Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype.

BACKGROUND: We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification. METHODS: Patients over 3-years-old received,after surgery,staging and histo-biological analysis,sequential high-dose-methotrexate(HD-MTX),high-dose-etoposide(HD-VP16),high-dose-cyclophosphamide(HD-Cyclo),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in twice daily 1.3 Gy-fractions reached a total dose tailored to the patients' age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease,39 Gy in other/older patients.Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy,respectively,but avoided if metastatic nodules were very big or patients very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available. RESULTS: Eighy-nine patients were enrolled,median age 8.8 years,median follow up 136 months.Overall-survival(OS) and event-free-survival(EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively;5/28 fatal events were not related to relapse(three developed secondary malignancies).Sex,age less than 10 years,histological subtype,presence of MYC/MYCN amplification,reduction in CSI dose,omission of RT-boosts,implementation of myeloablative therapy,presence/absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. CONCLUSIONS: This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.

Impact of Newly Diagnosed Cancer on Bleeding Events in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants.

BACKGROUND: In patients with atrial fibrillation (AF), the association between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy still remains unclear. PURPOSE: We aimed to assess the impact of cancer present at baseline (CB) or diagnosed during follow-up (CFU) on bleeding events in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF) compared with patients without CB or CFU, respectively. METHODS: All consecutive patients with NVAF treated with DOACs for stroke prevention were enrolled between January 2017 and March 2019. Primary outcomes were bleeding events or cardiovascular death, non-fatal stroke and non-fatal myocardial infarction, and the composite endpoint between patients with and without CB and between patients with and without CB. RESULTS: The study population comprised 1170 patients who were followed for a mean time of 21.6 ± 9.5 months. Overall, 81 patients (6.9%) were affected by CB, while 81 (6.9%) were diagnosed with CFU. Patients with CFU were associated with a higher risk of bleeding events and major bleeding compared with patients without CFU. Such an association was not observed between the CB and no CB populations. In multivariate analysis adjusted for anemia, age, creatinine, CB and CFU, CFU but not CB remained an independent predictor of overall and major bleeding (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.8-3.89, p < 0.001; HR 3.02, 95% CI 1.6-3.81, p = 0.001, respectively). CONCLUSION: During follow-up, newly diagnosed primitive or metastatic cancer in patients with NVAF taking DOACs is a strong predictor of major bleeding regardless of baseline hemorrhagic risk assessment. In contrast, such an association is not observed with malignancy at baseline. Appropriate diagnosis and treatment could therefore reduce the risk of cancer-related bleeding.

The emerging role of Artificial Intelligence in proton therapy: A review.

Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices.

Being diagnosed with a rhabdomyosarcoma in the era of artificial intelligence: Whom can we trust?

In the era of big data, young patients may be overwhelmed by artificial intelligence-based tools, like chatbots. Five clinical experts were asked to evaluate the performance of the most currently used chatbots in providing information on a rare cancer affecting young people, like rhabdomyosarcoma. Generally speaking, despite their high performance in giving general information about the disease, these chatbots were considered by the experts to be inadequate in providing suggestions on cancer treatments and specialized centers, and also lacking in "sensitivity." Efforts are planned by the pediatric oncology community to improve the quality of data used to train these tools.

Foreign patients and multicultural challenges in pediatric oncology: The experience of the Istituto Nazionale dei Tumori in Milan.

This paper describes the complexity of the clinical management of foreign minors suffering from cancer, through the clinical experience of an Italian referral center. The study includes 50 patients less than 18 years (22% of the patients admitted to the unit in 2023), 32 foreigners who were Italian resident and 18 who had come to Italy specifically to receive cancer treatment. Patients who migrate for healthcare reasons often arrive at the referral center with advanced disease or relapse. Numerous socio-cultural issues were reported. To address them, specific strategies were implemented to ensure equal and high-quality care for all patients, respecting their needs.

Spectrum of electrocardiographic abnormalities in a large cohort of cardiac masses.

