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The contemporary individual is immersed in a reality characterized by a rapid sequence of stimuli and actions and he is often unable to fully live the present moment.

Background and Objectives: Prostate cancer treatments paradigms are in continuous evolution, especially in metastatic setting. In this context, the Genito-Urinary (GU) Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO) aimed to create a Consensus on radiotherapy indication in de novo metastatic hormone sensitive prostate cancer both on primary tumour and metastatic sites., Methods: A panel of experts, involved in clinical management of prostate cancer, through the estimate-talk-estimate (ETE) method, developed a list of items and correspondent statements on the identified topic., Key Findings: Seven conclusive items were identified with 12 statements about the chosen topic, radiotherapy in metastatic hormone sensitive prostate cancer on primary tumour and metastatic sites., Conclusions and Clinical Implications: This consensus might help clinicians in prostate cancer managing in daily clinical practice., Competing Interests: Conflict of Interest Statement BAJF reported research funding from ACCURAY, IBA, AIRC (Italian Association for Cancer Research) and Fondazione IEO-CCM (Istituto Europeo di Oncologia-Centro Cardiologico Monzino). NGL reported funds from AstraZeneca, Amgen, Janseen. AL, ARA, GP, FP, LT, EC, AM, SF, GF, AR, RDA, CS had no funds to report., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The basilar artery is one of the two cases in our body where an arterial vessel is formed by the union of two others - the vertebral arteries. It provides vascular supply to essential structures for the main vital functions; the posterior cerebral arteries originate from it as terminal branches, and form part of the anastomotic circle of Willis., Imaging Findings: Congenital and acquired anomalies of the basilar trunk are described. We provide a schematic and detailed representation of normal anatomical variants - mainly represented by the fenestrated basilar artery or the persistence of carotid-basilar anastomosis; course anomalies are also illustrated, with reference to neuro-vascular conflicts and dolichoectasia. Among congenital anomalies, this pictorial review also shows the variants of the basilar origin, such as in the case of basilar trunk arising from only one of the two vertebral arteries, and the calibre changes - which are represented by aneurysm and hypoplasia. The latter appears to be a risk factor for posterior circulation stroke, when associated with a bilateral posterior foetal variant.Among the acquired forms, this pictorial essay describes some clinical cases of dissections, non-congenital aneurysms, thrombosis and tumour with vascular encasing or compression of basilar artery., Conclusion: CT angiography and MRI allow us to study the posterior intracranial circulation in detail, providing useful pre-treatment information. Therefore, knowledge of congenital or acquired anomalies of the basilar artery is essential for radiologists, neuroradiologists and neurosurgeons., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: “Conflict of Interest - State: - Stefano Palmucci received personal consulting fees and/or speaker fees from Boehringer Ingelheim, F. Hoffmann La Roche Ltd, Elma Research srl, DOT Tech srl; he received personal honorarium for trainer of Respiratory Endpoints Study from Metanoic Health Ltd; he also received traveling support and accomodation from Bracco Imaging, Bayer Schering and ECLAT srl. All mentioned relationships are not related to this submitted manuscript.”

Background : Patients treated with definitive radiotherapy for nasopharyngeal carcinoma (NPC) develop severe dysphagia, affecting their quality of life. Traditional prognosis biomarkers are insufficient, leading to a search for new predictors like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Methods : We retrospectively enrolled 44 NPC patients who underwent definitive radiotherapy between 2010 and 2018. EQUATOR and STROBE network guidelines were adopted. Pre-treatment evaluations were conducted, and post-treatment oropharyngeal dysphagia was assessed using the Sydney Swallow Questionnaire (SSQ) and FEES, then assigning a Dysphagia Outcome and Severity Scale (DOSS) level. Patients were divided based on NLR and PLR cut-offs, comparing subjective dysphagia (SSQ) scores and DOSS results at baseline and after a 5-year follow-up. Multiple linear regression was used for analysis. Results : At baseline, the mean NLR was 2.52 ± 1.10, and the PLR was 208.40 ± 94.35. Multivariate analysis indicated NLR and PLR as significant predictors of DOSS outcomes ( p < 0.001). Conclusions : Baseline inflammation markers, such as NLR and PLR, may be used to predict dysphagia severity in NPC patients undergoing definitive radiotherapy. These markers could help identify patients at higher risk for severe dysphagia and implement tailored therapeutic and rehabilitative strategies to improve their quality of life. Further studies with larger cohorts are needed to confirm these findings and explore additional prognostic factors for dysphagia outcomes in NPC patients.

