Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Carcinoma

Neoplastic Cells, Circulating

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

longitudinal blood samples for CTC monitoring

Blood sample

longitudinal MRI scans (non-contrast enhanced)

MRI scan

Georg Wurschi, MD

Andrea Wittig-Sauerwein, MD

This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.

Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management ("watch and wait") is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.

* histological analysis of tumor specimens (pre-treatment biopsy and resected tumor)
* blood samples (Circulating Tumor Cells, CTCs)

Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

Planning Adaptive Treatment by Longitudinal Response Assessment Implementing MR Imaging, Liquid Biopsy and Analysis of Microenvironment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)

Histological response assessment by TRG (Werner / Hoefler et al.); Response is defined as TRG 1a/b/2;

longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive)

surrogates of tumor and inflammation from routine blood draws \[ng/l\]

surrogates of tumor and inflammation from routine blood draws, \[mg/l\]

Jena University Hospital

Principal Investigator

Gland and Hormone Related Diseases

Rare Diseases

Neoplasm Metastasis

Pancreatic Neoplasms

Adenocarcinoma

Body Weight

Peritoneal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Processes

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Abdominal Neoplasms

Peritoneal Diseases

Pancreatic Cancer

Patients to undergo DWI-MRI (patients include in the study.

Whole-body diffusion-weighted magnetic resonance imaging

Alexandre Brind'Amour, MD

Alexandre Brind'Amour

Diffusion-weighted magnetic resonance imaging (DWI/MRI) has been described in recent literature as a highly sensitive and specific modality for the detection of peritoneal metastases (PM). It has been demonstrated to be superior to computed tomography (CT) for patients with known peritoneal disease from colorectal and gynaecological malignancies. However, the literature is scarce on the role of DWI/MRI in patients with pancreatic ductal-adenocarcinoma (PDAC). The aim of this study is to prospectively assess the added value of whole-body DWI/MRI (WB-DWI/MRI) to CT for detection of PM in the preoperative staging of patients with high-risk PDAC and evaluate how it correlates with intraoperative findings.

This is a prospective study from a single center. Patients will be evaluated and operated on by one of five surgeons with a subspeciality in hepato-biliary and pancreatic surgery. After thorough assessment for resectability, patients with PDAC considered resectable based on CT, but at high-risk for peritoneal disease, will be prospectively included in the study and assessed with WB-DWI/MRI within 4 weeks of the planned surgery, with the standard protocol including the following sequences: Patients will drink 1L of pineapple juice one hour prior to the examination in order to provide a negative intraluminal contrast. Patients will receive 20 mg of intravenous hyoscine butylbromide at the beginning of the MR exam in order to reduce bowel peristalsis. Sequences will include Axial et Coronal T2WI of the abdomen and pelvis, axial DWI with b values of 0, 50 and 1000 of the abdomen and pelvis, as well as Pre and post gadolinium-based contrast Axial and Coronal 3D T1WGRE. Patients with no evidence of PM on WB-DWI/MRI will be operated on and undergo pancreatic resection following the usual exploration of the peritoneal cavity in case of occult metastatic disease. Patients with suspicion of PM on WB-DWI/MRI will be approached with a diagnostic laparoscopy first, then undergo pancreatic resection if no evidence of PM is found. Each case will be followed for at least 6 months.

Diagnostic Value of DWI-MRI for Detection of Peritoneal Metastases in High-risk Pancreatic Ductal Adenocarcinoma.

Diagnostic Value of Diffusion-weighted Magnetic Resonance Imaging for Detection of Peritoneal Metastases in High-risk Pancreatic Ductal Adenocarcinoma: a Pilot Study.

The number of cases in which peritoneal findings on MRI altered clinical management.

The rate of unexpected aborted surgery due to peritoneal metastases discovery at surgery.

The number of cases with early distant recurrence (less than 6 months).

Laval University

Doctor

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Immunomodulating Agents

Patients will receive single agent PD-1/PD-L1 inhibitor in a predefined group.

Patients will receive combined immunotherapy in a predefined group. PD-1/PD-L1 inhibitor will be combined with target therapy, such as lenvatinib, enrotinib, herceptin et al.

Patients will receive diagnostic MRI test on d0.

MRI test

Patients will receive diagnostic MRI test on d8±1.

Patients will receive diagnostic MRI test on d30±2.

Lin Shen, professor

Lin Shen, MD PhD

Shen Lin, Professor

Shen Lin, professor

This is a prospective two cohorts observational study aimed to investigate the predicting value of MRI none-Gaussian model in digestive malignancies patients who received single agent PD-1/PD-L1 inhibitor or combined immunotherapy.

MRI DWI None-Gaussian Model Predicting Early Response to Immunotherapy in Digestive System Malignancies: a Prospective Observational Study

Magnetic Resonance Imaging (MRI) Diffusion-weighted Imaging (Dwi) None-Gaussian Model Predicting Early Response to Immunotherapy in Digestive System Malignancies: a Prospective Observational Study

The rate of patients reached complete response or partial response.

the time from enrollment to disease progression or death or loss of follow-up.

the time from enrollment to death or loss of follow-up.

Peking University

professor

Recurrence

Appendiceal Neoplasms

Cecal Neoplasms

Cecal Diseases

Patients to undergo DWI-MRI (patients included in the study).

Mikaël L. Soucisse, MD

Pierre Dubé, MD

Lucas Sidéris, MD

Jean-François Tremblay, MD

Julie Lafrance, MD

Cindy Boulanger-Gobeil, MD

Patricia Noël, MD

Diffusion-weighted magnetic resonance imaging (DWI/MRI) has been described in recent literature as a highly sensitive and specific modality for the detection of peritoneal metastases PM. It has been demonstrated to be superior to CT for patients with known peritoneal disease from colorectal and gynaecological malignancies as a staging tool for cytoreductive surgery. It was also demonstrated to be superior for the detection of PM for gastric cancer patients otherwise considered with a resectable tumor. However, the literature is scarce on the role of DWI/MRI in the detection of peritoneal recurrence for patients with high-risk features, either colorectal cancer (CRC) or appendiceal neoplasms (AN).

The aim of this study is to prospectively assess the added value of whole-body DWI/MRI (WB-DWI/MRI) to CT and diagnostic laparoscopy for detection of PM in the follow-up of patients presenting with CRC or AN and high-risk features for peritoneal recurrence and evaluate how it correlates with intraoperative findings.

This is a multicentric, prospective study (CHU de Québec and Hôpital Maisonneuve-Rosemont). Patients will be referred to one of six surgeons with a subspeciality in peritoneal surface oncology after their index surgery for CRC or AN. After thorough assessment, patients judged without residual peritoneal disease, but at high-risk for peritoneal recurrence, will be prospectively included in the study. Patients will be assessed with CT and WB-DWI/MRI twelve months after their index surgery. For WB-DWI/MRI, the standard protocol will include the following sequences: Patients will drink 1L of pineapple juice one hour prior to the examination in order to provide a negative intraluminal contrast. They will receive 20 mg of intravenous hyoscine butylbromide at the beginning of the MR exam in order to reduce bowel peristalsis. Sequences will include Axial et Coronal T2WI of the abdomen and pelvis, axial DWI with b values of 0, 50 and 1000 of the abdomen and pelvis, as well as Pre and post gadolinium-based contrast Axial and Coronal 3D T1WGRE. All patients included in the study will then undergo diagnostic laparoscopy, to provide correlation with imaging findings. Patients with no evidence of peritoneal recurrence on CT, WB-DWI/MRI and diagnostic laparoscopy will continue to be followed with serial CT and blood tumor markers (CEA, CA 19-9) as done on a routine basis. Patients with confirmed peritoneal disease at diagnostic laparoscopy will be further evaluated for cytoreductive surgery, with or without hyperthermic intraperitoneal chemotherapy. The study duration will be two years for all participants.

Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms

Diagnostic Value of Diffusion-weighted Magnetic Resonance Imaging for Detection of Peritoneal Recurrence in Patients With High-risk Colorectal and Appendiceal Neoplasms : a Pilot Study

The number of cases in which peritoneal findings on MRI matched with surgical exploration.

The number of cases with early peritoneal recurrence after MRI.

The number of cases with early distant recurrence.

Ciusss de L'Est de l'Île de Montréal

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Heikki R Minn, Professor

Grading of gliomas is of significant clinical importance since the prognosis as well as the treatment of choice are distinct in low-grade and high-grade gliomas. With standard MRI modalities, however, a reliable distinction is often impossible. Moreover, the gold standard for glioma grading by histopathology may also have limitations due to unrepresentative tumor samples. Therefore, more advanced MRI techniques are urgently needed that would have higher sensitivity and specificity in the definition of tumor type, grade and extent.

Assessment of radiologic response for high-grade gliomas utilizes the updated RANO criteria 12 weeks after completion of chemoradiotherapy. However, there is an urgent need to identify nonresponding patients earlier, preferentially midtreatment in order to consider alternative treatment strategies. Imaging biomarkers, such as diffusion weighted MR imaging (DWI), have provided promising results in assessing early treatment response. Furthermore, a serum biomarker with diagnostic value could improve tumor follow-up and clinical management of gliomas.

The aim of our study is to develop novel imaging protocols suitable for the magnetic resonance imaging (MRI) of glioma using advanced MRI techniques such as rotating frame imaging, novel DWI acquisition and post-processing methods We also study the correlation between advanced MRI parameters and histopathology of the tumor specimen. In addition, early treatment response is assessed with advanced MRI parameters at 3 week and 10 week after initiation of radiotherapy. Finally, our objective is to study the association between serum biomarkers and corresponding MRI with potential tumor progression.

Rotating Frame Relaxation and Diffusion Weighted Imaging of Human Gliomas

Different MR relaxation parameters (T1rho-adiabatic,T1rho-cw T2rho-adiabatic,... ) and diffusion values (ADCm, ADCk, K, f, Df, Ds,...) will be measured in the tumor and surrounding area. The quantitative values will be correlated with cancer aggressiveness and tissue bio-markers. Furthermore, tumor volume will be estimated using different quantitative values.

Change in the different MR relaxation parameters (T1rho-adaibatic,T1rho-cw T2rho-adiabatic,... ) and diffusion values (ADCm, ADCk, K, f, Df, Ds,...) during tumor therapy will be estimated from repeated MR examinations performed before, after 3 weeks, and after 10 weeks of the beginning of radiotherapy, and 12 weeks after completion of radiotherapy.

Turku University Hospital

Professor

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Hypoxia

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Recently, a polymerase chain reaction (PCR) -based hypoxia classifier gene signature was published that can be easily applied. Using this classifier, patients will be divided in hypoxic or non-hypoxic subgroups.

These subgroups will be correlated to locoregional control. The hypoxic signature will also be related to parameters on DCE-MRI, DWI and FDG-PET.

