Estudio Multidimensional Diseñado para Desarrollar un Marco Metodológico Basado en Datos de Resonancia Magnética (MRI) para Predecir la Respuesta Patológica Completa (pCR) en Pacientes con Cáncer de Recto Localmente Avanzado Tras Tratamiento Neoadyuvante (RESTAGE)
Estudio Multidimensional Diseñado para Desarrollar un Marco Metodológico Basado en Datos de Resonancia Magnética para Predecir la Respuesta Patológica Completa (pCR) en Pacientes con Cáncer de Recto Localmente Avanzado después del Tratamiento Neoadyuvante
Rectal cancer presents a significant global health challenge. Despite improvements in clinical outcomes, significant disparities persist across Europe. These differences are explained not only by the heterogeneity of risk factors and screening strategies, but also by variations in diagnostic and therapeutic approaches, which are highly dependent on medical imaging.
Standard treatment for locally advanced rectal cancer based on staging MRI is neoadjuvant treatment (NAT), for tumour downsizing and downstaging, followed by total mesorectal excision. In a significant proportion of cases, radical surgery leads to substantial long-term complications like sexual and urinary dysfunction, fecal incontinence, and impairment in daily activities. Given that up to 42% of patients show complete tumor regression at pathology (i.e. pathological complete response pCR), to avoid unnecessary radical surgery, non-operative management has become an attractive alternative when there are no signs of viable tumour after NAT (i.e. clinical complete response cCR). Such patients are candidates for Watch-and-Wait (W&W), an established active surveillance policy in specialized centers worldwide relying on clinical examination, endoscopy and MRI.
On the other hand, W&W carries a risk of local regrowth (persistence of microscopic residual disease despite apparent cCR). Even in expert hands, assessment of tumor response is not perfect and local regrowth based on current selection methods occurs in ~30% of cases. Although deferred surgery is a successful treatment with no apparent negative impact on local disease control, an increased rate of distant metastases has been recently reported.
Therefore, there is a critical unmet clinical need to detect complete responses after NAT and avoid unnecessary surgery with its associated morbidity and quality of life impairment risks, while also improving sensitivity for residual microscopic disease that will result in local regrowth and associated reduced disease-free survival.
Rectal cancer poses a burden not only on healthcare systems, but also on patient well-being. Patients frequently suffer from feelings of isolation and helplessness when faced with unpredicted disease-related situations, given the common difficulties to access high quality information and communicate with attending physicians. As such, there is a clear need to unburden healthcare facilities from unnecessary hospital visits, while improving patient outcomes, engagement, support and care.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Aurore MOUSSION
- Número de teléfono: +33 0467613102
- Correo electrónico: drci-icm105@icm.unicancer.fr
Ubicaciones de estudio
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Herault
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Montpellier, Herault, Francia, 34298
- ICM
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Contacto:
- Stéphanie NOUGARET, PHD
- Número de teléfono: +33 0467614725
- Correo electrónico: stephanie.nougaret@icm.unicancer.fr
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Preclinical phase: For patients requiring surgery after neoadjuvant chemoradiotherapy, a surgical consultation will be scheduled as part of routine care. The study will be explained, and an information sheet provided. Participation requires signing the informed consent by the patient and the investigating surgeon.
Clinical phase: When a patient requires an MRI as part of their standard care, the study will be presented during the radiology consultation with an information sheet. If the patient agrees to participate, the informed consent form must be signed by the patient and the investigating physician.
Patients may be included in the study at two possible times: during the MRI performed before neoadjuvant treatment (MRI staging), or during the re-evaluation MRI after neoadjuvant treatment (MRI restaging).
Descripción
Inclusion Criteria for the preclinical phase :
- Age ≥18 years old;
- Have a confirmed diagnosis of locally advanced rectal cancer;
- Have completed neoadjuvant chemoradiotherapy;
- Be a candidate for surgical treatment with total mesorectal excision;
- Be willing and able to provide written informed consent;
- Affiliation to the French Social Security System.
Inclusion criteria for the clinical phase:
- Age ≥18 years old;
- Have a confirmed diagnosis of locally advanced rectal cancer;
- Require neoadjuvant chemoradiotherapy or have completed neoadjuvant chemoradiotherapy;
- Requires either surgical treatment or a non-surgical strategy ("Watch-and-Wait") after neoadjuvant chemoradiotherapy;
- Be willing and able to provide written informed consent;
- Affiliation to the French Social Security System.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Número de grupos/cohortes
Cohortes e Intervenciones
Grupo / CohorteGrupo / Cohorte |
Intervención / TratamientoIntervención / Tratamiento |
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Phase 1 (Preclinical): An ex-vivo analysis of surgical specimens
15 surgical specimens will be collected after surgery following neoadjuvant treatment. They will be imaged using a 3T MRI with advanced sequences, then returned to the pathology department. This ex vivo MRI will not affect sample preparation or preservation. MRI images will be aligned with histological sections using non-linear registration to compare MRI parameters with digital pathology data. This step will help identify MRI biomarkers that differentiate healthy tissue, post-treatment fibrotic tissue, and residual tumor. We will assess whether diffusion MRI and relaxometry measurements can predict pathological outcomes by analyzing parameters such as fractional anisotropy, mean diffusivity, and kurtosis, using surgical pathological information when available |
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Phase 2 (Clinical): An in-vivo clinical MRI study.
The same advanced sequences will be added to MRIs performed during routine clinical care: the initial staging MRI before neoadjuvant chemoradiotherapy, the restaging MRI after treatment completion, and follow-up MRIs for patients managed with a non-operative Watch-and-Wait strategy. For each patient, we will collect imaging data, demographics, medical history, tumor characteristics, treatment details, pathology reports, and clinical follow-up (endoscopy and MRI). All data will be pseudonymized. The second phase involves developing a computational model to predict response to neoadjuvant therapy. A machine learning tool will be designed to predict complete pathological response based on quantitative MRI, standard clinical MRI, and clinical information |
For all patients, questionnaires will be completed:
The following validated questionnaires will be used:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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developpement and validation of a methodological framework based on advanced MRI data to predict pathological complete response in patients with locally advanced rectal cancer after neoadjuvant treatment
Periodo de tiempo: From the baseline to the end of follow up, assessed up to 27 months
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using the area under the ROC curve (AUC) to distinguish pathological complete response (pCR) from residual disease. |
From the baseline to the end of follow up, assessed up to 27 months
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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evaluation of the overall diagnostic performance of the predictive model.
Periodo de tiempo: From the baseline to the end of follow up, assessed up to 27 months
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The overall diagnostic performance of the model will be evaluated using various indicators: Diagnostic accuracy: defined as the overall proportion of correct classifications, Sensitivity, Specificity, Positive predictive value and Negative predictive value |
From the baseline to the end of follow up, assessed up to 27 months
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identification and validation of new MRI biomarkers capable of distinguishing residual tumor from benign fibrotic tissue, using ex vivo MRI of surgical specimens with direct correlation to histological data.
Periodo de tiempo: From the baseline to the end of follow up, assessed up to 27 months
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MRI-histology correlation: statistical correlation between advanced MRI data (derived from ex vivo acquisitions) and the corresponding histological measurements of surgical specimens. Regions of interest (ROIs) defined on ex vivo MRI will be matched with digitized histology. This criterion will validate the new biomarkers. |
From the baseline to the end of follow up, assessed up to 27 months
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establishment of a rectal MRI database to support this project and future research.
Periodo de tiempo: From the baseline to the end of follow up, assessed up to 27 months
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Establishment of a data registry: creation of a functional, populated database of rectal cancer cases that is compliant with the FAIR principles (Findable, Accessible, Interoperable, Reusable). |
From the baseline to the end of follow up, assessed up to 27 months
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assessment of the impact of the disease and therapeutic strategies on patients' quality of life.
Periodo de tiempo: From the baseline to the end of follow up, assessed up to 27 months
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Quality of life scores: scores obtained from standardized questionnaires collected via a digital application to assess the overall impact of the disease and treatments on patients' lives. These will be analyzed using linear mixed models, comparing the surgical group with the "Watch-and-Wait" group over time. |
From the baseline to the end of follow up, assessed up to 27 months
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Director de estudio: Stephanie NOUGARET, PHD, ICM Co. Ltd.
Publicaciones y enlaces útiles
Publicaciones Generales
- Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2.
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
- Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.
- van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, Habr-Gama A, Perez RO, Renehan AG, van de Velde CJH; IWWD Consortium. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018 Jun 23;391(10139):2537-2545. doi: 10.1016/S0140-6736(18)31078-X.
- Wrenn SM, Cepeda-Benito A, Ramos-Valadez DI, Cataldo PA. Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do Patients Really Want? Dis Colon Rectum. 2018 Aug;61(8):971-978. doi: 10.1097/DCR.0000000000001078.
