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Therapy and research in the Department of Internal Medicine III
Bronchial carcinoma is one of the most common malignant diseases. In Germany, bronchial carcinoma is the most common fatal malignancy in men. Bronchial carcinoma is divided into small cell (SCLC, approx. 15-20%) and non-small cell (NSCLC, approx. 80%) bronchial carcinoma. In NSCLC, a distinction is made between various histopathological subtypes (including adenocarcinoma, squamous cell carcinoma, large cell carcinoma). At the time of diagnosis, the tumour is usually at an advanced stage.
All stages and forms of bronchial carcinoma are treated at Ulm University Hospital. The Department of Internal Medicine III specialises in the treatment of advanced bronchial carcinoma and in conducting controlled clinical trials. The aim of these clinical trials is to improve current standard therapies and to research individual risk factors.
The treatment of advanced non-small cell lung cancer (NSCLC) is changing fundamentally. A number of molecular markers have now been identified that play an important role in the course of the disease, but also in therapy decisions. In addition to the determination of activating EGFR mutations, which have established themselves as a predictive biomarker for the use of EGFR-inhibiting tyrosine kinase inhibitors, other very interesting biomarker-dependent therapeutic strategies are developing, such as ALK/MET inhibitors in ALK-positive NSCLC, MEK inhibitors in N-Ras-mutated patients, or other new targeted substances for the inhibition of MAGE-A3, hTERT or IGFR
In bronchial carcinoma, genetic changes often occur in the tumour cells (see Fig. 2). These have both prognostic and predictive significance. Investigating the value of molecular predictive markers is of great importance in the Department of Internal Medicine III for various forms of leukaemia as well as for solid tumours.
Current biomarker-dependent overall concept of the Department of Internal Medicine III:
The Department of Internal Medicine III has developed a modern biomarker-based study concept for patients with NSCLC (see Figure 3).
Another focus of the department is the investigation of specific immune responses against tumour cells. Various phase II and III studies are being conducted worldwide on bronchial carcinoma and are showing encouraging results. In Ulm, specific immune responses of CD8-positive T cells against bronchial carcinoma tumour cells are being investigated in the Tumour Immunology Laboratory.
The aim of these immunological projects is to develop targeted immunotherapies for bronchial carcinoma. Two target structures are already being investigated in phase III trials (MAGE-A3 and hTERT). The Department of Internal Medicine III is taking part in an adjuvant therapy trial against the immunogenic antigen MAGE-A3.
Recurrences of the disease often occur after tumour resection. The aim of this study is to reduce the probability of recurrence. In this study (see Fig. 5), patients receive a tumour vaccine against MAGE-A3. This tumour vaccine can also be administered after adjuvant chemotherapy. Many patients are grateful if a well-tolerated therapy to reduce the likelihood of recurrence is actively carried out after tumour resection and adjuvant chemotherapy.
Clinical studies
Further information on the active studies can be found at:
Description of the disease
Bronchial carcinoma is divided into small cell and non-small cell bronchial carcinoma(small cell lung cancer (SCLC)/non-small cell lung cancer (NSCLC)). In NSCLC, a distinction is also made between various histopathological subtypes (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, etc.), which are relevant for prognosis and therapy. Recently, molecular markers such as EGFR and K-RAS mutations have been determined, which are of great importance for prognosis and therapy selection.
The main cause is tobacco smoking. In addition, there are some substances that can trigger the tumour (e.g. asbestos, chromium or radon). The cure rate for bronchial carcinoma is still poor, with a five-year survival rate of less than ten per cent.
Frequency and age of onset, localisation
With around 40,000 deaths per year, bronchial carcinoma is one of the most common malignant diseases in Germany. According to the Federal Statistical Office, around 29,000 men and around 11,000 women die from bronchial carcinoma every year. This makes lung cancer the most common cause of death from cancer in men and the third most common in women. The average age of onset is 68 years. The number of cases is increasing among women.
Signs of illness
In the early stages, bronchial carcinoma does not cause any typical symptoms. Symptoms may include Coughing, especially with a long-standing smoker's cough that suddenly changes, bronchitis that does not improve despite antibiotics, shortness of breath, chest pain, general fatigue and severe weight loss, haemoptysis or chest pain.
As with other types of tumour, the same applies here: The earlier the tumour is detected, the greater the chances of recovery.
Classification and staging
The TNM classification was modified in 2009 on the basis of a large data collective (see Fig. 6)
Therapeutic options
The treatment of bronchial carcinoma depends crucially on the subtype, stage, general condition and comorbidity of the patient.
Various treatment methods are used, such as surgery, radiotherapy and/or systemic therapy. Depending on the stage, these procedures are sometimes also combined (see also Figures 2 and 4). All treatment decisions are made on an interdisciplinary basis in our tumour board for thoracic tumours.
The treatment principles are briefly described below:
Surgery
Complete removal of non-metastasised bronchial carcinoma offers the best chance of a cure. Up to tumour stage IIB/IIIA, it is possible for the surgeon to completely remove the tumour with a sufficient safety margin without disproportionately impairing the function of the lung. However, the actual extent of the tumour can often only be determined with certainty during the operation. Depending on the extent of the tumour, the operation can be more or less extensive. Sometimes only individual lobes of the lung have to be removed, in less favourable cases an entire lung.
Radiotherapy (radiotherapy)
Primary radiotherapy is often carried out if the bronchial tumour cannot be surgically removed.
Palliative radiotherapy: In the case of painful metastases or bone metastases that threaten the stability of the bone, radiotherapy can often bring about a rapid improvement in symptoms.
System therapy/chemotherapy
Adjuvant chemotherapy (administered after surgery): In patients with tumours that have already metastasised to the lymph nodes, chemotherapy is often indicated after surgery in order to prolong survival.
Palliative systemic therapy/chemotherapy : New cytostatic drugs have given palliative chemotherapy a new significance for patients with metastasised non-small cell lung cancer. Modern chemotherapeutic agents are well tolerated and can prolong life and improve or delay the onset of tumour-related symptoms. Numerous new drugs and innovative treatment methods are currently being developed. New drugs are also available at Ulm University Hospital as part of clinical trials for the treatment of bronchial carcinoma (see Fig. 2 and 4).