COGNITION

The clinical workflow reflects the process of molecular stratification in the study. The aim is to identify patients who may benefit from a targeted therapeutic approach based on genetic alterations. In parallel with clinical procedures, data from the tumour genome analysis are utilised in cancer research. Researchers apply advanced experimental technologies and propose new therapeutic concepts based on these insights.
 

1. Contacting and introducing the patient

The attending physician registers the patient for the study. Patients may also register themselves. 

The following documents should be sent to one of the participating study centres near the patient`s place of residence: a recent doctor's letter, histology report, CT/MRI findings, surgical report, tumour board recommendation, the patient`s contact details including a telephone number, and referral form. 

During an appointment, the patient is informed by the study physician. A decision regarding participation is made, followed by signing of the written informed consent form.
 

2. Sampling

Tissue sample: High-throughput sequencing requires particularly gently extracted DNA and RNA. For this purpose, the tumour material must be deep-frozen immediately after removal, e.g., by biopsy or surgery. Since the biology of tumours can change during the course of disease, this tissue sample should be as recent as possible. At least 20 per cent tumour cells are required in the sample for sequencing so that changes can be reliably detected. Therefore, a pathologist examines the tissue under the microscope and determines the tumour cell content together along with other parameters.

Blood sample: To identify tumour-specific alterations, a healthy comparison sample is necessary. For this, DNA from leucocytes, obtained from a blood sample, is used.

Depending on individual requirements, further blood samples may be needed over the course of treatment to assess markers that help tracking disease recurrence. This may provide insight into how the tumour is responding to therapy.

Tissue and blood samples from study participants that are not required for the examinations described below, or for standard care, can be used in accompanying research programmes. These include, for example, immunophenotyping or characterisation of the tumour tissue micro-environment, but also further studies that provide a deeper insight into tumour biology. For instance, these results can be used to derive risk profiles or elucidate resistance mechanisms.
 

3. Molecular profiling

In the sample processing laboratory at NCT Heidelberg, DNA and RNA are extracted from tumour tissue, and DNA is isolated from blood samples. Sequencing is carried out at the Next Generation Sequencing Core Facility at DKFZ.

At the Computational Oncology Group within the Molecular Precision Oncology Programme of NCT Heidelberg, experts compare sequencing results from tumour and normal tissue to identify tumour-specific alterations.

The sensitivity of the tumour tissue to drugs can be tested in corresponding functional assays. 

All steps of sample preparation, molecular profiling, and data analysis are performed under strict quality control at the German Cancer Research Centre (DKFZ).
 

4. Clinical curation and data interpretation

Based on the molecular data collected, and, where applicable, additional laboratory analyses such as preclinical drug testing, scientists identify potential target structures for approved therapies and assess their likelihood of success. 
 

5. Molecular tumour board

Therapy-relevant alterations are discussed in the Molecular Tumour Board — a multidisciplinary panel comprising specialists in gynecological oncology, bioinformatics, molecular biology, pathology, and human genetics.
The board generates a prioritised list of potential targeted therapies and documents the recommendations in a formal report.
 

6. Notification of results, treatment recommendation

A study physician reviews the tumour board report with the patient, explaining potential treatment options. The report is also forwarded to the attending oncologist.
 

7. Treatment, possible inclusion in a clinical trial

For eligible patients, the proposed treatment is carried out, with the patient's consent, as part of the downstream COGNITION-GUIDE therapy study.

If no actionable targets are identified that fall within the scope of COGNITION-GUIDE, the following treatment options may be considered, in each case with the patient’s consent and at the discretion of the attending oncologist or study physician:

1. Within independent AMG trials (phases I–IV) for substances not yet authorised
2. With a drug authorised for the current indication
3. As off-label use with drugs authorised for another indication

For off-label use, efforts are made to secure cost coverage from the patient’s health insurance provider.
 

8. Follow-up

Follow-up is primarily based on the needs of the study participants, for example to clarify complaints. In addition, patients present themselves at 6-monthly intervals over a period of 10 years. In addition to clinical data on physical condition, the disease situation and current diagnostics and treatment, various quality-of-life metrics and other patient-reported outcomes (PrOs) of the study participants are collected using standardized questionnaires.