Ultrasound (US) is the primary tool for evaluating patients with thyroid nodules, and the risk of malignancy assessed is based on US features. These features help determine which patients require fine-needle aspiration (FNA) biopsy. Classification systems for US features have been developed to facilitate efficient interpretation, reporting, and communication of thyroid US findings. These systems have been validated by numerous studies and are reviewed in this article. Additionally, this overview provides a comprehensive description of the clinical and laboratory evaluation of patients with thyroid nodules, various imaging modalities, grayscale US features, color Doppler US, contrast-enhanced US (CEUS), US elastography, FNA biopsy assessment, and the recent introduction of molecular testing. The potential of artificial intelligence in thyroid US is also discussed.

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.

Introduction and Aim: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice., Methods: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated., Results: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity., Conclusion: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

The WWOX gene encodes a 414-amino-acid protein composed of two N-terminal WW domains and a C-terminal short-chain dehydrogenase/reductase (SDR) domain. WWOX protein is highly conserved among species and mainly expressed in the cerebellum, cerebral cortex, brain stem, thyroid, hypophysis, and reproductive organs. It plays a crucial role in the biology of the central nervous system, and it is involved in neuronal development, migration, and proliferation. Biallelic pathogenic variants in WWOX have been associated with an early infantile epileptic encephalopathy known as WOREE syndrome. Both missense and null variants have been described in affected patients, leading to a reduction in protein function and stability. The most severe WOREE phenotypes have been related to biallelic null/null variants, associated with the complete loss of function of the protein. All affected patients showed brain anomalies on magnetic resonance imaging (MRI), suggesting the pivotal role of WWOX protein in brain homeostasis and developmental processes. We provided a literature review, exploring both the clinical and radiological spectrum related to WWOX pathogenic variants, described to date. We focused on neuroradiological findings to better delineate the WOREE phenotype with diagnostic and prognostic implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Battaglia, Scorrano, Spiaggia, Basile, Palmucci, Foti, Spatola, Iacomino, Marinangeli, Francia, Comisi, Corsello, Salpietro, Vittori and David.)

Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient's clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity.

Histopathologically, uveal melanomas (UMs) can be classified as spindle cell, mixed cell and epithelioid cell type, with the latter having a more severe prognosis. The aim of our study was to assess the correlation between the apparent diffusion coefficient (ADC) and the histologic type of UMs in order to verify the role of diffusion-weighted magnetic resonance imaging (DWI) as a noninvasive prognostic marker. A total of 26 patients with UMs who had undergone MRI and subsequent primary enucleation were retrospectively selected. The ADC of the tumor was compared with the histologic type. The data were compared using both one-way analysis of variance (ANOVA) (assessing the three histologic types separately) and the independent t -test (dichotomizing histologic subtypes as epithelioid versus non-epithelioid). Histologic type was present as follows: the epithelioid cell was n = 4, and the spindle cell was n = 11, the mixed cell type was n = 11. The mean ADC was 1.06 ± 0.24 × 10 -3 mm 2 /s in the epithelioid cells, 0.98 ± 0.19 × 10 -3 mm 2 /s in the spindle cells and 0.96 ± 0.26 × 10 -3 mm 2 /s in the mixed cell type. No significant difference in the mean ADC value of the histopathologic subtypes was found, either when assessing the three histologic types separately ( p = 0.76) or after dichotomizing the histologic subtypes as epithelioid and non-epithelioid ( p = 0.82). DWI-ADC is not accurate enough to distinguish histologic types of UMs.

