Evaluating the role of plan complexity metrics in online adaptive radiotherapy for pancreatic cancer patients Samuele Cavinato, Matteo Galetto, Alessandro Scaggion, Andrea Bettinelli, Matteo Nardini, Giuditta Chiloiro, Angela Romano, Marta Paiusco, Luca Boldrini, Lorenzo Placidi Medical Physics, 2026 Purpose To systematically investigate the behavior of plan complexity metrics (PCMs) in an MR‐Linac online adaptive radiotherapy (oART) workflow for pancreatic cancer, and to evaluate their potential as surrogate indicators of delivery accuracy. Methods Thirty‐seven patients with locally advanced pancreatic cancer were retrospectively analyzed, yielding 222 MR‐Linac plans (37 reference and 185 delivered fractions). Fifteen PCMs were extracted from plans generated with three optimizers: Penalty, Objectives and Constraints, and A3i (current clinical practice). Plan specific quality assurance (PSQA) has been performed through an independent dose calculation algorithm. Statistical analyses included: (i) inter‐optimizer comparisons (ANOVA and mixed‐effects models), (ii) variance decomposition of adapted‐plan complexity metrics using linear mixed‐effects models (LMEMs), and (iii) evaluation of PSQA stability using statistical process control (SPC) and leave‐one‐patient‐out (LOPO) cross‐validation. Results Optimizer choice strongly influenced plan complexity. The Penalty optimizer generated higher‐complexity plans, whereas Objectives and Constraints and A3i produced more modulation‐efficient configurations with fewer small, low‐MU segments. Variance decomposition identified a subset of metrics that exhibited consistent behavior across all optimizers, serving as robust descriptors independent of the algorithm. Metrics dominated by between‐patient variance (σ 2 between ) emerged as reliable surrogates for patient‐specific complexity Tongue & Groove Index, Average Leaf Gap and Number of Active Leaves consistently showed high between‐patient contributions (σ 2 between > 74%) among others. In contrast, metrics related to low‐MU segments (Seg MU < 5 and Seg MU < 5 [%]) were dominated by within‐patient variance (σ 2 within ), with A3i showing the most pronounced fluctuations (85.8% and 84.8%, respectively). These descriptors are therefore more sensitive to plan‐specific or optimizer‐related stochasticity than to stable patient factors. SPC analyses demonstrated that the current adaptive workflow is robustly stable for most patients: 11 of 13 never experienced a fraction below the tolerance level (TL), and 12 of 13 never exceeded the action level (AL), even when thresholds were dynamically recalculated within the LOPO‐CV. Conclusion This study provides the first systematic assessment of PCMs in MR‐guided oART, demonstrating optimizer‐specific complexity signatures, predominant inter‐patient variability, and the predictive value of selected metrics for delivery accuracy. Although limited to a single tumor site and workflow, the methodology supports the development of institution‐specific, complexity‐aware scorecards to enhance adaptive planning and quality assurance.
