The Value of New Genetic Testing Methods for Evaluating Unclear or Challenging Treatment Cases in Hematological Diseases

Hematologic malignancies are malignant diseases that affect the blood, bone marrow, or lymphatic system. These include, among others, leukemias, lymphomas, and other rarer types of cancer. The cause of these diseases is often unknown, but they are very frequently caused by genetic mutations. In other words, errors in the cells’ genetic material have developed during cell division over the course of a person’s life, allowing malignant cells to form. Conventional diagnostic techniques for hematologic malignancies consist of a variety of tests. The structure and shape of the tumor and the cancer cells, the proteins on the surface of the cancer cells, and the patient’s chromosomes are examined, and molecular genetic tests are performed. This is referred to as “gold standard” diagnostics. These methods provide an accurate diagnosis in about 90% of cases. In about 10% of cases, however, the diagnosis remains unclear, which makes targeted treatment difficult. These diagnostic gaps could potentially be closed through the use of so-called next-generation sequencing methods. Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) enable an even more comprehensive analysis of a tumor’s genetic information, which can lead to a more accurate diagnosis.

The goal of the SIRIUS study is to compare these next-generation sequencing methods with current gold-standard diagnostic procedures. The study aims to investigate whether the new methods offer better or comparable accuracy and to what extent they are suitable for routine daily diagnostics. This study is based on over 5,500 cases that were diagnosed according to gold-standard criteria and subsequently analyzed using next-generation sequencing methods. As part of the study, patient samples are examined using next-generation sequencing methods and then assigned to a clinical presentation from this database using an algorithm. The study is observational, which means that no medications or new forms of therapy are being tested. The primary endpoint of the study is to determine how often the diagnosis obtained through next-generation sequencing matches the diagnosis based on gold-standard methods.

Women and men between the ages of 18 and 99 who are suspected of having a hematological disease that could not be clearly diagnosed using conventional methods, or who have a hematological disease with an unusual clinical course, or who have multiple concurrent hematological diseases, or who have rare or new types of cancer, are eligible to participate in the study.