To investigate the clinical impact of multiple courses of irradiation on pediatric patients with progressive diffuse intrinsic pontine glioma (DIPG), we conducted a retrospective case series on three children treated at our institution from 2018 to 2022. All children were candidates to receive systemic therapy with vinorelbine and nimotuzumab. Radiotherapy was administered to a total dose of 54 Gy. At any disease progression, our local tumor board evaluated the possibility of offering a new course of radiotherapy. To determine feasibility and assess toxicity rates, all children underwent clinical and hematological evaluation both during and after the treatment. To assess efficacy, all children performed contrast-enhanced MRI almost quarterly after the end of the treatment. In all children, following any treatment course, neurological improvement (>80%) was associated with a radiological response (41.7-46%). The longest overall survival (24 months) was observed in the child who underwent three courses of radiotherapy, without experiencing significant side effects. Even though it goes beyond the understanding of conventional radiobiology, first and second reirradiation in pediatric patients with progressive DIPG may represent a feasible and safe approach, capable of increasing overall survival and disease-free survival in selected patients and improving their quality of life.

Purpose: Nasopharyngeal cancers (NPC) are very aggressive, and the recurrence rate after radical therapy is high. This study aimed to evaluate the efficacy of brachytherapy (BT) also called interventional radiotherapy (IRT) in primary NPC in comparison with external beam radiotherapy (EBRT) alone., Material and Methods: A systematic search was performed in Scopus, Cochrane, and PubMed databases. Clinical query based on PICO framework was as follows: In patients with NPC (P), is EBRT plus IRT (I) superior to EBRT alone (C) in terms of local control (LC) and toxicity (O)? Full articles evaluating the efficacy of IRT as a boost after EBRT in patients with NPC were considered., Results: Eight papers, including 1,320 patients fulfilled the inclusion criteria. The median 5-year LC for IRT group and no-IRT group was 98% (range, 95.8-100%) and 86% (range, 80.2-91%), respectively; the median 5-year overall survival (OS) for IRT group and no-IRT group was 93.3% (range, 89.2-97.5%) and 82.9% (range, 74.8-91.1%), respectively; the median 5-year DFS for IRT group and no-IRT group was 94.2% (range, 92.5-96%) and 83.9% (range, 73.3-94.6%), respectively; the median 5-year cancer-specific survival (CSS) for IRT group and no-IRT group was 96% (range, 94.5-97.5%) and 88.2% (range, 83.4-93.1%), respectively. G1-2 and G3-4 toxicities were similar in some articles, or significantly lower in patients treated with IRT in other papers., Conclusions: Data suggest that IRT may improve results of external beam radiotherapy in primary NPCs, especially when using new technologies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Objectives: A two-arm parallel randomised controlled trial was conducted to evaluate the efficacy of a group acceptance-based treatment (ABT) in improving pain acceptance, pain catastrophising, kinesiophobia, pain intensity and physical functioning compared to treatment as usual in patients with fibromyalgia (FM) and comorbid obesity., Methods: Female individuals diagnosed with FM and obesity (n = 180) were randomly assigned to either a three-weekly group acceptance-based treatment plus treatment as usual (ABT+TAU) or only TAU. The variables of interest were assessed at baseline (T0) and after the interventions (T1). The treatment protocol for the ABT+TAU condition, designed for an inpatient rehabilitation context, is based on acceptance and commitment therapy but focuses specifically on pain acceptance, a crucial factor in fostering a more functional adaptation to chronic pain., Results: Participants in the ABT+TAU group showed significant improvements in pain acceptance (i.e. the primary outcome), but also in pain catastrophising, kinesiophobia, and performance-based physical functioning (i.e. the secondary outcomes) compared to those in the TAU group. However, there were no significant differences in pain intensity between the two groups., Conclusions: These findings indicate that a brief group-based ABT intervention is effective in enhancing pain acceptance, reducing pain catastrophising and kinesiophobia, and improving performance-based physical functioning. Furthermore, the observed improvements in kinesiophobia and physical functioning may have particular relevance for individuals with comorbid obesity, as they can facilitate greater adherence to physical activity and promote weight loss.