- Garcia-Aguilar J, Shi Q, Thomas CR Jr, Chan E, Cataldo P, Marcet J, Medich D, Pigazzi A, Oommen S, Posner MC. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012 Feb;19(2):384-91. doi: 10.1245/s10434-011-1933-7. Epub 2011 Jul 14.
- Park IJ, Yu CS. Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy. World J Gastroenterol. 2014 Feb 28;20(8):2023-9. doi: 10.3748/wjg.v20.i8.2023.
- Dattani M, Heald RJ, Goussous G, Broadhurst J, Sao Juliao GP, Habr-Gama A, Perez RO, Moran BJ. Oncological and Survival Outcomes in Watch and Wait Patients With a Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Systematic Review and Pooled Analysis. Ann Surg. 2018 Dec;268(6):955-967. doi: 10.1097/SLA.0000000000002761.
- Sao Juliao GP, Habr-Gama A, Vailati BB, Perez RO. The good, the bad and the ugly: rectal cancers in the twenty-first century. Tech Coloproctol. 2017 Jul;21(7):573-575. doi: 10.1007/s10151-017-1651-7. Epub 2017 Jun 19. No abstract available.
- Beets-Tan RGH, Lambregts DMJ, Maas M, Bipat S, Barbaro B, Curvo-Semedo L, Fenlon HM, Gollub MJ, Gourtsoyianni S, Halligan S, Hoeffel C, Kim SH, Laghi A, Maier A, Rafaelsen SR, Stoker J, Taylor SA, Torkzad MR, Blomqvist L. Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol. 2018 Apr;28(4):1465-1475. doi: 10.1007/s00330-017-5026-2. Epub 2017 Oct 17.
- Socha J, Kepka L, Michalski W, Paciorek K, Bujko K. The risk of distant metastases in rectal cancer managed by a watch-and-wait strategy - A systematic review and meta-analysis. Radiother Oncol. 2020 Mar;144:1-6. doi: 10.1016/j.radonc.2019.10.009. Epub 2019 Nov 8.
- Nasir I, Fernandez L, Vieira P, Pares O, Santiago I, Castillo-Martin M, Domingos H, Cunha JF, Carvalho C, Heald RJ, Beets GL, Parvaiz A, Figueiredo N. Salvage surgery for local regrowths in Watch & Wait - Are we harming our patients by deferring the surgery? Eur J Surg Oncol. 2019 Sep;45(9):1559-1566. doi: 10.1016/j.ejso.2019.04.006. Epub 2019 Apr 13.
- Fernandez LM, Sao Juliao GP, Renehan AG, Beets GL, Papoila AL, Vailati BB, Bahadoer RR, Kranenbarg EM, Roodvoets AGH, Figueiredo NL, Van De Velde CJH, Habr-Gama A, Perez RO; International Watch & Wait Database (IWWD) Consortium. The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database. Dis Colon Rectum. 2023 Jan 1;66(1):41-49. doi: 10.1097/DCR.0000000000002494. Epub 2022 Oct 21.
- Smith JJ, Strombom P, Chow OS, Roxburgh CS, Lynn P, Eaton A, Widmar M, Ganesh K, Yaeger R, Cercek A, Weiser MR, Nash GM, Guillem JG, Temple LKF, Chalasani SB, Fuqua JL, Petkovska I, Wu AJ, Reyngold M, Vakiani E, Shia J, Segal NH, Smith JD, Crane C, Gollub MJ, Gonen M, Saltz LB, Garcia-Aguilar J, Paty PB. Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy. JAMA Oncol. 2019 Apr 1;5(4):e185896. doi: 10.1001/jamaoncol.2018.5896. Epub 2019 Apr 11.
- Tsunoda A, Nakao K, Hiratsuka K, Yasuda N, Shibusawa M, Kusano M. Anxiety, depression and quality of life in colorectal cancer patients. Int J Clin Oncol. 2005 Dec;10(6):411-7. doi: 10.1007/s10147-005-0524-7.
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- PROICM 2025-07 RES
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
All data will be available after publication of the results in peer-reviewed revues, and in national and international meetings. It includes all de-identified participants' data, the study protocol, the statistical analysis plan and the clinical study report. The corresponding author will provide data and datasets generated and/or analyzed during the study upon reasonable request.
Marco de tiempo para compartir IPD
Access to study data upon written detailed request sent to ICM, from 6 months until 5 years after publication of summary data.
Criterios de acceso compartido de IPD
The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
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