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@ARTICLE{Veldwijk:142878,
      author       = {M. R. Veldwijk and P. Seibold$^*$ and A. Botma$^*$ and I.
                      Helmbold$^*$ and E. Sperk and F. A. Giordano and N. Gürth
                      and A. Kirchner and S. Behrens and F. Wenz and J.
                      Chang-Claude$^*$ and C. Herskind},
      title        = {{A}ssociation of {CD}4+ {R}adiation-{I}nduced {L}ymphocyte
                      {A}poptosis with {F}ibrosis and {T}elangiectasia after
                      {R}adiotherapy in 272 {B}reast {C}ancer {P}atients with
                      $\>10-{Y}ear$ {F}ollow-up.},
      journal      = {Clinical cancer research},
      volume       = {25},
      number       = {2},
      issn         = {1557-3265},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2019-00508},
      pages        = {562 - 572},
      year         = {2019},
      abstract     = {Radiation-induced lymphocyte apoptosis (RILA) has been
                      suggested as a predictive assay for adverse late reactions
                      after radiotherapy. Thus, low RILA values of T-lymphocyte
                      subpopulations have been associated with increased risk for
                      various endpoints at 2 to 3 years of follow-up. The purpose
                      was to test if such associations persist for specific
                      endpoints (subcutaneous fibrosis, telangiectasia) in breast
                      cancer patients with at least 10 years of
                      follow-up.Experimental Design: Two hundred and seventy-two
                      female patients who had received breast-conserving therapy
                      within the German ISE study were included (median follow-up:
                      11.6 years). Radiotherapy-induced side effects were scored
                      according to the Late Effects in Normal Tissues-Subjective,
                      Objective, Management, and Analytic (LENT-SOMA)
                      classification system. RILA in the CD4+, CD8+, and natural
                      killer (NK) subpopulations from peripheral blood was
                      analyzed by flow cytometry. Multivariate predictive modeling
                      was performed including relevant clinical risk factors.Low
                      CD4+ RILA was associated with increased risk for both
                      fibrosis (P = 0.011) and telangiectasia (P < 0.001). For
                      fibrosis, the association was stronger outside the surgical
                      area (Fibout; P = 0.004) than within (Fibin; P = 0.17).
                      Predictive multivariate modeling including clinical risk
                      factors yielded OR of 3.48 $(95\%$ confidence interval,
                      1.84-6.58) for any fibrosis and 8.60 (2.71-27.3) for
                      telangiectasia. Addition of CD4+ RILA to the clinical
                      variables improved discrimination (c statistics) from 0.62
                      to 0.68 for any fibrosis, 0.62 to 0.66 for Fibin, 0.61 to
                      0.69 for Fibout, and from 0.65 to 0.76 for telangiectasia.
                      CD8+ and NK RILA were not significantly associated with
                      radiotherapy-related late reactions.The results provide
                      first evidence that low CD4+ RILA is associated with
                      increased subcutaneous fibrosis and telangiectasia even
                      after 10 years. This supports the potential usefulness for
                      predicting individual clinical risk.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30327309},
      doi          = {10.1158/1078-0432.CCR-18-0777},
      url          = {https://inrepo02.dkfz.de/record/142878},
}