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Immunologic Consequences of Sequencing Cancer Radiotherapy and Surgery.
López Alfonso, Juan Carlos Poleszczuk, Jan Walker, Rachel Kim, Sungjune Pilon-Thomas, Shari Conejo-Garcia, Jose J Soliman, Hatem Czerniecki, Brian Harrison, Louis B Enderling, Heiko
López Alfonso, Juan Carlos
Poleszczuk, Jan
Walker, Rachel
Kim, Sungjune
Pilon-Thomas, Shari
Conejo-Garcia, Jose J
Soliman, Hatem
Czerniecki, Brian
Harrison, Louis B
Enderling, Heiko
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2019-01-01
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Abstract
PURPOSE Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy
before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and diseasefree survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced
antitumor immunity contributing to outcomes.
MATERIALS AND METHODS We analyzed a SEER data set of early-stage cancers treated with SR or RS. OS and
DFS were calculated for cancers with sufficient numbers for statistical power (cancers of lung and bronchus,
esophagus, rectum, cervix uteri, corpus uteri, and breast). We simulated the immunologic consequences of SR,
RS, and radiotherapy alone in a mathematical model of tumor-immune interactions.
RESULTS RS improved OS for cancers with low 20-year survival rates (lung: hazard ratio [HR], 0.88; P = .046)
and improved DFS for cancers with higher survival (breast: HR = 0.64; P , .001). For rectal cancer, with
intermediate 20-year survival, RS improved both OS (HR = 0.89; P = .006) and DFS (HR = 0.86; P = .04).
Model simulations suggested that RS could increase OS by eliminating cancer for a broader range of model
parameters and radiotherapy-induced antitumor immunity compared with SR for selected parameter
combinations. This could create an immune memory that may explain increased DFS after RS for certain
cancers.
CONCLUSION Study results suggest plausibility that radiation to the bulk of the tumor could induce a more robust
immune response and better harness the synergy of radiotherapy and antitumor immunity than postsurgical
radiation to the tumor bed. This exploratory study provides motivation for prospective evaluation of immune
activation of RS versus SR in controlled clinical studies
Citation
JCO Clin Cancer Inform. 2019 Apr;3:1-16. doi: 10.1200/CCI.18.00075.
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en
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2473-4276
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Attribution-NonCommercial-ShareAlike 4.0 International