RESUMEN
PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.
Asunto(s)
Radiómica , Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/radioterapia , Neoplasias del Recto/patología , Imagen por Resonancia Magnética/métodos , Recto , Terapia Neoadyuvante/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. MATERIALS AND METHODS: Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. RESULTS: From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14 months (range: 3-46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). CONCLUSION: MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.
Asunto(s)
Neoplasias Pulmonares , Radiocirugia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Estudios Retrospectivos , Supervivencia sin Progresión , Espectroscopía de Resonancia Magnética , Resultado del TratamientoRESUMEN
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/ß = 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.
Asunto(s)
Reirradiación , Neoplasias del Recto , Humanos , Reirradiación/métodos , Estudios Prospectivos , Recurrencia Local de Neoplasia/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , RectoRESUMEN
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).
Asunto(s)
Imagen por Resonancia Magnética , Terapia Neoadyuvante/métodos , Radioterapia Guiada por Imagen/métodos , Neoplasias del Recto/terapia , Adulto , Antineoplásicos/administración & dosificación , Capecitabina/administración & dosificación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias del Recto/patología , Recto/patología , Resultado del TratamientoRESUMEN
PURPOSE: Our study investigated the contribution that the application of radiomics analysis on post-treatment magnetic resonance imaging can add to the assessments performed by an experienced disease-specific multidisciplinary tumor board (MTB) for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This analysis included consecutively retrospective LARC patients who obtained a complete or near-complete response after nCRT and/or a pCR after surgery between January 2010 and September 2019. A three-step radiomics features selection was performed and three models were generated: a radiomics model (rRM), a multidisciplinary tumor board model (yMTB) and a combined model (CM). The predictive performance of models was quantified using the receiver operating characteristic (ROC) curve, evaluating the area under curve (AUC). RESULTS: The analysis involved 144 LARC patients; a total of 232 radiomics features were extracted from the MR images acquired post-nCRT. The yMTB, rRM and CM predicted pCR with an AUC of 0.82, 0.73 and 0.84, respectively. ROC comparison was not significant (p = 0.6) between yMTB and CM. CONCLUSION: Radiomics analysis showed good performance in identifying complete responders, which increased when combined with standard clinical evaluation; this increase was not statistically significant but did improve the prediction of clinical response.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias del Recto/terapia , Recto/diagnóstico por imagen , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner. METHODS: In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon-Mann-Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness. RESULTS: Three features were selected: maximum fractal dimension with IB = 0-50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0-50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively. CONCLUSIONS: The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features.
Asunto(s)
Quimioradioterapia Adyuvante , Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Área Bajo la Curva , Femenino , Fractales , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética/instrumentación , Masculino , Persona de Mediana Edad , Modelos Teóricos , Neoplasias del Recto/patología , Estudios Retrospectivos , Estadísticas no Paramétricas , Resultado del Tratamiento , Carga TumoralRESUMEN
Background and objectives: The diagnosis and therapy of squamous cell carcinoma of the anus may vary significantly in daily clinical practice, even if international guidelines are available. Materials and Methods: We conducted a pattern of care survey to assess the management of patients with anal cancer in Italy (38 questions). We analyzed 58 questionnaires. Results: Most of the respondents work in public and/or university hospitals (75.8%) in northern Italy (65.5%). The majority (88.0%) treat less than 20 patients/year. Common examinations for diagnosis and staging are anorectal endoscopy (84.5%), computed tomography scan (86.2%) and pelvic magnetic resonance imaging (MRI) (96.5%). The most frequently prescribed dose to primary tumor is 50-54 Gy (46.5-58.6%) for early stage disease and 54-59.4 Gy (62.1-32.8%) for locally advanced cases. Elective volumes are prescribed around 45 Gy (94.8%). Most participants use volumetric intensity modulated radiotherapy (89.7%) and a simultaneous integrated boost (84.5%). Concurrent radiotherapy, 5-fluorouracil and mitomycin is considered the standard of care (70.6%). Capecitabine is less frequently used (34.4%). Induction chemotherapy is an option for extensive localized disease (65.5%). Consolidation chemotherapy is rarely used (18.9%). A response evaluation is conducted at 26-30 weeks (63.9%) with a pelvic MRI (91.4%). Follow-up is generally run by the multidisciplinary tumor board (62.1%). Conclusions: Differences were observed for radiotherapy dose prescription, calling for a consensus to harmonize treatment strategies.
Asunto(s)
Neoplasias del Ano , Carcinoma de Células Escamosas , Canal Anal/diagnóstico por imagen , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Ano/radioterapia , Quimioradioterapia , Humanos , Oncología MédicaRESUMEN
PURPOSE: Magnetic Resonance-guided radiotherapy (MRgRT) systems allow continuous monitoring of therapy volumes during treatment delivery and personalized respiratory gating approaches. Treatment length may therefore be significantly affected by patient's compliance and breathing control. We quantitatively analyzed treatment process time efficiency (TE ) using data obtained from real-world patient treatment logs to optimize MRgRT delivery settings. METHODS: Data corresponding to the first 100 patients treated with a low T hybrid MRI-Linac system, both in free breathing (FB) and in breath hold inspiration (BHI) were collected. TE has been computed as the percentage difference of the actual single fraction's total treatment time and the predicted treatment process time, as computed by the TPS during plan optimization. Differences between the scheduled and actual treatment room occupancy time were also evaluated. Finally, possible correlations with planning, delivery and clinical parameters with TE were also investigated. RESULTS: Nine hundred and nineteen treatment fractions were evaluated. TE difference between BHI and FB patients' groups was statistically significant and the mean TE were 42.4%, and -0.5% respectively. No correlation was found with TE for BHI and FB groups. Planning, delivering and clinical parameters classified BHI and FB groups, but no correlation with TE was found. CONCLUSION: The use of BHI gating technique can increase the treatment process time significantly. BHI technique could be not always an adequate delivery technique to optimize the treatment process time. Further gating techniques should be considered to improve the use of MRgRT.
Asunto(s)
Neoplasias , Radioterapia Guiada por Imagen , Contencion de la Respiración , Humanos , Imagen por Resonancia Magnética , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Aceleradores de Partículas , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: Magnetic resonance-guided adaptive radiotherapy (MRgART) is considered a promising resource for pancreatic cancer, as it allows to online modify the dose distribution according to daily anatomy. This study aims to compare the dosimetric performance of a simplified optimizer implemented on a MR-Linac treatment planning system (TPS) with those obtained using an advanced optimizer implemented on a conventional Linac. METHODS: Twenty patients affected by locally advanced pancreatic cancer (LAPC) were considered. Gross tumor volume (GTV) and surrounding organ at risks (OARs) were contoured on the average 4DCT scan. Planning target volume was generated from GTV by adding an isotropic 3 mm margin and excluding overlap areas with OARs. Treatment plans were generated by using the simple optimizer for the MR-Linac in intensity-modulated radiation therapy (IMRT) and the advanced optimizer for conventional Linac in IMRT and volumetric modulated arc therapy (VMAT) technique. Prescription dose was 40 Gy in five fractions. The dosimetric comparison was performed on target coverage, dosimetric indicators, and low dose diffusion. RESULTS: The simplified optimizer of MR-Linac generated clinically acceptable plans in 80% and optimal plans in 55% of cases. The number of clinically acceptable plans obtained using the advanced optimizer of the conventional Linac with IMRT was the same of MR-Linac, but the percentage of optimal plans was higher (65%). Using the VMAT technique, it is possible to obtain clinically acceptable plan in 95% and optimal plans in 90% of cases. The advanced optimizer combined with VMAT technique ensures higher target dose homogeneity and minor diffusion of low doses, but its actual optimization time is not suitable for MRgART. CONCLUSION: Simplified optimization solutions implemented in the MR-Linac TPS allows to elaborate in most of cases treatment plans dosimetrically comparable with those obtained by using an advanced optimizer. A superior treatment plan quality is possible using the VMAT technique that could represent a breakthrough for the MRgART if the modern advancements will lead to shorter optimization times.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Neoplasias Pancreáticas/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Radioterapia de Intensidad Modulada/normas , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Órganos en Riesgo/efectos de la radiación , Aceleradores de Partículas/instrumentación , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodosRESUMEN
The aim of this study was to evaluate the variation of radiomics features, defined as "delta radiomics", in patients undergoing neoadjuvant radiochemotherapy (RCT) for rectal cancer treated with hybrid magnetic resonance (MR)-guided radiotherapy (MRgRT). The delta radiomics features were then correlated with clinical complete response (cCR) outcome, to investigate their predictive power. A total of 16 patients were enrolled, and 5 patients (31%) showed cCR at restaging examinations. T2*/T1 MR images acquired with a hybrid 0.35 T MRgRT unit were considered for this analysis. An imaging acquisition protocol of 6 MR scans per patient was performed: the first MR was acquired at first simulation (t0) and the remaining ones at fractions 5, 10, 15, 20 and 25. Radiomics features were extracted from the gross tumour volume (GTV), and each feature was correlated with the corresponding delivered dose. The variations of each feature during treatment were quantified, and the ratio between the values calculated at different dose levels and the one extracted at t0 was calculated too. The Wilcoxon-Mann-Whitney test was performed to identify the features whose variation can be predictive of cCR, assessed with a MR acquired 6 weeks after RCT and digital examination. The most predictive feature ratios in cCR prediction were the L_least and glnu ones, calculated at the second week of treatment (22 Gy) with a p value = 0.001. Delta radiomics approach showed promising results and the quantitative analysis of images throughout MRgRT treatment can successfully predict cCR offering an innovative personalized medicine approach to rectal cancer treatment.
