May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy?

PURPOSE: One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus. METHODS AND MATERIALS: Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020-and post-radiotherapy images in cases of relapse-were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences. RESULTS: We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it. CONCLUSION: These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.

KIT 1 (Keep in Touch) Project-Televisits for Cancer Patients during Italian Lockdown for COVID-19 Pandemic: The Real-World Experience of Establishing a Telemedicine System.

To evaluate the adoption of an integrated eHealth platform for televisit/monitoring/consultation during the COVID-19 pandemic. METHODS: During the lockdown imposed by the Italian government during the COVID19 pandemic spread, a dedicated multi-professional working group was set up in the Radiation Oncology Department with the primary aim of reducing patients' exposure to COVID-19 by adopting de-centralized/remote consultation methodologies. Each patient's clinical history was screened before the visit to assess if a traditional clinical visit would be recommended or if a remote evaluation was to be preferred. Real world data (RWD) in the form of patient-reported outcomes (PROMs) and patient reported experiences (PREMs) were collected from patients who underwent televisit/teleconsultation through the eHealth platform. RESULTS: During the lockdown period (from 8 March to 4 May 2020) a total of 1956 visits were managed. A total of 983 (50.26%) of these visits were performed via email (to apply for and to upload of documents) and phone call management; 31 visits (1.58%) were performed using the eHealth system. Substantially, all patients found the eHealth platform useful and user-friendly, consistently indicating that this type of service would also be useful after the pandemic. CONCLUSIONS: The rapid implementation of an eHealth system was feasible and well-accepted by the patients during the pandemic. However, we believe that further evidence is to be generated to further support large-scale adoption.

The Italian version of the Pediatric Quality of Life Inventory™ (PEDSQL™) 3.0 healthcare satisfaction hematology/oncology module: reliability and validity in radiation oncology.

BACKGROUND: Health-related quality of life (HRQOL) measurement has become an important health care outcome even in oncological pediatric scenario. During radiation therapy care path, pediatric patients and their relatives may suffer from emotional and psychosocial distress not only related to cancer diagnosis, but also due to the procedure and the required daily routine. Despite the high prevalence of psychosocial consequences in this setting, instruments that inquire pediatric HRQOL and healthcare satisfaction have rarely been studied in Italy. Purpose of this study was to investigate reliability and linguistic validation of the PedsQL™ healthcare satisfaction Hematology/Oncology module from its original English version to Italian language. METHODS: Three phases standard procedure of cross-culture adaptation were used to create Italian version of PedsQL™ healthcare satisfaction Hematology/Oncology module. Forward translations and backward translations were performed. Finally, a pilot-testing for understandability of the 'pre-final' version was conducted with parents of children attending our Radiotherapy Center using two methodologies of Cognitive Interviewing ("Think-aloud Interviews" and "Respondent Debriefing"), in order to obtain the final Italian version of the PedsQL™ healthcare satisfaction Hematology/Oncology module. RESULTS: Twenty-five parents (2 father, 23 mothers) were recruited during their children's radiotherapy treatment and the grammatically and conceptually acceptable pre-final version of the PedsQL™ Healthcare Satisfaction Hematology/Oncology Module was administered. The questionnaire was well understood reflecting its linguistic adaptation. Compliance with questionnaire administration was optimal. All subjects stated that the questions were interesting to express their opinion, most of them reported that all the questions of each section were clearly comprehensible and easy to understand, suggesting minimal changes that were double-checked with back translation. Furthermore, six of them spontaneously asked to complete the questionnaire in order to review the assistance received during radiotherapy. CONCLUSION: Our Italian version of the PedsQL™ 3.0 Healthcare Satisfaction Hematology/Oncology Module seems to be a valid and functional instrument to indagate Healthcare Satisfaction.

Dabrafenib-Trametinib and Radiotherapy for Oligoprogressive BRAF Mutant Advanced Melanoma.

The clinical management of metastatic melanoma has been changed by BRAF (BRAFi) and MEK inhibitors (MEKi), which represent a standard treatment for BRAF-mutant melanoma. In oligoprogressive melanoma patients with BRAF mutations, target therapy can be combined with loco-regional radiotherapy (RT). However, the association of BRAF/MEK inhibitors and RT needs to be carefully monitored for potential increased toxicity. Despite the availability of some reports regarding the tolerability of RT + target therapy, data on simultaneous RT and BRAFi/MEKi are limited and mostly focused on the BRAFi vemurafenib. Here, we report a series of metastatic melanoma patients who received fractioned RT regimens for oligoprogressive disease in combination with the BRAFi dabrafenib and the MEKi trametinib, which have continued beyond progression. None of the cases developed relevant adverse events while receiving RT or interrupted dabrafenib and trametinib administration. These cases suggest that a long period of dabrafenib/trametinib interruption during radiotherapy for oligoprogressive disease can be avoided. Prospective trials are warranted to assess the efficacy and safety of the contemporary administration of BRAF/MEK inhibitors and radiotherapy for oligoprogressive disease.

Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma.

Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.

Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience.

Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been attempted in the last years without a significant effect on OS. Although radiological imaging is the gold standard for DIPG diagnosis, the urgent need to improve the survival has led to the reconsideration of biopsy with the aim to better understand the molecular profile of DIPG and support personalized treatment. Methods: In this study, we present a single-center experience in treating DIPG patients at disease progression combining targeted therapies with standard of care. Biopsy was proposed to all patients at diagnosis or disease progression. First-line treatment included RT and nimotuzumab/vinorelbine or temozolomide. Immunohistochemistry-targeted research included study of mTOR/p-mTOR pathway and BRAFv600E. Molecular analyses included polymerase chain reaction, followed by Sanger sequences and/or next-generation sequencing. Results: Based on the molecular profile, targeted therapy was administered in 9 out of 25 patients, while the remaining 16 patients were treated with standard of care. Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (5/9), PI3K/AKT/mTOR pathway and BRAFv600E (1/9), ACVR1 (2/9) and PDGFRA (1/9); no severe side effects were reported during treatment. Response to treatment was evaluated according to Response Assessment in Pediatric Neuro-Oncology criteria, and the overall response rate within the cohort was 66%. Patients treated with targeted therapies were compared with the control cohort of 16 patients. Clinical and pathological characteristics of the two cohorts were homogeneous. Median OS in the personalized treatment and control cohort was 20.26 and 14.18 months, respectively (p = 0.032). In our experience, the treatment associated with the best OS was everolimus. Conclusion: Despite the small simple size of our study, our data suggest a prognostic advantage and a safe profile of targeted therapies in DIPG patients, and we strongly advocate to reconsider the role of biopsy for these patients.

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review.

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low ≥ G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.

Neuro-Oncology Multidisciplinary Tumor Board: The Point of View of the Neuroradiologist.

BACKGROUND: The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended to offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). The aim of the present paper is to describe our nMTB, to evaluate its impact on clinical management decisions, and to assess the role of neuroradiologists. METHODS: The retrospective evaluation of the cases discussed at our nMTB from March 2017 to March 2020. From the electronic records, we extracted epidemiological, clinical and other specific data of nMTB. From the radiological records, we calculated data relating to the number, time for revision, and other specifications of MRI re-evaluation. Statistical analysis was performed. RESULTS: a total of 447 discussions were analyzed, representing 342 patients. The requests for case evaluations came from radiation oncologists (58.8%) and neurosurgeons (40.5%), and were mainly addressed to the neuroradiologist (73.8%). The most frequent questions were about the treatment's changes (64.4%). The change in patient treatment was reported in 40.5% of cases, 76.8% of these were based on the neuroradiologic assessment. A total of 1514 MRI examinations were re-evaluated, employing approximately 67 h overall. The median of the MRI exams reviewed per patient was 3 (min-max 1-12). CONCLUSIONS: Our study supported that the multidisciplinary approach to patient care can be particularly effective in managing brain tumors. A review by an expert neuroradiologist impacts patient management in the context of nMTBs, but has costs in terms of the time and effort spent preparing for it.

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board.

BACKGROUND: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. METHODS: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. RESULTS: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). CONCLUSIONS: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy.

Dynamic 11C-Methionine PET-CT: Prognostic Factors for Disease Progression and Survival in Patients with Suspected Glioma Recurrence.

PURPOSE: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. METHODS: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression. RESULTS: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = 0.002) and T/B (p < 0.001); deceased patients (16/67) showed higher SUVmax (p = 0.03), SUVmean (p = 0.03) and T/B (p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS (p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmaxTTP (p = 0.02, p = 0.01, respectively). SUVmaxTTP was the only dynamic parameter associated with PFS (p = 0.02) and OS (p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmaxTTP were predictive for PFS (all p < 0.05); SUVmaxTTP was predictive for OS (p = 0.02). At multivariate analysis, SUVmaxTTP remained significant for PFS (p = 0.03). CONCLUSION: Semiquantitative parameters and SUVmaxTTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Patients' Satisfaction by SmileInTM Totems in Radiotherapy: A Two-Year Mono-Institutional Experience.