BACKGROUND: Cardiac masses represent a heterogeneous clinical scenario. Potential electrocardiographic (ECG) red flags of malignancy remain to be investigated. OBJECTIVES: The purpose of this study was to describe the spectrum of ECG abnormalities in a large cohort of cardiac masses and to evaluate potential red flags suggestive of malignancy. METHODS: This was an observational cohort study of 322 consecutive patients with a cardiac mass and available ECG at Bologna University Hospital. All masses were diagnosed by histologic examination or, in the case of cardiac thrombi, by radiologic resolution after proper anticoagulant therapy. Multivariable regression analysis was used to assess potential predictors of malignancy among ECG abnormalities. All-cause mortality at follow-up was evaluated. RESULTS: Of 322 patients, 98 (30.4%) had malignant tumors. Compared with patients with benign masses, those with malignant tumors exhibited a higher heart rate, right-axis deviation, greater depolarization, repolarization abnormalities, and bradyarrhythmia at presentation. Regarding specific ECG features, a higher heart rate on admission (P = .014), bradyarrhythmias (P = .009), ischemic-like repolarization abnormalities (ST-segment deviation, both depression and elevation, and negative T-wave; P <.001), low voltages (P = .001), and right-axis deviation (P = .025) were identified as independent predictors of malignancy. Considering these specific ECG alterations, a malignancy-oriented ECG was associated with higher mortality at follow-up (median 20.7 months). CONCLUSION: ECG frequently is abnormal in cases of malignant cardiac tumors. Some specific ECG changes are strongly suggestive for malignancy and type of infiltration.

Caring for children with cancer evacuated from Ukraine: The patients' perception.

BACKGROUND AND AIMS: Since the beginning of the war in Ukraine on February 24, 2022, many pediatric oncology centers welcomed evacuated patients. To better understanding the needs of patients and families arriving at two Lombardy hospitals in the period March to November 2022, an anonymous questionnaire investigated the families' backgrounds, feelings, and impressions about hospitality and care. METHODS: Twenty questions investigated how patients had reached Italy, from whom they had received help (logistically/financially); the emotions regarding their status as war refugees; the knowledge, expectations, and opinions about Italy and Italians; the quality of medical care received and the relationships with the healthcare staff; lastly, suggestions to improve assistance. RESULTS: The questionnaires were completed by 19/32 patients/parents in November 2022 in two different pediatric-oncology centers. Most families had reached Italy (58%) and received medical care (95%) with the help of charities and the Italian Public Health Care System. A significant majority (69%) expressed satisfaction with the assistance provided. The Italian population demonstrated remarkable warmth, for 95% exhibiting friendliness and for 58% generosity. An improvement in their stay could be linked with the positive outcome of their children's cancer (15%), achieving complete family reunification (15%), the cessation of the conflict (10%), and the overcoming of language barriers (10%). CONCLUSIONS: Providing care for children from another country, not only grappling with the trauma of fleeing their homeland but also battling cancer, is an immense undertaking. It demands a diverse range of efforts and resources to ensure a positive and fulfilling outcome for this experience.

Treatment at relapse for synovial sarcoma of children and adolescents: A multi-institutional European retrospective analysis.

PURPOSE: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. PATIENTS AND METHODS: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. RESULTS: The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. CONCLUSION: Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score.

BACKGROUND: Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses' malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability. METHODS: Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors. RESULTS: In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0-8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96-0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932; P=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (P<0.001; hazard ratio, 5.70) at follow-up. CONCLUSIONS: A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications.

A multicenter high-quality data registry for advanced proton therapy approaches: the POWER registry.

BACKGROUND: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. METHODS: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

Changes in glial cell activation and extracellular vesicles production precede the onset of disease symptoms in transgenic hSOD1G93A pigs.

SOD1 gene is associated with progressive motor neuron degeneration in the familiar forms of amyotrophic lateral sclerosis. Although studies on mutant human SOD1 transgenic rodent models have provided important insights into disease pathogenesis, they have not led to the discovery of early biomarkers or effective therapies in human disease. The recent generation of a transgenic swine model expressing the human pathological hSOD1G93A gene, which recapitulates the course of human disease, represents an interesting tool for the identification of early disease mechanisms and diagnostic biomarkers. Here, we analyze the activation state of CNS cells in transgenic pigs during the disease course and investigate whether changes in neuronal and glial cell activation state can be reflected by the amount of extracellular vesicles they release in biological fluids. To assess the activation state of neural cells, we performed a biochemical characterization of neurons and glial cells in the spinal cords of hSOD1G93A pigs during the disease course. Quantification of EVs of CNS cell origin was performed in cerebrospinal fluid and plasma of transgenic pigs at different disease stages by Western blot and peptide microarray analyses. We report an early activation of oligodendrocytes in hSOD1G93A transgenic tissue followed by astrocyte and microglia activation, especially in animals with motor symptoms. At late asymptomatic stage, EV production from astrocytes and microglia is increased in the cerebrospinal fluid, but not in the plasma, of transgenic pigs reflecting donor cell activation in the spinal cord. Estimation of EV production by biochemical analyses is corroborated by direct quantification of neuron- and microglia-derived EVs in the cerebrospinal fluid by a Membrane Sensing Peptide enabled on-chip analysis that provides fast results and low sample consumption. Collectively, our data indicate that alteration in astrocytic EV production precedes the onset of disease symptoms in the hSODG93A swine model, mirroring donor cell activation in the spinal cord, and suggest that EV measurements from the cells first activated in the ALS pig model, i.e. OPCs, may further improve early disease detection.

