% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Nicolay:177233,
      author       = {N. Nicolay$^*$ and A. Rühle$^*$ and M. Mix and N.
                      Wiedenmann$^*$ and R. G. Stoian$^*$ and G. Niedermann$^*$
                      and D. Baltas$^*$ and M. Werner$^*$ and B. Ruf$^*$ and G.
                      Kayser$^*$ and A. Grosu$^*$},
      title        = {{D}evelopment of a {H}ypoxia-{I}mmune {P}rognostic
                      {C}lassifier for {H}ead-and-{N}eck {C}ancer {P}atients
                      {U}ndergoing {R}adiotherapy - {R}esults {F}rom a
                      {P}rospective {I}maging {T}rial.},
      journal      = {International journal of radiation oncology, biology,
                      physics},
      volume       = {111},
      number       = {3S},
      issn         = {0360-3016},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2021-02367},
      pages        = {S63 - S64},
      year         = {2021},
      note         = {#EA:E050#},
      abstract     = {Tumor-infiltrating lymphocytes (TILs) correlate with an
                      improved outcome of head-and-neck squamous cell cancer
                      (HNSCC) patients undergoing radiotherapy and are influenced
                      by the tumor microenvironment and tumor-associated hypoxia.
                      The present analysis is based on a prospective imaging trial
                      and analyzes the value of TILs and tumor-associated hypoxia
                      to stratify HNSCC patients according to their response to
                      radiotherapy.A total of 49 patients with locoregionally
                      advanced HNSCCs were prospectively enrolled in this trial
                      and underwent longitudinal hypoxia PET imaging using
                      fluoro-18 misonidazole ([18F]FMISO) in weeks 0, 2 and 5
                      during chemoradiation. Tumor hypoxia was assumed for a
                      tumor-to-background SUV (contralateral sternocleidomastoid
                      muscle) exceeding 1.4, and an early hypoxia response was
                      defined as a decrease in the normalized maximum intratumoral
                      SUV (FMISO-SUVindex) between weeks 0 and 2. Pre-treatment
                      tumor biopsies were analyzed for TILs and the hypoxia tissue
                      marker carbonic anhydrase IX (CAIX). Trial patients were
                      stratified into 4 subgroups based on their TIL numbers (>
                      100 vs. < 100 TILs/HPF) and expression of CAIX (above vs.
                      below median H-score), and locoregional control (LRC) and
                      progression-free survival (PFS) rates for all subgroups were
                      assessed using Cox and subsequent concordance analyses
                      (Harrell's C).High TIL levels correlated with improved LRC
                      (HR = 0.279, P = 0.011) and PFS (HR = 0.276, P = 0.006).
                      Similarly, a decrease in the FMISO-SUVindex within the first
                      2 weeks of treatment corresponded with better LRC (HR =
                      0.321, P = 0.015) and PFS (HR = 0.402, P = 0.043). Harrell's
                      C was 0.68, when TILs and early hypoxia PET response were
                      combined. The hypoxia PET-based hypoxia-immune classifier
                      separated 3 distinct prognostic patient subgroups, a
                      favorable (TILhigh/ early PET response), and intermediate
                      (TILhigh/no early PET response or TILlow/early PET response)
                      and a poor (TILlow/no early PET response) prognostic group
                      with 2-year LRC of $71\%,$ $33\%$ and $0\%,$ respectively.
                      Low pre-treatment tissue levels of CAIX were also prognostic
                      for improved LRC (HR = 0.352, P = 0.050) but not PFS (HR =
                      0,468, P = 0,087). Harrell's C was 0.66 for CAIX and TILs
                      separately and 0.71 for the combination. The
                      immunohistochemistry-based immune-hypoxia classifier
                      similarly stratified between a favorable (CAIXlow/TILhigh),
                      an intermediate (CAIXlow/TILlow or CAIXhigh/TILhigh) and a
                      poor (CAIXhigh/TILlow) subgroup with 2-year LRC rates of
                      $73\%,$ $62\%$ and $11\%,$ respectively.We developed a
                      hypoxia PET-based hypoxia-immune classifier that was able to
                      separate HNSCC patients into 3 distinct prognostic subgroups
                      based on their tumor biology. These subgroups could also be
                      stratified in a clinically feasible,
                      immunohistochemistry-based classifier with comparable model
                      accuracy. Therefore, this hypoxia-immune classifier could
                      help to stratify prognoses of HNSCC patients undergoing
                      radiotherapy pending validation in an external cohort.},
      cin          = {FR01 / E055},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331 / I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34700599},
      doi          = {10.1016/j.ijrobp.2021.07.160},
      url          = {https://inrepo02.dkfz.de/record/177233},
}