RT-CT or alone CT with TMZ, KPS >60, and administration of BEV with or without concomitant CT. Single agent BEV was administered at the time of the first recurrence (early administration) after standard up-front treatment, or at the time of disease progression following a second or even further advanced line of CT (late administration). BEV response and progression were assessed using RANO criteria. Disease assessment was performed every 2 months following the start of BEV, using MRI with a contrast agent, or at the onset of symptoms. RESULTS: This analysis includes 129 pts from September 2008 to July 2017 treated with BEV for recurrent GBM. 51 pts received early administration of BEV and 77 delayed administration. The median age at the beginning of BEV was 56.4 years, MGMT methylation status was assessed in 52 pts, and clinical benefit due to BEV in 47. Median KPS at the time of BEV first administration was 80 (range 60–100). At a median follow-up of 22.4 months (range 5.26–19.2), the median lapse from diagnosis of GBM to disease recurrence was 11.6 months; 13.1 for pts treated with deferred administration of BEV and 11.1 for pts with early administration (P=0.047). Median OS in pts treated with early BEV was 19.5 months, and in pts treated with delayed BEV it was 26.7 months (P=0.040). PFS with early and delayed use of BEV was 3.45 and 2.92 months, respectively (p=0.504). OS from the start of BEV were 6.18 months in pts with early administration, and 6.47 in the delayed administration group (p=0.318). Toxicity profiles were similar in the 2 groups. Clinical benefit was observed in 12 out of 49 pts treated with early BEV, and in 20 out of 47 treated with delayed BEV. According to univariate analysis, KPS, MGMT methylation and time from diagnosis to start of BEV were predictors of OS in all pts, regardless of the timing of administration of BEV CONCLUSION: The results obtained in this study suggest that the delayed administration of BEV can be considered in select pts with recurrent GBM. Further prospective studies are needed to better define the best time for BEV administration in pts with recurrent GBM

Background To evaluate the safety of stereotactic body radiotherapy (SBRT) of bone metastases in oligometastatic disease and to investigate prognostic factors of local control (LC), progression/disease-free survival (PDFS), and overall survival (OS). Methods Eligibility criteria were number of metastates ≤5, controlled primary tumor without evidence of progression under systemic therapy, exclusion of surgery, and no previous radiotherapy of the lesion of interest. Oligometastatic status was classified into only bone (BOD) and outside bone disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography study of the lesion of interest was performed at baseline and at 3 months after SBRT to evaluate metabolic response according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was used for univariate and multivariate analysis. Results Between January 2010 and December 2013, 40 patients were enrolled. Only 1 patient experienced severe late toxicity (radiation-related fracture). Local control was longer among responders’ than nonresponders’ lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years, respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of PDFS showed a significant correlation with planning target volume (PTV) size (p = 0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS confirmed a statistically significant value of the oligometastatic status (p = 0.002) and a significant trend for PTV size (p = 0.065). Conclusions Stereotactic body radiotherapy is safe with a low incidence of severe toxicity. Positron emission tomography response was a strong prognostic factor of LC whereas BOD status and small PTV size could identify a subset of oligometastatic patients at better prognosis.

Generally speaking, the negative side of radiation treatment of the pelvic district is the toxicity that may compromise the patient's quality of life and lead to temporary suspension of treatment with possible negative effects on its effectiveness. In neoadjuvant radiochemotherapy for locally advanced rectal cancer (LARC), the toxicity that is most frequently observed is proctitis, usually treated with topical corticosteroids or mesalazine. Hyaluronic acid's function is to restore the regular trophism and elasticity of the connective tissues leading to faster repair of the damage, and this could represent a viable option for the control of actinic proctitis.Since March 2012, a neoadjuvant radiochemotherapy protocol has been active at the Pisa Universitary Hospital for patients with LARC; 23 patients have been enrolled up to the present. Treatment involves an induction chemotherapy phase according to the FOLFOXIRI + Bevacizumab regimen for 6 cycles, followed by chemotherapy (capecitabina + Bevacizumab) concomitant with radiotherapy (5040 cGy in 28 fractions). Surgery is scheduled 6-8 weeks after the end of RTCT. During the course of associated treatment (RTCT), 12/23 patients received topical therapy with hyaluronic acid (Proktis-M suppositories) for the prevention of proctitis.All 23 patients enrolled in the study completed the induction chemotherapy phase. In the first 11 enrolled patients who did not receive prior Proktis-M suppositories, intense rectal toxicity was observed. Proctalgia of grade G1-2 and G3-4 presented respectively in 64% and 36% of cases, with consequent interruption of treatment which, in 45% of patients, lasted longer than 10 days. In the remaining 12 patients who underwent prior treatment with Proktis-M suppositories, the percentage of rectal toxicity was lower. In those cases where it did present, onset was later and its intensity and duration lower. 25% of patients did not develop proctalgia, 33% developed proctalgia of grade G1 and 42% proctalgia of grade G2. In none of these was it found necessary to interrupt radiochemotherapy.Prior topical treatment with Proktis-M suppositories in patients undergoing preoperative RTCT for LARC, enabled us to carry out radiochemotherapy at scheduled times, so protecting the treatment's effectiveness on the down-staging of the disease and preserving the patient's quality of life.