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6-80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12-25) in Group A and 28 months (95% CI 0-56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0-34) in Group A and 45 months (95% CI 0-107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation.

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

Background: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us., Case Presentation: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function., Conclusions: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management., (© 2021. The Author(s).)

Therapy of uveal melanoma aims to preserve the eye and its function and to avoid metastatic dissemination. The treatment choice is difficult and must keep into account several factors; the therapeutic strategy of uveal melanoma should therefore be personalized, sometimes requiring to combine different treatment techniques. Nowadays globe-sparing radiotherapy techniques are often preferred to enucleation. Plaque brachytherapy, the most commonly used eye-preserving therapy, is suitable for small- and medium-sized uveal melanomas. Proton beam radiotherapy is indicated for tumours with noticeable size, challenging shape and location, but is more expensive and less available than brachytherapy. Enucleation is currently restricted to advanced tumours, uveal melanomas with orbital or optic nerve involvement, blind and painful eyes because of treatment-related complications (neovascular glaucoma, chronic inflammatory processes). The effect of proton beam therapy on neoplastic tissue is related to direct cytotoxic action of the radiations, impairment of neoplastic vascular supply and immunologic response. Complications after radiotherapy are frequent and numerous and mainly related to tumour thickness, radiation dose and distance between the tumour and optic nerve. The purpose of this pictorial review is to provide the radiologists with awareness about diagnostic methods and therapeutic options of uveal melanoma. In the present second section, we discuss the therapeutic management of uveal melanoma, describing the main ocular-conserving radiotherapic techniques. We subsequently present an overview of the effects of radiations on neoplastic tissue. Lastly, we review ocular complications following radiotherapy that should be evaluated by radiologists during follow-up MRI examinations.

Uveal melanoma is a malignant neoplasm that derives from pigmented melanocytes of the uvea and involves, in order of decreasing prevalence, the choroid, ciliary body and iris. Its prognosis is related to histopathologic and genetic features, tumor size and location, extraocular extension. The diagnosis is fundamentally based on clinical evaluation (ophthalmoscopy, biomicroscopy) and ultrasonography. MRI is useful in case of untransparent lens or subretinal effusion. Moreover, MRI has a significant role to confirm the diagnosis, in the evaluation of the local extent of the disease with implications for treatment planning, and in the follow-up after radiotherapy treatment. Uveal melanoma can show different morphologic features (lentiform, dome or mushroom shape) and often determines retinal detachment. MR appearance of uveal melanoma mainly depends on the melanin content. Uveal melanoma typically displays high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Nevertheless, imaging appearance may be variable based on the degree of pigmentation and the presence of areas of necrosis or cavitation. Differential diagnosis includes other uveal lesions. The radiologists and in particular MRI play a significant role in the clinical management of uveal melanoma. The purpose of this pictorial review is to provide the radiologists with awareness about diagnostic methods and therapeutic options of uveal melanoma. In the present first section we summarize the MR anatomy of the eye and describe ophthalmological and radiological imaging techniques to diagnose uveal melanomas, with emphasis on the role of MR imaging. Additionally, we review MR imaging appearance of uveal melanomas.

Background/aim: The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification., Patients and Methods: An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment)., Results: Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%)., Conclusion: A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Several studies have shown an inverse relationship between acute infections and cancer development. On the other hand, there is a growing evidence that chronic infections may contribute significantly to the carcinogenesis. Factors responsible for increased susceptibility to infections may include modifications of normal defence mechanisms or impairment of host immunity due to altered immune function, genetic polymorphisms, ageing and malnourishment. Studies have demonstrated that children exposed to febrile infectious diseases show a subsequent reduced risk for ovarian cancer, melanoma and many other cancers, while common acute infections in adults are associated with reduced risks for melanoma, glioma, meningioma and multiple cancers. Chronic inflammation associated with certain infectious diseases has been suggested as a cause for the development of tumours. Mechanisms of carcinogenesis due to infections include cell proliferation and DNA replication by mitogen-activated protein kinase pathway, production of toxins that affect the cell cycle and lead to abnormal cell growth and inhibition of apoptosis. This review was aimed to summarize the available evidence on acute infections as a means of cancer prevention and on the role of chronic infections in the development and progression of cancer., Competing Interests: None

