Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma.

PURPOSE: No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. METHODS: Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. RESULTS: From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5-20). Median re-RT dose was 24 Gy (range 18-36 Gy) for a median number of 5 fractions (range 1-6). Median regorafenib treatment duration was 12 weeks (range 3-26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6­month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9-12.7 months) and 75% (95% CI 50.9-89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7-8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand-foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. CONCLUSION: For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary.

Linear accelerator-based stereotactic arrhythmia radioablation for paroxysmal atrial fibrillation in elderly: a prospective phase II trial.

AIMS: Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. METHODS AND RESULTS: Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001). CONCLUSION: The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04575662.

Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial.

PURPOSE: Aim of this study is to evaluate safety and efficacy of SBRT in elderly patients affected by localized prostate cancer (PC). MATERIAL AND METHODS: Men aged 70 years or older were enrolled and analyzed. The SBRT schedule was 35 Gy in 5 fractions administered in 1-2 weeks. According to risk group, androgen deprivation therapy (ADT) was prescribed. Urinary symptoms were evaluated at baseline using the International Prostate Symptom Score (IPSS). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed at the end of treatment, 2 weeks after SBRT and during follow-up using the Common Terminology Criteria for Adverse Events (CTCAE). PSA values were recorded before treatment and during follow-up as biochemical response criteria. RESULTS: Between 07/2019 and 09/2021, 111 patients were enrolled. Median age was 77 years. At the end of treatment, no acute GU/GI toxicities ≥ G2 were observed. At 2-3 weeks after treatment, 3 patients reported G2 GU toxicity, while 14 patients referred G2 GI toxicity. During the last follow up, 26 and 2 patients reported, respectively, G1 and G2 GU toxicity, while 22 and 1 cases described, respectively, G1 and G2 GI toxicity. No late toxicities ≥ G3 were recorded. GU toxicity is related to absence of urethra sparing, increasing PTV volume, Dmax PTV and IPSS; GI toxicity is related to RT schedule (each other day is better than consecutive day), Dmax rectum and IPSS, At a median follow-up of 24 months, excellent biochemical disease control was achieved in all cases with median PSA of 0.5 ng/ml. CONCLUSION: SBRT in elderly patients affected by PC is feasible and well tolerated with excellent biochemical disease control. Longer follow-up is needed to assess late toxicity profile and long-term clinical outcome.

Impact on mental health of the COVID-19 pandemic in a radiation oncology department.

AIM: To evaluate the emotional state and organizational well-being of healthcare workers in radiation oncology departments, during the COVID pandemic. METHODS: A survey was carried out with three questionnaires: Impact of Event Scale-Revised (IES-R); Italian ANAC questionnaire; and Maslach Burnout Inventory (MBI). Comparisons between groups were done by Student's t test. RESULTS: Seventy-eight questionnaires for 26 workers were analyzed. Thirty-three percent of the sample obtained an IES-R high score, such as post-traumatic syndrome. In terms of organizational well-being, younger age and lower working seniority were statistically significant for higher score of ANAC items (p < 0.5). Regarding MBI, 0, 27 and 50% high scores of emotional exhaustion, depersonalization and personal accomplishment were reported, respectively. Low working seniority and male sex were correlated with high score of personal accomplishment (p:0.05; p:0.03). CONCLUSION: Intervention to promote mental health well-being should be implemented in radiation oncology department.

Radiomic analysis to predict local response in locally advanced pancreatic cancer treated with stereotactic body radiation therapy.

PURPOSE: Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up. METHODS: Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS. RESULTS: Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months). CONCLUSIONS: This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach.

Stereotactic Ablative radiation therapy (SABR) for cardiac arrhythmia: A new therapeutic option?

AIM: Stereotactic ablative radiation therapy (SABR) is used in non-oncologic indications, recently even for cardiac arrhythmias. Thus, aim of this analysis is to review preclinical, early clinical evidences and future direction of the latter new treatment approach. METHOD: A collection of available data regarding SABR and cardiac arrhythmias was made, by Pubmed research and 2 independent researchers, including preclinical and clinical data. A review of ongoing trials was conducted on ClinicalTrials.gov. RESULTS: Preclinical research conducted in animal models showed that a safe and effective noninvasive treatment approach for cardiac arrhythmias could be represented by SABR with a median time of response around 2-3 months. The treatment dose plays a crucial role: the atrioventricular node would seem more radiosensitive than the other cardiac electric zones. Clinical data, such as published case series, case reports and early prospective studies, have already suggested the feasibility, efficacy and safety of SABR (25 Gy in one session) for refractory ventricular arrhythmias. CONCLUSION: Considering the ongoing trials of SABR and new technological improvements in radiotherapy (e.g. hybrid magnetic resonance) and in arrhythmias noninvasive mapping systems, the future analyses will improve the reliability of those preliminary results.