A polymerase chain reaction -based hypoxia classifier

As part of the standard staging procedure all patients will undergo an MRI of the neck. We will however also take DWI and DCE images at this time point. Parameters of these images will be later on correlated with pathology.

Functional imaging before treatment.

At 3 levels of the tumour, chosen by the radiologist on the functional imaging modalities, 4µm thick slices will me taken. On each level an immunohistochemical staining will be carried out (GLUT-1, CA-IX, HIF-1alpha, VEGF, KI 67). The result of this staining will be correlated with parameters derived from the functional imaging modalities.

Immunohistochemical staining

To account for the shrinkage of the tumour due to fixation, the resection specimen will be placed in a box and scanned with an MRI. From this a shrinkage factor will be calculated using the original pre-treatment MRI.

MRI of the resection specimen

On the imaging modalities the tumor volume will be delineated. This will also be done on the resection specimen. Later on the different tumour volumes will be correlated.

Tumour volume delineation and comparison

Sandra Nuyts, PhD MD

Chemo-radiotherapy (CRT) is currently the cornerstone in the management of locoregional advanced head and neck cancer (HNC). Optimization of the quality of RT is therefore an important issue, if the investigators want to improve the therapeutic index in HNC. This could be achieved by a more accurate definition of the tumor volume and by identification of radioresistant volumes within the tumor. Recent literature puts in this regard the incorporation of functional imaging (FI) in the RT treatment planning forward as a promising tool.

FI modalities provide an outstanding contrast between tumor and surrounding tissues. This is in contrast to anatomical imaging. Using anatomical imaging in RT treatment planning, sufficient margins need to be placed around the tumor volume in order to compensate for geometric uncertainties. Consequently many surrounding functional structures receive high doses of irradiation, resulting in side effects. It is expected that, using FI in RT treatment planning will make these margins smaller or even unnecessary, which will result in less irradiation of the surrounding tissues. So far only one study has reported a comparison between tumor volume on anatomical (CT and MRI) and FI (PET-CT) modalities with pathological tumor volume. This study showed indeed that the tumor volumes delineated on PET-CT correlated more to tumor volumes defined by pathology and were significantly smaller.

Furthermore, FI provides us with a deeper insight in the tumor's underlying biological activity and microstructure. These techniques can thus help to identify radioresistant subvolumes which might benefit from treatment intensification.

A validation of these FI modalities with pathology is necessary to investigate their true power in tumor delineation and in the identification of radioresistant subvolumes.

1. BACKGROUND AND SETTING

   1.1. INTRODUCTION

   Concurrent (chemo-) radiotherapy (CRT) is the current standard of care for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The proximity of important functional structures with the tumour makes treatment however highly complex. Treatment related toxicity can be severe with xerostomia and dysphagia gravely complicating the patient's quality of life. The use of altered fractionation schedules and/or concurrent chemotherapy has resulted in substantial gains in loco-regional control, leading to significant improvements in overall survival. Although the prognosis of patients treated with RT for locally advanced HNSCC is continually improving, there are still a high number of locoregional failures.

   Using highly conformal radiotherapy the investigators can increase the therapeutic index by giving higher doses to the more radio-resistant parts of the tumour while maintaining or even reducing dose to the surrounding tissues. Functional imaging can help us to define these radio-resistant subvolumes and help us to delineate the gross tumour volume (GTV) better in the future. Positron emission tomography (PET), Diffusion weighted magnetic resonance imaging (DWI) and Dynamic contrast enhanced MRI (DCE-MRI) can give us further insight in the tumour's underlaying biological and microstructural characteristics. However, at the moment the investigators are not sure how to interpret the different imaging parameters obtained from these functional imaging modalities. Therefore, the investigators want to correlate the imaging parameters with the pathological characteristics of the tumour. On the other hand the investigators want to correlate the GTV defined on the functional imaging modalities with the pathological GTV, and see if these modalities can help us to delineate the GTV more accurately in the future.

   1.2. IMAGING MODALITIES

   1.2.1. FDG-Positron Emission Tomography (FDG-PET)

   Increased glucose metabolism is a fundamental characteristic of many malignant tumours, including HNSCC. Positron emission tomography (PET) after injection of radioactively labeled 2' fluorodeoxyglucose (18F-FDG) can help us measure and quantify this metabolism in tumours, using the standardized uptake value (SUV). Several studies have correlated high SUV prior to treatment with significantly worse outcome in HNSCC. Furthermore it appears that most local recurrences occur within the FDG-PET defined GTV. The molecular base for this is not completely understood.

   Proliferating tumour cells consume glucose at a high rate and release lactate and not CO2. This way they omit the mitochondria driven oxidative phosphorylation of glucose from the production of ATP (=Warburg-effect). Several molecular parameters have been associated with this glycolytic switch, such as activation of the hypoxia induced HIF1α and the increased presence of GLUT glucose transport proteins. So far no clear correlation was found between the presence of hypoxia and FDG-uptake.

   1.2.2. Diffusion-weighted Magnetic resonance imaging (DWI)

   Diffusion weighted magnetic resonance imaging (DWI) can characterize tissues based on the random displacement of water molecules. In biological tissues this displacement is limited by underlying tissue-specific barriers and this difference can be quantified and visualized using apparent diffusion coefficient (ADC) values. A study on 165 patients in our centre with HNSCC demonstrated that the pre-treatment ADC value is a strong and independent prognostic factor for outcome. Patients with a high ADC value respond worse to ionizing radiation than patients with a lower ADC value. There is currently no clear explanation why tumours with a higher cellular density are more radiosensitive than tumours with a low density. A number of microscopic features effect water diffusivity in tissue (presence of necrosis, cellular density, inflammation, integrity of cellular membranes). Many of these also affect the radio- and chemosensitivity of the tumours.

