Vascular and Circulating Blood Exposure to Proton or Photon Irradiation: Differentials in Lymphocyte Subset Metrics in Cancer Patients

@article{meirino2026vascular,
  title = {{Vascular and Circulating Blood Exposure to Proton or Photon Irradiation: Differentials in Lymphocyte Subset Metrics in Cancer Patients}},
  author = {Rosa Meiriño and Felipe A. Calvo and Enrique Amaya and Javier Burguete and Javier Serrano and Marina García Cardosa and Diego Pedrero and Diego Azcona and Jacobo Palma and María A. Fortuño and Mauricio Cambeiro and Marta Lasa and Elena Antolín San Martín and Marta Vidorreta and Javier Aristu},
  journal = {Cancers},
  year = {2026},
  month = nov,
  doi = {10.3390/cancers18213587},
  url = {https://www.mdpi.com/2072-6694/18/21/3587},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Vascular and Circulating Blood Exposure to Proton or Photon Irradiation: Differentials in Lymphocyte Subset Metrics in Cancer Patients
AU  - Rosa Meiriño
AU  - Felipe A. Calvo
AU  - Enrique Amaya
AU  - Javier Burguete
AU  - Javier Serrano
AU  - Marina García Cardosa
AU  - Diego Pedrero
AU  - Diego Azcona
AU  - Jacobo Palma
AU  - María A. Fortuño
AU  - Mauricio Cambeiro
AU  - Marta Lasa
AU  - Elena Antolín San Martín
AU  - Marta Vidorreta
AU  - Javier Aristu
PY  - 2026
DA  - 2026/11/08
JO  - Cancers
DO  - 10.3390/cancers18213587
UR  - https://www.mdpi.com/2072-6694/18/21/3587
AB  - Background/Objectives: Radiation-induced lymphopenia is consistently associated with adverse outcomes across solid tumours, yet the vascular compartment that carries the irradiated lymphocyte pool is not routinely delineated during treatment planning. The VASA project makes blood vessels an explicit, measurable structure in that process. Phase II aimed primarily to establish the feasibility of that delineation and secondarily to explore how dose–volume metrics computed on MRI-segmented vessels relate to serial immunophenotyping in patients treated with protons or photons. Methods: Thirty-nine patients treated between March 2021 and May 2022 were studied prospectively (30 proton, 9 photon). Flow-contrast three-dimensional MRI with three velocity-encoding directions was added to simulation; vessel masks segmented semi-automatically from the sum-of-magnitude reconstruction were imported into the treatment-planning system to generate dose–volume histograms. The effective dose to circulating immune cells (EDIC), the integral dose to vessels (IDVe) and the integral dose to target were computed. Blood was sampled at the start and at the end of irradiation for lymphocyte counts and B, T and NK immunophenotyping. Groups were compared with Welch’s t-test for continuous variables and Fisher’s exact test for categorical variables, without correction for multiple comparisons; the photon subgroup was not matched. Results: EDIC was higher with photons than protons (5.60 vs. 1.25 Gy; p = 0.005) and in patients who became lymphopenic (4.84 vs. 1.47 Gy; p = 0.027); IDVe differed in the same direction without reaching significance (3.60 vs. 0.53 Gy·L, p = 0.091; 3.08 vs. 0.67 Gy·L, p = 0.180). Within the proton cohort, EDIC and IDVe increased from brain to head-and-neck to thorax–abdomen targets (0.81, 1.11 and 2.17 Gy; 0.13, 0.26 and 1.63 Gy·L), and the IDVe ordering persisted after adjustment for target volume (p < 0.001). Lymphocyte counts fell from 1.92 to 1.43 × 103/µL in the proton cohort (p < 0.001), with the lowest end-of-treatment values in thorax–abdomen targets (1.31 × 103/µL). B, T and NK subpopulations all declined in the proton cohort; among regions, only head-and-neck targets showed significant T and NK losses. Conclusions: Patient-specific vascular delineation and dosimetry are feasible in a clinical planning workflow, and the resulting metrics track irradiation modality and the magnitude of lymphocyte depletion. These associations are exploratory; immune-sparing plan optimisation using vascular constraints remains a future application requiring prospective validation.
SN  - 2072-6694
ER  -