Unexpected response to palliative radiotherapy for subcutaneous metastases of an advanced small cell pancreatic neuroendocrine carcinoma: a case report of two different radiation schedules.

BACKGROUND: Skin metastases from pancreatic neuroendocrine carcinoma (PNEC) are rare and their palliative treatment is challenging. We report our experience in the multimodal management of one of the few reported cases of metastatic PNEC with multiple visceral and subcutaneous secondary lesions, focusing on the effectiveness of palliative radiotherapy for skin metastases. CASE PRESENTATION: A 61-years old woman affected by a metastatic PNEC - with subcutaneous growing and bleeding secondary lesions (at the scalp, right scapular region and at the back of the left thoracic wall, respectively) - obtained a successful control of visceral metastases with the use of chemotherapy and an unexpected local response of her skin metastases with palliative radiotherapy. In particular, two subsequent radiation treatments were performed using different fractionation schedules (30 Gy in 10 fractions and 20 Gy in 5 fractions, respectively). Both radiation treatments were well-tolerated and patient's quality of life was improved. Local response was maintained until patient's death - that occurred due to cachexia. CONCLUSIONS: The presented case highlights the effectiveness and the good tolerance of radiotherapy in the treatment of subcutaneous metastases; nevertheless, further knowledge of the optimal local palliative approach for PNEC metastatic sites is necessary. The experience gained in this work is the occasion to encourage a routine integrated multidisciplinary team management of metastatic PNECs because of their clinical complexity. The aim is to guarantee the optimization of the care with personalized and more effective systemic and local treatments - also including supportive cares and treatment-related side effects management.

Left atrial strain after paroxysmal atrial fibrillation linac-based cardiac radioablation in elderly population.

Catheter ablation of atrial fibrillation (AF) may increase the risk of complication in aged patients. Stereotactic arrhythmia radioablation (STAR) is a non-invasive therapeutic alternative for cardiac arrhythmia. This sub-study evaluated left atrial strain (LAS) in elderly AF patients underwent STAR. Symptomatic paroxysmal AF patients aged > 70 years, with antiarrhythmic drugs failure or intolerance, enrolled in a phase II trial that have demonstrated the feasibility of LINAC-based STAR (total dose of 25 Gy single fraction delivered in 3 min), performed a 15-day electrocardiogram Holter monitoring to detect AF episodes (≥ 30 s) and an echocardiographic LAS evaluation before and after STAR (at 1-, 3-, 6- and 12-month). Out 18 patients underwent STAR in the trial, 16 (7 males, 78 ± 5 years) completed the follow-up for LAS study. No baseline difference in echocardiographic and LAS parameters was observed between the 9 patients with AF recurrence during follow-up and those who maintained sinus rhythm. At 6- and 12-month after STAR, LAS reservoir was lower in patients with AF episodes than those without (respectively, p = 0.039 and p = 0.001). Values of left atrial area and volume as well as LAS conduit and contractile phase were not statistically significant different by patient's outcome across evaluations. Although no baseline LAS parameter before STAR seems predict AF recurrence after treatment in elderly patients, lower values of reservoir phase were observed during follow-up in those experiencing AF episodes. More research is needed to better assess the value of LAS monitoring in paroxysmal AF patients underwent Stereotactic cardiac radioablation.

Improving Quality Assurance in a Radiation Oncology Using ARIA Visual Care Path.

PURPOSE: Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. MATERIALS AND METHODS: The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients' reports were categorized based on treatment years period: 2019-2020 (A); 2021 (B); and 2022-2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients' positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5-10% in the case of zero or one major incident. RESULTS: From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0-3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients' photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. CONCLUSIONS: Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient's care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents.