   1.2.3. Dynamic contrast enhanced Magnetic resonance imaging (DCE-MRI)

   Dynamic contrast enhanced MRI (DCE-MRI) is a non-invasive imaging modality which has been developed and evaluated for the characterization of vascular properties of tissues. Adequate oxygen supply is essential for the effectivity if ionizing radiation. However tumor angiogenesis is far from perfect and newly formed vessels display permeability, tortuosity and a generally poor functionality. These vascular properties could provide us insight in the aggressiveness and radiosensitivity of the tumor. Dynamic computed tomography (CT) has demonstrated that perfusion measurements can predict outcome in head and neck cancer after radiotherapy. Similarly quantitative assessment of DCE-MRI has also been correlated with response to ionizing radiation in patients with HNSCC. A recent trial on a limited number of patients correlated certain DCE-MRI parameters with intratumoural hypoxia. However, so far no spatial correlation has been done.
2. STUDY OBJECTIVES

   2.1. PRIMARY OBJECTIVES

   The main objective of this study is to correlate DWI, DCE-MRI and FDG-PET with the spatial distribution of hypoxia in patients with head and neck cancer.

   2.2. SECONDARY OBJECTIVES

   A. To correlate findings on functional imaging with intrinsic molecular parameters depicting proliferation, hypoxia and glucose metabolism.

   B. To validate the use of the hypoxia markers and the 15-gene hypoxia gene expression classifier.

   C. To compare tumour volume as derived from pathology with the volumes delineated on the several anatomical and functional imaging modalities.
3. STUDY DESIGN

   The target group for this trial is patients with a histologically proven squamous cell carcinoma of the larynx, eligible for surgery, staged T3-4. Prior to treatment patients will undergo an FDG-PET/CT and MRI with DW and DCE, dedicated for optimal visualization of the primary tumor and analysis. The imaging modalities will be performed as close to the surgery as possible (PET/CT one week before surgery; MRI one day before surgery).

   Prior to treatment, three slices on the imaging modalities will be selected by a radiologist based on their visual quality and heterogeneity of functional parameters. These regions of interest will be compared to different histopathological parameters on the resection specimen. The radiologist will also select regions, based on DWI and DCE parameters, who are suspect to be hypoxic. From these regions a biopsy will be taken.

   After total laryngectomy, the resection specimen will be oriented, and biopsy material will be obtained from the regions in the tumour that have been selected on the imaging modalities The rest of the specimen will be fixed in formaldehyde. To account for the shrinkage of the tumour due to fixation, the resection specimen will be placed in a cardboard box with an agarose solution and scanned with an MRI with T1w/T2 images. From this a shrinkage factor will be calculated comparing the delineated T1 and T2 weighted images.

   After fixation the tumour will be cut up into macroslices with a thickness of about 5mm. On each macroslice tumour volume will be delineated. Using this, the pathological tumour volume will be determined taking into account the previously determined shrinkage factor. This pathological volume will be compared to the tumour volume delineated on the imaging modalities. On the different pre-surgery functional imaging modalities, 4 separate observers will delineate the GTV. The different volumes will be compared and overlap will be calculated after 3D specimen reconstruction and registration.

   The GTV obtained from the functional imaging will be correlated with the pathological tumor volume of the resection specimen. This information will give us more insight into the true power of the investigated functional imaging techniques in determining tumour volume. This is important to assess the role of functional imaging modalities in treatment planning in the future.

   At the three levels, chosen by the radiologist on the imaging modalities, 4µm thick slices will be taken. On each level an immunohistochemical staining will be carried out (GLUT-1, CA-IX, HIF-1α, VEGF and KI 67 staining will be performed ).

   IHC will be scored according to a semiquantitative scoring system using a field analysis where each field will be assigend a score of 1-4 according to the approximate area of immunostaining (0:0%, 1:1-5%, 2: 5-15%, 3: 15-30% and 4: \>30%.
4. SAMPLE SIZE Twenty patients with squamous cell carcinoma of the larynx, planned to undergo total laryngectomy, will be included.

Pathological Validation of Functional Imaging in Head and Neck Squamous Cell Carcinoma

Pathological Validation of Functional Imaging in Head and Neck Squamous Cell Carcinoma. A Prospective, Non-commercial and Mono-centric Study

The correlation of DWI, DCE-MRI and FDG-PET with the spatial distribution of hypoxia in patients with head and neck cancer.

Flemish League Against Cancer

Universitaire Ziekenhuizen KU Leuven

Full Professor, Clinical staff member

Functional MRI on day 22 of the chemoradiotherapy treatment. Parameters of these images will be later on correlated with outcome.

functional MRI

Tumour biopsies will be obtained as part of the staging procedure (standard). On this biopsies we will conduct a hypoxia gene expression profile (15 genes on PCR that can be analyzed individually or as a group through one binary variable). Hypoxia will be a parameter in our prognostic/predictive model.

Hypoxia gene expression profile.

As part of the standard staging procedure all patients will undergo an MRI of the neck. We will however also take DWI and DCE images at this time point. Parameters of these images will be later on correlated with outcome.

Functional MRI before start of treatment.