Aims: XRCC1 proteins are involved in DNA repair pathways. Given the association of XRCC1 activity and the resistance to chemo-radiotherapy, the aim of this study was to evaluate the possible predictive and therapeutic role of the XRCC1 SNPs on GBM patients treated with up front radiotherapy, alone or in combination with temozolomide. Methods: Fifty-five patients with a proven diagnosis of GBM, ECOG PS 0-2, age>18 years, and treated with radiotherapy with or without temozolomide were enrolled. Genomic DNA was extracted and XRCC1 gene SNPs were analyzed; the allelic discrimination was performed using an ABI PRISM 7900 SDS (Applied Biosystems, Carlsbad, CA, USA) and with validated TaqMan® SNP genotyping assays (Applied Biosystems). Kaplan Meier curves were performed for statistical association with genotypes. The study has been approved by the local IRB. Results: At the data analysis, the median progression-free survival (PFS) and median overall survival (OS) of these patients were 20 months and 11 months, respectively. A relevant finding of our study was the identification of a XRCC1 genotype that was significantly associated with OS: patients harboring the TT or CC genotype had 12 and 24-month OS ratio of 75 and 16%, respectively, whereas, patients with genotype TC 88 and 34%, respectively. Conclusions: The XRCC1 genotype is significantly associated with a shorter OS in GBM patients treated with radiotherapy and temozolomide schedule. The present, pilot study may represent the stimulus to prospectively investigate the role of XRCC1 polymorphisms as a predictive pharmacogenetic marker or as a target for new drug therapies for GBM patients.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and the second most common brain cancer after meningioma with a peak of incidence on the fifthy decades of life. Due to the progressive ageing of the developed country population, more than a half of new cases occurs in patients older than 65 years. The aim of the present study was to evaluate the clinical outcome of radio-chemotherapy with temozolomide in patients with glioblastoma aged more than 65 years. MATERIAL AND METHODS: Sixty-three patients treated with radiotherapy and chemotherapy at Pisa University Hospital between September 2004 and November 2017 were enrolled in this retrospective analysis. All patients had a proven diagnosis of glioblastoma grade IV WHO, ECOG PS 0–2, age ≥ 65. Radiotherapy was delivered in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy. During radiotherapy, temozolomide was administered at a dose of 75 mg per square meter of body-surface area per day from the first to the last day of radiotherapy. 5–6 weeks after the end of radiotherapy, adjuvant temozolomide was administered at 150–200 mg per square meter for five consecutive days, every 28 days. A maximum of 12 cycles were prescribed if MRI showed no disease progression and temozolomide was well tolerated. RESULTS: Data analysis was performed in April 2018. The present study was performed in 37 male and 26 female patients with a median age at diagnosis of 72,5 years (range=65–89). Fifty-seven patients underwent surgical resection, four patients stereotactic diagnostic biopsy, two patients had a radiologic diagnosis only. During follow up, we recorded 46 cases of disease progression with a median progression-free survival (PFS) of 12 months (range 1–88 months). Median overall survival (OS) were 25 months (range 1–107 months); at data analysis, 65 patients were died. After disease recurrence, based on ECOG, tumor burden and age, patients were treated with surgery (15 cases), chemotherapy (30 cases) and re-irradiation (11 cases). CONCLUSION: In our experience, progression free survival and overall survival were similar to those reported in literature for younger patients. We think that radiochemotherapy is a good option for older patients with a good performance status in glioblastoma treatment.

Passive systems play a crucial role in the development of future solutions for nuclear plant technology. A fundamental issue still to be resolved is the quantification of the reliability of such systems. In this paper, we firstly illustrate a systematic methodology to guide the definition of the failure criteria of a passive system and the evaluation of its probability of occurrence, through the identification of the relevant system parameters and the propagation of their associated uncertainties. Within this methodology, we propose the use of the analytic hierarchy process as a structured and reproducible tool for the decomposition of the problem and the identification of the dominant system parameters. An example of its application to a real passive system is illustrated in details.