Combined modifications of mexiletine pharmacophores for new lead blockers of Na(v)1.4 channels.

Previously identified potent and/or use-dependent mexiletine (Mex) analogs were used as template for the rational design of new Na(v)-channel blockers. The effects of the novel analogs were tested on sodium currents of native myofibers. Data and molecular modeling show that increasing basicity and optimal alkyl chain length enhance use-dependent block. This was demonstrated by replacing the amino group with a more basic guanidine one while maintaining a proper distance between positive charge and aromatic ring (Me13) or with homologs having the chirality center nearby the amino group or the aromatic ring. Accordingly, a phenyl group on the asymmetric center in the homologated alkyl chain (Me12), leads to a further increase of use-dependent behavior versus the phenyl Mex derivative Me4. A fluorine atom in paraposition and one ortho-methyl group on the xylyloxy ring (Me15) increase potency and stereoselectivity versus Me4. Charge delocalization and greater flexibility of Me15 may increase its affinity for Tyr residues influencing steric drug interaction with the primary Phe residue of the binding site. Me12 and Me15 show limited selectivity against Na(v)-isoforms, possibly due to the highly conserved binding site on Na(v). To our knowledge, the new compounds are the most potent Mex-like Na(v) blockers obtained to date and deserve further investigation.

Molecular dissection of lubeluzole use-dependent block of voltage-gated sodium channels discloses new therapeutic potentials.

Lubeluzole, which acts on various targets in vitro, including voltage-gated sodium channels, was initially proposed as a neuroprotectant. The lubeluzole structure contains a benzothiazole moiety [N-methyl-1,3-benzothiazole-2-amine (R-like)] related to riluzole and a phenoxy-propranol-amine moiety [(RS)-1-(3,4-difluorophenoxy)-3-(piperidin-1-yl)propan-2-ol (A-core)] recalling propranolol. Both riluzole and propranolol are efficient sodium channel blockers. We studied in detail the effects of lubeluzole (racemic mixture and single isomers), the aforementioned lubeluzole moieties, and riluzole on sodium channels to increase our knowledge of drug-channel molecular interactions. Compounds were tested on hNav1.4 sodium channels, and on F1586C or Y1593C mutants functionally expressed in human embryonic kidney 293 cells, using the patch-clamp technique. Lubeluzole blocked sodium channels with a remarkable effectiveness. No stereoselectivity was found. Compared with mexiletine, the dissociation constant for inactivated channels was ~600 times lower (~11 nM), conferring to lubeluzole a huge use-dependence of great therapeutic value. The F1586C mutation only partially impaired the use-dependent block, suggesting that additional amino acids are critically involved in high-affinity binding. Lubeluzole moieties were modest sodium channel blockers. Riluzole blocked sodium channels efficiently but lacked use dependence, similar to R-like. F1586C fully abolished A-core use dependence, suggesting that A-core binds to the local anesthetic receptor. Thus, lubeluzole likely binds to the local anesthetic receptor through its phenoxy-propranol-amine moiety, with consequent use-dependent behavior. Nevertheless, compared with other known sodium channel blockers, lubeluzole adds a third pharmacophoric point through its benzothiazole moiety, which greatly enhances high-affinity binding and use-dependent block. If sufficient isoform specificity can be attained, the huge use-dependent block may help in the development of new sodium channel inhibitors to provide pharmacotherapy for membrane excitability disorders, such as myotonia, epilepsy, or chronic pain.

The Role of Telemedicine for Psychological Support for Oncological Patients Who Have Received Radiotherapy.

