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Background and Purpose: The development of Magnetic Resonance Imaging (MRI)-only Radiotherapy (RT) represents a significant advancement in the field. This study introduces a Deep Learning (DL) algorithm designed to quickly generate synthetic CT (sCT) images from low-field MR images in the brain, an area not yet explored., Methods: Fifty-six patients were divided into training (32), validation (8), and test (16) groups. A conditional Generative Adversarial Network (cGAN) was trained on pre-processed axial paired images. sCTs were validated using mean absolute error (MAE) and mean error (ME) calculated within the patient body. Intensity Modulated Radiation Therapy (IMRT) plans were optimised on simulation MRI and calculated considering sCT and original CT as electron density (ED) map. Dose distributions using sCT and CT were compared using global gamma analysis at different tolerance criteria (2 %/2mm and 3 %/3mm) and evaluating the difference in estimating different Dose Volume Histogram (DVH) parameters for target and organs at risk (OARs)., Results: The network generated sCTs of each single patient in less than two minutes (mean time = 103 ± 41 s). For test patients, the MAE was 62.1 ± 17.7 HU, and the ME was -7.3 ± 13.4 HU. Dose parameters on sCTs were within 0.5 Gy of those on original CTs. Gamma passing rates 2 %/2mm, and 3 %/3mm criteria were 99.5 %±0.5 %, and 99.7 %±0.3 %, respectively., Conclusion: The proposed DL algorithm generates in less than 2 min accurate sCT images in the brain for online adaptive radiotherapy, potentially eliminating the need for CT simulation in MR-only workflows for brain treatments., 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., (© 2025 The Authors.)

Introduction: Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option. This study aims to review the current evidence on "modern" CRT for primary or recurrent unresectable BTC., Materials and Methods: A comprehensive search was conducted on PubMed, Scopus, and Cochrane Library to identify relevant papers. Prospective or retrospective trials reporting outcomes after concurrent CRT of unresectable non-metastatic, primary, or recurrent BTC were included. Only English-written papers published between January 2010 and June 2022 were considered., Results: Seventeen papers, comprising a total of 1961 patients, were included in the analysis. Among them, 11 papers focused solely on patients with primary unresectable BTC, while two papers included patients with isolated local recurrences and four papers encompassed both settings. In terms of tumor location, 12 papers included patients with intrahepatic, extrahepatic, and hilar BTC, as well as gallbladder cancer. The median CRT dose delivered was 50.4 Gy (range: 45.0-72.6 Gy) using conventional fractionation. Concurrent CHT primarily consisted of 5-Fluorouracil or Gemcitabine. The pooled rates of 1-year progression-free survival (PFS) and OS were 40.9% and 56.2%, respectively. The median 1- and 2-year OS rates were 63.1% and 29.4%, respectively. Grade ≥3 acute gastrointestinal toxicity ranged from 5.6% to 22.2% (median: 10.9%), while grade ≥3 hematological toxicity ranged from 1.6% to 50.0% (median: 21.7%)., Conclusion: Concurrent CRT is a viable alternative to standard CHT in patients with locally advanced BTC, offering comparable OS and PFS rates, along with an acceptable toxicity profile. However, prospective trials are needed to validate and further explore these findings., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Aim was to compare the efficacy of interventional radiotherapy (IRT) boost vs. external beam radiotherapy (EBRT) boost after chemoradiation (CCRT) in patients with anal cancer (AC)., Methods: The P.I.C.O. framework was: in patients with AC [P], is IRT boost [I] superior to EBRT boost [C] in terms of local control (LC), cancer specific survival (CSS), overall survival (OS), distant meta-static free Survival (DMFS), colostomy free survival (CFS) and toxicity [O]?, Results: 651 patients were analyzed. The median 5-year locoregional control rates was 87.8% in the IRT boost group versus 72.8% in the EBRT boost group. The 5-year cancer-specific survival rate was 91% in the IRT boost group versus 78% in the EBRT boost group. 5-years overall survival was 74.6% in IRT boost versus 67.7% in the EBRT boost. 5-years disease metastasis-free survival rate was 92.9% in IRT boost group vs. 85.6% for the EBRT boost group. Cancer-free survival rate was 76.8% in the IRT group vs. 63.1% in the EBRT boost group. Acute toxicity above grade 2 was less common in the IRT boost group while chronic toxicity was similar between both groups., Conclusion: IRT boost after CCRT could lead to better outcomes than EBRT boost in treating AC., Competing Interests: Declarations. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Ethical approval: A systematic review did not require ethics approval. Consent informed: A systematic review did not require a signed consent informed. Consent for publication: Not applicable., (© 2024. Italian Society of Medical Radiology.)