Asunto(s)
Adenocarcinoma/radioterapia , Imagen por Resonancia Magnética/métodos , Medicina de Precisión , Radioterapia Guiada por Imagen/métodos , Neoplasias del Recto/radioterapia , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Biopsia , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Recto/patología , Resultado del Tratamiento , Carga TumoralRESUMEN
The aim of this study was to propose a methodology to investigate the tumour heterogeneity and evaluate its ability to predict pathologically complete response (pCR) after chemo-radiotherapy (CRT) in locally advanced rectal cancer (LARC). This approach consisted in normalising the pixel intensities of the tumour and identifying the different sub-regions using an intensity-based thresholding. The spatial organisation of these subpopulations was quantified using the fractal dimension (FD). This approach was implemented in a radiomic workflow and applied to 198 T2-weighted pre-treatment magnetic resonance (MR) images of LARC patients. Three types of features were extracted from the gross tumour volume (GTV): morphological, statistical and fractal features. Feature selection was performed using the Wilcoxon test and a logistic regression model was calculated to predict the pCR probability after CRT. The model was elaborated considering the patients treated in two institutions: Fondazione Policlinico Universitario "Agostino Gemelli" of Rome (173 cases, training set) and University Medical Centre of Maastricht (25 cases, validation set). The results obtained showed that the fractal parameters of the subpopulations have the highest performance in predicting pCR. The predictive model elaborated had an area under the curve (AUC) equal to 0.77 ± 0.07. The model reliability was confirmed by the validation set (AUC = 0.79 ± 0.09). This study suggests that the fractal analysis can play an important role in radiomics, providing valuable information not only about the GTV structure, but also about its inner subpopulations.
Asunto(s)
Quimioradioterapia , Fractales , Imagen por Resonancia Magnética , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Neoplasias del Recto/patología , Resultado del TratamientoRESUMEN
MR-guided radiotherapy is a treatment approach that combines the advantages of magnetic resonance imaging (MRI) with the precision of radiation therapy. This practical review provides an overview of the current state-of-the-art of MR-guided radiotherapy for rectal cancer, including its technical aspects, clinical outcomes, and existing limitations. Even though some studies have demonstrated the feasibility and safety of this treatment modality, challenges remain in terms of patient selection, treatment planning optimization, and long-term follow-up. Despite these issues, MR-guided radiotherapy shows promise as a potentially valuable rectal cancer treatment approach.
Asunto(s)
Médicos , Radioterapia Guiada por Imagen , Neoplasias del Recto , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/radioterapia , Radioterapia Guiada por Imagen/métodos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.
Asunto(s)
Neoplasias Hepáticas , Imagen por Resonancia Magnética , Radiocirugia , Radioterapia Guiada por Imagen , Humanos , Radiocirugia/métodos , Radiocirugia/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Radioterapia Guiada por Imagen/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Anciano de 80 o más Años , AdultoRESUMEN
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.
Asunto(s)
Neoplasias del Ano , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Ano/radioterapia , Neoplasias del Ano/patología , Neoplasias del Ano/mortalidad , Anciano , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Adulto , Resultado del Tratamiento , Anciano de 80 o más Años , Estadificación de Neoplasias , Estudios Retrospectivos , Canal Anal/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidadRESUMEN
Introduction: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM. Materials and methods: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55-50.6 Gy at PTV1 and 45-39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients. Results: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed. Conclusion: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.
RESUMEN
BACKGROUND: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT). METHODS: The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac. EXPERIMENTAL DESIGN: The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements. DISCUSSION: We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments.
