Anatomical association of dose distribution with radiotherapy-related lymphopenia in oropharynx cancer
Abravan, Azadeh Vasquez Osorio, Eliana Green, Andrew McPartlin, Andrew J
Abravan, Azadeh
Vasquez Osorio, Eliana
Green, Andrew
McPartlin, Andrew J
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Abstract
Purpose/Objective(s): Lymphopenia during radiotherapy (RT) may be
related to adverse outcome for head and neck cancer and is a theoretical
concern for effectiveness of adjuvant immunotherapy. Prevention may be
possible via plan adaptation if the relationship between RT dose distribution and incidence of lymphopenia is known. This work utilized image-based data mining to identify anatomical regions associated with development of lymphopenia during RT.
Materials/Methods: 639 oropharyngeal cancer patients treated from 2005-
2016 at a single institution with curative intent RT and baseline lymphocytes ≥ 0.5 £ 109
/L were studied. To control for co-founders and improve
data mining sensitivity, two matched groups were defined - patients with
and without lymphopenia (defined as Grade 3 or higher based on lymphocytes at nadir during RT < 0.5 £ 109
/L according to CTCAE v5.0) -
matched on target volume, baseline lymphocytes, and prescribed dose
(propensity score matching, M = 1:1, caliper = 0.2). Following matching,
309 patients remained, and image-based data mining was used to identify
regions where dose correlates with lymphopenia. EQD2 dose matrices
(a/b = 10) were mapped onto a reference patient using deformable registration of the planning CT images. L-R mirrored images were included in the
cohort to compensate for potential laterality bias. Mean dose distributions
for the groups with/without lymphopenia were calculated and regions with
significant differences between the mean dose of the two groups detected
using permutation testing with 1000 permutations. Multivariable logistic
analysis was conducted for the full cohort including mean dose to the identified region, along with age, gender, smoking, performance status, HPV
status, stage, histology, target volume, prescribed dose, RT modality, RT
duration, baseline lymphocytes, and chemotherapy delivery to generate a
predictive model for development of lymphopenia.
Results: 74% of the patients developed lymphopenia ≥ G3 during RT. An
association with dose to a discrete anatomical region was found. Of interest,
this location corresponds to dense lymphoid tissue, bone marrow reserve, and
numerous blood vessels. Following elastic-net least absolute shrinkage and
selection operator regression, bootstrapped 100 times, a model including baseline lymphocytes (HR = 0.43, P < 0.001) and mean dose to the identified
region (HR = 1.02 Gy 1
, P = 0.006) adjusted for age (HR = 0.98, P = 0.09)
and target volume (HR = 1.83, P = 0.07) was proposed. The Hosmer-Leme show test indicated that the model was a good fit, C-statistics 94%.
Conclusion: In this large oropharynx cohort, RT related lymphopenia ≥
G3 was associated with dose to a discrete anatomical region including
structures containing blood, lymphoid tissue, and bone marrow that may
offer a mechanistic explanation. While hypothesis generating, this suggests
the possibility that treatment related lymphopenia may be mitigated by prioritizing dose reduction to this region. Further confirmatory studies are
indicated.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Abravan A, Osorio EV, Green A, McPartlin A, van Herk M. Anatomical Association of Dose Distribution With Radiotherapy-Related Lymphopenia in Oropharynx Cancer. International Journal of Radiation Oncology Biology Physics. 2021;111(3):E419-E.