Memantine in the Prevention of Radiation-Induced Brain Damage: A Narrative Review

Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects

Long-term results of chemoradiation plus pulsed-dose-rate brachytherapy boost in anal canal carcinoma: A mono-institutional retrospective analysis

Purpose: Concurrent chemoradiation (CCRT) is the standard curative treatment of anal canal cancer (ACC). The role of a brachytherapy (BRT) boost in this setting is still debated. Therefore, the aim of this analysis was to retrospectively evaluate the clinical outcomes in a large cohort of ACC patients treated with CCRT plus BRT boost or external beam radiotherapy (EBRT) boost.Material and methods: Patients with non-metastatic ACC, treated in our department between January 2003 and December 2014 were included in this analysis. The initial treatment was based on EBRT to the pelvis (prescribed dose, 45 Gy/1.8 Gy) plus concurrent chemotherapy (5-fluorouracil and mitomycin-C). Patients received a pulsed-dose-rate BRT boost on the primary tumor (median dose, 20 Gy; range, 13-25 Gy) 2-3 weeks after the end of CCRT. In patients with contraindications to BRT, an EBRT boost (prescribed dose, 16 Gy, 2 Gy/fraction) was delivered immediately after CCRT.Results: One-hundred-twenty-three patients were included in this analysis (median age, 61 years; range, 36-93 years; squamous-cell carcinoma, 78%; HIV+, 6%; median follow-up, 71 months; range, 2-158 months). The actuarial 5-year local control (LC), distant metastasis-free survival, colostomy-free survival, and overall survival (OS) rates were 81.7%, 92.3%, 62.3%, and 74.0%, respectively. At univariate analysis, patients aged <= 65 years (p < 0.010), cT1-2 stage (p = 0.004), and receiving a BRT boost (p = 0.015) showed significantly improved OS. At multivariate analysis, advanced tumor stage cT3-cT4 (HR, 2.12; 95% CI: 1.09-4.14; p = 0.027), and age > 65 years (HR, 3.03; 95% CI: 1.54-5.95; p = 0.001) significantly predicted increased risk of mortality. The crude rate of toxicity-related colostomies was 4.9%.Conclusions: The role of BRT boost in ACC remains unclear since the outcomes were not clearly different compared to CCRT alone. However, further improvement of clinical results in ACC treatment is needed, and therefore prospective trials based on advanced (image-guided/adapted) BRT techniques are warranted

Radiotherapy of prostate cancer: Impact of treatment characteristics on the incidence of second tumors

Background: It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. Methods: A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method. Results: With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p:.627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p:.033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p:.034). Conclusions: The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results

Theory of a quodon gas. With application to precipitation kinetics in solids under irradiation

Rate theory of the radiation-induced precipitation in solids is modified with account of non-equilibrium fluctuations driven by the gas of lattice solitons (a.k.a. quodons) produced by irradiation. According to quantitative estimations, a steady-state density of the quodon gas under sufficiently intense irradiation can be as high as the density of phonon gas. The quodon gas may be a powerful driver of the chemical reaction rates under irradiation, the strength of which exponentially increases with irradiation flux and may be comparable with strength of the phonon gas that exponentially increases with temperature. The modified rate theory is applied to modelling of copper precipitation in FeCu binary alloys under electron irradiation. In contrast to the classical rate theory, which disagrees strongly with experimental data on all precipitation parameters, the modified rate theory describes quite well both the evolution of precipitates and the matrix concentration of copper measured by different methodsComment: V. Dubinko, R. Shapovalov, Theory of a quodon gas. With application to precipitation kinetics in solids under irradiation. (Springer International Publishing, Switzerland, 2014

Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study

Objective: Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures. Methods: A multicenter retrospective case-control study included 165 patients. One group included 114 patients who were treated with at least one IT given at diagnosis or within 3 months from the start of GC. A second group included 51 GCA who received only GC or an IT more than 3 months later. Results: The most frequently used ITs were: methotrexate (138 patients), cyclophosphamide (48 patients) and tocilizumab (27 patients). No difference was observed as concerns the follow-up time between groups [48.5 (IQR 26\u201372) vs 40 (IQR 24\u201369), p \u200b= \u200b0.3)]. The first group showed a significantly lower incidence of steroid-induced diabetes (8/114, 7% vs 12/51, 23.5%; p \u200b= \u200b0.003) and no differences for the rate of infections (p \u200b= \u200b0.64). The group was also exposed to lower doses of GC at first (p \u200b< \u200b0.0001) and third (p \u200b< \u200b0.0001, rank-sum test) month. Forty-four patients in the first group (38.6%) compared with 34 in the second one (66.7%) experienced at least one relapse (p \u200b= \u200b0.001). Conclusion: Very early introduction of IT in GCA lowered the incidence of steroid-induced diabetes, possibly due to the lower doses of GC in the first three months. Relapse rate was even lower

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting.&nbsp;PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series.&nbsp;Overall, 18 studies were included in our analysis. In studies reporting “per patient” tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0–46.0%), and the pooled ORR was 80.6% (95%CI 68.7–90.1%). Regarding “per lesion” response, the pooled CR was 53.5% (95%CI 42.1–64.7%) and the pooled ORR was 77.0% (95%CI 56.0–92.6%). One-year LC rate was 80%, and 1-year OS was 67–86.2%. Pain (24.2–92.0%) and erythema (16.6–42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis.&nbsp;ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted