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Abstract Purpose Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale (“Cuneo score”). Methods We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients’ information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Results Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). Conclusions In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Background: To investigate changes of objective instrumental measures and correlate with patient reported outcomes (PROs) of radiation-induced dysphagia (RID) after swallowing organs at risk (SWOARs)-sparing IMRT., Methods: Patients (pts) underwent Fiberoptic Endoscopic Evaluation of Swallowing (FEES), Videofluoroscopy (VFS) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaire at baseline, 6 and 12 months after treatment. They were categorized in two groups: MDADI-C ≥ 80 and MDADI-C < 80. Pharyngeal residue (PR) and penetration (P) or aspiration (A) were considered as surrogate of RID., Results: Between 2016 and 2022 we enrolled 75 pts, 40 (53 %) MDADI-C ≥ 80 and 35 (47 %) MDADI-C < 80 at baseline. Among MDADI-C ≥ 80 the mean baseline PR score at FEES was 0,42 rising to 1,36 at 6 months (p = 0,001) and stabilizing to 1,15 at 12 months (p = 0,21); indeed, the mean baseline PR score at VFS was 0,55 rising to 1 at 6 months (p = 0,069) and slightly dropping to 0,7 at 12 months (p = 0,069). Among MDADI-C < 80 the mean baseline PR score at FEES was 0,56 rising to 1,07 at 6 months (p = 0,012) and stabilizing to 1,07 at 12 months (p = 0,99); indeed the mean baseline PR score at VFS was 0,67 rising to 1,19 at 6 months (p = 0,04) and dropping to 0,78 at 12 months (p = 0,04). No correlation was found between PROs and objective measures., Conclusion: Our results show optimal acceptable deglutition preservation from major complications after SWOARs-sparing IMRT by means of low objective scores in both MDADI-C groups. Lack of correlation between PROs and objective measures suggest that referred RID is likely associated to persistence of SWOARs inflammation rather than to a real impairment of function., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Recently, the availability of online medical resources for radiation oncologists and trainees has significantly expanded, alongside the development of numerous artificial intelligence (AI)-based tools. This review evaluates the impact of web-based clinical decision-making tools in the clinical practice of radiation oncology., Material and Methods: We searched databases, including PubMed, EMBASE, and Scopus, using keywords related to web-based clinical decision-making tools and radiation oncology, adhering to PRISMA guidelines., Results: Out of 2161 identified manuscripts, 70 were ultimately included in our study. These papers all supported the evidence that web-based tools can be transversally integrated into multiple radiation oncology fields, with online applications available for dose and clinical calculations, staging and other multipurpose intents. Specifically, the possible benefit of web-based nomograms for educational purposes was investigated in 35 of the evaluated manuscripts. As regards to the applications of digital and AI-based tools to treatment planning, diagnosis, treatment strategy selection and follow-up adoption, a total of 35 articles were selected. More specifically, 19 articles investigated the role of these tools in heterogeneous cancer types, while nine and seven articles were related to breast and head & neck cancers, respectively., Conclusions: Our analysis suggests that employing web-based and AI tools offers promising potential to enhance the personalization of cancer treatment., Competing Interests: Declarations Conflict of interests Isacco Desideri was an editor of La Radiologia Medica at the time of submission of the present manuscript. The authors declare no conflict of interest that are relevant to the content of this article. Ethics approval Not needed., (© 2024. Italian Society of Medical Radiology.)

Objective: This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT)., Materials and Methods: Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software., Results: In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage., Conclusion: Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events., (© 2024. Italian Society of Medical Radiology.)

