Acquisition of fresh tumor and normal tissue samples are necessary for the preparation of cDNA libraries, microarray chips, and tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications.

Acquisition of fresh tumor and normal tissue samples is necessary for the preparation of cDNA libraries, microarray chips, tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of patient samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications.

Tissue Acquisition for Molecular Diagnostics

National Cancer Institute (NCI)

Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Chlorotrianisene

Sorafenib

Patients with transarterial chemoembolization (TACE) will get an "Image Fingerprint" and "Molecular Fingerprint" for tumor characterization in vivo.

Patients with Sorafenib treatment will get an "Image Fingerprint" and "Molecular Fingerprint" for tumor characterization in vivo.

This is an observational study that uses in depth diagnostic procedures to characterize patients with a comprehensive Image Fingerprint that includes CT, MRI and PET diagnostics

Image Fingerprint

This is an observational study that uses in depth diagnostic procedures to characterize patients with a Molecular Fingerprint that includes next-generation sequencing

Molecular Fingerprint

Michael Bitzer, MD

This single center, open-label, uncontrolled, non-randomized observational study in patients with advanced HCC. The patients qualify either to a local treatment with transarterial chemoembolization (TACE) or to a systemic treatment with the multikinase inhibitor sorafenib. The aim of this feasibility study is to get a comprehensive image and molecular fingerprint of individual tumors, with the intention to govern therapy decisions. Furthermore, to improve the care of patients that get progressive disease under treatment, the investigators have to improve the investigators understanding of the development of therapy resistance, which will improve patient care at the time point of progressive disease. Therefore, the data of 20 patients in each group will be used to identify molecular and / or image patterns, that can be used to predict treatment responses and thus govern an optimized individual cancer treatment for patients with advanced HCC.

A single-center, open-label, uncontrolled, non-randomized clinical trial. The two treatment groups to receive:

Group A Transarterial Chemoembolization (TACE): 20 patients that are treated with TACE will get an image and molecular fingerprint of the tumor prior to the first treatment with TACE, a second image fingerprint between week 2 - 4 after the first treatment with TACE, and a third image and molecular fingerprint at the time point of progressive disease.

Group B Sorafenib: 20 patients that are treated with Sorafenib will get an image and molecular fingerprint of the tumor prior to the first treatment, between week 2 and 3 after the start of treatment and at the time point of progressive disease.

Biospecimens that will be investigated are tumor tissue and blood.

Fingerprint Characterization of Advanced HCC

Fingerprint Characterization of Advanced HCC to Optimize Treatment Decisions and Enable an Early Prediction of Therapy Resistance (HCC Multiscale Trial-1)

The aim of this feasibility study is to get comprehensive image and molecular fingerprints of individual tumors that can be used for systems biology approaches to predict therapy outcome and govern therapeutic decisions.

To set-up and optimize the workflow of data gathering and analysis for molecular and image fingerprints.

Correlation of results from image and molecular fingerprints at one point of time

Correlation of either image or molecular fingerprints at three different time points

To identify molecular and image patterns of early treatment failure.

To identify molecular and image patterns of early treatment success

To compare molecular and image patterns from HCC patients with respective patterns from different animal models which might identify suitable preclinical models for different clinical tumor patterns.

To determine ideal imaging methods for an early prediction of progressive disease

To set up a molecular diagnostic board that checks for data-based tailored treatment options

To identify clinical relevant biomarkers from tumor tissue or blood / urine analysis

German Federal Ministry of Education and Research

University Hospital Tuebingen

Deputy Director Department of Gastroenterology

Blood and Lymph Conditions

Immune System Diseases

Eye Diseases

Rare Diseases

Lymphoma

Intraocular Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Eye Neoplasms

Lymphosarcoma

Primary Central Nervous System Lymphoma

Liv Dollmann

Vinodh Kakkassery, PD Dr.med.

The goal of this observational study is to gain new insights into the changes in proteins, genes and other molecular biological substances in the aqueous humour, vitreous humour, blood serum and, in rare cases, retina/choroid samples in patients with ocular lymphoma disease. The hope is that this will expand the understanding of the mechanisms of the disease and thus contribute to improved and simplified diagnosis and treatment strategies in the future. The aim is the inclusion of at least 220 patients during the study period. The main questions it aims to answer are:

* to evaluate the diagnostic quality of extended molecular diagnostics (based on standard work-up) of vitreous samples for the specific VitreoRetinalLymphoma (a type of ocular lymphoma disease) diagnosis in comparison to standard work-up alone.
* To monitor VRL patients as part of regular tumour follow-up over a period of 24 months to determine the value of biomarkers with regard to treatment response and development of recurrence in the eye. Similarly, the vitritis patients are followed up by telephone every six months for a period of 24 months, during which questions of any interim occurrence of a VRL or other cancerous tumors are asked according to a defined catalogue of questions.

