Combined proton-photon radiotherapy

Proton beams are widely considered a superior radiation modality compared to high energy xrays for treating cancer patients. This is due to the favorable depth dose curve of protons, which deposit most of the energy at the Bragg peak. Instead, photons show an exponential falloff of dose as a function of depth inside the patient.

However, proton therapy is a limited resource due to cost and size of the facility. Currently, there are only in the order of 100 proton therapy centers worldwide compared to more than 10'000 conventional xray therapy units. In our research group we work on two aspects in that regard:

1. We develop novel cost-effective proton therapy concepts that may allow for a more widespread implementation of proton therapy.
2. We develop methods to optimally make use of limited proton therapy resources, both for individual patients but also for the population of all cancer patients.

Our approach to these problems is combined proton-photon radiotherapy, that is, we work on methods to optimally combine proton beams with conventional x-ray beams.

For an overview of our work on combined proton-photon radiotherapy, you may watch this presentation given at the AAPM annual meeting 2021.

The size and cost of the proton gantry is one of the main obstacles for a widespread implementation of proton therapy. Due to the size of the gantry, proton therapy can usually not be installed in existing radiotherapy departments designed for xray therapy units. However, installing a cyclotron and a fixed proton beamline may be possible in many situations. In our work, we explore the following concept: The treatment room consists of:

• A Linac for delivering intensity-modulated x-ray therapy (IMRT, VMAT)
• A robotic couch for treatment in lying position
• A fixed proton beam line equipped with pencil beam scanning

With this concept, protons and photons may be delivered in the same fraction with the same patient immobilization. Most of the dose may be delivered with protons to reduce the dose burden in normal tissues. However, were protons alone are suboptimal due to limitations in the available beam angles, this can be compensated for by photon beams to achieve optimal conformity. The concept is illustrated for a head & neck cancer patient in Figure 1.

Figure 1: Illustration of a combined proton-photon treatment (d-f) for a head & neck cancer patient. Most of the dose to the gross tumor volume (red contour) is delivered by protons. However, horizontal proton beams are suboptimal for minimizing dose to the parotid glands (green contours). Photon beams therefore improve conformity of the dose distribution around the parotid glands and the nodal target volume (blue contour).

Further details can be found in our recent publications.

• Fabiano S, Balermpas P, Guckenberger M, Unkelbach J. Combined proton–photon treatments - A new approach to proton therapy without a gantry, Radiotherapy and Oncology 145, 81-87, 2020
• L. Marc, S. Fabiano, N. Wahl, C. Linsenmeier, A. Lomax, J. Unkelbach. Combined proton-photon treatment for breast cancer. Phys. Med. Biol., 66(23):235002, 2021
• F. Amstutz, S. Fabiano, L. Marc, D. Weber, A. Lomax, J. Unkelbach, Y. Zhang. Combined proton‐photon therapy for non‐small cell lung cancer, Medical Physics, 2022

Currently, protons and photons are not available in the same treatment room. For the time being, the most practical way to combine protons and photons is to deliver some fractions with protons and the rest with photons. Institutions that currently perform multi-modality treatments optimize intensity modulated radiation therapy (IMRT) and proton therapy (IMPT) plans separately so that each modality delivers the prescribed dose per fraction to the target volume. Our group has demonstrated that one can improve on such simple combinations by simultaneously optimizing IMRT and IMPT plans.

The method can be applied when organs at risk (OARS) are located within or near the tumor, which can only be protected through fractionation. In this case, IMRT and IMPT fractions must deliver similar doses to the portions of the target volume that overlap with OARs. Meanwhile, if parts of the target volume are hypofractionated with protons, the total dose delivered with photons is reduced, leading to a reduction of the integral dose to normal tissues.

Figure 2 compares two combined proton-photon treatments using 1 IMPT and 4 IMRT fractions for a patient with a large liver tumor. The gross tumor volume (GTV) abuts bowel, stomach and chest wall. In a simple proportional combination of IMRT and IMPT plans (top row), each fraction delivers 10 Gy to the GTV to achieve the prescribed dose of 50 Gy in 5 fractions. In the optimized combination (bottom row), both proton and photon fractions deliver similar doses to serial OARs overlaying the target volume (red contour). However, protons deliver more than twice the dose to the GTV. As the photon bath is reduced compared to the reference plan, the optimized combination lowers the integral dose in the non-involved liver and the remaining healthy tissues.

Figure 2 : (a/b) dose distributions per fraction of the single-modality IMRT and IMPT plans; (c) cumulative EQD8 for the reference plan (i.e. a simple proportional combination of the single-modality plans); (d/e) dose distributions of an IMRT and the IMPT fraction in the optimized combination; (f) cumulative EQD8 for the optimized combination. The contours show the GTV (blue), PTV (red), liver (green), stomach (purple), bowel (pink) and chest wall (black).

Further details can be found in two publications:

• Unkelbach J, Bangert M, De Amorim Bernstein K, Andratschke N, Guckenberger M. Optimization of combined proton-photon treatments. Radiother. Oncol. 128(1):133-138, 2018
• Fabiano S, Bangert M, Guckenberger M, Unkelbach J. Accounting for range uncertainties in the optimization of combined proton-photon treatments via stochastic optimization. Int. J. Rad. Onc. Biol. Phys. 108(3), 792-801, 2020