Metastatic spread to the central nervous system (CNS) is frequent in anaplastic lymphoma kinase ( ALK )-rearranged non-small cell lung cancer (NSCLC) and has an important impact on patient prognosis and quality of life. Leptomeningeal involvement may occur in up to 10% of cases of ALK-positive NSCLC. Lorlatinib is a third-generation ALK inhibitor that has excellent CNS penetrability and demonstrated its efficacy both in pretreated and treatment-naive patients. Herein, we present the case of a 34-year-old patient diagnosed with stage IV ALK-rearranged NSCLC who received two lines of ALK inhibitors (crizotinib followed by alectinib) and several courses of brain stereotactic ablative radiotherapy until leptomeningeal involvement was detected. Third-line lorlatinib was then administered, and 2 months later encephalic MRI documented complete regression of the leptomeningeal involvement that is still maintained after 36 months while treatment with lorlatinib is still ongoing with good tolerability. To the best of our knowledge, this is the longer intracranial response reported in the literature, underlining the importance of the most appropriate choice of systemic treatments and their integration with loco-regional approaches to improve outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Cutaneous squamous cell carcinoma (SCC) is a common skin cancer with significant morbidity and mortality, particularly in advanced stages. Treatment options for metastatic cutaneous SCC in very elderly patients are limited due to concerns about treatment tolerability and potential adverse effects., Case Report: We report the case of a 90-year-old female patient with metastatic cutaneous SCC who was treated with cemiplimab, a monoclonal antibody (m-Ab) against programmed cell death protein 1 (PD-1), in combination with radiotherapy. The patient received cemiplimab for a limited period, during which time she demonstrated significant clinical improvement without severe adverse events. Radiotherapy was performed as a locoregional treatment with the aim to enhance immunotherapy efficacy., Discussion: This case highlights the feasibility and effectiveness of cemiplimab in very elderly patients with metastatic cutaneous SCC. Despite the common apprehensions regarding the use of immunotherapy in this age group, our patient tolerated cemiplimab well, and the combination with radiotherapy proved beneficial. This suggests that even in very elderly patients, short-term use of cemiplimab, in conjunction with locoregional treatments such as radiotherapy, can be a viable and successful therapeutic approach., Conclusion: Cemiplimab, even in combination with radiotherapy, can be effectively and safely administered to very elderly patients with metastatic cutaneous SCC. This case supports the consideration of immunotherapy, even for a limited duration, as a practical option in the management of advanced cutaneous SCC in elderly patients, expanding the potential treatment strategies for this population., Competing Interests: The Authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Introduction : The main goal of radiotherapy (RT) is to deliver a precise dose to the target while sparing the surrounding normal tissue and minimizing side effects. Appropriate patient immobilization is crucial, especially for head and neck cancer (HNC) and Brain Cancer (BC). Conventional closed-face masks (CFMs), while effective in minimizing head motion, can cause significant discomfort, anxiety, and claustrophobia. Open-face masks (OFMs) have been developed to increase patient comfort while providing precise immobilization. Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) extension for scoping reviews and the Arskey and O'Malley framework, an electronic search of EMBASE, PubMed, SCOPUS, and Web of Science was conducted to identify original studies reporting the use and description of OFMs in clinical practice up to April 2024. The inclusion criteria were English-language articles focusing on OFMs for HNC and BC patients undergoing RT. Results: Of 618 titles, 19 articles fulfilled the selection criteria. Most studies were comparative ( n = 13) or observational ( n = 6). The articles were categorized by treatment site, resulting in three groups: BC ( n = 14, 68.4%), HNC ( n = 4, 21.4%), and mixed ( n = 2, 10.5%), which includes both BC and HNC. Of note, 82.4% ( n = 16) of the included studies were published from 2020 onwards, emphasizing the recent adoption of OFM in clinical practice. Conclusions : The reviewed studies show that OFMs, in combination with SGRT, offer significant advantages in terms of patient comfort and positioning accuracy in HNC and BC treatments. Reproducibility in the sub-millimeter and sub-degree range can be achieved, which supports the use of OFMs in clinical practice. Future research should explore innovative combinations of immobilization and monitoring to further improve RT outcomes and ensure precise treatment while increasing patient comfort.

Background: Radiomics can provide quantitative features from medical imaging that can be correlated with various biological features and diverse clinical endpoints. Delta radiomics, on the other hand, consists in the analysis of feature variation at different acquisition time points, usually before and after therapy. The aim of this study was to provide a systematic review of the different delta radiomics approaches., Methods: Eligible articles were searched in Embase, Pubmed, and ScienceDirect using a search string that included free text and/or Medical Subject Headings (MeSH) with 3 key search terms: 'radiomics,' 'texture,' and 'delta.' Studies were analyzed using QUADAS-2 and the RQS tool., Results: Forty-eight studies were finally included. The studies were divided into preclinical/methodological (5 studies, 10.4%); rectal cancer (6 studies, 12.5%); lung cancer (12 studies, 25%); sarcoma (5 studies, 10.4%); prostate cancer (3 studies, 6.3%), head and neck cancer (6 studies, 12.5%); gastrointestinal malignancies excluding rectum (7 studies, 14.6%) and other disease sites (4 studies, 8.3%). The median RQS of all studies was 25% (mean 21% ± 12%), with 13 studies (30.2%) achieving a quality score < 10% and 22 studies (51.2%) < 25%., Conclusions: Delta radiomics shows potential benefit for several clinical endpoints in oncology, such asdifferential diagnosis, prognosis and prediction of treatment response, evaluation of side effects. Nevertheless, the studies included in this systematic review suffer from the bias of overall low methodological rigor, so that the conclusions are currently heterogeneous, not robust and hardly replicable. Further research with prospective and multicenter studies is needed for the clinical validation of delta radiomics approaches., (© 2024. The Author(s).)

Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis., Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering., Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively., Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma., (© 2024. The Author(s).)