Reversible oxidations of protein thiols have emerged as alternatives to free radical-mediated oxidative damage with which to consider the impacts of oxidative stress on cellular activities but the scope and pathways of such oxidations in tissues, including the brain, have yet to be fully defined. We report here a characterization of reversible oxidations of glutathione and protein thiols in extracts from rat brains, from two sources, which had been (1) frozen quickly after euthanasia to preserve in vivo redox states and (2) subjected to alkylation upon tissue disruption to trap reduced thiols. Brains were defined, relatively, as Reduced and Moderately Oxidized based on measured ratios of reduced (GSH) to oxidized (GSSG) glutathione. Levels of protein disulfides formed by the cross-linking of closely-spaced (vicinal) protein thiols, but not protein S-glutathionylation, were higher in extracts from the Moderately Oxidized brains compared to the Reduced brains. Moreover, the oxidized vicinal thiol proteome contains proteins that impact cellular energetics, signaling, neurotransmission, and cytoskeletal dynamics among others. These findings argue that kinetically-competent pathways for reversible, two-electron oxidations, of protein vicinal thiols can be activated in healthy brains in response to physiological oxidative stresses. We propose that such oxidations may link oxidative stress to adaptive, but also potentially deleterious, changes in neural cell activities in otherwise healthy brains.

A method is proposed for the study of enzymatic reactions affected by product inhibition. The use of continuous and stirred ultrafiltration membrane re A mathematical model has been defined which depicts Michaelis-Menten kinetics with a linear-type product inhibition for all competitive, non-competitiv The experimental procedure needed to identify the inhibition pattern and to evaluate the set of kinetic constants is detailed. Two model systems, the h

The use of ultrafiltration cells as membrane reactors is extended to the study of enzyme kinetics with product inhibition. This reactor configuration allows the lack of accuracy and instrument limitations typical of differential analysis and of time-course data analysis for experiments performed in batch reactors to be overcome. The hydrolysis of cellobiose to glucose, catalysed by β-glucosidase from Aspergillus niger (E.C. 3.2.1.4), was chosen as model system. The activity of this enzyme is suppressed by glucose according to a mixed-type inhibition pattern. Attention was paid to the possibility of determining the presence of either reversible or irreversible product inhibition. Details of the apparatus, experimental procedure and data correlation are given. Phenomena such as thermal deactivation, mechanical stress by shear and membraneto-enzyme affinity could alter the system response and mask the effects of inhibition.

Treatments were applied to 7 tree plots replicated 4 times in a randomized complete block design. The orchard block consisted of 'Empire', 'Red Delicious', and 'Rome' on M7a, planted in 1982 on a 15 by 18 ft spacing. Replicates 1 and 2 were on 'Red Delicious', while replicates 3 and 4 were on 'Empire'. Sprays were applied with an FMC handgun sprayer using a 5 HP diaphragm pump at 280 psi until run off, with approx. 4 gal of spray applied to each tree. One application of Pydrin 2.4 EC 178 ml/100 gal was made on 6 Jun in order to build mite populations, since few mites were present early in the season. Miticides were applied on 1 Jul and again on 10 Jul. Conditions during applications were 75°F on both dates, with 2 mph winds and cloudy skies on 1 Jul, and 2-4 mph winds and clear skies on 10 Jul. Treatments were as follows: 1) BAS 300 00 I 20 WP .05 lb AI/100 gal, 2) BAS 300 00 I 20 WP . 12 lb AI/100 gal, 3) BAS 300 11 I 75 WP .05 lb AI/100 gal, 4) BAS 300 11 I 75 WP . 12 lb AI/100 gal, 5) Omite (propargite) 30 WP .60 lb AI/100 gal, and 6) Omite 30 WP .30 lb AI/100 gal, 7) Untreated. ERM counts were taken in samples of 15 leaves per tree on 7 Jun (pre-treatment), and again on 3, 8, 15, 22, 29 Jul, and 5, 12 Aug. SP populations were evaluated on 12 Aug. Predacious mites and beetles were not present early in the season, since they had been eliminated by the Pydrin application. Fruit finish was evaluated by taking 30 fruit from each tree and evaluating for fruit russet on a 0 to 5 basis. Values were used as follows: 0 = no russet, 1 = raised lenticels, 2 = 1-10% russeted, 3 = 11-15% russeted, 4 = 16-50% russeted, and 5 = >51% russeted. Each fruit was evaluated, and an average per replicate was used in the calculations.

