Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

25 patients with pathologically confirmed invasive breast cancer who will undergo neoadjuvant chemotherapy treatment (NACT) and surgery will be recruited. During the study, patients will receive the standard care and the current study will not alter the care plan offered to them. All patients in the single arm will undergo 4 magnetic resonance imaging scan sessions. Histopathological analysis will be performed on the core biopsy and tumour tissue removed in surgery. Health questionnaire will be completed by each patient.

Patients will undergo 4 MRI sessions during NACT treatment. The first scan will take place at treatment baseline before their first cycle of NACT treatment. The second scan will take place following the first treatment cycle prior to the second treatment cycle. Likewise, the third and last scan will take place after the third treatment cycle and sixth (final) treatment cycle prior to surgery. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods.

Magnetic Resonance Imaging

Study specific analysis will be performed on the core biopsy and tissue removed in surgery following the completion of NACT treatment. Standard routine histological analysis will be performed, as well as study specific analysis for immunostaining, grading and slide scan imaging for measurement of cellularity markers.

Histopathological Analysis

Health and demographic information will be collected.

Health Questionnaire

Nicholas Senn, MPhys

Jiabao He, PhD

Breast cancer is the most prevalent cancer affecting women. To treat locally advanced breast cancers, neoadjuvant chemotherapy (NACT) is often carried out before surgery to reduce the tumour size to allow breast conservation surgery. However, treatment response for individual patients varies, where the tumour may not respond to treatment and the quality of patient care is compromised if the NACT treatment plan is not optimised. Therefore, the assessment of NACT efficacy is beneficial for the early identification of these patients and appropriate management of treatment.

Breast tumours have unique features compared to healthy tissue, including abnormal tissue structure and biochemical composition. With NACT there are specific changes to such tumour features indicating tumour treatment response.

The purpose of this study is to establish how the changes to breast tumour features following NACT treatment are seen in non-invasive imaging. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tissue structure will be measured by advanced diffusion MRI techniques and changes to tumour related biochemical substances will be measured by advanced magnetic resonance spectroscopy techniques. The investigators aim to assess if these techniques can provide information on the tumour treatment response following subsequent rounds of NACT treatment.

In this longitudinal study, 25 patients undergoing NACT will be recruited for four repeated MRI investigations over the course of NACT treatment. Magnetic resonance (MR) measurements of tissue microstructure and biochemical composition will be compared against histological measurements and radiological assessments of treatment response.

The study will recruit patients undergoing treatment at the NHS Grampian. This research is funded by Friends of ANCHOR, Tenovus Scotland Grampian and the NHS Grampian Endowment Research Fund.

In this single group longitudinal study, the investigators propose that functional images from magnetic resonance (MR) methods performed at baseline and after 6 cycles of neoadjuvant chemotherapy (NACT) are in agreement with histological findings from pre-treatment biopsy and post-treatment surgically excised tissue. MR methods will be performed at baseline (pre-treatment) and after the 1st, 3rd and 6th (post-treatment) cycles of NACT treatment. The investigators hypothesise that specific physiological changes detected through MR methods are a manifestation of tumour response to NACT confirmed by histology and radiological assessment (Hypothesis 1). The investigators further hypothesise that early sensitivity to physiological changes manifesting from tumour response to NACT can be revealed by MR measurements after the first and third cycle of treatment (Hypothesis 2).

Research Question 1: Is there a difference in physiological parameters revealed by MR measurements at baseline and after completion of NACT?

Research Question 2: Do the physiological measurements at the completion of NACT from MR measures agree with histological findings?

Research Question 3: Is there a difference between MR measurements at baseline and after the first and third cycle of NACT?

Research Question 4: Is there a difference in MR measurements at baseline, first and third cycle of NACT, between positive treatment responders and non-responders.

MR measurements will be compared against clinical and study specific results from histological analysis and radiological assessment of MRI, mammography and ultrasound measures of tumour treatment response. Information collected from a health questionnaire will supplement interpretation of the data.

To test the effects of NACT on specific aspects of tumour physiology, paired t-tests will be performed on MR measures of lactate concentration, lipid composition and diffusion parameters, between baseline and post-treatment assessments (Research Question 1).

To examine the relationship between MR measurements and histology, correlation analysis will be conducted between baseline and post-treatment assessments. MR measures will be correlated against corresponding percentage changes in histological findings between biopsy and tumour excision (Research Question 2).

To evaluate MR measures as early markers of NACT efficacy, paired t-tests will be carried out between MR measures at pre-treatment and post 1st and 3rd cycles of NACT treatment (Research Question 3), with independent group difference determined between responders and non-responders (Research Question 4).

Single group with one arm and no masking.