BACKGROUND: Patient's satisfaction is recognized as an indicator to monitor quality in healthcare services. Patient-reported experience measures (PREMs) may contribute to create a benchmark of hospital performance by assessing quality and safety in cancer care. METHODS: The areas of interest assessed were: patient-centric welcome perception (PCWP), punctuality, professionalism and comfort using the Lean Six Sigma (LSS) methodology. The RAMSI (Radioterapia Amica Mia SmileINTM (SI) My Friend RadiotherapySI), project provided for the placement of SI totems with four push buttons using HappyOrNot technology in a high-volume radiation oncology (RO) department. The SI technology was implemented in the RO department of the Fondazione Policlinico Universitario A. Gemelli IRCCS. SI totems were installed in different areas of the department. The SI Experience Index was collected, analyzed and compared. Weekly and monthly reports were created showing hourly, daily and overall trends. RESULTS: From October 2017 to November 2019, a total of 42,755 votes were recorded: 8687, 10,431, 18,628 and 5009 feedback items were obtained for PCWP, professionalism, punctuality, and comfort, respectively. All areas obtained a SI-approved rate ≥ 8.0. CONCLUSIONS: The implementation of the RAMSI system proved to be doable according to the large amount of feedback items collected in a high-volume clinical department. The application of the LSS methodology led to specific corrective actions such as modification of the call-in-clinic system during operations planning. In order to provide healthcare optimization, a multicentric and multispecialty network should be defined in order to set up a benchmark.

Psychological Impact of COVID-19 on Parents of Pediatric Cancer Patients.

The changes and general alarm of the current COVID-19 pandemic have amplified the sense of precariousness and vulnerability for family members who, in addition to the emotional trauma of the cancer diagnosis, add the distress and fear of the risks associated with infection. The primary objectives of the present study were to investigate the psychological impact of the COVID-19 pandemic on the parents of pediatric cancer patients, and the level of stress, anxiety, and the child's quality of life perceived by the parents during the COVID-19 epidemic. The parents of 45 consecutive children with solid and hematological tumors were enrolled. Four questionnaires (Impact of Event Scale-Revised - IES-R; Perceived Stress Scale - PSS; Spielberger State - Trait Anxiety Inventory - STAI-Y; Pediatric Quality of Life Inventory - PedsQL) were administered to the parents at the beginning of the pandemic lockdown. A 75% of parents exhibited remarkable levels of anxiety, with 60 subjects in state scale and 45 subjects in trait scale having scores that reached and exceeded the STAI-Y cut off. The bivariate matrix of correlation found a significant positive correlation between the IES-R and PSS scores (r = 0.55, P < 0.001). There was a positive correlation between the PSS and PedsQL (emotional needs) scale (P < 0.001) and a negative correlation between IES-R and STAI-Y (P < 0.001). The results confirm that parents of pediatric cancer patients have a high psychological risk for post-traumatic symptoms, high stress levels, and the presence of clinically significant levels of anxiety.

The Multidimensional Assessment for Pediatric Patients in Radiotherapy (M.A.P.-RT) Tool for Customized Treatment Preparation: RADAR Project.

Aims: Pediatric patients may experience considerable distress during radiotherapy. Combining psychological interventions with standard therapies can reduce the need for sedation. The RADAR Project aims to use a systematic method of recording data that can reveal patients' difficulties and fragility during treatment. In this context, the aim of our study was to investigate the ability of a multidimensional assessment tool (M.A.P.-RT schedule) to predict the need for sedation during radiotherapy. The schedule, which is administered during the first evaluation, was created to collect information on patients and their families in a standardized way. Materials and Methods: The study enrolled pediatric patients (aged 0-18 years or 18-21 with cognitive impairment). Data were collected by means of the M.A.P.-RT module; this explores various thematic areas, and is completed by the radiation oncologist, psychologist and nurse during their first evaluation. Features were selected by means of the Boruta method (random forest classifier), and the totals of the significant partial scores on each subsection of the module were inserted into a logistic model in order to test for their correlation with the use of anesthesia and with the frequency of psychological support. The results of logistic regression (LR) were used to identify the best predictors. The AUC was used to identify the best threshold for the scores in the evaluation. Results: A total of 99 patients were considered for this analysis. The feature that best predicted both the need for anesthesia and the frequency of psychological support was the total score (TS), the AUC of the ROC being 0.9875 for anesthesia and 0.8866 for psychological support. Conclusion: During the first evaluation, the M.A.P.-RT form can predict the need for anesthesia in pediatric patients, and is a potential tool for personalizing therapeutic and management procedures.

Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management.

Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s- had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.

Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis.

Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB development via inhibition of neuroectodermal differentiation. Moreover, the NOTCH/WNT dysregulation in DS, which is probably associated with an increased risk of leukemia, suggests a pivotal role of this pathway alteration in the pathogenesis of MB; therefore, this condition should be further investigated in future studies by molecular characterizations.

Managing children with brain tumors during the COVID-19 era: Don't stop the care!

The COVID-19 pandemic has substantially stressed health care systems globally, subsequently reducing cancer care services and delaying treatments. Pediatric populations infected by COVID-19 have shown mild clinical symptoms compared to adults, perhaps due to decreased susceptibility. Several scientific societies and governments have released information on the management of patients with cancer, wherein they warn against exposure to SARS-CoV-2 infection and suggest continuing treatment. To determine the best diagnostic and therapeutic approach, multidisciplinary tumor boards should convene regularly, including through conference calls and telematics platforms. A prompt diagnostic workup may reduce children's suffering and prevent loss of confidence in the health care system among parents. Moreover, ensuring adequate support and information regarding measures for preventing SARS-CoV-2 infection in pediatric patients and their families is essential for avoiding panic and excessive stress, allowing early reporting of any suspected symptoms of cancer and, in turn, facilitating early diagnosis and prompt modulation of treatment.

Personalised support of brain tumour patients during radiotherapy based on psychological profile and quality of life.

PURPOSE: Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence patients' quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support. METHODS: Psychological questionnaires-Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)-were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions ('typical' schedule) and a maximum of eight sessions ('intensive' schedule), depending on the patients' psychological profiles, clinical evaluations, and requests. Patients' survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent. RESULTS: Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as 'not distressed' at T0, no statistically significant changes were noted. In contrast, patients who were 'distressed' at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. 'Not distressed' patients required less psychological sessions over the study duration than 'distressed' patients. Interestingly, 'not distressed' GBM patients survived longer than 'distressed' GBM patients. CONCLUSIONS: Increased psychological support improved distress, mood, and QoL for patients identified as 'distressed', whereas psychological well-being was maintained with typical psychological support in patients who were identified as being 'not distressed'. These results encourage a standardisation of psychological support for all RT patients.

Regorafenib in Glioblastoma Recurrence: How to Deal With MR Imaging Treatments Changes.

The treatment of recurrent high-grade gliomas remains a major challenge of daily neuro-oncology practice, and imaging findings of new therapies may be challenging. Regorafenib is a multi-kinase inhibitor that has recently been introduced into clinical practice to treat recurrent glioblastoma, bringing with it a novel panel of MRI imaging findings. On the basis of the few data in the literature and on our personal experience, we have identified the main MRI changes during regorafenib therapy, and then, we defined two different patterns, trying to create a simple summary line of the main changes of pathological tissue during therapy. We named these patterns, respectively, pattern A (less frequent, similar to classical progression disease) and pattern B (more frequent, with decreased diffusivity and decrease contrast-enhancement). We have also reported MR changes concerning signal intensity on T1-weighted and T2-weighted images, SWI, and perfusion imaging, derived from the literature (small series or case reports) and from our clinical experience. The clinical implication of these imaging modifications remains to be defined, taking into account that we are still at the dawn in the evaluation of such imaging modifications.

Case Report: A Case Report of Stereotactic Ventricular Arrhythmia Radioablation (STAR) on Large Cardiac Target Volume by Highly Personalized Inter- and Intra-fractional Image Guidance.

Introduction: Although catheter ablation is the current gold standard treatment for refractory ventricular arrhythmias, sometimes its efficacy is not optimal and it's associated with high risks of procedural complication and death. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted for such clinical presentation, considering its efficacy and safety. Case Presentation: We do report our experience managing a case of high volume of left ventricle for refractory ventricular tachycardia in advanced heart failure patient, by delivering a single fraction of STAR through an highly personalization of dose delivery applying repeated inter- and continuous intra-fraction image guidance. Conclusion: According to the literature reports, we recommend considering increasing as much as possible the personalization features and safety technical procedure as long as that is not significantly affecting the STAR duration. Moreover, the duration in itself shouldn't be the main parameter, but balanced into the frame of possibly obtainable outcome improvement. At best of our knowledge, this is the first report applying such specific technology onto this clinical setting. Future studies will clarify these issues.