Giuditta Chiloiro
@policlinicogemelli.it
Fondazione Policlinico Gemelli
Scopus Publications
Scopus Publications
Vincenzo Valentini, Sergio Alfieri, Claudio Coco, Domenico D'Ugo, Antonio Crucitti, Fabio Pacelli, Roberto Persiani, Luigi Sofo, Aurelio Picciocchi, Giovanni Battista Doglietto,et al.
Elsevier BV
Brunella Barbaro, Maria Rachele PIa Carafa, Laura Maria Minordi, Priscilla Testa, Giulia Tatulli, Davide Carano, Claudio Fiorillo, Giuditta Chiloiro, Angela Romano, Vincenzo Valentini,et al.
Elsevier BV
Marica Vagni, Huong Elena Tran, Angela Romano, Giuditta Chiloiro, Luca Boldrini, Konstantinos Zormpas-Petridis, Maria Kawula, Guillaume Landry, Christopher Kurz, Stefanie Corradini,et al.
Elsevier BV
Claudio Votta, Sara Iacovone, Gabriele Turco, Valerio Carrozzo, Marica Vagni, Aurora Scalia, Giuditta Chiloiro, Guenda Meffe, Matteo Nardini, Giulia Panza,et al.
Elsevier BV
Luca Boldrini, Giuditta Chiloiro, Davide Cusumano, Poonam Yadav, Gao Yu, Angela Romano, Antonio Piras, Claudio Votta, Lorenzo Placidi, Sara Broggi,et al.
Springer Science and Business Media LLC
Matteo Pavone, Rosa Autorino, Nicolò Bizzarri, Giuditta Chilorio, Vincenzo Valentini, Giacomo Corrado, Gabriella Ferrandina, Gabriella Macchia, Maria Antonietta Gambacorta, Giovanni Scambia,et al.
Elsevier BV
Marco Lupattelli, Elisa Palazzari, Jerry Polesel, Giuditta Chiloiro, Ilaria Angelicone, Valeria Panni, Luciana Caravatta, Saide Di Biase, Gabriella Macchia, Rita Marina Niespolo,et al.
MDPI AG
Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.
Giuditta Chiloiro, Angela Romano, Davide Cusumano, Luca Boldrini, Giulia Panza, Lorenzo Placidi, Elisa Meldolesi, Matteo Nardini, Guenda Meffe, Gianluca Nicolini,et al.
Springer Science and Business Media LLC
Abstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence. Methods Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale. Results From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463). Conclusions MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.
Luca Boldrini, Angela Romano, Giuditta Chiloiro, Stefanie Corradini, Viola De Luca, Valeria Verusio, Andrea D’Aviero, Alessandra Castelluccia, Anna Rita Alitto, Francesco Catucci,et al.
Springer Science and Business Media LLC
Abstract 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).
Luca Boldrini, Giuditta Chiloiro, Davide Cusumano, Angela Romano, Lorenzo Placidi, Gabriele Turco, Marco Valerio Antonelli, Matteo Nardini, Matteo Galetto, Luca Indovina,et al.
Springer Science and Business Media LLC
Abstract Background Mesorectal motion (MM) is a source of uncertainty during neoadjuvant chemoradiotherapy (nCRT) delivery for locally advanced rectal cancer (LARC). Previously published experiences using cone-beam computed tomography imaging have already described significant movement. Aim of this analysis is to assess inter-fraction MM using the higher tissue contrast provided by hybrid magnetic resonance imaging (MRI) in LARC patients (pts) treated with MRI guided radiation therapy (MRgRT). Methods The total mesorectum, its superior (Msup), middle (Mmid) and lower (Mlow) regions were contoured on the positioning MRIs acquired on simulation day and on each treatment day. Six PTVs were obtained adding 0.5, 0.7, 1, 1.3, 1.5 and 2 cm margin to the whole mesorectum, starting from the simulation MRI. Margins including 95% of the mesorectal structures during whole treatment in 95% of patients (pts) were considered adequate. Results A total number of 312 fractions of 12 consecutive pts was retrospectively analyzed. The different mesorectum regions show specific motion variability. In particular, Msup shows larger variability in left, right and anterior directions, while the Mlow in caudal and posterior ones. The anterior margin is significantly larger in the Msup than in the other regions. Conclusion Different mesorectal regions move differently throughout the radiotherapy treatment, with the largest MM in the Msup anterior direction. Asymmetrical margins are recommended.