What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?

What Are the Factors Affecting Neoadjuvant Chemotherapy Efficacy in Breast Cancer? A Non-invasive in Vivo Study Using Specialist Magnetic Resonance (MR) Methods

The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

Lipid peak volume ratio value with units of ratio

Ki-67 staining percentage with units of %, assessed on core biopsy tissue taken prior to start of treatment cycles.

Ki-67 staining percentage with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.

Serotonin staining score with arbitrary units (multiplication of staining percentage and stain intensity scored 1 - 3), assessed on core biopsy tissue taken prior to start of treatment cycles.

Serotonin staining score with arbitrary units (multiplication of staining percentage and stain intensity scored 1 - 3), assessed on excised tissue taken from surgery following completion of treatment cycles.

Cellularity with units of %, assessed on core biopsy taken prior to start of treatment cycles.

Cellularity with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.

NHS Grampian

University of Aberdeen

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Anti-Infective Agents

All Drugs and Chemicals

Herbal and Botanical

Formaldehyde

Chrysanthemum

Diagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Diagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Diagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Morphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud.

A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm.

Histopathological analysis

Next-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels.

RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL).

Molecular analysis

Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.

Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.

A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.

FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.

MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.

Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.

The samples analyzed will have been collected as part of routine medical care for each patient before inclusion in the study.

These are formalin-fixed, paraffin-embedded (FFPE) tissue samples. They will be packaged and stored in the Biological Resources Center of the Hospices Civils de Lyon.

BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.

Study of Clinical, Histological, Immunohistochemical and Molecular Impact of BCL6 Gene Rearrangement in Most Prevalent Non-Hodgkin Lymphomas

An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.

Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.

Hospices Civils de Lyon

Symptoms and General Pathology

Gland and Hormone Related Diseases

Syndrome

Cushing Syndrome

Pheochromocytoma

Death

Endocrine Gland Neoplasms

Hyperaldosteronism

Death, Sudden

Paraganglioma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Cushing's Syndrome

Paragangliomas 1

Neuroendocrine Tumor

Neuroepithelioma

Hyperadrenalism

Anti-Inflammatory Agents

Vasoconstrictor Agents

Respiratory System Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Epinephrine

Racepinephrine

Epinephryl borate

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Adrenergic beta-Agonists

Bronchodilator Agents

Anti-Asthmatic Agents

Mydriatics

Sympathomimetics

Unexpected witnessed death occurring within an hour of the onset of symptoms in a person with or without previously known cardiac disease without an extra-cardiac cause, or unexpected unwitnessed death without extra-cardiac cause occurring in the previous 24 hours

Death because of an exogenic reason for sudden death such as trauma or suicide as a control group i.e. non-disease-induced sudden death

Immunoshistochemical diagnosis of primary aldosteronism

Adrenal aldosterone synthase (CYP11B2) staining

Immunoshistochemical diagnosis of adrenal hypercortisolism

Adrenal cortisol synthase (CYP11B1) staining

Diagnosis of any endocrine neoplasia other than primary aldosteronism or adrenal hypercortisolism

Niina Matikainen, MD, PhD, Assoc Prof

Sudden Cardiac Death is a leading cause of mortality and remains a major public health burden worldwide. Cardiac arrest due to coronary heart disease explains a large proportion of the cases, but if autopsy is not performed the exact underlying cause remains obscure in many adults who face sudden death outside heath care organizations. The investigators aim to find proof that primary aldosteronism is a risk factor for sudden death and to characterize the prevalence of adrenal pathology in sudden death of undetermined cause in a case-control study. In addition, the study aims to characterize the prevalence of other adrenal pathology i.e. silent adenomas, cortisol-producing adenomas and pheochromocytomas in sudden death. The investigators also seek evidence that other endocrine hormone overproduction-causing diseases are more prevalent in persons with sudden death compared with those experiencing traumatic or suicidal death sudden death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?	NCT03501394	Breast Neoplasm...	Magnetic Resona... Histopathologic... Health Question...	18 Years -	University of Aberdeen
BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.	NCT06424379	Non Hodgkin Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B...	Histopathologic... Molecular analy...	25 Years - 100 Years	Hospices Civils de Lyon
Postmortem Evaluation of Adrenal and Other Endocrine Tumors in Patients With Sudden Death	NCT05446779	Primary Aldoste... Adrenal Cushing... Pheochromocytom... Endocrine Neopl...	Adrenal aldoste... Adrenal cortiso... Histopathologic...	35 Years - 70 Years	Helsinki University Central Hospital
BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.	NCT06424379	Non Hodgkin Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B...	Histopathologic... Molecular analy...	25 Years - 100 Years	Hospices Civils de Lyon

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