Daan Nevens, MD

Sandra Nuyts, PhD, MD

Despite uniform histopathological definition the response of locally advanced squamous cell carcinomas of the head and neck (HNSCC) to ionizing radiation differs greatly with locoregional recurrences burdening this patient population. The addition of concurrent chemotherapy and the use of altered fractionation schedules has significantly increased locoregional control and overall survival over the last decade however, this has come at the cost of increased acute and late toxicity, preventing further treatment intensification in all patients. If the investigators want to increase the therapeutic index of HNSCC, we need to be able to tailor the treatment more individually to each patient. The project aims at developing a prognostic model for head and neck cancer patients based on the combination of known clinical parameters with 1) genetic characteristics of the tumor and 2) parameters derived from diffusion weighted and dynamic contrast enhanced magnetic resonance imaging (MRI) obtained before and during treatment. The investigators plan a prospective trial where 120 patients with locally advanced head and neck cancer treated with chemoradiotherapy will be included. Prior to treatment biopsy material will be collected for genetic analysis and before and during treatment functional MRI with diffusion weighted and dynamic contrast enhanced imaging will be performed. All patients will be followed up multidisciplinary afterwards with follow-up of tumor status and toxicity.

1. BACKGROUND AND SETTING

   1.1. Introduction

   Concurrent (chemo-) radiotherapy (CRT) is the current standard of care for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The proximity of important functional structures with the tumour makes treatment however highly complex. While locoregional control rates have improved over the last decade, treatment related toxicity can be severe with xerostomia and dysphagia gravely complicating the patient's quality of life.

   Furthermore, it becomes increasingly clear that while these tumours can be identical in location and basic histology, their response to treatment differs greatly. This implies that for a subgroup of patients, equal locoregional control rates could be achieved using a less intense and consequently less toxic treatment schedule. This in contrast to the group of patients who develop a locoregional recurrence during follow up, for whom current treatment is apparently insufficient. These patients might benefit from a more intense treatment schedule, i.e. a higher dose of radiation.

   These differences in sensitivity to treatment can be explained by variations in biological, molecular and genetic factors. Clinical parameters alone are insufficient for response prediction. Identifying the different molecular and genetic factors, would help us increase the accuracy of response prediction and based on these factors tailor the treatment more individually to each patient. Therefore we want to develop a prognostic and predictive model incorporating well-defined molecular and imaging parameters which show great promise in response prediction after ionizing radiation.

   1.2. Genetic and molecular tumour characteristics

   The first parameter we want to investigate further is tumour hypoxia. Hypoxia has been identified as a factor that increases tumour aggressiveness and decreases radiosensitivity. In the past, several techniques have been applied to detect biologically relevant tumour hypoxia, but none of them are used today in routine clinical practice. Recently, a polymerase chain reaction (PCR) -based hypoxia classifier gene signature was published by Toustrup et al. This classifier allows us to study biologically relevant tumour hypoxia and consequently tumour aggressiveness and resistance to ionizing irradiation. This analysis will be performed on biopsies obtained prior to treatment. Part of this biopsy material will also be stored into our biobank. This will facilitate future research on promising molecular and genetics parameters (such as HPV correlated overexpression of p16 for example) on a well-defined and structured patient database.

   1.3. Imaging parameters

   Aside from these important molecular and genetic tumour characteristics, several functional imaging parameters will also be included in our model. In contrast to anatomical imaging, functional imaging modalities provide us with a deeper insight in the tumour's underlying biological activity and microstructure.

   Diffusion weighted magnetic resonance imaging (DWI) can characterize tissues based on the random displacement of water protons. This displacement can be quantified using the apparent diffusion coefficient (ADC). Preliminary studies in HNSCC have demonstrated the prognostic and predictive potential of repetitive DWI early during and after treatment.

   Dynamic contrast enhanced magnetic resonance imaging(DCE-MRI) is a second technique, which shows great promise as an early indicator of response to ionizing radiation. Many malignant tumors manifest neovascularity or angiogenesis. These processes are however flawed and as a result these newly synthesized vessels manifest a high permeability, tortuosity and generally a poor functionality. This might result in poor oxygen supply to the tumour cells, which may compromise the effectiveness of radiation treatment of the tumour. Therefore the vascular properties of a tumour, assessed with DCE-MRI, could prove a prognostic indicator of its aggressiveness.
2. STUDY OBJECTIVES

   2.1. Primary objectives

   The main objective of this study is to correlate clinical, molecular and radiological predictors with outcome, as defined by locoregional control and disease free survival. In this way we will develop a prognostic/predictive model. The predictive model will be instrumental in the individualization of treatment ensuring optimized treatment and avoiding under- and overtreatment.

   2.2. Secondary objectives
   * We want to get new insights in the tumor biology and microstructure by correlating imaging and molecular/genetic markers in a well-defined patient population.
   * We want to validate the different imaging techniques.
   * We want to make a correlation between hypoxia and other predictive biomarkers in the future, by storing the tissue obtained in this study in our biobank.
3. STUDY DESIGN

   We propose to set up a study where we will prospectively include patients with locally advanced head and neck cancer who will be treated with concurrent chemoradiotherapy as decided after multidisciplinary consultation. An outline of the trial is presented in the figure below. All patients recognized eligible (non-metastatic locally advanced head and neck squamous cell carcinoma, treated with chemoradiotherapy, karnofsky performance status ≥ 70% and ≥ 18 years old) will be included after written informed consent. Staging with a laryngoscopy, CT of the neck, MRI of the neck and a PET-CT will be routinely performed.

   The CRT treatment consists of radiotherapy up to 72 Gy using an accelerated hyperfractionated schedule. Day 1 and day 22 of the treatment Cisplatin at 100mg/m² will be administered.

