Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Pathologic Complete Response

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Leucovorin

Fluorouracil

Patients with complete clinical response obtained 8 weeks after chemoradiation or 10 weeks after short-course radiation.

50 Gy, 2 Gy per fraction with simultaneous 5-Fu and leucovorin or 5 x 5 Gy for patients unfit for chemotherapy.

Patients with complete clinical response 8-10 weeks after radiotherapy will be closely observed and rescue surgery will be performed in a case of local recurrence.

Patients with persistent tumour 8-10 weeks after radiotherapy will undergo transanal endoscopic microsurgery or total mesorectal excision. After transanal endosciopic microsurgery, patients with ypT0-1 disease and negative surgical margins will be closely observed and rescue total mesorectal excision will be performed in a case of local recurrence; those with ypT2-3 disease or with positive margin will undergo immediate conversion to total mesorectal excision.

Radiochemotherapy or radiotherapy

Krzysztof Bujko, Prof.

In elderly patients postoperative mortality measured 3-6 months after total mesorectal excision is high. Thus, less toxic treatments may lead to a survival benefit for elderly patients even if a risk of local recurrence is slightly higher compared to the open surgery. The investigators addressed the question whether watch and wait policy is safe in clinical complete responders after (chemo)radiation for elderly patients with small or moderately advanced tumours.

There are two steps of selection. In the first step, the elderly patients with small or moderately advanced tumours who should routinely receive neoadjuvant chemoradiation (or radiation alone in those unfit for chemotherapy) prior to full-thickness local excision using transanal endoscopic microsurgery or prior to total mesorectal excision will be included. In the next step, only patients with clinical complete response obtained 8-10 weeks from completion of (chemo)radiation are selected. Those patients constitute study group and will be observed without further treatment. The remaining patients with residual cancer will proceed to routine management, namely transanal endoscopic microsurgery or total mesorectal excision. Patients undergoing transanal endoscopic microsurgery and having poor response to (chemo)radiation (ypT2-3 disease or positive margin) will proceed to the conversion to total mesorectal excision.

Neoadjuvant chemoradiation: 50 Gy total dose over 5 weeks with 2 Gy per fraction delivered with simultaneous chemotherapy consisting of three cycles of 5-Fu 200 mg/m2 i.v. bolus and leucovorin 100 mg/m2 i.v. short infusion over 2 days given during 1-2, 15-16, and 29-30 days of radiotherapy. Patients unfit for chemotherapy will receive 25 Gy total dose over 5 days with 5 Gy per fraction.

The study hypothesis is that in clinical complete responders after (chemo)radiation treated without initial surgery, the local recurrence rate will be less than 25% and results of the rescue surgery (local and distant recurrence rate) will be not worse (or only slightly worse) than that seen after up-front total mesorectal excision in patients with similar stage of the disease.

Organ Preservation in Elderly Patients With Rectal Cancer

Organ Preservation in Elderly Patients With Rectal Cancer: a Prospective Observational Study

Maria Sklodowska-Curie National Research Institute of Oncology

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Progression

Disease Attributes

rectal resection

Many data suggest that patients with low rectal adenocarcinoma who achieved ypT0N0 status have improved survival and disease-free survival (DFS) compared to all other stages however only few data are available regarding the specific prognosis factors of this subgroup. This retrospective multicentric study aimed to predict the prognosis of patients with complete pathological response after neoadjuvant treatment.

Predictive Factors of Disease-free Survival After Complete Pathological Response to Neoadjuvant Radiotherapy in Rectal Adenocarcinoma

A postoperative local recurrence was defined by biopsy-proven or radiographic evidence of local recurrent disease.

A postoperative distant recurrence was defined by biopsy-proven or radiographic evidence of distant recurrent disease.

Disease free survival was defined as the period between the day of surgery and the date of recurrence or the last date of follow-up

Moroccan Society of Surgery

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Initially, patients will be analyzed in a single group. After determining the status of the biomarkers, the patient sample will be divided into specific groups for comparative purposes.

Jesse L da Silva, MD

A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.

Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.

Objectives and Hypotheses:

Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.

Methods:

Study design: A cohort with retrospective data collection and sectional analysis of pathological material.

Data Source(s): Medical records and pathological material. Study Population: Women with locally advanced triple negative breast cancer consecutively enrolled at Brazilian National Cancer Institute (INCA) submitted to neoadjuvant treatment and subsequently operated.