Giovanna Mantello, Elena Galofaro, Silvia Bisello, Giuditta Chiloiro, Angela Romano, Luciana Caravatta, and Maria Antonietta Gambacorta
MDPI AG
Background: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. Methods: A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). Results: Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. Conclusion: data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence.
Giovanna Mantello, Elena Galofaro, Luciana Caravatta, Clelia Di Carlo, Sabrina Montrone, Donatella Arpa, Giuditta Chiloiro, Antonino De Paoli, Vittorio Donato, Maria Antonietta Gambacorta,et al.
Springer Science and Business Media LLC
Abstract Purpose Radical resection (R0) represents the best curative treatment for local recurrence (LR) rectal cancer. Re-irradiation (re-RT) can increase the rate of R0 resection. Currently, there is a lack of guidelines on Re-RT for LR rectal cancer. The Italian Association of Radiation and clinical oncology for gastrointestinal tumors (AIRO-GI) study group released a national survey to investigate the current clinical practice of external beam radiation therapy in these patients. Material and methods In February 2021, the survey was designed and distributed to members of the GI working group. The questionnaire consisted of 40 questions regarding center characteristics, clinical indications, doses, and treatment techniques of re-RT for LR rectal cancer. Results A total of 37 questionnaires were collected. Re-RT was reported as an option for neoadjuvant treatment in resectable and unresectable disease by 55% and 75% of respondents, respectively. Long-course treatment with 30–40 Gy (1.8–2 Gy/die, 1.2 Gy bid) and hypofractionated regimen of 30–35 Gy in 5 fractions were used in most centers. A total dose of 90–100 Gy as EqD2 dose (α/β = 5 Gy) was delivered by 46% of the respondents considering the previous treatment. Modern conformal techniques and daily image-guided radiation therapy protocols were used in 94% of centers. Conclusion Our survey showed that re-RT treatment is performed with advanced technology that allow a good management of LR rectal cancer. Significant variations were observed in terms of dose and fractionation, highlighting the need for a consensus on a common treatment strategy that could be validated in prospective studies.
Maria Antonietta Gambacorta, Giuditta Chiloiro, Carlotta Masciocchi, Silvia Mariani, Angela Romano, Alessandra Gonnelli, Jean-Pierre Gerard, Samuel Ngan, Claus Rödel, Krzysztof Bujko,et al.
MDPI AG
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.
Giuditta Chiloiro, Davide Cusumano, Angela Romano, Luca Boldrini, Giuseppe Nicolì, Claudio Votta, Huong Elena Tran, Brunella Barbaro, Davide Carano, Vincenzo Valentini,et al.
MDPI AG
Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC.
Giuditta Chiloiro, Luca Boldrini, Angela Romano, Lorenzo Placidi, Huong Elena Tran, Matteo Nardini, Mariangela Massaccesi, Francesco Cellini, Luca Indovina, and Maria Antonietta Gambacorta
Springer Science and Business Media LLC
Luca Boldrini, Filippo Alongi, Angela Romano, Diepriye Charles Davies, Michael Bassetti, Giuditta Chiloiro, Stefanie Corradini, Maria Antonietta Gambacorta, Lorenzo Placidi, Alison C. Tree,et al.
Elsevier BV
Giuditta Chiloiro, Angela Romano, Silvia Mariani, Gabriella Macchia, Diana Giannarelli, Luciana Caravatta, Pierfrancesco Franco, Luca Boldrini, Alessandra Arcelli, Almalina Bacigalupo,et al.
Elsevier BV
Matteo Galetto, Matteo Nardini, Amedeo Capotosti, Guenda Meffe, Davide Cusumano, Luca Boldrini, Giuditta Chiloiro, Angela Romano, Claudio Votta, Maria A. Gambacorta,et al.
Frontiers Media SA
IntroductionPatients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection.Material and methodsA total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP.ResultsGTV centroid motion is <2.2 mm in the antero-posterior and cranio-caudal direction in DIBH. For FB patients, GTV motion is lower than 1.7 mm, and motion during the treatment was always in agreement with the one measured during the simulation. No differences have been observed in GTV coverage between the TP with 3-mm and 5-mm margins. Using a 3-mm margin, the mean reduction in the chest wall and trachea–bronchus Dmax was 2.5 Gy and 3.0 Gy, respectively, and a reduction of 1.0 Gy, 0.6 Gy, and 2.3% in Dmax, Dmean, and V5Gy, respectively, of the homolateral lung and 1.7 Gy in the contralateral lung Dmax.DiscussionsCine-MRI allows to select FB lung patients when GTV motion is <2 mm. The use of narrower PTV margins reduces OARs dose and maintains target coverage.
Matteo Nardini, Guenda Meffe, Matteo Galetto, Luca Boldrini, Giuditta Chiloiro, Angela Romano, Giulia Panza, Andrea Bevacqua, Gabriele Turco, Claudio Votta,et al.
Frontiers Media SA
IntroductionContouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment.Materials and methods21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose.ResultsAverage HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively.DiscussionsGIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.
Mariachiara Savino, Giuditta Chiloiro, Carlotta Masciocchi, Nikola Dino Capocchiano, Jacopo Lenkowicz, Benedetta Gottardelli, Maria Antonietta Gambacorta, Vincenzo Valentini, and Andrea Damiani
Frontiers Media SA
In the era of evidence-based medicine, several clinical guidelines were developed, supporting cancer management from diagnosis to treatment and aiming to optimize patient care and hospital resources. Nevertheless, individual patient characteristics and organizational factors may lead to deviations from these standard recommendations during clinical practice. In this context, process mining in healthcare constitutes a valid tool to evaluate conformance of real treatment pathways, extracted from hospital data warehouses as event log, to standard clinical guidelines, translated into computer-interpretable formats. In this study we translate the European Society of Medical Oncology guidelines for rectal cancer treatment into a computer-interpretable format using Pseudo-Workflow formalism (PWF), a language already employed in pMineR software library for Process Mining in Healthcare. We investigate the adherence of a real-world cohort of rectal cancer patients treated at Fondazione Policlinico Universitario A. Gemelli IRCCS, data associated with cancer diagnosis and treatment are extracted from hospital databases in 453 patients diagnosed with rectal cancer. PWF enables the easy implementation of guidelines in a computer-interpretable format and visualizations that can improve understandability and interpretability of physicians. Results of the conformance checking analysis on our cohort identify a subgroup of patients receiving a long course treatment that deviates from guidelines due to a moderate increase in radiotherapy dose and an addition of oxaliplatin during chemotherapy treatment. This study demonstrates the importance of PWF to evaluate clinical guidelines adherence and to identify reasons of deviations during a treatment process in a real-world and multidisciplinary setting.
Quoc Riccardo Bao, Stefania Ferrari, Giulia Capelli, Cesare Ruffolo, Marco Scarpa, Amedea Agnes, Giuditta Chiloiro, Elisa Palazzari, Emanuele Damiano Luca Urso, Salvatore Pucciarelli,et al.
MDPI AG
Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31–2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75–3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20–3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37–1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.
Luca Boldrini, Jacopo Lenkowicz, Lucia Clara Orlandini, Gang Yin, Davide Cusumano, Giuditta Chiloiro, Nicola Dinapoli, Qian Peng, Calogero Casà, Maria Antonietta Gambacorta,et al.