Objective: Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity., Methods: This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT., Results: Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%., Conclusions: The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Squamous cell carcinoma of the nasal vestibule is considered a rare malignancy that differs from other sinonasal malignancies in many respects. Four staging systems currently exist for this disease, the most recent addition being the "Rome" classification. This study assesses the use of this new classification and its prognostic value regarding various outcome measures. A retrospective multicenter cohort study of patients with a primary squamous cell carcinoma of the nasal vestibule who were treated in three tertiary head and neck oncology referral centers was conducted. A total of 149 patients were included. The median follow-up duration was 27 months. Five-year locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS) were 81.6%, 90.1, and 62.5% respectively. A statistically significant association was observed between the Rome classification and all survival outcomes in both univariable and multivariable analyses. Moreover, it appeared to perform better than the Union for International Cancer Control TNM classification for tumors of the nasal cavity and paranasal sinuses. The new Rome classification can be used effectively and is associated with LRC, DSS, and OS. However, it requires further validation in a larger (prospective) study population.

Purpose: One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus., Methods and Materials: Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020-and post-radiotherapy images in cases of relapse-were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences., Results: We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it., Conclusion: These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005-2018). Survival curves were calculated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95% CI 0.34-0.92, p = 0.022) or SBRT (HR: 0.27, 95% CI 0.13-0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95% CI 0.28-0.70, p < 0.001) and SBRT (HR: 0.40, 95% CI 0.22-0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

Squamous cell carcinoma of the nasal vestibule is reported to account for less than one percent of all head and neck malignancies. It lacks a designated WHO ICD-O topography code, and multiple systems are available for the staging of this disease, which results in unwanted variability and the subsequent poor reliability of data. The aim of this study was to evaluate the currently available staging systems for cancer of the nasal vestibule, including the recently introduced classification by Bussu et al., which built on Wang's original concept but with clearer anatomical cutoffs. Different staging systems for cancer of the nasal vestibule (UICC nasal cavity, UICC skin cancer of the head and neck, Wang and Bussu et al.) were evaluated via a retrospective analysis of 148 patients. The staging system, per Bussu et al., had the most balanced allocation of patients among the stages. When using the Wang classification as a reference, stage migration occurred less frequently with the Bussu classification. The widespread adoption of a single staging system, as well as the introduction of a designated topography code for cancer of the nasal vestibule, could lead to more uniformity in data reporting and improve an understanding of the incidence and disease outcome. The newly proposed carcinoma of the nasal vestibule classification by Bussu et al. has the potential to improve the staging and allocation among stages. Further analysis of survival data is needed to assess which classification system is best suited for nasal vestibule carcinoma.

Aims: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit., Methods: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up., Results: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/β of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%)., Conclusion: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs)., (© 2023. The Author(s).)

Background: Nasal vestibule squamous cell carcinoma (NVSCC) is an ill-defined underestimated condition., Aim/objective: To define the current standard of care., Material and Methods: We review recent acquisitions concerning clinical features and therapeutic approaches., Results: The current AJCC staging system, which attributes to nasal vestibule the same topographic code as nasal cavity proper and the same T-classification criteria as ethmoid, appears inadequate.As for treatment of primary lesions without bone invasion, current evidence suggests that brachytherapy is at least equivalent to surgery and superior to external beams in terms of oncological outcomes, and superior to both modalities in terms of cosmesis and function., Conclusions: As for classification and staging, the nasal vestibule should be defined as a subsite of the nose and paranasal sinuses, distinct from the 'nasal cavity proper and ethmoid', with specific topographic code and T-classification criteria. This will improve the assessment of prognosis and prevalence, underestimated also because of misdiagnosis with skin cancers.Secondly, brachytherapy should become the new standard for the treatment of primary lesions without bone invasion. To optimize the advantages of brachytherapy, we propose novel anatomic criteria for the implantation., Significance: Increasing evidence supports a paradigm shift in staging and treatment of NVSCC.