Local treatment in initially unresected non-rhabdomyosarcoma soft-tissue sarcomas of children and adolescents: A retrospective single-center experience.

BACKGROUND: Pediatric non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS) are a heterogeneous group of aggressive tumors. Patients with locally advanced/initially unresected disease represent a subset of patients with unsatisfactory outcome: limited data are available on the best treatment approach, in particular regarding local therapy. METHODS: This retrospective analysis concerned 71 patients < 21 years old with nonmetastatic, initially unresected adult-type NRSTS, treated at a referral center for pediatric sarcomas from 1990 to 2021. Patients were treated using a multimodal approach, based on the protocols adopted at the time of their diagnosis. RESULTS: The series included a selected group of patients with unfavorable clinical characteristics, i.e., most cases had high-grade and large tumors, arising from axial sites in 61% of cases. All patients received neoadjuvant chemotherapy, 58 (82%) had delayed surgery (R0 in 45 cases), and 50 (70%) had radiotherapy. Partial response to chemotherapy was observed in 46% of cases. With a median follow-up of 152 months (range, 18-233), 5-year event-free survival (EFS) and overall survival (OS) were 39.9% and 56.5%, respectively. Survival was significantly better for patients who responded to chemotherapy, and those who had a delayed R0 resection. Local relapse at 5 years was 7.7% for patients who did not undergo delayed surgery. CONCLUSIONS: Our series underscores the unsatisfactory outcome of initially unresected NRSTS patients. Improving the outcome of this patient category requires therapeutic strategies able to combine novel effective systemic therapies with a better-defined local treatment approach to offer patients the best chances to have R0 surgery.

Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report.

PURPOSE: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. METHODS: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. RESULTS: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. CONCLUSIONS: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.

More than Five Decades of Proton Therapy: A Bibliometric Overview of the Scientific Literature.

BACKGROUND: The therapeutic potential of proton therapy (PT) was first recognized in 1946 by Robert Wilson, and nowadays, over 100 proton centers are in operation worldwide, and more than 60 are under construction or planned. Bibliometric data can be used to perform a structured analysis of large amounts of scientific data to provide new insights, e.g., to assess the growth and development of the field and to identify research trends and hot topics. The aim of this study is to provide a comprehensive bibliometric analysis of the current status and trends in scientific literature in the PT field. METHODS: The literature on PT until the 31st December 2022 in the Scopus database was searched, including the following keywords: proton AND radiotherapy AND cancer/tumor in title, abstract, and/or keywords. The open-source R Studio's Bibliometrix package and Biblioshiny software (version 2.0) were used to perform the analysis. RESULTS: A total of 7335 documents, mainly articles (n = 4794, 65%) and reviews (n = 1527, 21%), were collected from 1946 to 2022 from 1054 sources and 21,696 authors. Of these, roughly 84% (n = 6167) were produced in the last 15 years (2008-2022), in which the mean annual growth rate was 13%. Considering the corresponding author's country, 79 countries contributed to the literature; the USA was the top contributor, with 2765 (38%) documents, of whom 84% were single-country publications (SCP), followed by Germany and Japan, with 535 and 531 documents of whom 66% and 93% were SCP. Considering the themes subanalysis (2002-2022), a total of 7192 documents were analyzed; among all keywords used by authors, the top three were radiotherapy (n = 1394, 21% of documents), intensity-modulated radiotherapy (n = 301, 5%), and prostate cancer (n = 301, 5%). Among disease types, prostate cancer is followed by chordoma, head and neck, and breast cancer. The change in trend themes demonstrated the fast evolution of hotspots in PT; among the most recent trends, the appearance of flash, radiomics, relative biological effectiveness (RBE), and linear energy transfer (LET) deserve to be highlighted. CONCLUSIONS: The results of the present bibliometric analysis showed that PT is an active and rapidly increasing field of research. Themes of the published works encompass the main aspects of its application in clinical practice, such as the comparison with the actual photon-based standard of care technique and the continuing technological advances. This analysis gives an overview of past scientific production and, most importantly, provides a useful point of view on the future directions of the research activities.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

