Protons or Photons in Pituitary Neuroendocrine Tumors-That Is Not the Question

Liv Cathrine Heggebø; Frank Leonel Bello Garrote; Lars Fredrik Fjæra; Maziar Hervani; Christina Ramberg; Andreas Ottestad; Hanne Blakstad; Trine Martens; Corina S Rueegg; Magnus Gustavsson; Thomas Henry; Malin Blomstrand; Taran Paulsen Hellebust; Petter Brandal

doi:10.1016/j.ijpt.2025.101194

Protons or Photons in Pituitary Neuroendocrine Tumors-That Is Not the Question

Int J Part Ther. 2025 Jun 18:17:101194. doi: 10.1016/j.ijpt.2025.101194. eCollection 2025 Sep.

Authors

Liv Cathrine Heggebø^{1

2}, Frank Leonel Bello Garrote³, Lars Fredrik Fjæra³, Maziar Hervani¹, Christina Ramberg³, Andreas Ottestad¹, Hanne Blakstad^{1

2}, Trine Martens¹, Corina S Rueegg⁴, Magnus Gustavsson^{5

6}, Thomas Henry^{5

6}, Malin Blomstrand^{7

8}, Taran Paulsen Hellebust^{3

9}, Petter Brandal^{1

2

10}

Affiliations

¹ Department of Oncology, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Medical Physics, Oslo University Hospital, Oslo, Norway.
⁴ Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶ Department of Medical Radiation Science, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
⁷ Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹ Faculty of Health and Social Sciences, University of South-Eastern Norway, Oslo, Norway.
¹⁰ Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.

Abstract

Purpose: With the long-life expectancy of patients with pituitary neuroendocrine tumors (PitNETs), reducing long-term toxicity is essential to preserve quality of life. We aimed to investigate whether 2- or 3-field proton beam therapy (PBT) plans better spare organs at risks (OARs), including healthy tissue, than volumetric modulated arc photon therapy (VMAT).

Materials and methods: Fifteen consecutive patients who had received radiation therapy for PitNETs were included. We made 4 treatment plans for each patient: one 3-field PBT plan (3F), two 2-field PBT plans (2F-L and 2F-IV), and 1 VMAT plan. Dosing was set to 1.8 Gy × 30 to allow for dosimetric comparisons.

Results: All 4 treatment techniques showed excellent target volume coverage. Compared to VMAT, the 3 PBT techniques had lower doses to OARs. Median D_40% to the hippocampi varied from 0.4 to 1.1 Gy (relative biological effectiveness [RBE]) with PBT and was 5.2 Gy for both hippocampi for VMAT. Median mean dose to brain-CTV and head-CTV were lowest for 2F-L (3.1 and 2.3 Gy [RBE]), followed by 3F (3.9 and 2.5 Gy [RBE]), 2F-IV (4.1 and 2.6 Gy [RBE]), and highest for VMAT (4.8 and 4.7 Gy). A relative reduction in integral dose compared to VMAT was seen for all PBT techniques, with a median reduction of 38.5% to 45.9% for head-CTV.

Conclusion: Proton techniques spared OARs better than VMAT; however, absolute dose sparing was relatively small, and the clinical value remains uncertain. Nonetheless, the dose reduction, especially for the hippocampi and integral dose, is probably clinically meaningful. We argue that head-CTV should be assessed, as much of the volume receiving dose is located outside the brain. The size and location of the target volume impacted which proton plan was preferable. We conclude that individualized planning is more important than a mere question on protons or photons in PitNET patients.

Keywords: Pituitary neuroendocrine tumors; Plan comparison; Proton therapy; Radiation therapy; Treatment planning.