Introduction: This study aims to apply a conditional Generative Adversarial Network (cGAN) to generate synthetic Computed Tomography (sCT) from 0.35 Tesla Magnetic Resonance (MR) images of the thorax., Methods: Sixty patients treated for lung lesions were enrolled and divided into training (32), validation (8), internal (10,T A ) and external (10,T B ) test set. Image accuracy of generated sCT was evaluated computing the mean absolute (MAE) and mean error (ME) with respect the original CT. Three treatment plans were calculated for each patient considering MRI as reference image: original CT, sCT (pure sCT) and sCT with GTV density override (hybrid sCT) were used as Electron Density (ED) map. Dose accuracy was evaluated comparing treatment plans in terms of gamma analysis and Dose Volume Histogram (DVH) parameters., Results: No significant difference was observed between the test sets for image and dose accuracy parameters. Considering the whole test cohort, a MAE of 54.9 ± 10.5 HU and a ME of 4.4 ± 7.4 HU was obtained. Mean gamma passing rates for 2%/2mm, and 3%/3mm tolerance criteria were 95.5 ± 5.9% and 98.2 ± 4.1% for pure sCT, 96.1 ± 5.1% and 98.5 ± 3.9% for hybrid sCT: the difference between the two approaches was significant (p = 0.01). As regards DVH analysis, differences in target parameters estimation were found to be within 5% using hybrid approach and 20% using pure sCT., Conclusion: The DL algorithm here presented can generate sCT images in the thorax with good image and dose accuracy, especially when the hybrid approach is used. The algorithm does not suffer from inter-scanner variability, making feasible the implementation of MR-only workflows for palliative treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Organs at risk (OARs) delineation is a crucial step of radiotherapy (RT) treatment planning workflow. Time-consuming and inter-observer variability are main issues in manual OAR delineation, mainly in the head and neck (H & N) district. Deep-learning based auto-segmentation is a promising strategy to improve OARs contouring in radiotherapy departments. A comparison of deep-learning-generated auto-contours (AC) with manual contours (MC) was performed by three expert radiation oncologists from a single center., Methods: Planning computed tomography (CT) scans of patients undergoing RT treatments for H&N cancers were considered. CT scans were processed by Limbus Contour auto-segmentation software, a commercial deep-learning auto-segmentation based software to generate AC. H&N protocol was used to perform AC, with the structure set consisting of bilateral brachial plexus, brain, brainstem, bilateral cochlea, pharyngeal constrictors, eye globes, bilateral lens, mandible, optic chiasm, bilateral optic nerves, oral cavity, bilateral parotids, spinal cord, bilateral submandibular glands, lips and thyroid. Manual revision of OARs was performed according to international consensus guidelines. The AC and MC were compared using the Dice similarity coefficient (DSC) and 95% Hausdorff distance transform (DT)., Results: A total of 274 contours obtained by processing CT scans were included in the analysis. The highest values of DSC were obtained for the brain (DSC 1.00), left and right eye globes and the mandible (DSC 0.98). The structures with greater MC editing were optic chiasm, optic nerves and cochleae., Conclusions: In this preliminary analysis, deep-learning auto-segmentation seems to provide acceptable H&N OAR delineations. For less accurate organs, AC could be considered a starting point for review and manual adjustment. Our results suggest that AC could become a useful time-saving tool to optimize workload and resources in RT departments.

Introduction: Adjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST-FORWARD trial recently demonstrated that 1-week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1-week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three-dimensional conformal radiation therapy (3D-CRT) with tangential fields., Methods: Patients affected by left-side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST-FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D-CRT tangential fields and VMAT plans were generated for each patient., Results: The analysis included 21 patients. PTV coverage comparison between 3D-CRT and VMAT plans showed significant increases for GCI (P < 0.05) in VMAT technique; no statistically significant differences were observed regarding HI. For organs at risks (OAR), statistically significant increases were observed in terms of skin V103% (P < 0.002) and ipsilateral lung V30% (P < 0.05) with 3D-CRT and of heart V5% (P < 0.05) with VMAT technique., Conclusions: This in silico study showed that both 3D-CRT and VMAT are dosimetrically feasible techniques in the framework of 1-week hypofractionated treatments for left EBC., (© 2021 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Purpose: As a discipline in its infancy, online adaptive RT (ART) needs new ontologies and ad hoc criteria to evaluate the appropriateness of its use in clinical practice. In this experience, we propose a predictive model able to quantify the dosimetric impact due to daily inter-fraction variability in a standard RT breast treatment, to identify in advance the treatment fractions where patients might benefit from an online ART approach., Methods: The study was focused on right breast cancer patients treated using standard adjuvant RT on an artificial intelligence (AI)-based linear accelerator. Patients were treated with daily CBCT images and without online adaptation, prescribing 40.05 Gy in 15 fractions, with four IMRT tangential beams. ESTRO guidelines were followed for the delineation on planning CT (pCT) of organs at risk and targets. For each patient, all the CBCT images were rigidly aligned to pCT: CTV and PTV were manually re-contoured and the original treatment plan was recalculated. Various radiological parameters were measured on CBCT images, to quantify inter-fraction variability present in each RT fraction after the couch shifts compensation. The variation of these parameters was correlated with the variation of V95% of PTV (ΔV95%) using the Wilcoxon Mann-Whitney test. Fractions where ΔV95% > 2% were considered as adverse events. A logistic regression model was calculated considering the most significant parameter, and its performance was quantified with a receiver operating characteristic (ROC) curve., Results: A total of 75 fractions on 5 patients were analyzed. The body variation between daily CBCT and pCT along the beam axis with the highest MU was identified as the best predictor ( p = 0.002). The predictive model showed an area under ROC curve of 0.86 (95% CI, 0.82-0.99) with a sensitivity of 85.7% and a specificity of 83.8% at the best threshold, which was equal to 3 mm., Conclusion: A novel strategy to identify treatment fractions that may benefit online ART was proposed. After image alignment, the measure of body difference between daily CBCT and pCT can be considered as an indirect estimator of V95% PTV variation: a difference larger than 3 mm will result in a V95% decrease larger than 2%. A larger number of observations is needed to confirm the results of this hypothesis-generating study., 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., (Copyright © 2022 Iezzi, Cusumano, Piccari, Menna, Catucci, D’Aviero, Re, Di Dio, Quaranta, Boschetti, Marras, Piro, Tomei, Votta, Valentini and Mattiucci.)