AIM: In our radiation departments, all patients received psycho-oncological support during RT and during follow-up. Based on the latter, the aim of this retrospective analysis was to evaluate the role of tele-visits and in-person psychological support for cancer patients after RT, and to report a descriptive analysis pointing out the needs of psychosocial intervention in a radiation department during radiation treatment. METHODS: According to our institutional care management, all patients receiving RT were prospectively enrolled to receive charge-free assessment of their cognitive, emotional and physical states and psycho-oncological support during treatment. For the whole population who accepted the psychological support during RT, a descriptive analysis was reported. For all patients who agreed to be followed up by a psycho-oncologist, at the end of RT, a retrospective analysis was conducted to evaluate the differences between tele-consultations (video-call or telephone) and on-site psychological visits. Patients were followed up by on-site psychological visit (Group-OS) or tele-consult (Group-TC) visit. For each group, to evaluate anxiety, depression and distress, the Hospital Anxiety Depression Scale (HADS), Distress Thermometer and Brief COPE (BC) were used. RESULTS: From July 2019 to June 2022, 1145 cases were evaluated during RT with structured psycho-oncological interviews for a median of 3 sessions (range 2-5). During their first psycho-oncological interview, all the 1145 patients experienced the assessment of anxiety, depression and distress levels with the following results: concerning the HADS-A scale, 50% of cases (574 patients) reported a pathological score ≥8; concerning the HADS-D scale, 30% of cases (340 patients) reported a pathological score ≥8, concerning the DT scale, 60% (687 patients) reported a pathological score ≥4. Eighty-two patients were evaluated after RT: 30 in the Group-OS and 52 in the Group-TC. During follow-up, a median of 8 meetings (range 4-28) were performed. Comparing psychological data at baseline (beginning of RT) and at the last follow-up, in the entire population, a significant improvement in terms of HADS-A, global HADS and BC was shown (p 0.04; p 0.05; and p 0.0008, respectively). Compared to baseline, statistically significant differences were observed between the two groups in terms of anxiety in favor of on-site visit: Group-OS reported a better anxiety score compared with Group-TC. In each group, a statistical improvement was observed in BC (p 0.01). CONCLUSION: The study revealed optimal compliance to tele-visit psychological support, even if the anxiety could be better controlled when patients were followed up on-site. However, rigorous research on this topic is needed.

Phase II Trial of LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for Paroxysmal Atrial Fibrillation in Elderly: Planning and Dosimetric Point of View.

Purpose: Approaching treatment for elderly patients with atrial fibrillation is difficult. A prospective phase II trial evaluating LINAC-based stereotactic arrhythmia radioablation (STAR) safety in this population started in 2021. Dosimetric and planning data were reported. Materials and Methods: A vac-lock bag was used for immobilization in the supine position and a computed tomography (CT, 1 mm) was performed. The clinical target volume (CTV) was defined as the area around the pulmonary veins. An internal target volume (ITV) was added to the CTV to compensate heart and respiratory movement. The planning target volume (PTV) was defined by adding 0-3 mm to the ITV. STAR was performed during free-breathing with a PTV prescription total dose (Dp) of 25 Gy/1 fraction. Flattening filter-free volumetric-modulated arc therapy plans were generated, optimized, and delivered by TrueBeamTM. Image-guided radiotherapy with cone-beam CT and surface-guided radiotherapy with Align-RT (Vision RT) were employed. Results: From May 2021 to March 2022, 10 elderly patients were treated. Mean CTVs, ITVs, and PTVs were 23.6 cc, 44.32 cc, and 62.9 cc, respectively; the mean prescription isodose level and D2% were 76.5% and 31.2 Gy, respectively. The average heart and left anterior descending artery (LAD) Dmean were 3.9 and 6.3 Gy, respectively; the mean Dmax for LAD, spinal cord, left and right bronchus, and esophagus were 11.2, 7.5, 14.3, 12.4, and 13.6 Gy, respectively. The overall treatment time (OTT) was 3 min. Conclusions: The data showed an optimal target coverage, sparing surrounding tissue, in 3 min of OTT. LINAC-based STAR for AF could represent a valid non-invasive alternative for elderly patients who were excluded from catheter ablation.

Adding Concomitant Chemotherapy to Postoperative Radiotherapy in Oral Cavity Carcinoma with Minor Risk Factors: Systematic Review of the Literature and Meta-Analysis.

When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2−5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5−79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8−86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1−86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors.

Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas.

PURPOSE: For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. MATERIAL/METHODS: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2-3 months. RESULTS: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15-36 Gy), and median fractions was 5 (range 1-6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6-56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3-4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. CONCLUSION: Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed.

Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review.