Stereotactic body radiotherapy combined with immunotherapy: a systematic review focus on timing and toxicity profile Carlo Gugliemo Cattaneo, Giuditta Chiloiro, Angela Romano, Giulia Panza, Matteo Galetto, Matteo Nardini, Lorenzo Placidi, Maria Antonietta Gambacorta, Luca Boldrini Technical Innovations and Patient Support in Radiation Oncology, 2026 Background: The combination of Stereotactic Body Radiotherapy (SBRT) with immune checkpoint inhibitors (ICIs) has gained increasing interest due to its potential to enhance antitumor immune responses. However, the optimal timing, dose, and safety profile of this combined approach remain unclear, and available clinical evidence is highly heterogeneous. Methods: A systematic review of the literature was conducted in accordance with PRISMA guidelines. PubMed/MEDLINE, Embase, and Cochrane Library databases were searched for clinical studies evaluating the combination of SBRT and ICIs. Studies were included if they reported toxicity outcomes and involved patients with solid tumors treated with SBRT in combination with ICIs. Data on study design, patient characteristics, SBRT dose and fractionation, treatment sequencing, and treatment-related toxicities were extracted and qualitatively analyzed. Results: values spanning approximately 43-113 Gy; detailed dosimetric data were lacking in about 38% of studies. The overall incidence of grade ≥ 3 treatment-related toxicity was comparable between concurrent and sequential approaches (approximately 12-15%). High-grade adverse events were predominantly immune-related, with pneumonitis more frequently reported in concurrent regimens, while gastrointestinal and dermatologic toxicities were slightly more common in sequential strategies. No consistent signal of increased severe toxicity attributable to the addition of SBRT was observed. Conclusions: Current clinical evidence suggests that the combination of SBRT and ICIs is generally feasible and does not appear to systematically increase the risk of severe toxicity compared with immunotherapy alone. However, substantial heterogeneity in study design, SBRT parameters, treatment sequencing, and toxicity reporting limits definitive conclusions regarding safety and efficacy. Future prospective trials with harmonized protocols, standardized toxicity attribution, and integrated translational endpoints are needed to define the optimal therapeutic window for SBRT-ICI combinations across different tumor types.
“Surviving is not enough”: shifting the focus from treatment success to quality of life in anal cancer survivors. Patient- reported outcomes and the evolving landscape of survivorship care Stefania Manfrida, Natalia Barogi, Viola De Luca, Diana Giannarelli, Loredana Dinapoli, Bruno Fionda, Giuditta Chiloiro, Fabio Marazzi, Daniela Pia Rosaria Chieffo, Luca Tagliaferri, Maria Antonietta Gambacorta Frontiers in Oncology, 2026 Background Chemoradiotherapy (CRT) is the standard treatment for squamous cell carcinoma of the anal canal (ACC), achieving excellent local control and sphincter preservation. However, many long-term survivors experience persistent bowel, urinary, sexual, and psycho social sequelae affecting quality of life (QoL). The PROACT study (Patient – Reported Outcomes in Anal Cancer Patients Treated with Intensity-Modulated Radiotherapy; NCT06364579) wants to explore the relationship between oncologic outcomes and patient-reported QoL in the era of modern radiotherapy. Methods This single-institution ambispective study included patients with a diagnosis of ACC treated between 2011 and 2024 with intensity modulated radiotherapy (IMRT)-based CRT, followed—when indicated—by an image guided interventional radiotherapy (IRT) boost. Oncologic outcomes and toxicity were assessed using standard criteria. QoL was evaluated annually up to 5 years post-treatment using the EORTC QLQ-C30 and anal cancer–specific QLQ-ANL27 questionnaires. Statistical analyses explored associations between QoL domains and patient-, disease-, and treatment-related factors. Results Median age was 62 years (range 34–83); 82.2% were female. Median follow-up was 51 months. Three- and five-year overall survival were both 97.5%. Disease-free survival was 88.2% and 84.5% at three and five years, respectively, while locoregional relapse-free survival was 92.8% and 89.0%. Colostomy-free survival showed identical rates at three and five years (97.3%). Late≥ G3 Gastrointestinal toxicity occurred in 6 patients (6.7%). Compared with the general population, both sexes reported significantly higher global QoL (males p = 0.002; females p = 0.001), while diarrhea was worst in women ( p = 0.0008). Younger age (<70 years), female sex, and late GI toxicity correlated with poorer functional outcomes, particularly in bowel and sexual domains. Conclusions PROACT underscores that treatment success in anal cancer extends beyond cure, encompassing survivorship, functionality, and well-being. Integrating oncologic and patient-reported outcomes offers a comprehensive, patient-centered framework for optimizing long-term care.