Introduction: Pancreatic cancer (PC) is one of the most aggressive tumours, and better risk stratification among patients is required to provide tailored treatment. The meaning of radiomics and texture analysis as predictive techniques are not already systematically assessed. The aim of this study is to assess the role of radiomics in PC., Methods: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in PC. The search strategy was 'radiomics [All Fields] AND ("pancreas" [MeSH Terms] OR "pancreas" [All Fields] OR "pancreatic" [All Fields])' and only original articles referred to PC in humans in the English language were considered., Results: A total of 123 studies and 183 studies were obtained using the mentioned search strategy on PubMed and Embase, respectively. After the complete selection process, a total of 56 papers were considered eligible for the analysis of the results. Radiomics methods were applied in PC for assessment technical feasibility and reproducibility aspects analysis, risk stratification, biologic or genomic status prediction and treatment response prediction., Discussion: Radiomics seems to be a promising approach to evaluate PC from diagnosis to treatment response prediction. Further and larger studies are required to confirm the role and allowed to include radiomics parameter in a comprehensive decision support system., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Radiotherapy is highly involved in the management of prostate cancer. Its features and potential applications experienced a radical evolution over last decades, as they are associated to the continuous evolution of available technology and current oncological innovations. Some application of radiotherapy like brachytherapy have been recently enriched by innovative features and multidisciplinary dedications. In this report we aim to put some questions regarding the following issues regarding multiple aspects of modern application of radiation oncology: the current application of radiation oncology; the modern role of stereotactic body radiotherapy (SBRT) for both the management of primary lesions and for lymph-nodal recurrence; the management of the oligometastatic presentations; the role of brachytherapy; the aid played by the application of the organ at risk spacer (spacer OAR), fiducial markers, electromagnetic tracking systems and on-line Magnetic Resonance guided radiotherapy (MRgRT), and the role of the new opportunity represented by radiomic analysis.

Background: The mucosal high-risk (HR) human papillomavirus (HPV) is associated with oropharyngeal carcinogenesis. Aims of this study were to evaluate the prevalence of HR-HPV infection in laryngeal squamous cell carcinoma (LSCC) from different subsites, and the clinico-biological meaning of p16 overexpression. Methods: Ninety-seven LSCCs submitted to primary surgery ( n = 75) or to post-irradiation salvage laryngectomy ( n = 22) were evaluated for HR-HPV DNA and RNA using Luminex-based assays. p16 immunohistochemistry was performed. Results: HR-HPV DNA from HPV16 was detected in seven cases (8.75%), without significant differences between supraglottic and glottic lesions. HPV RNA was never detected. p16 overexpression correlated with HR-HPV DNA, but the kappa agreement score was poor. HPV DNA showed no impact on prognosis. p16 overexpression was associated with a better survival (OS, RFS) in primarily operated cases, while an inverse association with OS was observed in the salvage surgery group. Conclusions: HR-HPV infection appears to have a marginal role in LSCC independent of the anatomical subsite. p16 expression is deregulated in LSCC independent of HPV but displays a prognostic role in patients submitted to primary surgery. The negative predictive role of p16 overexpression in patients undergoing salvage surgery deserves more investigations for validation and elucidation of its clinical relevance.