   Tumour biopsies will be obtained a few days prior to treatment. The hypoxia gene expression profile will be derived from the tumour material (15 genes on PCR that can be analyzed individually or as a group through one binary variable).

   The tissue used for RNA and DNA extraction needs to be flanked by H\&E staining confirming tumor presence. From the biopsy the two ends will be cut off and fixed in paraffin. This tissue will be stored in the biobank. The middle part of the tissue will be stored into RNA-later, and will be used in part to extract DNA and RNA. RNA will be used to synthesize cDNA to perform the qPCR analysis for the hypoxic classifier.

   Patients will also undergo a DWI MRI and DCE imaging before and 3 weeks into CRT. Lesions will be quantitatively assessed by manual delineation of regions of interest (ROI) over the tumour on the native DWI and DCE-MRI images. ADC values and (semi-) quantitative DCE parameters will be calculated respectively.

   All the above described data will be integrated into the prognostic model together with the available clinical data.
4. DEFINITION OF ENDPOINTS The main endpoint of this study is to validate the above described prognostic model. Using this prognostic model, we can predict response to treatment. This will help us to tailor the treatment more individually to each patient.

Prediction of Outcome After Chemoradiotherapy for Head and Neck Cancer Using Functional Imaging and Tumor Biology

Prediction of Outcome After Chemoradiotherapy for Head and Neck Cancer Using Functional Imaging and Tumor Biology. A Prospective, Non-commercial and Mono-centric Study.

The predictive model will be instrumental in the individualization of treatment ensuring optimized treatment and avoiding under- and overtreatment.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Wilms Tumor

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Wilms' Tumor

Initially and after pre-operative chemotherapy To evaluate the differences in ADC values according to the malignancy degree of nephroblastoma in children

MRI DWI sequence (ADC values)

Evelina f Nazarova

Galina f Tereshchenko, PhD

Initially, or after preoperative chemotherapy, patients with a kidney tumor are examined on 3T MR scanner or 1.5T MR scanner. A standard MRI study of the abdomen with contrast enhancement is performed. DWI (diffusion weighted) images are included in the standard investigation package and consist of diffusion maps. Then, using Philips workstation (ISP 9.0, Philips, Netherlands), DWI mapping and ADC values collection (mm2/s) are performed. The placement of region of interest (ROI) is selected in the kidney mass in a solid and cystic area with a size up to 100 mm2.

After the preoperative abdomen MRI, a surgical treatment is performed. Histological material is directed to the pathologist, who carried out the histological staging by the malignancy degree (low, intermediate, high). The data is entered into the database and the relationship between ADC values and histological degrees of malignancy of nephroblastoma is investigated

Initially, or after preoperative chemotherapy, patients with a kidney tumor are examined on 3T MR scanner or 1.5T MR scanner, using 8-channel body coil. A standard MRI study of the abdomen with contrast enhancement is performed. DWI (diffusion weighted) images are included in the standard investigation package and consist of diffusion maps (DWI 3b) with 3 b-factors (50; 600; 800 or others, optional). Then, using Philips workstation (ISP 9.0, Philips, Netherlands), DWI mapping and ADC values collection (mm2/s) are performed. The placement of region of interest (ROI) is selected in the kidney mass in a solid and cystic area with a size up to 100 mm2. The values are entered in the table due to the stage of the chemotherapy.

After the preoperative abdomen MRI, a surgical treatment is performed. Histological material is directed to the pathologist, who carried out the histological staging by the malignancy degree (low, intermediate, high). The data is entered into the database and the relationship between ADC values and histological degrees of malignancy of nephroblastoma is investigated.

DWI in the Diagnosis of Histological Types of Nephroblastoma in Children

Diffusion-weighted Images as an Additional Method for Diagnosing Histological Types of Nephroblastoma in Children

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Carcinoma, Hepatocellular

Liver Neoplasms

Liver Diseases

Hematinics

Liver Extracts

The patients responding to the chemotherapy, i.e. who show at least a non progressive disease

The patients non responding to the chemotherapy, i.e. who show a progressive disease

Stefano Colagrande, MD

One of the most recent and interesting field of diagnostic imaging is diffusion-weighted MR imaging (DW-MRI). Various studies evaluated the application of DW-MRI to diffuse liver disease and focal liver lesions providing controversial results, probably due to the difficult reproducibility of the apparent diffusion coefficient (ADC) measurements. It is conceivable that a wide inter/intra-individual variability actually exists in the apparent diffusion coefficient (ADC)-values, and that each apparent diffusion coefficient (ADC)-value presents an higher reliability in measuring the temporal changes of water diffusion within the same individual (longitudinal-evaluation), than in characterizing tissues between different patients (transverse-evaluation). For these reasons, some previous studies assessed the application of DW-MRI in predicting the chemotherapy (CHT) outcome in liver metastases. The rationale of these studies was the overt biochemical changes shown by the neoplastic cells after CHT and the sensitivity of DW-MRI in the identification of such changes. The same authors noticed that the metastatic lesions with the lowest ADC-values present also the best outcome after CHT. Moreover, these studies suggest that it could be possible to assess if each single patient will respond (R) or not (NR) to the CHT through liver DW-MRI performed from 3 days to 3 weeks after the beginning of CHT.

