Kaplan lecture 2023: lymphopenia in particle therapy

Abstract

Purpose

Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy. Here we will review the current knowledge about the difference in lymphopenia between particle and photon therapy and the consequences.

Conclusions

There is nowadays an overwhelming evidence that particle therapy reduces significantly the radiotherapy-induced lymphopenia in several tumor sites. Because lymphopenia turns down the immune response to checkpoint inhibitors, it can be predicted that particle therapy may be the ideal partner for combined radiation and immunotherapy treatment and should be selected for patients where severe lymphopenia is expected after X-rays.

Keywords:

• Lymphopenia
• proton therapy
• carbon ions
• immunotherapy
• radioimmunotherapy
• chromosomal aberrations
• particle therapy

Acknowledgements

I am very grateful to IARR for their decision to select me as recipient of the prestigious Kaplan award. This is a great honour, and looking at the list of previous winners makes me feel amazed. I also thank the Italian (SIRR) and German (DeGBS) Societies of Radiation Research for their nomination and support. I would have a very long list of friends and colleagues that helped me in my career and to whom I owe this award, but the list would be definitely too long. I have to mention though Kerry George, Mariagabriella Pugliese and all my team at the GSI Helmholtz Center in Darmstadt. This paper is dedicated to the memory of my mentor and guide, Prof. Gerhard Kraft, who passed away on March 18, 2023, and is sorely missed.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Marco Durante

Marco Durante is Head of the Biophysics Department at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt (Germany) and professor pf Physics at the Technische Universität Darmstadt (Germany) and University Federico II in Naples (Italy). He received the Kaplan award at the 17th International Congress for Radiation Research in Montreal (Canada), August 27–30, 2023.