INTRODUCTION: Neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is the current standard-of-care for locally advanced UICC II-III stage rectal cancer (LARC). A pathological complete response (pCR) correlates with survival. Improvements of pCR, including dose escalation, should be explored. The aim of this explorative analysis is to assess the impact on pCR of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). AREAS COVERED: A literature search via PICO (Population, Intervention, Comparison, Outcome) in MEDLINE/PubMed and EMBASE and a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalysis) methodology were performed. Studies that reported pCR rate in patients with LARC in clinical stage T2N+M0 or cT3/4 N0/+M0 treated with preoperative CRT with SIB-IMRT/VMAT (Volumetric Modulated Arc Therapy) were included. Sixty-two studies were identified, but only eight clinical trials with a total of 311 patients were included . Median follow-up was 16-61 months. pCR reached the value of 38%. Good survival outcomes were observed with a mild toxicity profile. EXPERT OPINION: Radiotherapy dose intensification in LARC showed a slight increase of pCR compared to historical studies. Prospective evaluations are necessary to define which patients would benefit most.

Paroxysmal Atrial Fibrillation in Elderly: Worldwide Preliminary Data of LINAC-Based Stereotactic Arrhythmia Radioablation Prospective Phase II Trial.

Treatment approach for elderly patients with atrial fibrillation (AF) is difficult. The present prospective phase-II trial evaluated LINAC-based stereotactic arrhythmia radioablation safety in this population. The reported data of the first 5 patients worldwide, showed no side effects, absence of AF episodes and without antiarrhythmic drugs. Trial Registration: ClinicalTrials.gov, identifier: NCT04575662.

Synergism Between Immunotherapy and Radiotherapy in Esophageal Cancer: An Overview of Current Knowledge and Future Perspectives.

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. Immunotherapy is a promising therapeutic approach that is currently highly investigated in association to standard therapies, including RT, with the aim to improve patients' outcomes. Materials and Methods: A PubMed search was performed with the following keywords in all fields: "esophageal cancer" and "radiotherapy" and "radiation" and "immunotherapy" and "PD-1" and "PD L1." For an overview of ongoing trials, an additional search on ClinicalTrials.gov website was performed using the keywords "esophageal cancer" and "immunotherapy" and "PD-L1" and "CTLA-4" and "radiation" and "radiotherapy." Emerging data from preclinical and clinical studies are suggesting a synergistic effect between immunotherapy and RT. With the aim to update the knowledge of this synergistic immune-mediated antitumor activity and discuss current challenges, the authors summarize published data concerning the basic mechanisms and the effectiveness and tolerance of the combination between immunotherapy and RT for patients with EC, followed by an overview of ongoing clinical trial. Conclusions: Published results encourage the use of personalized therapeutic approaches for EC patients in the future; results from ongoing studies will help to identify the optimal strategies for patient selection and treatment response evaluation.

Investigation of Radiation-Induced Toxicity in Head and Neck Cancer Patients through Radiomics and Machine Learning: A Systematic Review.

Background. Radiation-induced toxicity represents a crucial concern in oncological treatments of patients affected by head and neck neoplasms, due to its impact on survivors' quality of life. Published reports suggested the potential of radiomics combined with machine learning methods in the prediction and assessment of radiation-induced toxicities, supporting a tailored radiation treatment management. In this paper, we present an update of the current knowledge concerning these modern approaches. MATERIALS AND METHODS: A systematic review according to PICO-PRISMA methodology was conducted in MEDLINE/PubMed and EMBASE databases until June 2019. Studies assessing the use of radiomics combined with machine learning in predicting radiation-induced toxicity in head and neck cancer patients were specifically included. Four authors (two independently and two in concordance) assessed the methodological quality of the included studies using the Radiomic Quality Score (RQS). The overall score for each analyzed study was obtained by the sum of the single RQS items; the average and standard deviation values of the authors' RQS were calculated and reported. RESULTS: Eight included papers, presenting data on parotid glands, cochlea, masticatory muscles, and white brain matter, were specifically analyzed in this review. Only one study had an average RQS was ≤ 30% (50%), while 3 studies obtained a RQS almost ≤ 25%. Potential variability in the interpretations of specific RQS items could have influenced the inter-rater agreement in specific cases. CONCLUSIONS: Published radiomic studies provide encouraging but still limited and preliminary data that require further validation to improve the decision-making processes in preventing and managing radiation-induced toxicities.

Linac-based STereotactic Arrhythmia Radioablation (STAR) of ventricular tachycardia: Case report and literature review.

Linac-based STereotactic Arrhythmia Radioablation (STAR) is a safety and effective approach for selected patients with ventricular arrhythmias.