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Dosimetric predictors of treatment-related lymphopenia induced by palliative radiotherapy: predictive ability of dose-volume parameters based on body surface contour

Tetsuo Saito
Tetsuo Saito
, 
Ryo Toya
Ryo Toya
, 
Tomohiko Matsuyama
Tomohiko Matsuyama
, 
Akiko Semba
Akiko Semba
 and 
Natsuo Oya
Natsuo Oya
   | Oct 13, 2016
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Article Category: Research Articles
Published Online: Oct 13, 2016
Page range: 228 - 234
Received: Jul 18, 2016
Accepted: Aug 30, 2016
DOI: https://doi.org/10.1515/raon-2016-0050
© 2017 Tetsuo Saito, Ryo Toya, Tomohiko Matsuyama, Akiko Semba, Natsuo Oya
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Delineation of the three organs at risk. Body A is the volume enclosed by the body surface contour. Body B excludes air, pleural effusion, ascites, bile, urine, and the intestinal content. BM = bone marrow.
Delineation of the three organs at risk. Body A is the volume enclosed by the body surface contour. Body B excludes air, pleural effusion, ascites, bile, urine, and the intestinal content. BM = bone marrow.

Overall survival according to the grade of radiationrelated lymphopenia.CI = confidence interval.
Overall survival according to the grade of radiationrelated lymphopenia.CI = confidence interval.

Patient and treatment characteristics (n = 54)

CharacteristicNo. of patients%
Patient characteristics
Male gender3361
Age (years)
 Median69
Range39-86
Primary tumor
 Lung1426
 Gastrointestinal917
 Skin47
 Liver36
 Uterus36
 Others

Others include head and neck (3 patients), breast (3 patients), mediastinal (3 patients), urogenita (8 patients), and soft tissue (4 patients) tumors;

2139
Previous radiotherapy1528
Previous chemotherapy2648
Concurrent steroid use2343
Bone metastasis2750
Brain metastasis1120
Interval from tumor diagnosis to radiotherapy (months)
 Median13
 Range0-168
Pre-radiotherapy absolute lymphocyte count (× 106/L)
 Median1356
 Range844-3468
Treatment characteristics
Total radiation dose (Gy)
 Median30
 Range16-50
Number of fractions
 Median10
 Range4-25
Fraction size (Gy)
 Median3
 Range2-5
Total monitor units for all fractions
 Median4433
 Range1896–13890
Total irradiation time for all fractions (minutes)
 Median7.5
 Range3.2-37.7
Treatment site
 Head and neck1426
 Chest2444
 Abdomen1019
 Pelvis1120
 Limb12
Splenic irradiation

Yes, if any part of the spleen was covered by the 5 Gy idodose line;

917
Thymic irradiation

Yes, if any part of the thymus was covered by the 5 Gy idodose line.

1528

Univariate logistic regression analysis for lymphopenia of grade 3 or higher

VariableOR95% CIp-value
Patient characteristics
Male vs. female1.390.46–4.220.55
Age (per 1 year increase)0.990.94–1.030.53
Previous radiotherapy (yes vs. no)1.020.30–3.470.98
Previous chemotherapy (yes vs. no)0.530.18–1.580.26
Concurrent steroid use (yes vs. no)1.070.36–3.170.91
Bone metastasis (yes vs. no)0.860.29–2.530.78
Brain metastasis (yes vs. no)0.720.18–2.840.64
Interval from tumor diagnosis to radiotherapy (per 1 month increase)1.000.99–1.020.81
Pre-radiotherapy absolute lymphocyte count (per increase of 1 × 106/l)0.990.99–1.000.23
Treatment characteristics
Total radiation dose (per 1-Gy increase)1.060.99–1.140.11
Number of fractions (per 1-fraction increase)1.181.01–1.380.036
Total monitor units over the entire treatment
course (per increase of 100 monitor units)1.010.99–1.030.29
Total irradiation time over the entire treatment course (per 1-minute increase)0.990.92–1.080.91
Splenic irradiation (yes vs. no)

Yes, if any part of the spleen was covered by the 5 Gy idodose line

6.341.18–34.240.032
Thymic irradiation (yes vs. no)

Yes, if any part of the thymus was covered by the 5 Gy idodose line.

