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AimThe goal was to evaluate feasibility, side effects and biochemical no evidence of disease (bNED) after stereotactic body radiation therapy (SBRT) delivered on 5 consecutive days for localized prostate cancer (PC).MethodsThe study was approved by the ethical committee and started in March 2014. Inclusion criteria were age ≤85 years, WHO performance status ≤2, histologically proven adenocarcinoma, low–intermediate risk, no previous surgery (except transurethral resection of the prostate), and a pre-SBRT International Prostatic Symptoms Score of 0–7. The radiotherapy regimen consisted of 35 Gy for low-risk and 37.5 Gy for intermediate-risk PC in 5 consecutive fractions.ResultsAt the time of the analysis, 52 patients were recruited to the study (median age 73 years, range 55–83 years; median follow-up 34 months, range 12–49 months; 34 patients low-risk and 18 intermediate risk). The median initial prostate-specific antigen (PSA) was 5.9 ng/ml (range 1.8–15.7). Acute genitourinary (GU) toxicity was G0 (grade 0) 36/52 (69%), G1 11/52 (21%), G2 5/52 (10%), while acute rectal (GI) toxicity was G0 43/52 (83%), G1 8/52 (15%), G2 1/52 (2%). No acute toxicity ≥G3 was recorded. At the time of analysis late GU and GI toxicities were as follows: GU-G0 43/52 (83%), GU-G1 7/52 (13%), GU-G2 2/52 (4%); GI-G0 48/52 (92%), GI-G1 2/52 (4%), GI-G2 2/52 (4%). No late toxicities ≥G3 were recorded. bNED was 98%. One patient with intermediate PC had distant progression.ConclusionsAccelerated SBRT for low-intermediate PC is feasible and well tolerated with comparable oncological outcome as described for other series with the same RT technique but treatment delivery on every other day. Longer follow-up is needed to the assess late toxicity profile and long-term clinical outcome.

Background/Aim: This study aimed to assess whether the patient’s abdominal adiposity affects the performance of the Exactrac imaging system compared to the cone beam computed tomography (CBCT)-based setup, which was used as the reference positioning for the image-guided radiotherapy (IGRT) delivery to patients with localized prostate cancer. Patients and Methods: The daily positionings of patients with localized prostate cancer undergoing definitive or adjuvant/salvage radiotherapy (RT) were analyzed. The abdominal fat areas and pelvic incidence angle were determined on the CT simulation for each patient. A couple of ExacTrac images and a CBCT were acquired daily to verify the patient setup. We recorded every daily set of the three residual translational errors detected on the CBCT after the ExacTrac-based setup. These sets were clustered within three different thresholds (0.1 mm, 0.2 mm, and 0.3 mm), for each of which the influence of adipose tissues on Exactrac accuracy was assessed as the percentage of sub-threshold displacements as the fat parameters varied. A full bladder and empty rectum preparation protocol was adopted as much as possible. Results: From the assessment of 1,770 daily positionings in 55 patients (38 definitive RT, 17 adjuvant/salvage RT), a good agreement between ExacTrac and CBCT could be inferred, which was quite robust against slight variations in the bladder and rectal filling, and the presence or not of the prostate. The percentages of above-threshold corrections increased with increasing abdominal fat, which therefore seemed to reduce the ExacTrac accuracy. This might be influenced by any intrafraction prostate displacement, likely induced by abdominal respiratory movements, and are more pronounced among overweight men. Conclusion: Our results promote the CBCT use over ExacTrac for IGRT of overweight patients with localized prostate cancer, while calling for attention to the probable need for personalization of planning target volume margins depending on the patient’s body habitus.

Aim: To evaluate the role of stereotactic body radiation therapy in the retreatment of locally recurrent cervical cancers. Brachytherapy is the main choice to treat gynecologic cancers. Methods: Patients with recurrent cervical cancer, previously submitted to radiotherapy, were treated with stereotactic body radiation therapy using a CyberKnife system (Accuray Incorporated, Sunnyvale, California) with a fiducial tracking system. Results: From August 2011 to October 2014, 5 patients have been treated. Median age was 81 years (range, 70-84 years). Two patients were diagnosed with adenocarcinoma endometrioid and 3 with squamous cell carcinoma. Toxicity was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. After a median follow-up of 12 months (range, 8-34 months), no severe (>grade 3) acute/late genitourinary or low gastrointestinal toxicity was observed. Conclusion: Our preliminary results of stereotactic body radiation therapy “simulating” high dose rate for recurrent cervical cancers confirm a minimal toxicity and an optimal outcome. The stereotactic body radiation therapy is an alternative to high dose rate brachytherapy for gynecologic tumors.

