Mid-Ventilation Radiotherapy Approach for Lung Cancer: A Way To Save More Healthy Tissue?

Radiation therapy requires a delicate balance between effectively treating the tumor and limiting the damage to surrounding healthy tissue. Moving tumors like lung cancer often require larger target margins to capture the whole range of motion thus also exposing some organs to unncessary radiation. Applying the mid-ventilation approach may be a way to reduce these margins and potentially reduce the risk of toxicity.

Photos: Morten Koldby

Saving as much healthy tissue as possible, both in the lungs and in nearby organs, is critical to keep the risk of treatment-related side effects at an accepted level for lung cancer patients. “The mid-ventilation approach is a key step in this process,” explains Mirjana Josipovic, senior medical physicist and PhD fellow at Rigshospitalet, Copenhagen, Denmark, and a leading expert in radiation therapy and medical imaging. Rigshospitalet specializes in the mid-ventilation approach for the treatment of moving tumors – and is one of the world’s leading centers for lung cancer radiotherapy.

To address the uncertainties in the position of the tumor, including its respiratory movement, margins are applied around the tumor, resulting in the so-called planning target volume (PTV). While these margins ensure that the tumor is adequately covered with the prescribed radiation dose, they unavoidably contain healthy tissue that will also be exposed to radiation.

A major challenge when treating lung cancer has always been that the tumor moves as the patient breathes. Some tumors exhibit a range of motion of several centimeters. One widely used approach to take account of this motion is the internal target volume (ITV). In this approach, a volume enclosing the whole envelope of the tumor motion is defined and the PTV margin is added to this volume, and not to the tumor itself, resulting in a relatively large PTV.

Since the movement of the tumor makes it so difficult to target it, why not just let the patient hold his or her breath? “Breath-hold CT scanning and breath-hold treatment has been applied broadly for patients with breast cancer and also mediastinal lymphoma. In lung cancer it has only been investigated sparsely, due to assumption that the patients will not be able to hold their breath. However, our experience is the opposite and we are currently receiving lung cancer patients for treatment using the deep inspiration breath-hold technique (DIBH). This method has its benefits even apart from tumor motion mitigation,” says Josipovic. “When you inhale and hold your breath, the lung volume increases, while the tumor remains the same. This results in a larger amount of healthy lung tissue outside the radiation treatment area.”

Even though the majority of lung cancer patients can cooperate with DIBH in the experience of clinicians at Rigshospitalet, not all of them can – and, in very few, the DIBH approach is not better than free breathing due to complex tumor geometry. Therefore, improvement of free breathing techniques is also warranted. In this area, the mid-ventilation approach offers an alternative to ITV, aiming to minimize the irradiated volume.

The mid-ventilation approach uses the information on tumor movement from phase-based 4D CT scans to calculate the time-weighted mean position of the tumor – the so-called mid-position. The breathing phase from the 4D CT closest to the mid-position is chosen as the basis for the treatment plan. This phase is called the mid-ventilation phase and the PTV margins are then applied around the position of the tumor in this phase.

So unlike with the ITV approach, the treatment does not cover the whole range of movement of the tumor but only the area where it is most of the time, but the resulting PTV is substantially smaller.

The mid-ventilation approach was first developed at the Netherlands Cancer Institute in Amsterdam, in the early 2000s. Josipovic points out that she did not invent this approach. She has been working clinically with it for more than ten years, however. Rigshospitalet is now one of the leading centers worldwide employing this approach. “Today, the mid-ventilation approach is well known to a number of research centers and hospitals around the world. Here at Rigshospitalet, we believe this method to be useful for the treatment of moving tumors.”

So what are possible outcomes of the mid-ventilation approach? “To put numbers on potential improvements is next to impossible,” Josipovic cautions. “We need to remember that we are talking about high disease burden and lung cancer patients often have more than one health problem.” At present, the prognosis for NSCLC shows a five-year survival rate of approximately 15 percent.[1]

“However, the mid-ventilation approach helps to tailor the irradiating volume for a particular patient, avoiding excess irradiation of healthy tissue. When it comes to improved outcomes, this is one of many steps.”
“In parallel with the development of the mid-ventilation method, other improvements have been implemented clinically, as well. More efficient computers give us the possibility of more exact dose calculation, for example, and daily image guidance ensures precise positioning of the treatment target.”

One thing that has hindered a more widespread adoption of the mid-ventilation approach is the need to extract the tumor motion from a 4D CT scan and then calculate the mid-position and the related mid-ventilation phase. Today, these fairly complex and relatively time-consuming calculations are done either manually or with individually designed software tools.

Josipovic is supporting work to develop a commercially available software product that would make the calculations easier to handle. “A more automatic and standardized calculation would certainly be welcome. It would save time, obviously, but it would also mean that calculations would be made in the same way every time. Today, there is an element of individual assessment and estimation, which means that results may be observer dependent.”

The mid-ventilation approach may help to better spare healthy tissue during radiation therapy. A new software solution might help to speed up the adoption of this method in more cancer centers.

Nils Lindstrand has been working as a science, business, and technology writer for more than 30 years. He is based in Stockholm, but has worked in more than 20 countries so far. His academic background is in chemistry, natural sciences, and technology.