Exposure(s): Status of specified biomarkers. Outcome(s): Complete Pathologic Response and Progression free Survival and Sample Size Estimations: With a type I error of 5% and study power of 80%, it is estimated that 155 patients are needed.

Statistical Analysis: Statistical analysis will be performed using SPSS (version 18.0 for windows, statistical package for social science (SPSS) Inc., Chicago, IL). Survival curves will be constructed using the Kaplan-Meier method.

Paraffin-embedded Hematoxylin \& Eosin (H \& E) core biopsy/early biopsy and surgical specimens previously analyzed in the Department of Patology of the Brazilian National Cancer Institute (INCA) will be doubly reviewed by two pathologists in our study for histological grade (Scarff-Bloom-Richardson method, modified by Elston and Ellis), histological type (according to World Health Organization, 2012), presence of carcinoma component "in situ", angiolymphatic invasion, perineural infiltration, presence of lymphocytic inflammatory infiltrate.

Triple-negative Breast Cancer: a New Perspective on Biomarkers

Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers

The first event defined as local recurrence or distant relapse, or death, whichever come first.

To determine the clinical response rate in patients with palpable disease.

To compare overall objective response rate in both treatment groups.

To determine predictive markers for sensitivity and resistance to chemotherapy.

To determine prognostic markers for progression free survival after neoadjuvant chemotherapy and surgery.

Instituto Nacional de Cancer, Brazil

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

CT/PET/WSI-based Deep Learning Signature for Predicting Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in Non-small Cell Lung Cancer

CT/PET/WSI-based Deep Learning Signature

Yongxiang Song, Dr

Bentong Yu, Dr

Minglei Yang, Dr

The purpose of this study is to evaluate the performance of a CT/PET/ WSI-based deep learning signature for predicting complete pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer

Deep Learning Signature for Predicting Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in Non-small Cell Lung Cancer

An Integration of a Computed Tomography/Positron Emission Tomography/Whole Slide Image (CT/PET/WSI) Based Deep Learning Signature for Predicting Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in Non-small Cell Lung Cancer: A Multicenter Study

The specificity of the deep learning model in predicting complete pathological response. CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

The positive predictive value of the deep learning model in predicting complete pathological response. CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

The negative predictive value of the deep learning model in predicting complete pathological response. CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

The accuracy of the deep learning model in predicting complete pathological response. CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

The area under the receiver operating characteristic curve (ROC) of the deep learning model in predicting complete pathological response (CPR). CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

The sensitivity of the deep learning model in predicting complete pathological response. CPR was defined as no residual tumor in both resected primary tumor and lymph nodes. Patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy will achieve either CPR or non-CPR, which can be confirmed by pathological examination after surgical resection. And the model will output the predictive value (CPR/non-CPR) for each patient receiving neoadjuvant chemoimmunotherapy.

Ningbo No.2 Hospital

Zunyi Medical College

The First Affiliated Hospital of Nanchang University

Shanghai Pulmonary Hospital, Shanghai, China

Professor

Immune System Diseases

Hypersensitivity

Neoplasm, Residual

Immunomodulating Agents

Stage 3 NSCLC eligible for chemoradiotherapy

Stage 3 NSCLC eligible for neoadjuvant chemo-immunotherapy followed by surgery

Stage 3 NSCLC eligible for surgery followed by immunotherapy

ctDNA will be tested retrospectively, no treatment decisions will be made prospectively

ctDNA

T.Jeroen N Hiltermann, MD, PhD

Ed Schuuring, PhD

Jonathan Benzaquen, MD,PhD

Jennifer Griffonnet

Paul Hofman, MD,PhD

Jonathan Benzaquen, MD

Victoria Ferrari, MD

Jean Philippe Berthet, MD

Ferrari Victoria, MD

Nicola Martin, MD

Mustafa Abdo, MD

Martin Reck, MD, PhD

Remge Pieterman, MD

Alice Staats-Niemeijer, BSC

T.Jeroen Hiltermann, MD

Ed Schuuring, Dr

T.Jeroen Hiltermann, MD, PhD

Paul Hofman, MD, PhD

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for non small cell lung cancer (NSCLC), the methods used to decide who gets additional post radical (surgery or definite chemo-radiotherapy) treatment are suboptimal. Some patients get too much treatment, while others do not get enough.

There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points.

The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient.

GUIDE.MRD-03-NSCLC is a part of the GUIDE.MRD project.

GUIDE.MRD-03-NSCLC is a part of WP3 of the overarching GUIDE.MRD project. Each study chair has a local clinical trial protocol where patients are recruited. After the end of recruitment, samples will be analyzed under the GUIDE.MRD consortium.