BackgroundStereotactic body radiation therapy (SBRT) represents a new treatment option for locally advanced pancreatic cancer (LAPC). An accurate treatment planning with risk-adapted dose prescription with adherence to specific dose constraints for organs at risk (OARs) and the use of daily cone beam CT (CBCT) for image guidance could allow an effective and safe treatment delivery. Here, feasibility and efficacy of SBRT in LAPC treated in our cancer care center are reported.Patients and methods33 unresectable LAPC patients underwent SBRT. In order to respect OAR dose constraints, a risk-adapted dose prescription strategy was adopted, choosing between the following schedules: 42 Gy or 45 Gy in 6 daily fractions with a biologically effective dose (BED) > 70 Gy10 or 36 Gy/6 fractions (estimating a BED 57.6 Gy10). SBRT was delivered with volumetric modulated arc technique (VMAT) and flattening filter-free (FFF) mode. Image guidance was performed by means of CBCT before every treatment session. The patients were evaluated at the end of treatment for acute toxicity and at 3, 6, and 12 months for late toxicity and treatment response.ResultsAt the time of analysis, the median follow-up was 18 months (range 5–34 months). Prior to SBRT, 24 out of 33 patients received induction chemotherapy. Although all patients were previously judged as unresectable, 6 out of 33 (18%) underwent surgery after SBRT; all of them received a BED > 70 Gy10. One-year LC and OS were 81% and 75%, respectively. A total of 12 patients (37%) had an extra-pancreatic progression. No cases of ≥G3 acute or late toxicity were reported.ConclusionIn our experience, risk-adapted dose prescription and image-guided SBRT represents an effective treatment option for LAPC patients.

Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine–kinase inhibitor (TKI). Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI–TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6–12–18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. Results: After a median follow-up of 24 months, 6–12–18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs–TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine–kinase inhibitor (TKI). Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI–TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6–12–18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. Results: After a median follow-up of 24 months, 6–12–18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs–TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Background Parkinson’s disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum’s connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance. Objective This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR + ) in individuals with PD and FoG. Methods Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR + with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1. Results Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group. Conclusions C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.

Background Temporomandibular disorders (TMD) are a set of musculoskeletal conditions involving the temporomandibular joint, masticatory muscles, and/or associated structures, characterized by symptoms as pain, joint stiffness with limited mouth opening, and joint sounds as crepitus. Rheumatic diseases (RD) are a heterogeneous group of conditions affecting the musculoskeletal system, including temporomandibular joint (TMJ). To date, there is a lack of systematic reviews that properly investigated the efficacy of conservative approaches in reducing pain in rheumatic patients affected by TMJ arthritis. Therefore, this systematic review aimed to evaluate the effectiveness of rehabilitative approaches in pain relief in rheumatic patients with TMJ arthritis. Methods PubMed, Scopus, and Web of Science were searched from inception until February 25th, 2024, to identify studies including patients with diagnosis of rheumatic disease affecting the temporomandibular joint who underwent specific rehabilitative approaches to reduce pain intensity. The risk of bias of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Results Out of 479 search results, 115 duplicates were removed, and 364 studies were considered as eligible for inclusion and screened for title and abstract. Out of these, we included 19 papers for full-text screening. Then, 5 papers were included in the synthesis by this systematic review. Four studies assessed patients affected by rheumatoid arthritis, one systemic sclerodermia, and one included patients affected by ankylosing spondylitis, psoriatic arthritis, Sjogren’s syndrome, fibromyalgia, common variable immunodeficiency, and chronic polyarthritis. In the included studies, the interventions consisted of intraarticular TMJ injection of corticosteroids performed with or without anesthetics, or irrigation in three studies, dextrose subcutaneous TMJ perineural injection, and lower-level laser therapy (LLLT). Conclusions This systematic review showed that rehabilitative approaches (e.g., intra-articular injections and LLLT) might be effective in terms of pain relief in TMD RD-related. However, the heterogeneity of the rehabilitative approaches performed, and the low quality of the included studies do not allow to draw certain conclusions regarding the efficacy of these approaches. Further high-quality studies are mandatory to improve the robustness of the efficacy of the different rehabilitative techniques for pain relief in TMD patients affected by rheumatic diseases.