Purpose: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities., Materials and Methods: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis., Results: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively)., Conclusions: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT., Methods: Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored., Results: Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases., Conclusions: The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed., (© 2024. The Author(s).)

Background: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting., Patients and Methods: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs)., Results: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O 6 -methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs., Conclusions: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV., Methods: An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP)., Results: Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed., Conclusions: The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP., (© 2024. The Author(s).)

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 reviewer ND is currently organizing a Research Topic with the authors GCI, ID.

Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patientstreated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference -0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference -0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios., Competing Interests: Declaration of competing interest 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. Conflict of Interest IM received a small fee for occasional attendance at the advisory board supported by Lilly, Novartis, Pfizer, Seagen, Accuray which is not related to the contents of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT., Methods: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered., Results: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques., Discussion: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies., (© 2023. Italian Society of Medical Radiology.)

The ongoing global health challenge of cancer is driving the pursuit of innovative avenues for prevention, treatment, and enhanced outcomes. The convergence of nutrition and immune modulation, known as immunonutrition, is ready to act as a catalyst for transformative change in cancer research and therapy. Our study employs a bibliometric analysis to uncover the evolving trends within immunonutrition and cancer research across the past 25 years. Bibliometric data, including authors, journals, affiliations, and countries, were analyzed using the Bibliometrix R package. Clustering algorithms were applied to keywords to identify thematic areas and their evolution. A total of 489 documents were analyzed, showing an annual growth rate of 8.7%, with a collaboration index of 5.41, highlighting comprehensive multidisciplinary involvement within this landscape. Core authors demonstrated sustained productivity, while occasional authors indicated widespread interest. The Medical University of Warsaw led in institutional contributions. Country-wise, Italy, France, and the USA emerged as forerunners in fostering research productivity. Key journals like 'Clinical Nutrition' served as beacons, emphasizing the multidimensional nature of this topic. The analysis highlighted growing research output and several collaborations, indicating the importance of immunoenriched nutrition in cancer treatment. The interplay of core authors and diversified engagement harmoniously accentuates the cross-disciplinary nature of this burgeoning field. International collaboration facilitated knowledge exchange. Prominent documents shaped the field, emphasizing the significance of nutritional interventions. Thematic clusters revealed varied focuses, including pharmaconutrients, surgical approaches, inflammation, and specific cancers. The expanding research output suggests further development, particularly in exploring immunoenriched nutrition's impact on cancer types and patient populations. The multidisciplinary nature and international collaborations enhance the field's progress. Gaps in research underscore the need for original studies and personalized approaches. This study guides future research, informing evidence-based nutritional interventions and advancing cancer care practices., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: ARTO (ClinicalTrials.gov identifier: NCT03449719) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC)., Materials and Methods: All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA < 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points., Results: One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92% v 68.3% in the experimental v control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88; P = .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56% v 23.2% in the experimental v control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38; P < .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57; P < .001) in the experimental versus control arm., Conclusion: The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.

Purpose: Taste alteration (TA) is a frequent acute side effect of radiation treatment in HNSCC patients. Principal aim of our study was to investigate dosimetric parameters in relation to patient-assessed taste impairment in a prospective cohort treated with intensity-modulated radiotherapy., Methods: All patients with locally advanced HNSCC and amenable to radical treatment were included. Chemotherapy-induced taste alteration scale (CITAS), EORTC QLQ-C30 and QLQ-HN43 questionnaires at baseline (T0), 3 weeks (T1) and 3 months (T2) after radiotherapy conclusion were used to assess taste impairment. Base of tongue, submandibular glands (SG), parotid glands (PG) and taste buds, along with anterior and medium third of the tongue, were considered as organs at risk and thus delineated according to consensus guidelines. The mean dose to the above-mentioned structures was correlated with patient-reported outcomes., Results: Between September 2019 and November 2020, 33 patients were recruited, 31 of which analyzed. 71% had oropharyngeal carcinoma, mostly HPV-related (60%). All were treated with tomotherapy. 77.4% had concurrent cisplatin. Mean scores of general taste alterations, global health status and dry mouth and sticky saliva were assessed. The mean doses to the anterior third, medium third and base of the tongue were 23.85, 35.50 and 47.67 Gy, respectively. Taste buds received 32.72 Gy; right and left parotid 25 and 23 Gy; right and left submandibular glands 47.8 and 39.4 Gy. At univariate analysis, dysgeusia correlated with SG mean dose (95% CI 0-0.02 p = 0.05) and PG mean dose (95% CI 0-0.02 p = 0.05); dry mouth with mean dose to anterior (95% CI 0.03-1.47 p = 0.04) and medium third (95% CI 0.02-0.93 p = 0.04) of the tongue, to taste buds (95% CI 0.06-0.96 p = 0.03) and to SGs (95% CI 0.06-0.63 p = 0.02); pain mouth with mean dose to taste buds (95% CI 0-0.02 p = 0.04), to SGs (95% CI 0-0.03 p = 0.03) and to base tongue (95% CI 0-0.02 p = 0.02)., Conclusions: Our analysis supports the influence of dose distribution on the development of TA in HNSCC patients. The contribution of dose to taste buds and tongue subvolumes remains unclear and worthy of further investigation., (© 2023. The Author(s).)