The overall aim of GUIDE.MRD is to investigate the clinical utility of ctDNA analysis to predict and guide the choice of multi-modal therapies prospectively. The fundamental steps towards this aim are assessment and benchmarking of the many available ctDNA diagnostics to identify the best-suited tests for clinical application. Clinical samples will be used to benchmark ctDNA diagnostics and assess their true clinical performance. The samples should reflect clinical situations where the ctDNA diagnostics are particularly useful, such as post-operatively, post-adjuvant, during chemotherapy, and longitudinally during post-treatment surveillance. In these situations, ctDNA diagnostics could be used to either monitor treatment response (in case of MRD after surgery or definite chemoradiotherapy) or to identify relapse at an early time point. Based on ctDNA information, medical treatment could be changed, or radiology could be used to reveal the location of residual disease.

The rationale for the observational clinical study GUIDE.MRD-03-NSCLC is to prospectively collect the clinical samples needed to enable assessment of the performance of ctDNA diagnostics in the setting of non small cell lung cancer (NSCLC). There are three main scenarios where ctDNA diagnostic is useful in NSCLC in a MRD setting:

For this study stage III NSCLC will be included treated with curative intent using:

1. chemo-radiotherapy (concurrent or sequential) followed by adjuvant immunotherapy. This patient group is particularly relevant because adjuvant therapy is recommended for all stage III patients (in some countries for those with PD-L1\>1% only), due to their high recurrence risk around 58%. Additionally, most of these do not need therapy at all, because they were already cured by chemo-radiotherapy alone, which leads to substantial overtreatment. Furthermore, the 58% of patients who recur despite both chemoradiotherapy and adjuvant immunotherapy, probably could benefit from further multimodal therapies. The challenge is, however, that currently there is no marker in clinical use that can identify those patients with residual disease and need for therapy. Circulating tumor DNA is potentially such a marker.
2. Neoadjuvant treatment followed by surgery (or radiotherapy with curative intent). In this setting up to 30% have a complete pathological response (pCR). These patients are probably cured by the neoadjuvant treatment alone, where surgery thus might have been avoided if the MRD biomarker would be sensitive enough. Patients that did not receive a pCR do worse with a median overall survival around 24 month even when they are treated with immunecheckpoint inhibitors adjuvantly. Better strategies for selecting patients and treatments are urgently needed here as well. Again ctDNA could be a marker that may help here when sensitive enough to select those that are negative for no adjuvant and those that are positive for ctDNA guided multimodality treatment.
3. Surgery followed by adjuvant chemotherapy and immunotherapy. Patients in this setting may be treated by immunotherapy adjuvantly only when PD-L1\>1% (FDA) or PD-L1\>50% (EMA). Also here recurrence risk is high around 50%. Additionally, most of these do not need therapy at all, because they were already cured by surgery alone, which leads to substantial overtreatment. Furthermore, the 50% of patients who recur despite both surgery and adjuvant therapy, probably could benefit from further multimodal therapies. The challenge is, however, that currently there is no marker in clinical use that can identify those patients with residual disease and need for therapy. Circulating tumor DNA is potentially such a marker.

However, currently, it is unknown, which, if any,of the many different ctDNA diagnostics developed in recent years have the required, performance to provide clinical utility in the management in these settings of stage III NSCLC.

Primary objectives:

To assess the performance of ctDNA diagnostics using samples collected at four to five -landmark time-points "baseline"; "post neoadjuvant treatment"; "post-surgery or chemoradiotherapy"; "post-adjuvant therapy" and "at the end of study or disease progression".Sensitivity, specificity, and positive and negative predictive values of the ctDNA diagnostics will be determined to enable a head-to-head performance assessment and benchmarking of ctDNA diagnostics.

Secondary objectives To assess the ctDNA stratified 3-year recurrence-free survival (RFS). To assess the lead time between ctDNA detection and clinical recurrence. To assess the capacity of the ctDNA diagnostics to predict response to neoadjuvant therapy.

To assess the capacity of the ctDNA diagnostics to predict response to adjuvant therapy.