0.580.17–2.030.39
Body A V5 (per 1 × 103 mL increase)1.551.06–2.260.025
Body A V10 (per 1 × 103 mL increase)1.601.04–2.450.032
Body A V20 (per 1 × 103 mL increase)1.600.96–2.680.074
Body A V30 (per 1 × 103 mL increase)1.870.95–3.680.069
Body B V5 (per 1 × 103 mL increase)1.581.05–2.380.027
Body B V10 (per 1 × 103 mL increase)1.631.04–2.560.035
Body B V20 (per 1 × 103 mL increase)1.590.94–2.720.087
Body B V30 (per 1 × 103 mL increase)1.840.93–3.670.082
BM V5 (per 1 × 103 mL increase)3.620.37–35.360.27
BM V10 (per 1 × 103 mL increase)2.880.27–31.100.38
BM V20 (per 1 × 103 mL increase)1.780.15–20.920.65
BM V30 (per 1 × 103 mL increase)4.730.19–115.780.34

Multivariate logistic regression analysis for lymphopenia of grade 3 or higher

VariableOR95% CIp-value
Body A V5 (per 1 × 103 mL increase)1.581.03–2.420.036
Number of fractions (per 1-fraction increase)1.261.03–1.530.027
Splenic irradiation (yes vs. no)

Yes, if any part of the spleen was covered by the 5 Gy idodose line; Factors with p < 0.05 by univariate analysis (number of fractions and splenic irradiation) were taken into account to test the indep

5.120.74–35.280.098
Body A V10 (per 1 × 103 mL increase)1.681.04–2.700.034
Number of fractions (per 1-fraction increase)1.261.03–1.550.026
Splenic irradiation (yes vs. no)

Yes, if any part of the spleen was covered by the 5 Gy idodose line; Factors with p < 0.05 by univariate analysis (number of fractions and splenic irradiation) were taken into account to test the indep

5.250.77–35.760.090
Body B V5 (per 1 × 103 mL increase)1.631.03–2.570.038
Number of fractions (per 1-fraction increase)1.251.03–1.530.028
Splenic irradiation (yes vs. no)

Yes, if any part of the spleen was covered by the 5 Gy idodose line; Factors with p < 0.05 by univariate analysis (number of fractions and splenic irradiation) were taken into account to test the indep

5.460.79–37.530.085
Body B V10 (per 1 × 103 mL increase)1.721.04–2.870.036
Number of fractions (per 1-fraction increase)1.261.03–1.550.027
Splenic irradiation (yes vs. no)

Yes, if any part of the spleen was covered by the 5 Gy idodose line; Factors with p < 0.05 by univariate analysis (number of fractions and splenic irradiation) were taken into account to test the indep

5.590.82–37.990.078

Spearman correlation coefficients between the dose-volume parameters and the nadir lymphocyte count

Nadir lymphocyte count
Absolute lymphocyte count at nadirLymphocyte count ratio

The lymphocyte count ratio was calculated by dividing the nadir absolute lymphocyte count by the pre-radiotherapy absolute lymphocyte count.

VariableSpearman’s rhop-valueSpearman’s rhop-value
Body A V5-0.2650.053-0.3500.010
Body A V10-0.2830.038-0.3670.006
Body A V20-0.2310.093-0.2550.063
Body A V30-0.3050.025-0.2810.039
Body B V5-0.2740.045-0.3470.010
Body B V10-0.2800.040-0.3520.009
Body B V20-0.2360.086-0.2600.057
Body B V30-0.3020.027-0.2800.041
BM V5-0.1520.27-0.2100.13
BM V10-0.1610.25-0.2070.13
BM V20-0.1350.33-0.1610.25
BM V30-0.1680.23-0.1850.18
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