Inguinal CTV contouring in anal cancer: comparative validation of inguinal lymph nodes contouring guidelines and implications for consensus Viola De Luca, Stefania Manfrida, Natalia Barogi, Flavia De Giacomo, Raffaella Michela Rinaldi, Bruno Fionda, Roberta Bertolini, Giuditta Chiloiro, Rosa Autorino, Gabriella Macchia, Nicola Dinapoli, Christopher L.Hallemeier, Allison E. Garda, Maria Antonietta Gambacorta Clinical and Translational Radiation Oncology, 2026 Background and purpose: Contouring Inguinal lymph nodes (ILNs) in anal squamous cell cancer (ASCC) remains challenging. Accurate delineation is essential to optimize treatment efficacy with sparing of organs at risk (OaRs). Garda et al. proposed a contouring guideline based on the anatomical distribution of inguinal lymphadenopathy. This study evaluates their effectiveness in ensuring adequate ILNs coverage. Materials and methods: We retrospectively analyzed ASCC patients with radiologically positive inguinal lymph nodes treated with IMRT in our institution between 2015 and 2024. ILNs were mapped relative to the femoral vessels and delineated based on the Garda's guidelines. Descriptive analyses were conducted. Results: Among 46 patients with positive ILNs, 27 (59%) had cT3-T4 stage and 27 (59%) had bilateral inguinal nodal involvement. Overall, 203 ILNs were analyzed: 88% (178 nodes) were anteromedial to the femoral vessels. Garda's CTV encompassed 182 nodes (90%), while 22 nodes (11%) across 14 patients (30%) were not covered. Most of the uncovered nodes were in the superolateral region (n = 15, 7% of all nodes), whereas 6 nodes (3%) from six patients were identified in the inferior region. Only one node was found in the superomedial quadrant, while no nodes were located posteriorly. Conclusions: These findings validate the proposed guidelines, confirming their effectiveness in reducing unnecessary irradiation of the posterolateral quadrant. However, coverage gaps highlight the need for further refinements to optimize target delineation. These findings offer disease-specific evidence to inform the harmonization of inguinal CTV delineation and support the development of standardized, consensus-based contouring protocols.
ESTRO consensus guidelines on GTV delineation and dose-escalation in rectal cancer Giuditta Chiloiro, Angela Romano, Regina Beets-Tan, Krzysztof Bujko, Davide Cusumano, Emmanouil Fokas, Karin Haustermans, Florence Huguet, Martijn PW Intven, Corrie AM Marijnen, Ilaria Nacci, Iris D Nagtegaal, Femke P Peters, Alexandra Stewart, Vincenzo Valentini, Maria Antonietta Gambacorta Clinical and Translational Radiation Oncology, 2026 •Dose escalation, in rectal cancer, is defined as radiotherapy doses exceeding 54 Gy.•MRI-based GTV definition is central to dose-escalated rectal cancer RT.•Dose escalation supports organ preservation in selected rectal cancer patients.•Delphi methodology achieved consensus across key clinical and imaging domains.
Towards quantitative MRI Driving online adaptive MRgRT for lung tumors I. Moretti, M. Nardini, C. Mazzarella, A. Romano, G. Chiloiro, G. Panza, M. Galetto, H.E. Tran, K. Zormpas-Petridis, L. Boldrini, M.De Spirito, L. Placidi Physica Medica, 2026 INTRODUCTION: Successful delivery of lung cancer radiotherapy is hindered by respiratory motion, low soft-tissue contrast and anatomical variabilities, often compromising precision. Magnetic Resonance Image-guided Radiotherapy (MRgRT) has emerged as a promising approach, particularly with hybrid MR-Linac systems that offer superior soft-tissue visualization and enable online adaptive radiotherapy (online MRgART). PURPOSE: This review synthesizes current evidence for online MRgART in lung cancer and examines emerging roles for quantitative MRI (qMRI). A PubMed search covering the period from January 2020 to September 2025 identified 19 studies, 3 of which focused specifically on quantitative imaging. MAIN FINDINGS: Online MRgART consistently demonstrated workflow feasibility, frequent online adaptation, improved target coverage while respecting Organs-At-Risk (OARs) constraints and encouraging Local Control (LC) with low high-grade toxicity. qMRI on MR-Linacs, most commonly Diffusion-Weighted Imaging (DWI) and cine-MRI-derived ventilation/perfusion mapping, showed feasibility and early signals for treatment adaptation, toxicity prediction and response assessment. PRINCIPAL CONCLUSIONS: qMRI studies integrated in online MRgART for lungs are, at present, extremely limited; nevertheless, establishing a clear snapshot of the current state-of-the-art is essential, as this topic is expected to become highly prevalent and of particular interest in the near future. To our knowledge, this is the first review centered on online MRgART for lung tumors, with a dedicated subsection summarizing the nascent evidence on qMRI. Looking ahead, integrating AI-driven motion compensation, auto-segmentation and adaptive replanning with qMRI-enabled biomarkers could standardize workflows and accelerate truly personalized online MRgART. Prospective multi-center studies are needed to validate biomarkers and demonstrate clinical benefit.