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

Introduction: Pancreatic cancer (PC) represents an unfavorable prognosis condition, even in patients with resectable disease. The aim of this series was to investigate the role of treatment intensification with adjuvant chemoradiation (CRT) in radically resected PC patients., Methods: Data from PC patients who underwent radical surgery, adjuvant chemotherapy (CT), and CRT throughout a 20-year period were retrospectively collected. Actuarial local control (LC) and the overall survival (OS) were the primary endpoints, with disease-free survival and metastasis-free survival (MFS) representing secondary endpoints., Results: The analysis included 108 PC patients treated with adjuvant CRT and CT from January 2000 to August 2019. Median age was 66 years (range: 40-83), and all patients underwent radical surgical resection with adjuvant CT (88, 81.5%) plus concomitant CRT (101, 93.5%) or radiotherapy alone (7, 6.5%). The median dose delivered to the tumor bed was 50.4 Gy (range: 45-50.6 Gy), while median dose to regional lymphatic drainage stations was 39.6 Gy (range 39.6-45 Gy). Concomitant CT was a gemcitabine-based regimen in the vast majority of patients (87, 80.6%). Median follow-up time was 21 months; the 2- and 5-year LC rates were 75.8% and 59.1%, respectively. Perineural invasion at pathological assessment was found significantly associated with LC (p = 0.028). Median OS was 40 months with 2- and 5-year OS rates of 73.9% and 41.6%, respectively., Conclusions: The outcomes of this series suggest to investigate the possible impact of adding adjuvant CRT to CT in PC patients. Timing and combination of modern CRT with new systemic therapies need to be further investigated to personalize therapy and optimize clinical advantages., (© 2022 S. Karger AG, Basel.)

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

Purpose: Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors., Methods: We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment-response assessment., Results: Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1-25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child-Pugh before and after treatment remained unchanged in all but one patient., Conclusion: MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.

Over the last years, technological innovation in Radiotherapy (RT) led to the introduction of Magnetic Resonance-guided RT (MRgRT) systems. Due to the higher soft tissue contrast compared to on-board CT-based systems, MRgRT is expected to significantly improve the treatment in many situations. MRgRT systems may extend the management of inter- and intra-fraction anatomical changes, offering the possibility of online adaptation of the dose distribution according to daily patient anatomy and to directly monitor tumor motion during treatment delivery by means of a continuous cine MR acquisition. Online adaptive treatments require a multidisciplinary and well-trained team, able to perform a series of operations in a safe, precise and fast manner while the patient is waiting on the treatment couch. Artificial Intelligence (AI) is expected to rapidly contribute to MRgRT, primarily by safely and efficiently automatising the various manual operations characterizing online adaptive treatments. Furthermore, AI is finding relevant applications in MRgRT in the fields of image segmentation, synthetic CT reconstruction, automatic (on-line) planning and the development of predictive models based on daily MRI. This review provides a comprehensive overview of the current AI integration in MRgRT from a medical physicist's perspective. Medical physicists are expected to be major actors in solving new tasks and in taking new responsibilities: their traditional role of guardians of the new technology implementation will change with increasing emphasis on the managing of AI tools, processes and advanced systems for imaging and data analysis, gradually replacing many repetitive manual tasks., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints., Materials and Methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up., Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1-156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2-139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1-139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%., Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.

Background: The implementation of multidisciplinary tumor board (MDTB) meetings significantly ameliorated the management of oncological diseases. However, few evidences are currently present on their impact on pancreatic cancer (PC) management. The aim of this study was to evaluate the impact of the MDTB on PC diagnosis, resectability and tumor response to oncological treatment compared with indications before discussion., Patients and Methods: All patients with a suspected or proven diagnosis of PC presented at the MDTB from 2017 to 2019 were included in the study. Changes of diagnosis, resectability and tumor response to oncological/radiation treatment between pre- and post-MDTB discussion were analyzed., Results: A total of 438 cases were included in the study: 249 (56.8%) were presented as new diagnoses, 148 (33.8%) for resectability assessment and 41 (9.4%) for tumor response evaluation to oncological treatment. MDTB discussion led to a change in diagnosis in 54/249 cases (21.7%), with a consequent treatment strategy variation in 36 cases (14.5%). Change in resectability was documented in 44/148 cases (29.7%), with the highest discrepancy for borderline lesions. The treatment strategy was thus modified in 27 patients (18.2%). The MDTB brought a modification in the tumor response assessment in 6/41 cases (14.6%), with a consequent protocol modification in four (9.8%) cases., Conclusions: MDTB discussion significantly impacts on PC management, especially in high-volume centers, with consistent variations in terms of diagnosis, resectability and tumor response assessment compared with indications before discussion., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)