Background and Objectives: To retrospectively assess the value of magnetic resonance enterography (MRE) parameters derived from conventional and diffusion weighted imaging (DWI) sequences to differentiate fibrotic strictures from inflammatory ones in adult patients with Crohn's disease (CD), using surgical specimens as the histopathological reference standard. Material and Methods : Twenty-three patients with CD who had undergone surgical resection of ileal strictures with full-thickness histopathologic analysis within 3 months from preoperative MRE were included. Two radiologists blinded to histopathology in consensus evaluated the following biomarkers on MRE images matched to resected pathological specimens: T1 ratio, T2 ratio, enhancement pattern, mural thickness, pre-stenotic luminal diameter, and apparent diffusion coefficient (ADC). A blinded pathologist graded stricture histological specimens with acute inflammation score (AIS) and fibrosis score (FS). MRE measurements were correlated with the reference standard. Results: Inflammation and fibrosis coexisted in 78.3% of patients. T2 ratio was reduced in patients with severe fibrosis ( p = 0.01). Pre-stenotic bowel dilatation positively correlated with FS ( p = 0.002). The ADC value negatively correlated with FS ( p < 0.001) and was different between FS grades ( p < 0.05). The area under the receiver operating characteristic curve for discriminating between none and mild/moderate-severe bowel wall fibrosis was 0.75 for pre-stenotic bowel dilatation (sensitivity 100%, specificity 44.4%) and 0.97 for ADC (sensitivity 80%, specificity 100%). Conclusions: Inflammation and fibrosis often coexist in CD bowel strictures needing surgery. The combination of parameters derived from conventional MR sequences (T2 ratio, pre-stenotic dilatation) and from DWI (ADC) may provide a contribution to detect and grade bowel fibrosis in adult CD patients.

The literature assumes that activating patients in the treatment is associated with positive health-related outcomes, such as clinical indicators in the normal range, high medication adherence, and low emergency department utilization. In the cardiac population, patient activation, that is the patient's knowledge, skills, confidence, and behaviors needed for managing one's own health and health care, has been less investigated. In addition, limited attention has been given to the role of the partner as an informal caregiver. However, the patient in the care process is rarely alone, and the partner may play a key role in this process. The goal of this dyadic study (N = 100 heterosexual couples with one partner suffering from an acute cardiac event) is to analyze how individual factors (patients' anxiety, depression, medication adherence, pessimistic perception of illness) and the couple's relationship functioning (e.g., different kinds of partner support and dyadic coping) are associated with patient activation. The results showed that patient activation is not a mere question of age. It is positively related to medication adherence and to the partner's support patient activation. It is negatively correlated with the patient's psychological distress, pessimistic perception of illness, and to the partner's hostility. The need for a dyadic approach to both research and intervention with this population is discussed.

Aim: Adenoid cystic carcinoma is a rare tumor of head and neck region and its development in the thoracic region is even less frequent. This implies the absence of guidelines for therapeutic management and a consequent case-by-case approach. The role of radiotherapy is not yet clearly defined, but intensity-modulated radiotherapy allows for improved organ-at-risk sparing. Materials & methods: We have collected the cases of four patients treated at our institutions by the means of intensity-modulated radiotherapy, after endoscopic resection. Results & conclusion: Patients treated achieved long-term disease control of about 5 years, with a minimal acute toxicity. Longer follow-up is needed to drain conclusion on the impact of this treatment on overall survival.

Background: Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor., Conclusion: This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.