Optimizing thoracic synthetic computed tomography generation from magnetic resonance imaging: the role of Fourier transform and other key factors Alessandro Bombini, Luca Vellini, Flaviovincenzo Quaranta, Jacopo Lenkowicz, Sebastiano Menna, Elisa Pilloni, Francesco Catucci, Andrea D’Aviero, Claudio Votta, Giuditta Chiloiro, Martina Iezzi, Francesco Preziosi, Alessia Re, Althea Boschetti, Floranna Mauro, Sami Aburas, Lana Smiljanic, Antonio Piras, Carmela Di Dio, Lorenzo Placidi, Luca Boldrini, Maria Antonietta Gambacorta, Gian Carlo Mattiucci, Davide Cusumano Physics and Imaging in Radiation Oncology, 2026
Comment on: “Risk of distant metastasis after local excision for near-complete response versus salvage surgery for local regrowth in rectal cancer: Results from an international registry” Quoc Riccardo Bao, Lorenzo Dell’Atti, Marco Scarpa, Daniela Rega, Paolo Delrio, Angelo Restivo, Giuditta Chiloiro, Maria Antonietta Gambacorta, Salvatore Pucciarelli, Gaya Spolverato, Gaya Spolverato, Quoc Riccardo Bao, Paolo Delrio, Mario Guerrieri, Monica Ortenzi, Nicola Cillara, Angelo Restivo, Simona Deidda, Antonino Spinelli, Carmela Romano, Francesco Bianco, Giacomo Sarzo, Emilio Morpurgo, Claudio Belluco, Elisa Palazzari, Giuditta Chiloiro, Elisa Meldolesi, Claudio Coco, Donato Paolo Pafundi, Cosimo Feleppa, Carlo Aschele, Michele Bonomo, Andrea Muratore, Alfredo Mellano, Germana Chiaulon, Filippo Crimì, Isacco Maretto, Alessandro Perin, Emanuele Damiano Luca Urso, Marco Scarpa, Mariasole Bigon, Francesca Bergamo, Paola Del Bianco, Maria Antonietta Gambacorta, Daniela Rega, Salvatore Pucciarelli European Journal of Surgical Oncology, 2025
Rectal Cancer Segmentation: A Methodical Approach for Generalizable Deep Learning in a Multi-Center Setting Jovana Panic, Arianna Defeudis, Lorenzo Vassallo, Stefano Cirillo, Marco Gatti, Roberto Sghedoni, Michele Avanzo, Angelo Vanzulli, Luca Sorrentino, Luca Boldrini, Huong Elena Tran, Giuditta Chiloiro, Giuseppe Roberto D'Agostino, Enrico Menghi, Roberta Fusco, Antonella Petrillo, Vincenza Granata, Martina Mori, Claudio Fiorino, Barbara Alicja Jereczek‐Fossa, Marianna Alessandra Gerardi, Serena Dell'Aversana, Antonio Esposito, Daniele Regge, Samanta Rosati, Gabriella Balestra, Valentina Giannini International Journal of Imaging Systems and Technology, 2025
RT for the management of locally advanced rectal cancer: Don't throw the baby with the bath water! Luca Nicosia, Marco Lorenzo Bonù, Ilaria Angelicone, Gianluigi Lunardi, Rita Marina Niespolo, Micol Zannetti, Linda Agolli, Giuditta Chiloiro, Angela Romano, Fatemeh Jafari, Mahdi Aghili, Reza Ghalehtaki, Giampaolo Montesi, Francesca De Felice, Filippo De Renzi, Alessandro Magli, Jennifer Le Guevelou, Marco Lupattelli, Giuseppe Minniti, Maria Antonietta Gambacorta, Daniel Habermehl, Pierfrancesco Franco, Stefano Arcangeli, Michela Buglione di Monale e Bastia, Filippo Alongi, Mattia Falchetto Osti Radiotherapy and Oncology, 2025