In R patients an increase of the mean diameter of the neoplastic cells should be present from the first week of CHT with a consequent reduction of the ADC-value. Then, the ADC-value should increase after 2-3 weeks due to the reduction of the cellular volume and to the increase of the membrane permeability. In NR patients, these biochemical changes should not be present with a consequent constant ADC-value before/after CHT. Our multicentre study will allow the recruitment of a higher number of patients vs. previous studies. Moreover, presently the outcome of CHT in liver metastases is evaluated only after 2-3 cycles of CHT according to the RECIST (Response-Evaluation-Criteria-In-Solid-Tumors) and then merely on a dimensional basis. Anyway, frequently liver metastases in R patients, can not show any significant dimensional change, while they present several biochemical/metabolic changes, not included in the RECIST, but probably detectable by DW-MRI.

The principal objective of the study is the early assessment of CHT outcome in liver metastases and advanced hepatocellular carcinoma (HCC). Patients with liver metastasis will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 20 days after the beginning of the second cycle of CHT; patients with HCC undergoing therapy with Sorafenib will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 90 days after the beginning of the therapy. The ADC-values obtained before and after the first CHT cycle will be compared between each patient category to assess the grade of agreement between the dimensional and functional parameters. Moreover, the investigators' aim is to assess whether those liver metastases or HCCs presenting a lower ADC-value before CHT are actually more responsive to CHT in comparison to liver metastases and HCCs presenting a higher ADC-value.

Secondary objectives: to propose some additional functional criteria to the RECIST 1.1 and mRECIST (for HCC) criteria based on water diffusion and biochemical changes of the neoplastic cells. As a further objective it is possible to hypothesize a different response to CHT of the different tumor histotypes detectable from the different ADC changes induced by CHT.

Patient population

Inclusion criteria:

* of age, compliant, patients enrolled for CHT, without major contraindications to the MR examination;
* non-confluent liver metastases, from every primary carcinoma histotype biopsy/surgical-proven, without intralesional necrosis/calcification involving \>30% of their volume;
* multiple confluent hepatocellular carcinomas, histotype biopsy/surgical-proven in prevision of treatment with Sorafenib;
* at least one marker lesion allowing reproducible ADC measurements, i.e. placed at the level of the lower right liver segments;
* detection/enrolment by contrast-enhanced CT before CHT that allow to define the lesion size or the gross parenchymal involvement (if HCC).

Each patient will sign an informed consent, after the procedure will be completely explained.

For the metastasis: three diameter of each marker lesion will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by region-of-interests (ROIs) placed within the lesion avoiding lesion margins and the necrotic/intratumoral calcification areas. All measurements will be repeated for three times even at the level of the adjacent liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared.

For HCC: three diameter of gross parenchymal involvement will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by large region-of-interests (ROIs) placed within the liver lobe containing the involvement. All measurements will be repeated for three times even at the level of the adjacent normal liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared.

Imaging

For metastasis: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated within one week (Time 1) and 20 days from the beginning of the first cycle of CHT (Time 2), and 20 days from the beginning of the second cycle of CHT (Time 3).

For HCC: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated after 30 days (Time 1), 60 days and 90 days (Time 3) from the beginning of the CHT.

Contrast-enhanced CT will be performed contemporarily or within one week after the last MRI examination.

Contrast-enhanced CT examination will be performed according to an established protocol by using a 16/64-row equipment according to the centre involved, contrast bolus-track technology, slice- thickness reconstruction of 3 mm, before/after ev. injection of iodinated contrast agent (3 mL/s), during arterial/portal phase.

All MR examinations will be carried out using the following 1.5-T units:

* Gyroscan ACS NT Intera Release 12 (Philips, Eindhoven, The Netherlands) (Trieste and Florence), gradient strength, 30 mT/m; slew rate, 120 T/m/s; six-channel phased array multicoil;
* Magnetom Avanto (Siemens, Erlangen, Germany) (Treviso and Napoli), gradient strength, 45 mT/m; slew rate, 200 T/m/s; 2 phased-array coils with 18 elements. The different MR equipments employed by the different centers will be calibrated by a dedicated phantom.

The phased array multicoil will be adequately positioned to cover the upper abdomen of the subject lying in a supine position, the arms extended over the head to avoid artifacts. Patients, fasting from 4 hours, will be instructed to maintain a constant respiration depth, even with the possibility to use exogenous oxygen delivery to avoid deep respiration. All acquisitions will be obtained by single-shot sequence to obtain immediately/automatically the ADC-values.

The protocol included the following acquisitions:

1. T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) free-breath sequence; transverse/coronal plane; TR/TE, 810/80 ms; echo-train length, 69; slice number, 40; slice thickness, 5 mm; intersection gap, 10%; field of view, 300-420 mm; effective matrix size, 256 x 165; number signal averages (NSA), 1; total acquisition time, 2-3 min;
2. T1-weighted 2D gradient echo in/out phase breath-hold sequence; transverse plane; TR/TE, 231-121/ 14.6-2.3 ms; slice thickness, 5 mm; slice number, 24; intersection gap,10%; flip angle, 80°; sense factor, 1.5; field of view, 300-420 mm; effective matrix size, 256 x 165; NSA, 1; total acquisition time, 18 s;
3. D-weighted echo-planar imaging (EPI) single-shot free-breath sequences will be acquired on transverse plane with variable EPI factor and the following parameters. Fat suppression will be obtained by spectral pre-saturation inversion recovery. Isotropic motion probing gradients will be applied for each DwI acquisition and for each b-value will be obtained images and corresponding ADC map.

The investigators presently define as R those patients who show a reduction of the liver metastasis or HCC diameter ≥30% on contrast-enhanced CT at three weeks after the beginning of the second CHT cycle; if not, it was considered NR. Changes in tumor size after treatment were calculated by using the formula % Vend =(VB -Vend)/VBx100, where VB was lesion size before treatment (maximum transverse diameter) and Vend was lesion size 20 days after the second administration.