Treatments were applied to 5 tree plots replicated 4 times in a randomized complete block design. The orchard block consisted of'Red Delicious' on Mill planted in 1970 on a 20' by 20' spacing. Sprays were applied with an FMC handgun sprayer using a 5 HP diaphragm pump at 280 psi until run off, with approx. 4 gal of spray applied to each tree. There were 5 treatments in this test; 1) = AC-303630 50.9 g AI/100 gal, 2) = AC-303630 101.8 g AI/100 gal, 3) = AC-303630 203.7 g AI/100 gal, 4) = Standard Program, and 5) = untreated control. The Standard Program consisted of: Pink—Thiodan 50 WP 454 g/100 gal, Petal Fall—Imidan 50 WP 454 g/100 gal + Carzol 92 SP 60 g/ 100 gal, 1st Cover—Imidan 454 g/100 gal, 2nd Cover—Imidan 454 g/100 gal + Lannate 1.8 L 235 ml/100 gal, 3rd Cover—Imidan 454 g/100 gal, 4th Cover— Imidan 454 g/100 gal, 5th Cover—Imidan 454 g/100 gal, and 6th Cover—Imidan 454 g/100 gal. Spray dates for all treatments and conditions were: Pink— 12 Apr 57°F, 2 mph wind & clear, Petal Fall—2 May 62°F, 0-2 mph wind & clear, 1st Cover—20 May 65°F, 0-2 mph wind & clear, 2nd Cover—10 Jun 85°F, 5 mph wind & clear, 3rd Cover—1 Jul 75°F 0-2 mph wind & cloudy, 4th Cover—17 Jul 83°F, 5 mph wind & clear, 5th Cover—6 Aug 75°F, 2-3 mph wind & clear, and 6th Cover—28 Aug 75°F, 0-2 mph wind & clear. All treatments received regular fungicide cover sprays of Captan or Captan + Rubigan. Mite and mite predator counts were done on a weekly basis, with each mite sample consisting of 25 leaves per tree, brushed and counted with a binocular scope. SP counts are reported as a 3 min count per tree. SJS counts were done on 1 Aug, and reported as the number damaged per 100 fruit per tree and as the number of sites present in the 20 maximally infested fruit per tree. AA counts were made on 6 Jun and 14 Jun. Data are reported as average aphis per colony of the 10 maximally infested colonies per tree. STLM, WALH, EAS, and RAA counts were done on 21 May. STLM counts are reported as mines per 3 min count per tree. WALH counts are reported as damaged leaves out of 300 leaves per tree. EAS counts are reported as infestations per 300 fruit. RAA counts are reported as colonies per tree. A post-harvest fruit evaluation was done, using 100 fruit per tree and reported as percent damage by AM, CM, EAS, PC, SJS, TABM/LR, and TPB. A postharvest fruit finish evaluation consisted of 30 fruit per tree. Each fruit was rated on a 0 to 5 scale for percent russet. Values used were as follows: 0 = no russet, I = raised lenticels, 2 = 1-10% russeted, 3 = 11-15% russeted, 4 = 16-50% russeted, and 5 = >51% russeted. Mean values of each replicate were used for calculations. Data were transformed to log(x + 1) for analysis at P = 0.01 except on the 15 Jul mite count where P = 0.05.

Soluble polymers bearing ribonuclease have been produced by a co- crosslinking method. The kinetic properties have been studied with the polymer in solution and gelified as a membrane, and the effects of chemical modification and of insolubilization studied separately. The results obtained have been compared with those generated by native enzyme and ribonuclease immobilized within an artificial membrane. Experiments have been performed with a high molecular weight substrate (RNA) and a low molecular weight substrate (cytidine-2′, 3′-phosphate). With the data obtained using these substrates, it is possible to evaluate the effects of the diffusion and accessibility constraints on the kinetic behavior of the enzyme.

Octopus α-amylase has been purified to homogeneity by single-step affinity chromatography on Sepharose-bound wheat albumin inhibitors. Two electrophoretically distinguishable isoamylases are obtained, both consisting of a single polypeptide chain with molecular weight 45,000. Octopus α-amylase is more effectively inhibited by a monomeric than by a dimeric protein inhibitor from wheat. The inhibition is dependent on pH, temperature, and time of preincubation. Properties are compared with those of other animal α-amylases.