Comparing local excision with watch and wait for the management of rectal cancer patients responding to neoadjuvant chemoradiotherapy: Composite endpoint analysis using the win ratio Giulia Capelli, Giulia Lorenzoni, Maria Vittoria Chiaruttini, Paolo Delrio, Mario Guerrieri, Monica Ortenzi, Nicola Cillara, Angelo Restivo, Simona Deidda, Antonino Spinelli, Carmela Romano, Francesco Bianco, Giacomo Sarzo, Dajana Glavas, Emilio Morpurgo, Claudio Belluco, Elisa Palazzari, Giuditta Chiloiro, Elisa Meldolesi, Claudio Coco, Donato Paolo Pafundi, Cosimo Feleppa, Carlo Aschele, Michele Bonomo, Andrea Muratore, Alfredo Mellano, Germana Chiaulon, Francesca Bergamo, Maria Antonietta Gambacorta, Daniela Rega, Dario Gregori, Gaya Spolverato, Salvatore Pucciarelli Colorectal Disease, 2025
MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer Luca Boldrini, Giuditta Chiloiro, Silvia Di Franco, Angela Romano, Lana Smiljanic, Elena Huong Tran, Francesco Bono, Diepriye Charles Davies, Loris Lopetuso, Maria De Bonis, Angelo Minucci, Luciano Giacò, Davide Cusumano, Lorenzo Placidi, Diana Giannarelli, Evis Sala, Maria Antonietta Gambacorta Radiation Oncology, 2024
Impact of data transfer between treatment planning systems on dosimetric parameters Guenda Meffe, Claudio Votta, Gabriele Turco, Elena Chillè, Matteo Nardini, Angela Romano, Giuditta Chiloiro, Giulia Panza, Matteo Galetto, Amedeo Capotosti, Roberto Moretti, Maria Antonietta Gambacorta, Luca Boldrini, Luca Indovina, Lorenzo Placidi Physica Medica, 2024
Why we should care about gas pockets in online adaptive MRgRT: a dosimetric evaluation Matteo Nardini, Guenda Meffe, Matteo Galetto, Luca Boldrini, Giuditta Chiloiro, Angela Romano, Giulia Panza, Andrea Bevacqua, Gabriele Turco, Claudio Votta, Amedeo Capotosti, Roberto Moretti, Maria Antonietta Gambacorta, Luca Indovina, Lorenzo Placidi Frontiers in Oncology, 2023
Smile InTM Totems in Radiotherapy: Patients’ Satisfaction with Limited Equipment and COVID-19 Marzia Borgia, Fiorella Cristina Di Guglielmo, Marco Lucarelli, Rosario Bonelli, Lucrezia Gasparini, Angelo Di Pilla, Lucia Anna Ursini, Maria Taraborrelli, Annamaria Vinciguerra, Antonietta Augurio, Monica Di Tommaso, Marianna Trignani, Marianna Nuzzo, Consuelo Rosa, Giuditta Chiloiro, Stephanie Sartori, Lucia Ferrari, Roberta Marchione, Fabio Adalgiso D’Orazio, Paola Di Renzo, Giustino Orlando, Domenico Genovesi, Luciana Caravatta Healthcare Switzerland, 2022
