Spatially fractionated radiation therapy for bulky tumors: a systematic review of clinical outcomes and dosimetric challenges R. Di Franco, R. Mottareale, D. Pezzulla, S. Mercogliano, V. Borzillo, E. Scipilliti, G. Silvestro, G. De Palma, M. Serra, G. Ametrano, F. Buonanno, C. Arrichiello, V. d’Alesio, M. A. di Franco, S. Cilla, A. Cuomo, E. Cavalcanti, E. Maranzano, C. Donati, F. Cellini, V. Ravo Radiation Oncology London England, 2026 Conventional radiotherapy for bulky tumors is often limited by normal tissue tolerance, restricting dose escalation and increasing toxicity. Spatially Fractionated Radiation Therapy (SFRT), including GRID and Lattice Radiotherapy (LRT), delivers intentionally heterogeneous dose distributions to overcome these limitations. This systematic review summarizes the clinical application, outcomes, and dosimetric variability of SFRT in the treatment of bulky tumors. A systematic literature search of the MEDLINE database was performed for studies published between January 2010 and June 2025. Eligible English-language studies reporting original clinical data on SFRT, including case reports, case series, retrospective analyses, and prospective trials, were included. Data on patient and tumor characteristics, treatment intent, SFRT technique, clinical response, and toxicity were extracted, and methodological quality was assessed using the ROBINS-I framework. Twenty-nine studies involving 513 patients and 553 lesions were included. The most commonly treated sites were the thorax (28.8%), pelvis (24.7%) and abdomen (23.3%), with sarcomas (48.0%) carcinomas (14.5%) and non-small cell lung cancer (10.4%) being the predominant histologies. SFRT was mainly delivered with palliative intent (216 cases). Tumor shrinkage was reported in approximately 80% of lesions, with consistent symptom relief. Treatment-related toxicity was generally mild, with most adverse events graded as 1-2; severe toxicities (Grade ≥ 3) were rare. Despite favorable clinical outcomes and an acceptable safety profile, substantial heterogeneity in dosimetric parameters, including valley-to-peak dose ratio and fractionation schemes, was observed across studies. SFRT appears to be a feasible and effective option for bulky tumors, particularly in the palliative setting. However, the lack of dosimetric standardization and prospective data highlights the need for harmonized protocols and well-designed clinical trials.
Optimizing Left-Sided Breast Cancer Radiotherapy: Strategy-Dependent Trade-Offs Among VMAT and Hybrid Techniques Rocco Mottareale, Francesca Buonanno, Valentina d'Alesio, Sara Falivene, Marcello Serra, Cecilia Arrichiello, Gianluca Ametrano, Piera Ferraioli, Gaetano Gagliardo, Rossella Di Franco, Simona Mercogliano, Paolo Muto, Vincenzo Ravo Cancer Management and Research, 2026 Purpose: To compare dosimetric trade-offs among two full-VMAT and two hybrid 3D-CRT/VMAT strategies for left-sided whole-breast irradiation (WBI), and to evaluate the influence of planning strategy, introducing a novel tangential hybrid approach (H-tVMAT). Patients and Methods: Twenty patients with left-sided breast cancer treated with WBI (40.05 Gy in 15 fractions) were retrospectively analyzed. For each patient, four plans were generated within a single treatment planning system under free-breathing conditions: large-angle VMAT, tangential VMAT (tVMAT), Hybrid VMAT (H-VMAT), and the novel tangential Hybrid tVMAT (H-tVMAT). Primary dosimetric endpoints included heart and pulmonary structures and the contralateral breast, with dedicated evaluation of low-dose exposure. Target conformity, homogeneity index (HI), and monitor units (MUs) were also assessed. Results: All strategies achieved clinically acceptable target coverage and homogeneity. Hybrid configurations consistently reduced cardiac, pulmonary, and contralateral low-dose exposure compared with full-VMAT solutions. Among the evaluated strategies, H-tVMAT provided the most favorable balance between heart/LAD sparing, low-dose containment, and target coverage. Appropriately configured tangential VMAT achieved dosimetric results close to hybrid solutions, underscoring the importance of arc geometry. No statistically significant differences in delivery complexity were observed across strategies. Conclusion: Dosimetric performance in left-sided WBI is strongly influenced by planning implementation rather than nominal technique category alone. Hybrid tangential VMAT achieved the most balanced dosimetric profile, while optimized tangential VMAT provided comparable results. These findings support a strategy-specific approach to technique selection, emphasizing the central role of implementation choices in breast radiotherapy planning.