Full blood samples processed into plasma, buffy coat,and serum Formalin-fixed paraffin-embedded tumor tissue

Clinical Validation and Benchmarking of Top Performing ctDNA Diagnostics - Stage III NSCLC

GUIding Multi-moDal thErapies Against MRD by LiquidBiopsies in Non Small Cell Lung Cancer- GUIDE.MRD-03-NSCLC

For head-to-head performance assessment and benchmarking of ctDNA diagnostics

for complete pathological response, disease progression, event free and overall survival

LungenClinic Grosshansdorf

Centre Hospitalier Universitaire de Nice

University Medical Center Groningen

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Patients with STS of the limbs and trunk will be accrued during the initial radiotherapy consultation radiotherapy (prior to receiving radiotherapy).

Two quantitative multiparametric MRI will be performed. The first one will be acquired less than 14 days before the dosimetric scan, the second one 4 to 6 weeks after the end of the radiotherapy.

A tumor resection will be performed 6 to 8 weeks post-RT and an anatomopathological observation of the surgical specimen will be performed.

Dosimetric CT scan with contrast injection for treatment planning. Radiation therapy at a dose of 50Gy in 25 fractions, 5 fractions per week. Daily pre-treatment positioning tomographic imaging (either high energy (MVCT) or cone beam computed tomography (CBCT)).

Delineation of the tumor volume and evaluation of its evolution. In case of change of volume and if medically relevant, new dosimetric scan and collection of the tumor volume.

Neoadjuvant RT

Performed less than 14 days before the dosimetric scan. Conventional morphological T1-weighted, T2-weighted, and T1-weighted imaging sequences after injection of contrast agent.

Quantitative imaging sequences including multiple b-value diffusion imaging. Chemical shift sensitized sequences.

Pre-radiotherapy mpMRI

Performed 4 to 6 weeks after the end of the radiotherapy. Conventional morphological T1-weighted, T2-weighted, and T1-weighted imaging sequences after injection of contrast agent.

Quantitative imaging sequences including multiple b-value diffusion imaging. Chemical shift sensitized sequences.

Post-radiotherapy mpMRI

Performed 6 to 8 weeks after the end of radiotherapy. An anatomopathological observation of the surgical specimen will be performed.

Tumor resection

Benoît ALLIGNET, MD

Benjamin LEPORQ, MD, PhD

This trial is a prospective, monocentric, with minimal risks and constraints study, conducted in patients with Soft Tissue Sarcoma (STS) of the limbs and trunk with indication for neoadjuvant radiotherapy (RT).

Patients will be treated by neoadjuvant RT and will have a pre-RT and a post-RT multiparametric quantitative Magnetic Resonance Imaging (MRI).

A tumor resection will be performed 6 to 8 weeks post-RT and an anatomopathological observation of the surgical specimen will be performed.

This study will allow to describe the initial remnographic characteristics and their evolution after neoadjuvant RT using quantitative multiparametric MRI (mpMRI).

This study is prospective, monocentric and with minimal risks and constraints.

Patients with STS of the limbs and trunk will be accrued during the initial radiotherapy consultation radiotherapy (prior to receiving radiotherapy).

Two quantitative multiparametric MRI will be performed. The first one will be acquired less than 14 days before the dosimetric scan, the second one 4 to 6 weeks after the end of the radiotherapy.

This study will allow to describe the initial remnographic characteristics and their evolution after neoadjuvant RT using quantitative multiparametric MRI.

STATISTICAL ANALYSIS

Patients will be systematically recruited from December 2022 to August 2023, i.e. a potential of approximately 20-30 patients.

Analysis conventions:

Categorical variables will be expressed as numbers and percentages, and continuous variables as median (minimum-maximum). The normality of the distributions of the quantitative MRI data will be assessed by a Shapiro-Wilk test. A p-value \<0.05 will be considered significant with two-tailed tests. No imputation will be performed in case of missing data. Statistical analyses will be performed using R software (R Foundation for Statistical Computing, Vienna, Austria).

Analysis of the primary endpoint:

The remnographic parameters observed pre- and post-radiotherapy will be described, both qualitatively in T1 weighting, T2 with and without fat saturation, T1 with gadolinium injection, and quantitatively in Chemical Shift-Encoded (CSE) MRI sequence, T2 mapping and multi-echo gradient diffusion.

Analysis of secondary endpoints:

The clinico-remnographic data of the groups with and without complete pathological response will be compared using Student's t test, Wilcoxon test, Chi2 test or Fisher's exact test when appropriate.

ROC curves will be generated to assess the performance of the remnographic parameters in predicting pathological complete response as well as in predicting per-treatment progression via the use of the area under the Receiver Operator Characteristic (ROC) curve (AUC). The Youden index will be used to identify the optimal threshold.