Treatment at Relapse for Synovial Sarcoma of Children, Adolescents and Young Adults: From the State of Art to Future Clinical Perspectives.

While the overall prognosis is generally quite satisfactory in children, adolescents and young adults with localised synovial sarcoma at first diagnosis, the outcome remains poor for patients after relapse. Conversely to the front-line standardised treatment options, patients with relapse generally have an individualised approach and to date, there is still a lack of consensus regarding standard treatment approaches. Studies on relapsed synovial sarcoma were able to identify some prognostic variables that influence post-relapse survival, in order to plan risk-adapted salvage protocols. Treatment proposals must consider previous first-line treatments, potential toxicities, and the possibility of achieving an adequate local treatment by new surgery and/or re-irradiation. Effective second-line drug therapies are urgently needed. Notably, experimental treatments such as adoptive engineered TCR-T cell immunotherapy seem promising in adults and are currently under validation also in paediatric patients.

Prevalence of Pericardial Late Gadolinium Enhancement in Patients After Cardiac Surgery: Clinical and Histological Correlations.

BACKGROUND: Pericardial late gadolinium enhancement (LGE) is usually associated with active pericarditis, but it is not infrequently found in patients after cardiac surgery even a long time after the intervention. The clinical relevance of this finding and its histological correlates are unknown. We sought to determine the prevalence of chronic pericardial LGE in patients after cardiac surgery. METHODS: All consecutive patients with previous cardiac surgery, who were referred to cardiovascular magnetic resonance between January 2017 and December 2021 were enrolled in the study. Cardiovascular magnetic resonance examination protocol was adapted to clinical indication but always included standard LGE acquisitions. Two independent observers blinded to clinical data assessed the presence of pericardial enhancement on LGE sequences. Fifteen patients underwent cardiac reintervention and pericardial biopsies were obtained. The primary study end point was to assess the prevalence of pericardial enhancement after cardiac surgery and identify possible determinants. The secondary end point was to correlate pericardial enhancement with clinical symptoms and histopathology. RESULTS: Two hundred four patients were included in the study. The median time between surgery and cardiovascular magnetic resonance was 160 months (35-226 months). Pericardial LGE was observed in 90 patients (44%). All patients were asymptomatic, and no specific treatment for pericarditis was started. All patients remained asymptomatic at a 1-year clinical follow-up. Pericardial LGE was significantly correlated with the number of previous surgeries (P=0.03). Pericardial fibrosis was detected in all 15 pericardial biopsy specimens; pericardial LGE was present in 7 patients (47%) who underwent biopsy. Histological signs of low-grade inflammation were detected in 6 patients (40%) with severe, circumferential pericardial LGE but in no patient without pericardial enhancement. CONCLUSIONS: Pericardial LGE is a frequent finding even several years after cardiac surgery. Its histological correlate is a chronic subclinical post-pericardiotomy inflammation.

Hypofractionated proton therapy for benign tumors of the central nervous system: A systematic review of the literature.

AIMS: Aim of the present analysis was to report results of a systematic review of the literature in the setting of patients treated with hypoF PT for benign lesions of the central nervous system (CNS). METHODS: The methodology complied with the PRISMA recommendations. PubMed, EMBASE and Scopus databases were interrogated in September 2022. RESULTS: Twelve papers have been selected including patients treated for base of the skull meningiomas (6 papers), vestibular schwannoma (3 papers) and pituitary adenomas (3 papers). Clinical outcomes were evaluated with both radiologic images and clinical parameters. Long-term toxicity was reported in all but one series with an incidence ranging from 2 % to 7 % in patients treated for base of skull meningioma and 1-9 % for schwannoma. CONCLUSIONS: HypoF PT is a safe and effective treatment in selected benign tumors of the CNS. Further dosimetric and clinical comparisons are required to better refine the patients' selection criteria.