Vitreoretinal lymphoma (VRL) is a rare intraocular neoplasm that is considered a variant of primary CNS lymphoma (PCNSL) and may manifest primarily or secondarily in the vitreous and retina. The distinction between vitritis/uveitis and VRL is clinically difficult and requires cytological examination of invasively obtained vitreous material for definitive diagnosis. Due to the time-consuming material collection and the clinical masquerade as vitritis, there are often significant delays in diagnosis. In addition, only a few centres have sufficient experience in the diagnosis and therapy of this rare lymphoma entity. The sensitivity of established tests (cytology, immunophenotyping, clonality analysis) on vitrectomy specimens is at most 70% for VRL. A standardised diagnostic procedure has not yet been defined.

This study aims to implement a network for standardised molecular analysis of VRL, to evaluate the impact of standardised molecular diagnostics on diagnostic quality prospectively through clinical follow-up.The network partners will prospectively send diagnostic vitreous samples from patients with suspected VRL, process them centrally in a standardised manner and subject them to multiparametric molecular diagnostics (mutation analysis and clonality detection using next generation sequencing, miRNA analysis). Due to the rarity of the disease, a recruitment period of 4 years is planned with the inclusion of at least 220 patients with suspected VRL, including 50 in whom VRL can ultimately be confirmed. At the time of surgery, the diagnostic chain (including type and duration of symptoms, clinical course up to vitrectomy) will be evaluated using questionnaires and a qualitative interview with stakeholders (patients, ophthalmologists, pathologists, oncologists). In order to validate the quality of molecular diagnostics and to evaluate the significance for the course of the disease (treatment failure, local recurrence, CNS involvement and recurrence), a prospective clinical documentation of the course of the disease with an observation period of 2 years for VRL patients is being carried out in cooperation with the CNS Lymphoma Working Group of the German Lymphoma Alliance.

Analogous to the VRL patients, the vitritis patients are asked by telephone every six months for two years whether they have been diagnosed with VRL or PCNSL. All VRL patients will be included in a clinical registry. Remaining biomaterial from vitreous bodies will be deposited in a central biobank for future research projects and biomarker establishment, independent of diagnosis.

The aim of the project is to implement a standardised and quality-assured molecular genetic analysis of VRL in specialised centres throughout Germany and thus to achieve an improved and more time-efficient diagnosis of this rare and aggressive disease. The network for the diagnosis of VRL and the clinical registry can also serve as a basis for the development of therapy studies in the future in cooperation with the CNS Lymphoma Working Group of the German Lymphoma Alliance, which is largely lacking in this entity.

Vitreous aspirates, Anterior chamber water samples, whole blood.

Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma

DECODE VRL - Multicentric Implementation and Clinical Validation of Standardized, Innovative Molecular Diagnostics for VitreoRetinal Lymphoma

The diagnostic work-up would be from patients with suspected VRL including NGS-based mutation and B-cell clonality analysis and quantification of miRNAs 19b, 21 and 92 for the participating ophthalmology centres.

The evaluation of the diagnostic sensitivity and specificity of extended molecular diagnostics (based on standard work-up) of vitreous samples for VRL diagnosis in comparison to standard work-up alone.

Follow-up of VRL patients during regular tumour follow-up over a period of 24 months to determine the predictive significance of the biomarkers with regard to therapy response, development of recurrence in the eye, second eye involvement as well as CNS involvement and recurrence. Similarly, the vitritis patients are followed up by telephone every six months for a period of 24 months, during which any interim occurrence of a VRL or a PCNSL as well as further questions are asked according to a defined catalogue of questions.

A central VRL clinical registry should be established to facilitate the exchange of information. The registry will be established with the support of the German Lymphoma Alliance and Retina.net.

Establishment of a residual material biobank (especially DNA and RNA) of VRL and the control group vitritis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tissue Acquisition for Molecular Diagnostics	NCT00001580	Neoplasm		-	National Institutes of Health Clinical Center (CC)
Fingerprint Characterization of Advanced HCC	NCT02372162	Carcinoma, Hepa...	Image Fingerpri... Molecular Finge...	18 Years -	University Hospital Tuebingen
Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma	NCT05841914	Vitreoretinal L...		18 Years -	University of Luebeck
Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma	NCT05841914	Vitreoretinal L...		18 Years -	University of Luebeck
Fingerprint Characterization of Advanced HCC	NCT02372162	Carcinoma, Hepa...	Image Fingerpri... Molecular Finge...	18 Years -	University Hospital Tuebingen

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