Purpose: Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy., Methods and Materials: Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions., Results: All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60-80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3-58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months, p = 0.03 and 22.7 vs. 27 months, p = 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months, p = 0.02 and 33.5 vs. 53.1 months, p = 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5-10.6, p = 0.007). No grade > /2 adverse were recorded., Conclusions: After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, Cyberknife R rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa., (© 2023. Italian Society of Medical Radiology.)

Background: M1a disease represents an intermediate status between loco-regional relapse and bone metastatic disease. Metastasis directed therapy (MDT), through stereotactic body RT (SBRT) may be offered to patients, aiming to exclusively treat sites of macroscopic relapse and avoiding wide prophylactic treatment volumes. This appears as a viable treatment, especially after the rise of PSMA tailored treatment approaches., Materials and Methods: Data about patients treated in two different institutions were retrieved from a prospectively collected dataset. All included patients were affected by oligo-recurrent M1a disease after definitive RT or radical prostatectomy, defined as ≤ 3 nodal lesions situated above aortic bifurcation and below renal arteries. Both castration resistant PCa (CRPC) and castration sensitive (CSPC) PCa patients were included. All imaging methods were allowed to detect recurrence (CT scan, Choline or PSMA PET/CT).All sites of recurrences were treated with SBRT., Results: Median PFS was 10 months (95% CI 8-17). Twelve patients died, with a median OS of 114 months (95% CI 85-114). Out of the 83 recurrences, 2 (2.4%), 11 (13.25%), 36 (43.37%) and 15 (18%) patients had respectively prostate bed only, pelvic nodal, para-aortic or distant relapse. Furthermore, 19 (22.9%) patients experienced a biochemical only relapse with negative imaging at re-staging., Discussion: MDT conferred a remarkable PFS outcome in a mixed cohort of CSPC and CRPC patients with m1a disease, with an optimal safety profile. Prospective trials are needed in order to compare MDT and ENRT for these patients, allowing to select the best treatment option., (© 2023. Italian Society of Medical Radiology.)

Background: Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers preferentially use stereotactic radiotherapy (SRT) and reserve WBRT for those with >15 lesions, leptomeningeal presentation, rapidly progressive disease, or limited estimated survival. Despite regional differences among preferred dose, fractionation, and treatment technique, we predict survival post-WBRT will remain poor-indicating appropriate application of WBRT in this era of SRT and improved systemic therapies., Methods: A multi-center, international retrospective analysis of patients receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. De-identified data were analyzed centrally. Patients receiving WBRT as part of a curative regimen, prophylactically, or as bridging therapy were excluded. The collected data consisted of patient parameters including prescription dose and fractionation, use of neurocognitive sparing techniques and survival after WBRT. Survival was calculated via the Kaplan-Meier method., Results: Of 29,943 international RT prescriptions written at ten participating centers in 2022, 462 (1.5%) were for palliative WBRT. Participating centers were in the United States (n=138), the United Kingdom (n=111), Hong Kong (n=72), Italy (n=49), Belgium (n=45), Germany (n=27), Ghana (n=15), and Cyprus (n=5). Twenty-six different dose regimens were used. The most common prescriptions were for 3,000 cGy over 10 fractions (45.0%) and 2,000 cGy over 5 fractions (43.5%) with significant regional preferences (P<0.001). Prior SRT was delivered in 32 patients (6.7%), hippocampal avoidance (HA) was used in 44 patients (9.5%), and memantine was prescribed in 93 patients (20.1%). Survival ranged from 0 days to still surviving at 402 days post-treatment. The global median overall survival (OS) was 84 days after WBRT [95% confidence interval (CI): 68.0-104.0]. Actuarial survival at 7 days, 1 month, 3 months, and 6 months were 95%, 78%, 48%, and 32%, respectively. Twenty-seven patients (5.8%) were unable to complete their prescribed WBRT., Conclusions: This moment-in-time analysis confirms that patients with poor expected survival are being appropriately selected for WBRT-illustrating the dwindling indications for WBRT-and demonstrates the variance in global practice. Since poor survival precludes patients from deriving benefit, memantine and HA are best suited in carefully selected cases.