High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience STEFANIA MANFRIDA, BRUNO FIONDA, SILVIA MARIANI, VIOLA DE LUCA, ROBERTA BERTOLINI, BRUNELLA BARBARO, GIUDITTA CHILOIRO, VINCENZO FRASCINO, LUCA TAGLIAFERRI, MARIA ANTONIETTA GAMBACORTA In Vivo, 2024 BACKGROUND/AIM The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.
The Italian version of the Pediatric Quality of Life Inventory™ (PEDSQL™) 3.0 healthcare satisfaction hematology/oncology module: reliability and validity in radiation oncology Elisa Marconi, Francesco Beghella Bartoli, Elisa Meldolesi, Silvia Mariani, Giulia Panza, Alessia Nardangeli, Loredana Dinapoli, Teresa Carmen Lees, Antonella Guido, Angela Mastronuzzi, Antonio Ruggiero, Maria Antonietta Gambacorta, Vincenzo Valentini, Mario Balducci, Daniela Pia Rosaria Chieffo, Silvia Chiesa Health and Quality of Life Outcomes, 2023 Background Health-related quality of life (HRQOL) measurement has become an important health care outcome even in oncological pediatric scenario. During radiation therapy care path, pediatric patients and their relatives may suffer from emotional and psychosocial distress not only related to cancer diagnosis, but also due to the procedure and the required daily routine. Despite the high prevalence of psychosocial consequences in this setting, instruments that inquire pediatric HRQOL and healthcare satisfaction have rarely been studied in Italy. Purpose of this study was to investigate reliability and linguistic validation of the PedsQL™ healthcare satisfaction Hematology/Oncology module from its original English version to Italian language. Methods Three phases standard procedure of cross-culture adaptation were used to create Italian version of PedsQL™ healthcare satisfaction Hematology/Oncology module. Forward translations and backward translations were performed. Finally, a pilot-testing for understandability of the ‘pre-final’ version was conducted with parents of children attending our Radiotherapy Center using two methodologies of Cognitive Interviewing (“Think-aloud Interviews” and “Respondent Debriefing”), in order to obtain the final Italian version of the PedsQL™ healthcare satisfaction Hematology/Oncology module. Results Twenty-five parents (2 father, 23 mothers) were recruited during their children’s radiotherapy treatment and the grammatically and conceptually acceptable pre-final version of the PedsQL™ Healthcare Satisfaction Hematology/Oncology Module was administered. The questionnaire was well understood reflecting its linguistic adaptation. Compliance with questionnaire administration was optimal. All subjects stated that the questions were interesting to express their opinion, most of them reported that all the questions of each section were clearly comprehensible and easy to understand, suggesting minimal changes that were double-checked with back translation. Furthermore, six of them spontaneously asked to complete the questionnaire in order to review the assistance received during radiotherapy. Conclusion Our Italian version of the PedsQL™ 3.0 Healthcare Satisfaction Hematology/Oncology Module seems to be a valid and functional instrument to indagate Healthcare Satisfaction.
May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy? Ciro Mazzarella, Silvia Chiesa, Lucrezia Toppi, Stefan Hohaus, Simona Gaudino, Francesco D’Alo, Nicola Dinapoli, Resta Davide, Tiziano Zinicola, Serena Bracci, Antonella Martino, Francesco Beghella Bartoli, Elisabetta Lepre, Roberta Bertolini, Silvia Mariani, Cesare Colosimo, Vincenzo Frascino, Gian Carlo Mattiucci, Maria Antonietta Gambacorta, Vincenzo Valentini, Mario Balducci Radiation Oncology, 2023 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.
pCR and 2-Year Disease-Free Survival: A Combination of the Two Endpoints as a New Classification for Locally Advanced Rectal Cancer Patients—An Updated Pooled Analysis of Eleven International Randomized Trials Maria Antonietta Gambacorta, Giuditta Chiloiro, Carlotta Masciocchi, Silvia Mariani, Angela Romano, Alessandra Gonnelli, Jean-Pierre Gerard, Samuel Ngan, Claus Rödel, Krzysztof Bujko, Robert Glynne-Jones, Johan van Soest, Andre Dekker, Andrea Damiani, Vincenzo Valentini Cancers, 2023 LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome.
Predictive and prognostic value of inflammatory markers in locally advanced rectal cancer (PILLAR) – A multicentric analysis by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Study Group Giuditta Chiloiro, Angela Romano, Silvia Mariani, Gabriella Macchia, Diana Giannarelli, Luciana Caravatta, Pierfrancesco Franco, Luca Boldrini, Alessandra Arcelli, Almalina Bacigalupo, Liliana Belgioia, Antonella Fontana, Elisa Meldolesi, Giampaolo Montesi, Rita Marina Niespolo, Elisa Palazzari, Cristina Piva, Vincenzo Valentini, Maria Antonietta Gambacorta Clinical and Translational Radiation Oncology, 2023 Background: Patients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts. Methods: Patients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Results: 808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS. Conclusions: Higher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.
The impact of radiomics in diagnosis and staging of pancreatic cancer Calogero Casà, Antonio Piras, Andrea D’Aviero, Francesco Preziosi, Silvia Mariani, Davide Cusumano, Angela Romano, Ivo Boskoski, Jacopo Lenkowicz, Nicola Dinapoli, Francesco Cellini, Maria Antonietta Gambacorta, Vincenzo Valentini, Gian Carlo Mattiucci, Luca Boldrini Therapeutic Advances in Gastrointestinal Endoscopy, 2022 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.
MRI-guided stereotactic radiation therapy for hepatocellular carcinoma: a feasible and safe innovative treatment approach Luca Boldrini, Angela Romano, Silvia Mariani, Davide Cusumano, Francesco Catucci, Lorenzo Placidi, Gian Carlo Mattiucci, Giuditta Chiloiro, Francesco Cellini, Maria Antonietta Gambacorta, Luca Indovina, Vincenzo Valentini Journal of Cancer Research and Clinical Oncology, 2021 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. 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. 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. MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.
Role of radiation oncology in modern multidisciplinary cancer treatment Vincenzo Valentini, Luca Boldrini, Silvia Mariani, Mariangela Massaccesi Molecular Oncology, 2020 Cancer care is moving from a disease‐focused management toward a patient‐centered tailored approach. Multidisciplinary management that aims to define individual, optimal treatment strategies through shared decision making between healthcare professionals and patient is a fundamental aspect of high‐quality cancer care and often includes radiation oncology. Advances in technology and radiobiological research allow to deliver ever more tailored radiation treatments in an ever easier and faster way, thus improving the efficacy, safety, and accessibility of radiation therapy. While these changes are improving quality of cancer care, they are also enormously increasing complexity of decision making, thus challenging the ability to deliver quality affordable cancer care. In this review, we provide an updated outline of the role of radiation oncology in the modern multidisciplinary treatment of cancer. Particularly, we focus on the way some developments in key areas of cancer management are challenging multidisciplinary cancer care in the different clinical settings of early, locally advanced, and metastatic disease, thus highlighting some priority areas of research.
Fertility preservation in chemo-radiotherapy for rectal cancer: A combined approach S. Mariani, G. Chiloiro, P. Villa, E. Meldolesi, B. Barbaro, A. Di Giorgio, G. Corrado, B. Corvari, M. Giraffa, G. Scambia, V. Valentini, M.A. Gambacorta Clinical and Translational Radiation Oncology, 2019 Highlights • Young females affected by rectal cancer need counselling on fertility preservation.• Ovarian transposition and cryopreservation are feasible.• Advances in radiation therapy techniques can help reducing fertility impairment.• A multidisciplinar approach is recommended.