Springer Science and Business Media LLC
Abstract Background Predicting pathological complete response (pCR) in patients affected by locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (nCRT) is a challenging field of investigation, but many of the published models are burdened by a lack of reliable external validation. Aim of this study was to evaluate the applicability of a magnetic resonance imaging (MRI) radiomic-based pCR model developed and validated in Europe, to a different cohort of patients from an intercontinental cancer center. Methods The original model was based on two clinical and two radiomics features extracted from T2-weighted 1.5 T MRI of 161 LARC patients acquired before nCRT, considered as training set. Such model is here validated using the T2-w 1.5 and 3 T staging MRI of 59 LARC patients with different clinical characteristics consecutively treated in mainland Chinese cancer center from March 2017 to January 2018. Model performance were evaluated in terms of area under the receiver operator characteristics curve (AUC) and relative parameters, such as accuracy, specificity, negative and positive predictive value (NPV and PPV). Results An AUC of 0.83 (CI 95%, 0.71–0.96) was achieved for the intercontinental cohort versus a value of 0.75 (CI 95%, 0.61–0.88) at the external validation step reported in the original experience. Considering the best cut-off threshold identified in the first experience (0.26), the following predictive performance were obtained: 0.65 as accuracy, 0.64 as specificity, 0.70 as sensitivity, 0.91 as NPV and 0.28 as PPV. Conclusions Despite the introduction of significant different factors, the proposed model appeared to be replicable on a real-world data extra-European patients’ cohort, achieving a TRIPOD 4 level.
Giuditta Chiloiro, Davide Cusumano, Luca Boldrini, Angela Romano, Lorenzo Placidi, Matteo Nardini, Elisa Meldolesi, Brunella Barbaro, Claudio Coco, Antonio Crucitti,et al.
Springer Science and Business Media LLC
Abstract Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).
Matteo Nardini, Amedeo Capotosti, Lorenzo Nicola Mazzoni, Davide Cusumano, Luca Boldrini, Giuditta Chiloiro, Angela Romano, Vincenzo Valentini, Luca Indovina, and Lorenzo Placidi
Frontiers Media SA
PurposeThis study aims to assess the quality of a new diffusion-weighted imaging (DWI) sequence implemented on an MR-Linac MRIdian system, evaluating and optimizing the acquisition parameters to explore the possibility of clinically implementing a DWI acquisition protocol in a 0.35-T MR-Linac.Materials and methodsAll the performed analyses have been carried out on two types of phantoms: a homogeneous 24-cm diameter polymethylmethacrylate (PMMA) sphere (SP) and a homemade phantom (HMP) constating in a PMMA cylinder filled with distilled water with empty sockets into which five cylindrical vials filled with five different concentrations of methylcellulose water solutions have been inserted. SP was used to evaluate the dependence of diffusion gradient inhomogeneity artifacts on gantry position. Four diffusion sequences with b-values of 500 s/mm2 and 3 averages have been acquired: three with diffusion gradients in the three main directions (phase direction, read direction, slice direction) and one with the diffusion gradients switched off. The dependence of diffusion image uniformity and SNR on the number of averages in the MR sequences was also investigated to determine the optimal number of averages. Finally, the ADC values of HMP have been computed and then compared between images acquired in the scanners at 0.35 and 1.5 T.ResultsIn order to acquire high-quality artifact-free DWI images, the “slice” gradient direction has been identified to be the optimal one and 0° to be the best gradient angle. Both the SNR ratio and the uniformity increase with the number of averages. A threshold value of 80 for SNR and 85% for uniformity was adopted to choose the best number of averages. By making a compromise between time and quality and limiting the number of b-values, it is possible to reduce the acquisition time to 78 s. The Passing–Bablok test showed that the two methods, with 0.35 and 1.5 T scanners, led to similar results.ConclusionThe quality of the DWI has been accurately evaluated in relation to different sequence parameters, and optimal parameters have been identified to select a clinical protocol for the acquisition of ADC maps sustainable in the workflow of a hybrid radiotherapy system with a 0.35-T MRI scanner.