On the basis of the dimensional reduction of liver metastases and parenchymal involvement (for HCC) on contrast-enhanced CT on Time 3 vs. Time 0 scan, each patient will be classified as R or NR according to the RECIST and mRECIST criteria. Afterwards, on the basis of the ADC-values measured during the different MR examinations, the inter/intra-individual ADC-values will be compared to the results of contrast-enhanced CT to assess the relation between reduction of the liver metastasis diameter and:

* increase of the ADC-value on Time 3 (after the end of CHT);
* reduction of the ADC-value on Time 1 (very early assessment);
* increase of the ADC-value on Time 2 (early assessment); and to assess whether the lesions with the highest pre-treatment ADC-value present also the highest dimensional reduction and the highest ADC-value at the end of CHT; In each center each evaluation will be performed three times by two blinded observers (all trained how to place the ROI by an inter-centre conference) to assess the reproducibility of all measurements. The observers who will assess the MR images will be different from the observers assessing the CT images and will not be aware about the size changes after CHT. The investigators will perform data mathematical fitting on multi-b DW-MRI data sets to calculate the true diffusion and the perfusion fraction.

Statistical analysis will employ linear regression analysis to assess the association between the ADC-value changes and the CHT outcome.

The transferability of the results of the present study to the clinical practice will be possible after the achievement of the primary objective, corresponding to the possibility of stratifying patients as R and NR to CHT through DW-MRI just after one week of treatment and/or with the pre-treatment ADC assessment. Nowadays, it is necessary to wait 20-30 days after the end of the second or third CHT cycle to know the individual outcome of CHT. This determines 2-3 months of ineffective therapy with consequent avoidable pain for the patients related to drug administration, and unusable costs. The possibility to know the response of each patient to CHT well in advance will allow avoiding vain drug administration to patients who could attempt a different treatment or drug combinations reducing treatment costs.

The clinical transferability of the present study will be performed after the achievement of one or both the secondary objectives, corresponding to the identification of functional criteria based on water diffusion and biochemical features of the neoplastic cells which can be proposed as additional or alternative criteria to the RECIST 1.1 and mRECIST, and to the identification of a different response to CHT of different tumor histotypes. If only one of these objectives will be reached this study will achieve an important result, allowing a more correct assessment of individual response to CHT.

Use of DwI-MR to Predict Chemotherapy Response of Liver Metastases and Hepatocarcinoma

Assessment of Diffusion-weighted Magnetic Resonance (MR) Imaging to Predict Chemotherapy Outcome in Liver Metastases and Hepatocellular Carcinoma (HCC)

Linear regression analysis to assess the association between the ADC-value changes and the CHT outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer	NCT05524012	Locally Advance... Neoadjuvant Tre... Radiotherapy Adaptive Treatm...	Blood sample MRI scan	18 Years -	Jena University Hospital
Diagnostic Value of DWI-MRI for Detection of Peritoneal Metastases in High-risk Pancreatic Ductal Adenocarcinoma.	NCT05340569	Pancreas Cancer... Pancreas Adenoc... Peritoneal Meta... Peritoneal Carc...	Whole-body diff...	18 Years -	Laval University
Diagnostic Value of DWI-MRI for Detection of Peritoneal Metastases in High-risk Pancreatic Ductal Adenocarcinoma.	NCT05340569	Pancreas Cancer... Pancreas Adenoc... Peritoneal Meta... Peritoneal Carc...	Whole-body diff...	18 Years -	Laval University
MRI DWI None-Gaussian Model Predicting Early Response to Immunotherapy in Digestive System Malignancies: a Prospective Observational Study	NCT04500990	Immunotherapy Digestive Syste...	MRI test MRI test MRI test	18 Years -	Peking University
Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms	NCT05623787	Peritoneal Carc... Peritoneal Meta... Appendix Cancer Appendix Neopla... Colorectal Canc...	Whole-body diff...	18 Years -	Laval University
Rotating Frame Relaxation and Diffusion Weighted Imaging of Human Gliomas	NCT02186262	Low Grade Gliom... Malignant Gliom...		18 Years - 80 Years	Turku University Hospital
Pathological Validation of Functional Imaging in Head and Neck Squamous Cell Carcinoma	NCT01827709	Head and Neck C...	A polymerase ch... Functional imag... Immunohistochem... MRI of the rese... Tumour volume d...	18 Years -	Universitaire Ziekenhuizen KU Leuven
Prediction of Outcome After Chemoradiotherapy for Head and Neck Cancer Using Functional Imaging and Tumor Biology	NCT01829646	Head and Neck C...	functional MRI Hypoxia gene ex... Functional MRI ...	18 Years -	Universitaire Ziekenhuizen KU Leuven
DWI in the Diagnosis of Histological Types of Nephroblastoma in Children	NCT04814758	Nephroblastoma ...	MRI DWI sequenc...	6 Days - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
DWI in the Diagnosis of Histological Types of Nephroblastoma in Children	NCT04814758	Nephroblastoma ...	MRI DWI sequenc...	6 Days - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Use of DwI-MR to Predict Chemotherapy Response of Liver Metastases and Hepatocarcinoma	NCT01411579	Liver Metastase... Hepatocarcinoma		18 Years - 80 Years	University of Florence

Spots Global Cancer Trial Database for dwi

Every month we try and update this database with for dwi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dwi

Every month we try and update this database with for dwi cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dwi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.