Univariate and multivariate logistic regressions will be performed to assess the clinico-remnographic parameters predictive of complete pathological response as well as those predictive of per-treatment progression.

A Student's t test or a Wilcoxon test will be performed to evaluate the correlation between pre-radiotherapy remnographic parameters and the percentage of variation in tumour volume during treatment, as well as between pre-operative remnographic parameters and the percentage of necrosis on anatomopathological examination of the surgical specimen.

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING

Data generated within the framework of the study will be entered, for each patient, by the investigator of the centre (or a person designated by delegation) on an Excel file in a secure location on the internal network of the Centre Léon Bérard.

Only New Safety Issues occurring in the course of the study will be reported. A New Safety Issue is defined as any new data that could lead to reevaluate the ratio between the benefits and the risks of the research, or that could be sufficiently important to consider modifications of the research documents, the research management or, to suspend, to interrupt or to modify the protocol of the research or of similar researches. The Sponsor should report without delay any New Safety Issue, as well as any safety measures to be proposed, discussed with the principal investigator, to the Ethics Committee and the principal investigators. Relevant follow-up information will be provided within a further 8 days.

The sponsor will assist the investigator in the conduct of the study in accordance with the study protocol, Good Clinical Practice and the regulations in force.

At regular intervals during the study, a representative of the coordinating centre may contact the investigating team in order to control the progress of the project, investigator and patient compliance with the protocol and to identify any potential problem in the study.

Multiparametric Quantitative MRI and Response to Neoadjuvant Radiotherapy for Soft-tissue Sarcoma

Neoadjuvant Radiotherapy of Soft Tissue Sarcomas of Limbs and Trunk : Interest of Multiparametric Quantitative MRI for Response Assessment and Per-treatment Progression Prediction

ROC curves will be generated to evaluate the performance of remnographic parameters for the prediction of per-treatment progression using the area under the ROC curve (AUC).

Qualitative geographic correlation between post-radiotherapy remnographic data and pathological observation of necrosis, fibrosis and perennial cell areas.

Evolution of the maximum axial dimension (mm) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI

Evolution of the volume of the region of interest (ROI) (mm3) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI

Evolution of the minimum, maximum, mean, median, 10th, 25th, 75th and 90th percentile values of free diffusion (D) and microperfusion-related diffusion (D\*) (mm2/s) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI

Evolution of the fraction of perfusion (f) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI

ROC curves will be generated to evaluate the performance of remnographic parameters for the prediction of complete pathological response using the area under the ROC curve (AUC).

Centre Leon Berard

The cancer surgery is practice 11 weeks after neoadjuvant radio-chemotherapy

The cancer surgery is practice 7 weeks after neoadjuvant radio-chemotherapy

Surgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 11 weeks of delay after the end of chemoradiotherapy.

Surgery after 11 weeks of delay after chemoradiotherapy.

Surgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 7 weeks of delay after the end of chemoradiotherapy

Surgery after 7 weeks of delay after chemoradiotherapy

Jérémie Lefèvre, MD

At the end of the neoadjuvant radiochemotherapy, patients are seen by their surgeon to planify the surgery. During this visit, the study will be explained them and their consent obtained. They will then be randomized between the two groups 7 weeks vs. 11 weeks. Patients were reviewed 15 days before surgery and at 1 and 3 months after surgery. Participation in this study does not change treatment, investigations and consultations usually necessary for management of rectal cancer. The objective is to improve the pathological complete response rate of the rectal cancer.

D0: Visit of inclusion and randomization After the end of chemoradiotherapy, the patient is seen in consultation by her / him a surgeon who propose him to participate in the study. At the end of the visit if the patient agrees to participate in it, the investigator at each center will conduct the collection of written consent to the inclusion of the patient. Inclusion will be recorded in the electronic Case Report Form (e-CRF) by the investigator at each center. Randomization (7 or 11 weeks of delay) is performed by the surgeon via the software module CleanWeb randomization.

M1- 1.5 or M2.5 depending of the group randomisation A consultation with the surgeon is held within 15 days (+/- 5 days) of intervention to check the clinical response (tumor regression in rectal tumor distance from the dentate line) and planify surgery. During this visit, the surgeon noted in the e-CRF, clinical findings of the lesion and the results of further investigations.

Not specific exam is requested in the study.

M2 or M3

Surgical procedure:

The anesthesia consultation is planned before the surgery according to the habits of service. Participation in the study does not alter the anesthetic procedures.The patient is admitted the day before surgery in the surgical ward.