SHORT-COURSE RADIOTHERAPY FOR OLDER PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER AND UNFIT FOR CHEMOTHERAPY: THE SOFT STUDY Gerardo Rosati, Alfonso De Stefano, Angelo Restivo, Valentina Fanotto, Giuseppe Cicero, Alfredo Colombo, Emanuela Dell’Aquila, Alessandro Parisi, Silvia Ortolani, Stefania Eufemia Lutrino, Chiara Carlomagno, Francesca Dapoto, Giorgio Reggiardo, Fabrizio Tonetto, Vincenzo Ravo, Giuseppe Aprile, Domenico Bilancia, Antonio Avallone, Carmen Romano, Valerio Argiolas, Giuseppe Giovinazzo Radiotherapy and Oncology, 2026
Total mesorectal excision after rectal-sparing approach in locally advanced rectal cancer patients after neoadjuvant treatment: a high volume center experience Daniela Rega, Vincenza Granata, Carmela Romano, Roberta Fusco, Alessia Aversano, Vincenzo Ravo, Antonella Petrillo, Biagio Pecori, Elena Di Girolamo, Fabiana Tatangelo, Antonio Avallone, Paolo Delrio Therapeutic Advances in Gastrointestinal Endoscopy, 2024 Background: In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. Method: In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group – five patients in W&W group), with a median follow-up of 42 months. Results: Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE – a complete response was confirmed. Conclusion: Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary.
Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study Alessandro Ottaiano, Antonella De Luca, Mariachiara Santorsola, Giosuè Scognamiglio, Annabella Di Mauro, Paolo Chiodini, Matilde Lambiase, Alessandra Sacco, Antonella Petrillo, Vincenza Granata, Roberta Fusco, Edoardo Mercadante, Nicola Martucci, Giuseppe De Luca, Antonello La Rocca, Egidio Celentano, Anna Crispo, Piergiacomo Di Gennaro, Fabiana Tatangelo, Gerardo Ferrara, Francesco Izzo, Andrea Belli, Renato Patrone, Paolo Delrio, Daniela Rega, Silvia De Franciscis, Paolo Muto, Vincenzo Ravo, Rossella Di Franco, Valentina Borzillo, Sara Santagata, Giuseppina Rea, Daniela Castaldo, Ugo Pace, Gianfranco De Feo, Stefania Scala, Guglielmo Nasti, Nicola Normanno BMC Cancer, 2023 Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151.
Patterns of Care for Breast Radiotherapy in Italy: Breast IRRadiATA (Italian Repository of Radiotherapy dATA) Feasibility Study † Antonella Ciabattoni, Fabiana Gregucci, Giuseppe D’Ermo, Alessandro Dolfi, Francesca Cucciarelli, Isabella Palumbo, Simona Borghesi, Alessandro Gava, Giovanna Maria Cesaro, Antonella Baldissera, Daniela Giammarino, Antonino Daidone, Francesca Maurizi, Marcello Mignogna, Lidia Mazzuoli, Vincenzo Ravo, Sara Falivene, Sara Pedretti, Edy Ippolito, Rosaria Barbarino, Daniela di Cristino, Alba Fiorentino, Cynthia Aristei, Sara Ramella, Rolando Maria D’Angelillo, Icro Meattini, Cinzia Iotti, Vittorio Donato, Silvia Chiara Formenti Cancers, 2022 Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.
Electrochemotherapy of Primary Colon Rectum Cancer and Local Recurrence: Case Report and Prospective Analysis Daniela Rega, Vincenza Granata, Antonella Petrillo, Ugo Pace, Massimiliano Di Marzo, Roberta Fusco, Valeria D’Alessio, Guglielmo Nasti, Carmela Romano, Antonio Avallone, Vincenzo Ravo, Fabiana Tatangelo, Piera Maiolino, Raffaele Palaia, Francesco Izzo, Paolo Delrio Journal of Clinical Medicine, 2022 Purpose: Surgery, radiotherapy, and oncological treatment (chemotherapy and antineoplastic antibodies) are standard treatments of rectal cancer. ECT has shown its effectiveness and suitability in deep solid tumors conducted in both preclinical and clinical studies. We show here an update and preliminary results with locally advanced rectum cancer (LARC) treated with ECT. Methods: Two patients with major clinical response to restaging after neoadjuvant treatment for LARC were subjected to ECT 12 weeks after completing chemo-radiation therapy. One patient was subjected to ECT on a colorectal local recurrence formed after neoadjuvant treatment for LARC and surgery. Computed Tomography and Magnetic Resonance Imaging were used to assess ECT response. Results: The results showed stable disease in two of the three patients treated, while one patient achieved a complete response. The local control of disease is maintained in the patient follow-up. For each patient, a reduction in pain was observed and for the patient with local recurrence, a reduction in bleeding present before ECT was also achieved. Conclusion: Preliminary results showed that ECT is a safe and effective treatment in patients with a major clinical response or local recurrence after neoadjuvant therapy for LARC and allows a reduction in pain and bleeding with a consequent improvement to quality of life.