Asunto(s)
Neoplasias del Recto , Neoplasias del Recto/radioterapia , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Humanos , Terapia Neoadyuvante/métodos , Microbioma Gastrointestinal , Imagen por Resonancia Magnética , Radioterapia Guiada por Imagen/métodos , Quimioradioterapia/métodos , ADN Tumoral Circulante/genética , Biomarcadores de Tumor , Genómica/métodos , Masculino , Femenino , MultiómicaRESUMEN
BACKGROUND: Accurate nodal restaging is becoming clinically more important in patients with locally advanced rectal cancer (LARC) with the emergence of organ-preserving treatment after a good response to neoadjuvant chemoradiotherapy (nCRT). PURPOSE: To evaluate the accuracy of MRI in identifying negative N status (ypN0 patients) in LARC after nCRT. MATERIAL AND METHODS: 191 patients with LARC underwent MRI before and 6-8â¯weeks after nCRT and subsequent total mesorectal excision. Short-axis diameter of mesorectal lymph nodes was evaluated on the high resolution T2-weighted images to compare MRI restaging with histopathology.. RESULTS: 146 and 45 patients had a negative N status (ypN0) and positive N status (ypNâ¯+â¯), respectively. On restaging MRI, the 70â¯% reduction in size of the largest node was associated with an area under the curve (AUC) of 0.818 to predict ypN0 stage, with a sensitivity of 93.3â¯% and a negative predictive value (NPV) of 95.4â¯%. No nodes were observed in 38 pts (37 pts ypN0 and 1 patient ypNâ¯+â¯), with sensitivity and NPV of nodes disappearance for ypN0 stage of 93.3â¯% and 92.5â¯% respectively. A 2.2â¯mm cut-off in short-axis diameter was associated with an AUC of 0.83 for the prediction of ypN0 nodal stage, with sensitivity and NPV of 79,5% and 91.1â¯% respectively. CONCLUSION: A reduction in size of 70â¯% of the largest limph-node on MRI at rectal cancer restaging has high sensitivity and NPV for prediction of ypN0 stage after nCRT. The high NPV of node disappearance and of aâ¯≤â¯2.2â¯mm short-axis diameter is confirmed.
Asunto(s)
Imagen por Resonancia Magnética , Neoplasias del Recto , Humanos , Estadificación de Neoplasias , Imagen por Resonancia Magnética/métodos , Quimioradioterapia/métodos , Neoplasias del Recto/terapia , Neoplasias del Recto/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Estudios RetrospectivosRESUMEN
Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p < 0.05) longer than the SMP workflow (19 min). The time required for ADP treatments is significantly influenced by TDt, constituting 40 % of the total time. The oART steps (RCt + RPt) took 11 min (median), representing 27 % of the entire procedure. Overall, 79.2 % of oART fractions were completed in less than 45 min, and 30.6 % were completed in less than 30 min. Conclusion: This preliminary analysis, along with the comparative assessment against existing literature, underscores the potential of CPW to diminish the overall treatment duration in MRgRT-oART. Additionally, it suggests the potential for CPW to promote a more integrated multidisciplinary approach in the execution of oART.
RESUMEN
PURPOSE: Manual recontouring of targets and Organs At Risk (OARs) is a time-consuming and operator-dependent task. We explored the potential of Generative Adversarial Networks (GAN) to auto-segment the rectum, bladder and femoral heads on 0.35T MRIs to accelerate the online MRI-guided-Radiotherapy (MRIgRT) workflow. METHODS: 3D planning MRIs from 60 prostate cancer patients treated with 0.35T MR-Linac were collected. A 3D GAN architecture and its equivalent 2D version were trained, validated and tested on 40, 10 and 10 patients respectively. The volumetric Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95th) were computed against expert drawn ground-truth delineations. The networks were also validated on an independent external dataset of 16 patients. RESULTS: In the internal test set, the 3D and 2D GANs showed DSC/HD95th of 0.83/9.72 mm and 0.81/10.65 mm for the rectum, 0.92/5.91 mm and 0.85/15.72 mm for the bladder, and 0.94/3.62 mm and 0.90/9.49 mm for the femoral heads. In the external test set, the performance was 0.74/31.13 mm and 0.72/25.07 mm for the rectum, 0.92/9.46 mm and 0.88/11.28 mm for the bladder, and 0.89/7.00 mm and 0.88/10.06 mm for the femoral heads. The 3D and 2D GANs required on average 1.44 s and 6.59 s respectively to generate the OARs' volumetric segmentation for a single patient. CONCLUSIONS: The proposed 3D GAN auto-segments pelvic OARs with high accuracy on 0.35T, in both the internal and the external test sets, outperforming its 2D equivalent in both segmentation robustness and volume generation time.