During surgery, the operating data are provided on the e-CRF (digital rectal examination under general anesthesia, type of surgery (anterior resection or abdominal-perineal resection), operative time, intraoperative bleeding, macroscopic appearance of the mesorectum, distance from the distal limit of resection). The postoperative complications are noted by the surgeon in the e-CRF during hospitalization (about 10-15 days), and data reporting pathological (Annex 2).

Pathological examination of the specimen of proctectomy is performed according to recommendations for clinical practice using the standard form (Annex 2). The tumor response is evaluated by inclusion of all residual tumor and the response to chemoradiotherapy is graded with the scale of Rödel (Annex 5). A double reading of slides will be made for each patient by two independent pathologists blinded to the randomization group of the patient.

M2 - M5 or M3 - M6 :

Postoperative follow-up :

Following the intervention, no specific consultation is necessary. At follow-up consultations (1 month, 3 months) the surgeon evaluate the postoperative course, planify the stoma closure, noted the potential adverse events and results of morphological examinations (computed tomography, ultrasound, endoscopy) and biological (markers) eventually prescribed.

M6 - M60 :

Cancer surveillance :

Regular follow-up every 3-4 months fo the first two years and every 6 months for the last remaining 3 years (clinical examination, CT-scan and biological marker (CEA))

Influence of Lengthening the Interval Between Radiochemotherapy and Surgery on Complete Pathological Response in Rectal Cancer

Randomized Control Trial Comparing the Impact of a Lengthening of the Interval Between the Radiochemotherapy and Surgery (7 Weeks vs. 11 Weeks) on Complete Pathological Response in Rectal Cancer

LARS questionnaire (Low Anterior Resection Syndrome questionnaire) completed at 24 months and 36 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Organ Preservation in Elderly Patients With Rectal Cancer	NCT01863862	Rectal Cancer	Radiochemothera...	70 Years -	Maria Sklodowska-Curie National Research Institute of Oncology
Predictive Factors of Disease-free Survival After Complete Pathological Response to Neoadjuvant Radiotherapy in Rectal Adenocarcinoma	NCT03601689	Rectal Neoplasm...	rectal resectio...	18 Years -	Moroccan Society of Surgery
Triple-negative Breast Cancer: a New Perspective on Biomarkers	NCT03539965	Triple Negative... Triple Negative...		18 Years - 80 Years	Instituto Nacional de Cancer, Brazil
Predictive Factors of Disease-free Survival After Complete Pathological Response to Neoadjuvant Radiotherapy in Rectal Adenocarcinoma	NCT03601689	Rectal Neoplasm...	rectal resectio...	18 Years -	Moroccan Society of Surgery
Deep Learning Signature for Predicting Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in Non-small Cell Lung Cancer	NCT05925751	Non-small Cell ... Neoadjuvant Che... Complete Pathol...	CT/PET/WSI-base...	20 Years - 75 Years	Shanghai Pulmonary Hospital, Shanghai, China
Deep Learning Signature for Predicting Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in Non-small Cell Lung Cancer	NCT05925751	Non-small Cell ... Neoadjuvant Che... Complete Pathol...	CT/PET/WSI-base...	20 Years - 75 Years	Shanghai Pulmonary Hospital, Shanghai, China
Clinical Validation and Benchmarking of Top Performing ctDNA Diagnostics - Stage III NSCLC	NCT06111807	Lung Cancer Sta...	ctDNA	18 Years -	University Medical Center Groningen
Multiparametric Quantitative MRI and Response to Neoadjuvant Radiotherapy for Soft-tissue Sarcoma	NCT05684874	Soft Tissue Sar... Adult Soft Tiss... Resectable Soft...	Neoadjuvant RT Pre-radiotherap... Post-radiothera... Tumor resection	18 Years -	Centre Leon Berard
Influence of Lengthening the Interval Between Radiochemotherapy and Surgery on Complete Pathological Response in Rectal Cancer	NCT01648894	Rectal Cancer	Surgery after 1... Surgery after 7...	18 Years -	Assistance Publique - Hôpitaux de Paris
Multiparametric Quantitative MRI and Response to Neoadjuvant Radiotherapy for Soft-tissue Sarcoma	NCT05684874	Soft Tissue Sar... Adult Soft Tiss... Resectable Soft...	Neoadjuvant RT Pre-radiotherap... Post-radiothera... Tumor resection	18 Years -	Centre Leon Berard

Spots Global Cancer Trial Database for complete pathological response