The dosimetric impact of axillary nodes contouring variability in breast cancer radiotherapy: An AIRO multi-institutional study Maria Cristina Leonardi, Matteo Pepa, Rosa Luraschi, Sabrina Vigorito, Samantha Dicuonzo, Lars Johannes Isaksson, Maria Rosa La Porta, Lorenza Marino, Edy Ippolito, Alessandra Huscher, Angela Argenone, Fiorenza De Rose, Francesca Cucciarelli, Maria Carmen De Santis, Francesca Rossi, Agnese Prisco, Roberta Guarnaccia, Paola Tabarelli de Fatis, Isabella Palumbo, Sarah Pia Colangione, Maria Mormile, Vincenzo Ravo, Alessandra Fozza, Cynthia Aristei, Roberto Orecchia, Federica Cattani, Barbara Alicja Jereczek-Fossa, Cristina Leonardi, Matteo Pepa, Simone Giovanni Gugliandolo, Rosa Luraschi, Sabrina Vigorito, Anna Morra, Samantha Dicuonzo, Marianna Alessandra Gerardi, Lars Johannes Isaksson, Maria Alessia Zerella, Maria Rosa La Porta, Domenico Cante, Edoardo Petrucci, Lorenza Marino, Giuseppina Borzì, Edy Ippolito, Maristella Marrocco, Alessandra Huscher, Matteo Chieregato, Angela Argenone, Luciano Iadanza, Fiorenza De Rose, Francesca Lobefalo, Francesca Cucciarelli, Marco Valenti, Maria Carmen De Santis, Anna Cavallo, Francesca Rossi, Serenella Russo, Agnese Prisco, Marika Guernieri, Roberta Guarnaccia, Tiziana Malatesta, Ilaria Meaglia, Marco Liotta, Paola Tabarelli de Fatis, Isabella Palumbo, Marta Marcantonini, Sarah Pia Colangione, Emilio Mezzenga, Sara Falivene, Maria Mormile, Vincenzo Ravo, Cecilia Arrichiello, Alessandra Fozza, Maria Paola Barbero, Giovanni Battista Ivaldi, Gianpiero Catalano, Cristiana Vidali, Cynthia Aristei, Caterina Giannittb, Delia Ciardo, Antonella Ciabattoni, Icro Meattini, Roberto Orecchia, Federica Cattani, Barbara Alicja Jereczek-Fossa Radiotherapy and Oncology, 2022
Prospective evaluation of radiotherapy-induced immunologic and genetic effects in colorectal cancer oligo-metastatic patients with lung-limited disease: The prelude-1 study Alessandro Ottaiano, Angela Petito, Mariachiara Santorsola, Valerio Gigantino, Maurizio Capuozzo, Daniela Fontanella, Rossella Di Franco, Valentina Borzillo, Sergio Buonopane, Vincenzo Ravo, Esmeralda Scipilliti, Giuseppe Totaro, Marcello Serra, Gianluca Ametrano, Roberta Penta, Fabiana Tatangelo, Giosuè Scognamiglio, Annabella Di Mauro, Maurizio Di Bonito, Maria Napolitano, Stefania Scala, Giuseppina Rea, Sara Santagata, Angela Lombardi, Anna Grimaldi, Carlo Caputo, Anna Crispo, Egidio Celentano, Gianfranco De Feo, Luisa Circelli, Giovanni Savarese, Raffaella Ruggiero, Francesco Perri, Vincenza Granata, Gerardo Botti, Michele Caraglia, Guglielmo Nasti, Paolo Muto Cancers, 2021
Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study Maria Cristina Leonardi, Matteo Pepa, Simone Giovanni Gugliandolo, Rosa Luraschi, Sabrina Vigorito, Damaris Patricia Rojas, Maria Rosa La Porta, Domenico Cante, Edoardo Petrucci, Lorenza Marino, Giuseppina Borzì, Edy Ippolito, Maristella Marrocco, Alessandra Huscher, Matteo Chieregato, Angela Argenone, Luciano Iadanza, Fiorenza De Rose, Francesca Lobefalo, Francesca Cucciarelli, Marco Valenti, Maria Carmen De Santis, Anna Cavallo, Francesca Rossi, Serenella Russo, Agnese Prisco, Marika Guernieri, Roberta Guarnaccia, Tiziana Malatesta, Ilaria Meaglia, Marco Liotta, Paola Tabarelli de Fatis, Isabella Palumbo, Marta Marcantonini, Sarah Pia Colangione, Emilio Mezzenga, Sara Falivene, Maria Mormile, Vincenzo Ravo, Cecilia Arrichiello, Alessandra Fozza, Maria Paola Barbero, Giovanni Battista Ivaldi, Gianpiero Catalano, Cristiana Vidali, Cynthia Aristei, Caterina Giannitto, Eleonora Miglietta, Antonella Ciabattoni, Icro Meattini, Roberto Orecchia, Federica Cattani, Barbara Alicja Jereczek-Fossa British Journal of Radiology, 2021
