Predictive factors of severe radiation-induced lymphopenia in proton-treated patients
Pan, Shermaine ; Sitch, Peter ; Gaito, Simona ; McPartlin, Andrew J ; Sashidaran, S. ; Smith, Ed ; Whitfield, Gillian A ; Abravan, Azadeh
Pan, Shermaine
Sitch, Peter
Gaito, Simona
McPartlin, Andrew J
Sashidaran, S.
Smith, Ed
Whitfield, Gillian A
Abravan, Azadeh
Citations
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Abstract
Purpose or Objective
Radiation-induced lymphopenia (RIL) has been reported in solid tumours and is associated with worse survival outcomes.
There is little known thus far of potential predictive factors for developing severe RIL.
This single institution study is aimed at establishing potential predictive factors of severe RIL in a cohort of patients treated
with proton beam therapy (PBT).
Materials and Methods
One hundred and twenty patients treated with pencil beam scanning PBT without synchronous chemotherapy, from
December 2018 to March 2020 at The Christie PBT centre were included in the study. All patients had pre-treatment
lymphocyte count and on-treatment serial lymphocyte counts. Treatment sites were divided into three categories: central
nervous system (CNS), head and neck (H&N), which included base of skull, and spine (for paraspinal and spinal treatment
of the cervical, thoracic, lumbar or sacro-coccygeal region).
Severe RIL was defined as grade 3 or higher based on nadir lymphocyte count < 0.5x109/L during PBT according to CTCAE
v5.0. Clinical target volume (CTV) was obtained from planning images. Vx was calculated from RT images as the volume
receiving x Gy or higher normalized to body weight to account for patients’ size. For patients without weight data (n=4),
it is imputed using a 3rd power fit of weight vs age from the available data. To investigate the association between the
incidence of severe RIL and dosimetric factors, multivariate logistic regression was used. To avoid multi-collinearity,
dosimetric parameters were included in the multivariate regression one at a time together with other factors known to
affect lymphocyte count.
Results
Fifty-four (45%) of the patients were female. The median age was 15 years (range 1 – 82). Treatment sites were CNS 69
(58%), H&N 26 (22%) and spine 25 (21%). Diagnoses are shown in Table 1. Prescribed PBT dose ranged from 50.4 Gy (RBE)
to 75.6Gy (RBE). The median absolute lymphocyte count prior to treatment was 1.9X109/L (range 0.3 – 6.4) and during
treatment 1.2X109/L (range 0.1-2.8). Seventeen patients (14%) developed grade 3 or 4 lymphopenia.
In univariate analysis, severe RIL was associated with pre-treatment lymphocyte count (Odds Ratio (OR) 0.29, p=0.004),
age (OR 0.93, p=0.018), spinal treatment site (OR 8.53, p<0.001), CTV (Ln) (OR 2.42, p<0.001), and V2-V30Gy. On
multivariate analysis, severe RIL was associated with pre-treatment lymphocyte count, and V2-20Gy. Conclusion
Severe RIL is seen most commonly in patients having treatment involving their spine. Baseline lymphocytes and low to
intermediate dose volumes, V2 through V20 Gy, are predictive factors of developing severe RIL in patients treated with
PBT. Further work in progress will better define dose volume limits to predict patients likely to develop severe RIL who
may therefore require prophylactic antibiotics.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Pan S, Sitch P, Gaito S, McPartlin A, Sashidaran S, Smith E, et al. Predictive factors of severe radiation-induced lymphopenia in proton-treated patients. Radiotherapy and Oncology. 2022 May;170:S51-S3. PubMed PMID: WOS:000806759200051.