The aim of the study is to investigate morphofunctional circuits underlying musical hallucinations (MH) in a 72-years old female that underwent a simultaneous 18fluoredeoxyglucose positron emission tomography (PET) and advanced magnetic resonance (MR) exam. This represents a particular case of MH occurred in an healthy subject, not displaying neurological or psychopathological disorders, and studied simultaneously with a multimodal approach. For the resting-state fMRI analysis a seed to seed approach was chosen. For the task-based fMRI, 4 different auditory stimuli were presented. Imaging findings were compared with data obtained by ten healthy controls matched for age and sex. Neuropsychological evaluation and questionnaires investigating depression and anxiety were also administered. PET findings showed hypermetabolism of: superior temporal gyri, anterior cingulate, left orbital frontal, and medial temporal cortices. Structural MRI did not show macroscopical lesions except for gliotic spots along the uncinate fascicle pathways with an increased cortical thickness for the right orbitofrontal cortex ( = 0.003). DTI showed increased fractional anisotropy values in the left uncinate fascicle, when compared to controls ( = 0.04). Resting-state fMRI showed increased functional connectivity between the left inferior frontal gyrus and the left temporal fusiform cortex ( = 0.01). Task-based fMRI confirmed PET findings showing an increased activation of the superior temporal gyrus in all the auditory tasks except for the monotone stimulus, with a significant activation of the left orbital frontal cortex only during the song in foreign language, object of MH. Results on cognitive test did not show cognitive impairment, excepting for the performance on Frontal Assessment Battery where the patient fails in the cognitive domains of conceptualization, sensitive to interference, and inhibitory control. The subject did not show depressive or anxiety symptoms. Summarizing, multimodal imaging analyses in the MH case showed a microstructural alteration of the left uncinate fascicle paralleled by an increased metabolism and functional connectivity of cortical regions that receive left uncinate projections (orbital frontal cortex, and medial temporal cortex). This alteration of fronto-hyppocampal circuits could be responsible of retrieval of known songs even in the absence of real stimuli.

The development of effective tools for the sustainable supply of phyto-ingredients and natural substances with reduced environmental footprints can help mitigate the dramatic scenario of climate change. Plant cell cultures-based biorefineries can be a technological advancement to face this challenge and offer a potentially unlimited availability of natural substances, in a standardized composition and devoid of the seasonal variability of cultivated plants. Monounsaturated (MUFA) fatty acids are attracting considerable attention as supplements for biodegradable plastics, bio-additives for the cosmetic industry, and bio-lubricants. Cardoon ( Cynara cardunculus L. var. altilis ) callus cultures accumulate fatty acids and polyphenols and are therefore suitable for large-scale production of biochemicals and valuable compounds, as well as biofuel precursors. With the aim of boosting their potential uses, we designed a biotechnological approach to increase oleic acid content through Agrobacterium tumefaciens -mediated metabolic engineering. Bioinformatic data mining in the C. cardunculus transcriptome allowed the selection and molecular characterization of SAD (stearic acid desaturase) and FAD2.2 (fatty acid desaturase) genes, coding for key enzymes in oleic and linoleic acid formation, as targets for metabolic engineering. A total of 22 and 27 fast-growing independent CcSAD overexpressing (OE) and CcFAD2.2 RNAi knocked out (KO) transgenic lines were obtained. Further characterization of five independent transgenic lines for each construct demonstrated that, successfully, SAD overexpression increased linoleic acid content, e.g., to 42.5%, of the relative fatty acid content, in the CcSAD OE6 line compared with 30.4% in the wild type (WT), whereas FAD2.2 silencing reduced linoleic acid in favor of the accumulation of its precursor, oleic acid, e.g., to almost 57% of the relative fatty acid content in the CcFAD2.2 KO2 line with respect to 17.7% in the WT. Moreover, CcSAD OE6 and CcFAD2.2 KO2 were also characterized by a significant increase in total polyphenolic content up to about 4.7 and 4.1 mg/g DW as compared with 2.7 mg/g DW in the WT, mainly due to the accumulation of dicaffeoyl quinic and feruloyl quinic acids. These results pose the basis for the effective creation of an engineered cardoon cells-based biorefinery accumulating high levels of valuable compounds from primary and specialized metabolism to meet the industrial demand for renewable and sustainable sources of innovative bioproducts.