% 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{Diefenhardt:299579,
      author       = {M. Diefenhardt and R. Kosmala and M. Fleischmann and D.
                      Martin$^*$ and R.-D. Hofheinz and M. Ghadimi and C.
                      Rödel$^*$ and B. Polat and E. Fokas},
      title        = {{C}hemotherapy before or after preoperative
                      chemoradiotherapy and surgery for locally advanced rectal
                      cancer: 5-year results of the {CAO}/{ARO}/{AIO}-12 trial - a
                      general pairwise comparison.},
      journal      = {ESMO open},
      volume       = {10},
      number       = {3},
      issn         = {2059-7029},
      address      = {[London]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00520},
      pages        = {104483},
      year         = {2025},
      abstract     = {Total neoadjuvant treatment (TNT) has been increasingly
                      adopted for multimodal rectal cancer treatment. Here, we
                      present the 5-year results of our CAO/ARO/AIO-12 randomized
                      phase II trial that compared two TNT sequences.Patients were
                      initially randomized 1 : 1 to arm A (induction chemotherapy
                      followed by chemoradiotherapy) or arm B (chemoradiotherapy
                      followed by consolidation chemotherapy) followed by total
                      mesorectal excision surgery. This report on the 5-year
                      results involved a general pairwise comparison (GPC) of the
                      following parameters, ranked as indicated: overall survival,
                      incidence of locoregional recurrence, incidence of distant
                      metastasis, rate of pathological/clinical complete
                      remission, long-term quality of life (at least 24 months
                      after randomization) based on global health assessed by the
                      European Organisation For Research And Treatment Of Cancer
                      Quality of Life Questionnaire Core 30 questionnaire, and
                      incidence of toxicity, ranked by grade, during follow-up.A
                      total of 306 patients were eligible for this analysis. After
                      a median follow-up of 60 months (interquartile range 58-62
                      months), we found that long-term oncological outcome was
                      comparable in both arms [e.g. 5-year overall survival
                      $85.8\%$ $(95\%$ confidence interval $80.2\%$ to $91.8\%)$
                      in arm A and $84.2\%$ $(95\%$ confidence interval $78.2\%$
                      to $90.5\%)$ in arm B], regardless of whether patients
                      received induction chemotherapy and chemoradiotherapy or
                      chemoradiotherapy and consolidation chemotherapy. The GPC
                      showed no clinically meaningful overall treatment benefit
                      $(-1.38\%)$ or win ratio difference (0.97) between the two
                      treatment sequences. The incidence of pathological or
                      sustained clinical complete remission remained higher in
                      patients treated with consolidation chemotherapy after
                      adjusting for long-term outcome between both arms $(11\%$
                      versus $6.5\%).Our$ 5-year GPC confirmed the 3-year findings
                      that chemoradiotherapy followed by consolidation
                      chemotherapy resulted in higher rates of pathological
                      complete remission without compromising oncological outcome,
                      toxicity, or quality of life. The TNT sequence
                      chemoradiotherapy/chemotherapy may be preferred for organ
                      preservation strategies.},
      keywords     = {clinical trial (Other) / general pairwise comparison
                      (Other) / radiotherapy (Other) / rectal cancer (Other) /
                      total neoadjuvant treatment (Other)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40056849},
      doi          = {10.1016/j.esmoop.2025.104483},
      url          = {https://inrepo02.dkfz.de/record/299579},
}