**3. Target volume definition, clinical target volume, and radiotherapy**

The treatment of locally advanced cancers patients is a subject of debate in the last decades. A complex treatment including surgery, chemotherapy, hormone therapy, and radiotherapy is a standard today. New concepts had to be developed since the progress in diagnostic methods, tumor characterization, and progress in treatment delivery (more aggressive surgery and radiotherapy) made possible new approaches for locally advanced cancers.

In recent decades, tumor imaging by the introduction of computer tomography (CT), magnetic resonance imaging (NMR), and of positron emission tomography (PET/CT) made possible real progress in radiotherapy. From the 2D radiotherapy standard routine, for example, in breast cancer radiotherapy, a transition to 3D radiotherapy was possible. The high frequency of acute and late side effects to the normal structures around the real target volume (the breast tissue, chest wall, and lymphatic areas as axilla, internal mammary chain, and supraclavicular lymph nodes) made necessary new developments. The most important step forward was realized by the introduction of the concept of the anatomical defined clinical target volume (CTV) which included the microscopical disease and the gross tumor volume regarding the macroscopic visible tumor (GTV). The normal tissues around the above-defined target volumes were the loco-regional lymphatics (axillary nodes, internal mammary chain node, and the supraclavicular lymphatics), the brachial plexus, the lung tissue, the myocardium, and the ribs are so, well visualized. The concept of target volumes and real advanced conformal radiotherapy to apply the necessary curative dose to the CTV and GTV and to reduce the dose delivered to the organs of risk was developed and routinely applied, in the late eighties, by the team conducted by professor W. Bohndorf at the University of Würzburg, Germany. The initial concept of target volume definition was published by Richter and Bohndorf [4]. The development of conformal irradiation techniques to cover the CTV and GTV and to reduce the applied dose to the organs at risk was realized by the department of medical physics conducted by professor Richter (**Figure 1**) [6].

Reducing the irradiated volume by irradiation of a well-defined GTV (gross tumor volume) and CTV (clinical target volume) made it possible for the application of larger total dose of irradiation and a reduction of the acute and late side effects. These irradiated volumes included the tumor microenvironment (TME) which contains the tumor cells and the remodeled tissue now defined as the extracellular microenvironment (ECM).

#### **Figure 1.**

*PTV (planning target volumes) (left side), [5] and CTV and GTV and the organs at risk (middle and right side) for advanced breast cancer radiotherapy [6].*
