Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 1;47(8):373-382.
doi: 10.1097/COC.0000000000001108. Epub 2024 May 20.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma

Grace Lee  1 , Daniel W Kim  2 , Alicia C Smart  1 , Nora K Horick  3 , Christine E Eyler  4 , Hannah J Roberts  1 , Priyadarshini Pathak  5 , Lipika Goyal  6 , Joseph Franses  7 , James M Heather  8 , William L Hwang  1 , Clemens Grassberger  9 , Samuel J Klempner  5 , Lorraine C Drapek  1 , Jill N Allen  5 , Lawrence S Blaszkowsky  5 , Aparna R Parikh  5 , David P Ryan  5 , Jeffrey W Clark  5 , Theodore S Hong  1 , Jennifer Y Wo  1
Affiliations

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma

Grace Lee et al. Am J Clin Oncol. .

Abstract

Objective: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT).

Methods: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT.

Results: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia.

Conclusions: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Overall survival stratified by (A) severe lymphopenia (absolute lymphocyte count <0.5 k/μl) and (B) Grade 4 lymphopenia (absolute lymphocyte count <0.2 k/μl) within 12 weeks of initiating radiotherapy
Figure 1.
Figure 1.
Overall survival stratified by (A) severe lymphopenia (absolute lymphocyte count <0.5 k/μl) and (B) Grade 4 lymphopenia (absolute lymphocyte count <0.2 k/μl) within 12 weeks of initiating radiotherapy
See this image and copyright information in PMC

References

    1. Altekruse SF, Devesa SS, Dickie LA, McGlynn KA, Kleiner DE. Histological classification of liver and intrahepatic bile duct cancers in SEER registries. J Registry Manag. 2011;38(4):201–205. - PMC - PubMed
    1. Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis. 1994;14(2):109–114. doi: 10.1055/s-2007-1007302 - DOI - PubMed
    1. Chou FF, Sheen-Chen SM, Chen YS, Chen MC, Chen CL. Surgical treatment of cholangiocarcinoma. Hepatogastroenterology. 1997;44(15):760–765. - PubMed
    1. Shinohara ET, Mitra N, Guo M, Metz JM. Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys. 2008;72(5):1495–1501. doi: 10.1016/j.ijrobp.2008.03.018 - DOI - PubMed
    1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–1281. doi: 10.1056/NEJMoa0908721 - DOI - PubMed