Radiosurgery and stereotactic radiotherapy with cyberknife system for meningioma treatment Rossella Di Franco, Valentina Borzillo, Vincenzo Ravo, Sara Falivene, Francesco Jacopo Romano, Matteo Muto, Fabrizio Cammarota, Giuseppe Totaro, Gianluca Ametrano, Sabrina Rossetti, Carla Cavaliere, Carmine D’ Aniello, Gelsomina Iovane, Maria Assunta Porricelli, Massimiliano Berretta, Gerardo Botti, Luigi Starace, Enrico La Salvia, Gaetano Facchini, Paolo Muto Neuroradiology Journal, 2018
Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform Delia Ciardo, Angela Argenone, Genoveva Ionela Boboc, Francesca Cucciarelli, Fiorenza De Rose, Maria Carmen De Santis, Alessandra Huscher, Edy Ippolito, Maria Rosa La Porta, Lorenza Marino, Ilaria Meaglia, Isabella Palumbo, Francesca Rossi, Paolo Alpi, Mario Bignardi, Alessio Bonanni, Domenico Cante, Tino Ceschia, Letizia Fabbietti, Marco Lupattelli, Elisa Donatella Mantero, Alessia Monaco, Patrizia Porcu, Vincenzo Ravo, Sonia Silipigni, Angelo Tozzi, Vincenza Umina, Dario Zerini, Luigi Bordonaro, Giorgia Capezzali, Elena Clerici, Sarah Pia Colangione, Michela Dispinzieri, Jessica Dognini, Laura Donadoni, Sara Falivene, Alessandra Fozza, Barbara Grilli, Roberta Guarnaccia, Eva Iannacone, Valentina Lancellotta, Agnese Prisco, Rosalinda Ricotti, Roberto Orecchia, Barbara Alicja Jereczek-Fossa, Maria Cristina Leonardi, and Acta Oncologica, 2017
Locally advanced paranasal sinus carcinoma: A study of 30 patients Francesco Perri, Raffaele Addeo, Manuel Conson, Adriana Faiella, Giuseppina Della Vittoria Scarpati, Gabriella Torre, Angela Di Biase, Paola Romanelli, Carlo Buonerba, Giuseppe Di Lorenzo, Antonio Daponte, Francesco Caponigro, Salvatore Pisconti, Roberto Pacelli, Vincenzo Ravo, Paolo Muto, Raffaele Solla Oncology Letters, 2017
Rectal/urinary toxicity after hypofractionated vs. Conventional radiotherapy in high risk prostate cancer: Systematic review and meta analysis European Review for Medical and Pharmacological Sciences, 2017
Management of breast cancer in elderly patients Alfonso Reginelli, Mariagrazia Calvanese, Vincenzo Ravo, Rossella Di Franco, Giustino Silvestro, Gianluca Gatta, Ettore Squillaci, Roberto Grassi, Salvatore Cappabianca International Journal of Surgery, 2014
Hypofractionated breast cancer radiotherapy. Helical tomotherapy in supine position or classic 3DConformal radiotherapy in prone position: Which is better? Anticancer Research, 2014
Management of painful bone metastases: Our experience according to scientific evidence on palliative radiotherapy Anticancer Research, 2014
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Prognostic Value of CD40 in Adult Soft Tissue Sarcomas Alessandro Ottaiano, Anna De Chiara, Francesco Perrone, Gerardo Botti, Flavio Fazioli, Vincenzo De Rosa, Nicola Mozzillo, Vincenzo Ravo, Brunello Morrica, Ciro Gallo, Carmela Pisano, Maria Napolitano, Paolo Antonio Ascierto, Rosario Vincenzo Iaffaioli, Gaetano Apice Clinical Cancer Research, 2004
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