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@ARTICLE{Diefenhardt:285065,
      author       = {M. Diefenhardt and D. Martin and M. Fleischmann and R.-D.
                      Hofheinz and M. Ghadimi and C. Rödel$^*$ and E. Fokas$^*$},
      title        = {{O}verall {S}urvival {A}fter {T}reatment {F}ailure {A}mong
                      {P}atients {W}ith {R}ectal {C}ancer.},
      journal      = {JAMA network open},
      volume       = {6},
      number       = {10},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DKFZ-2023-02208},
      pages        = {e2340256 -},
      year         = {2023},
      abstract     = {Oncologic outcomes among patients with rectal cancer after
                      developing local recurrence and/or distant metastases remain
                      poorly studied.To analyze the trend of overall survival
                      after treatment failure for patients with rectal cancer
                      within three consecutive phase 2 or 3 trials of the German
                      Rectal Cancer Study Group.This cohort study is a post hoc
                      analysis of 3 randomized phase 2 or 3 trials
                      (CAO/ARO/AIO-94, -04, and -12 trials, conducted in Germany)
                      that included 1948 patients with locally advanced rectal
                      adenocarcinoma. The CAO/ARO/AIO-94 trial recruited patients
                      between February 1995 and September 2002, the CAO/ARO/AIO-04
                      trial recruited patients between July 2006 and February
                      2010, and the CAO/ARO/AIO-12 trial recruited patients
                      between June 2015 and January 2018. Statistical analysis was
                      conducted between September 2022 and March 2023.A total of
                      119 of 391 patients in the CAO/ARO/AIO-94 trial group A, 295
                      of 1236 patients in the CAO/ARO/AIO-04 trial, and 69 of 306
                      in the CAO/ARO/AIO-12 trial experienced treatment failure
                      (R2 resection or local recurrence or distant metastases) and
                      were included in further analyses.Characteristics of
                      treatment failure and overall survival were assessed in all
                      3 trial cohorts.Of the 1948 patients treated in the 3
                      trials, 15 were excluded because of missing data. Of the
                      remaining 1933 patients (median age, 62.5 years [range,
                      19-84 years]; 1363 men $[71\%]$ and 570 women $[29\%])$ with
                      locally advanced rectal adenocarcinoma (cT3 or 4 or cN+)
                      treated within 3 consecutive clinical trials, 483
                      experienced treatment failure and were analyzed. After a
                      median follow-up of 36 months (IQR, 24-51 months) for all
                      patients, overall survival after treatment failure was
                      significantly improved in the CAO/ARO/AIO-04 trial (at 3
                      years, $44\%$ [IQR, $37\%-51\%];$ hazard ratio [HR], 0.61
                      $[95\%$ CI, 0.47-0.79]) and further improved in the
                      CAO/ARO/AIO-12 trial (at 3 years, $73\%$ [IQR, $60\%-87\%];$
                      HR, 0.32 $[95\%$ CI, 0.18-0.54]) compared with the
                      CAO/ARO/AIO-94 trial (at 3 years, $30\%$ [IQR, $22\%-39\%])$
                      (both P < .001). Distant metastasis was the main reason for
                      treatment failure throughout a 5-year follow-up (range,
                      $67\%-87\%),$ and the relative risk for treatment failure
                      was highest in the first 18 months in all 3 trials. ypTNM
                      stage was significantly associated with the risk and time
                      interval to treatment failure. Improvement in overall
                      survival after treatment failure was independent of sex.This
                      cohort study suggests that advancements in salvage
                      strategies during the past decades have likely improved
                      overall survival among patients with rectal cancer who
                      experienced treatment failure.},
      keywords     = {Male / Humans / Female / Middle Aged / Cohort Studies /
                      Germany / Rectal Neoplasms: therapy / Treatment Failure /
                      Adenocarcinoma: therapy},
      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:37902752},
      doi          = {10.1001/jamanetworkopen.2023.40256},
      url          = {https://inrepo02.dkfz.de/record/285065},
}