Development of a prognostic model of overall survival in oropharyngeal cancer from real-world data: PRO.M.E.THE.O. Francesco Miccichè, Giuditta Chiloiro, Silvia Longo, Rosa Autorino, Mariangela Massaccesi, Jacopo Lenkowicz, Pierluigi Bonomo, Isacco Desideri, Liliana Belgioia, Almalina Bacigalupo, Elisa D’Angelo, Federica Bertolini, Anna Merlotti, Nerina Denaro, Pierfrancesco Franco, Francesco Bussu, Gaetano Paludetti, Umberto Ricardi, Vincenzo Valentini Acta Otorhinolaryngologica Italica, 2022
The 2017 Assisi Think Tank Meeting on rectal cancer: A positioning paper Vincenzo Valentini, Corrie Marijnen, Geerard Beets, Krzysztof Bujko, Berardino De Bari, Andres Cervantes, Giuditta Chiloiro, Claudio Coco, Maria Antonietta Gambacorta, Robert Glynne-Jones, Karin Haustermans, Elisa Meldolesi, Femke Peters, Claus Rödel, Harm Rutten, Cornelis van de Velde, Cynthia Aristei Radiotherapy and Oncology, 2020
Evaluation of a simplified optimizer for MR-guided adaptive RT in case of pancreatic cancer Davide Cusumano, Luca Boldrini, Sebastiano Menna, Stefania Teodoli, Elisa Placidi, Giuditta Chiloiro, Lorenzo Placidi, Francesca Greco, Gerardina Stimato, Francesco Cellini, Vincenzo Valentini, Luigi Azario, Marco De Spirito Journal of Applied Clinical Medical Physics, 2019
Magnetic Resonance, Vendor-independent, Intensity Histogram Analysis Predicting Pathologic Complete Response After Radiochemotherapy of Rectal Cancer Nicola Dinapoli, Brunella Barbaro, Roberto Gatta, Giuditta Chiloiro, Calogero Casà, Carlotta Masciocchi, Andrea Damiani, Luca Boldrini, Maria Antonietta Gambacorta, Michele Dezio, Gian Carlo Mattiucci, Mario Balducci, Johan van Soest, Andre Dekker, Philippe Lambin, Claudio Fiorino, Carla Sini, Francesco De Cobelli, Nadia Di Muzio, Calogero Gumina, Paolo Passoni, Riccardo Manfredi, Vincenzo Valentini International Journal of Radiation Oncology Biology Physics, 2018
Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients Gabriella Macchia, Maria Antonietta Gambacorta, Carlotta Masciocchi, Giuditta Chiloiro, Giovanna Mantello, Maika di Benedetto, Marco Lupattelli, Elisa Palazzari, Liliana Belgioia, Almalina Bacigalupo, Aldo Sainato, Sabrina Montrone, Lucia Turri, Angela Caroli, Antonino De Paoli, Fabio Matrone, Carlo Capirci, Giampaolo Montesi, Rita Marina Niespolo, Mattia Falchetto Osti, Luciana Caravatta, Alessandra Galardi, Domenico Genovesi, Maria Elena Rosetto, Caterina Boso, Piera Sciacero, Lucia Giaccherini, Salvatore Parisi, Antonella Fontana, Francesco Romeo Filippone, Vincenzo Picardi, Alessio Giuseppe Morganti, Vincenzo Valentini Clinical and Translational Radiation Oncology, 2017
Radiomics for rectal cancer Nicola Dinapoli, Calogero Casà, Brunella Barbaro, Giuditta Valentina Chiloiro, Andrea Damiani, Marialuisa Di Matteo, Alessandra Farchione, Maria Antonietta Gambacorta, Roberto Gatta, Vito Lanzotti, Carlotta Masciocchi, Vincenzo Valentini Translational Cancer Research, 2016