Purpose: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma., Methods: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan's grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded., Results: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 μm at baseline to 223 ± 34 μm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded., Conclusion: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.

Aim: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies., Methods: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period., Results: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%)., Conclusion: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Purpose: To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma., Methods: Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography., Results: The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 μm to 243 ± 58 μm and from 437 ± 71 μm to 254 ± 44 μm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups., Conclusion: Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

Aim: The multimodal approach to malignant pleural mesothelioma is gradually becoming the standard of care for this disease in patients with good performance status. Materials & methods: We report our experience concerning eight cases treated with the use of static step-and-shoot intensity-modulated radiotherapy to the whole pleural cavity, in patients already undergoing surgical and/or antiblastic therapy. Results & conclusion: Results at a median follow-up of 16 months showed a median survival from the initial treatment of 29 months, with lung toxicity of grade II reported only in two patients.

We describe our experience, gained over the past 3 years, in the treatment of gastroesophageal junction adenocarcinoma, whose incidence has been increasing in recent years. In our series, we present the results to a follow-up of about 2 years for a total of 18 patients, treated with a particularly intensive combination treatment. It consists of neoadjuvant induction chemotherapy with the protocol docetaxel-cisplatin-5-fluorouracil for four cycles, before a concomitant chemoradiotherapy treatment. During combined phase, patients received an intensity-modulated radiotherapy and a weekly cisplatin. We will present the data to a long follow-up time and we will discuss the literature, the integration with thoracoabdominal surgery and other specific issues of this pathology.

[This corrects the article on p. 223 in vol. 7, PMID: 28971066.].

The CATANA proton therapy center was the first Italian clinical facility making use of energetic (62 MeV) proton beams for the radioactive treatment of solid tumors. Since the date of the first patient treatment in 2002, 294 patients have been successful treated whose majority was affected by choroidal and iris melanomas. In this paper, we report on the current clinical and physical status of the CATANA facility describing the last dosimetric studies and reporting on the last patient follow-up results. The last part of the paper is dedicated to the description of the INFN-LNS ongoing activities on the realization of a beamline for the transport of laser-accelerated ion beams for future applications. The ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) project is introduced and the main scientific aspects will be described.

Purpose: The purpose of this prospective study was to investigate the proton-beam-induced changes in apparent diffusion coefficient (ADC) values of ocular melanoma treated with proton-beam therapy (PBT) in patients undergoing long-term magnetic resonance imaging (MRI) follow-up and to assess whether variations in ADC constitute a reliable biomarker for predicting and detecting the response of ocular melanoma to PBT., Methods: Seventeen patients with ocular melanoma treated with PBT were enrolled. All patients underwent conventional MRI and diffusion-weighted imaging (DWI) at baseline and 1, 3, 6, and 18 months after the beginning of therapy. Tumor volumes and ADC values of ocular lesions were measured at each examination. Tumor volumes and mean ADC measurements of the five examination series were compared; correlation of ADC values and tumor regression was estimated., Results: Mean ADC values of ocular melanomas significantly increased already 1 month after therapy whereas tumor volume significantly decreased only 6 months after therapy. Pretreatment ADC value of ocular melanomas and early change in ADC value 1 month after therapy significantly correlated with tumor regression., Conclusions: In ocular melanoma treated with PBT, ADC variations precede volume changes. Both pretreatment ADC and early change in ADC value may predict treatment response, thus expanding the role of DWI from diagnostic to prognostic.

The management of pediatric thoracic synovial sarcoma remains a matter of debate in clinical oncology, especially as regard to the local control of the disease. Surgery remains the gold standard, while the role and timing of radiotherapy is still controversial. We report a 14-year-old male, who has not received proper treatment at the time of diagnosis and initial management. Intensity-modulated irradiation was performed only at relapse, as a salvage treatment and, at 10-month follow-up, the young patient was free from relapse, without significant acute and subacute toxicity. We discuss the role and timing of radiotherapy in thoracic synovial sarcoma, a disease in which the need to increase local control should be placed in the foreground.