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. 2017 Feb 1;97(2):323-332.
doi: 10.1016/j.ijrobp.2016.10.046. Epub 2016 Nov 8.

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

Awalpreet S Chadha  1 , Guan Liu  1 , Hsiang-Chun Chen  2 , Prajnan Das  1 , Bruce D Minsky  1 , Usama Mahmood  1 , Marc E Delclos  1 , Yelin Suh  3 , Gabriel O Sawakuchi  4 , Sam Beddar  3 , Matthew H Katz  5 , Jason B Fleming  5 , Milind M Javle  6 , Gauri R Varadhachary  6 , Robert A Wolff  6 , Christopher H Crane  1 , Xuemei Wang  2 , Howard Thames  1 , Sunil Krishnan  7
Affiliations

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

Awalpreet S Chadha et al. Int J Radiat Oncol Biol Phys. .

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 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.

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Comment in

  • In Regard to Chadha et al.
    Yazici G, Sari SY, Cengiz M. Yazici G, et al. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):484-485. doi: 10.1016/j.ijrobp.2017.02.025. Int J Radiat Oncol Biol Phys. 2017. PMID: 28463173 No abstract available.
  • In Reply to Yazici et al.
    Chadha AS, Suh Y, Krishnan S. Chadha AS, et al. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):485-486. doi: 10.1016/j.ijrobp.2017.02.029. Int J Radiat Oncol Biol Phys. 2017. PMID: 28463175 No abstract available.

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