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Title: Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

Abstract

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20more » (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less

Authors:
;  [1];  [2]; ; ; ;  [1];  [3];  [3];  [4];  [3]; ;  [5]; ; ;  [6];  [1];  [2];  [1];  [1]
  1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  3. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  4. (United States)
  5. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  6. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
Publication Date:
OSTI Identifier:
22645770
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; GY RANGE 01-10; GY RANGE 10-100; LYMPHOPENIA; MULTIVARIATE ANALYSIS; NEOPLASMS; PANCREAS; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.046.
Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, & Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?. United States. doi:10.1016/J.IJROBP.2016.10.046.
Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Wed . "Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?". United States. doi:10.1016/J.IJROBP.2016.10.046.
@article{osti_22645770,
title = {Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?},
author = {Chadha, Awalpreet S. and Liu, Guan and Chen, Hsiang-Chun and Das, Prajnan and Minsky, Bruce D. and Mahmood, Usama and Delclos, Marc E. and Suh, Yelin and Sawakuchi, Gabriel O. and Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas and Beddar, Sam and Katz, Matthew H. and Fleming, Jason B. and Javle, Milind M. and Varadhachary, Gauri R. and Wolff, Robert A. and Crane, Christopher H. and Wang, Xuemei and Thames, Howard and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org},
abstractNote = {Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.},
doi = {10.1016/J.IJROBP.2016.10.046},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}