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@ARTICLE{Trautwein:277115,
      author       = {N. F. Trautwein and J. Schwenck and J. Jacoby and G.
                      Reischl and F. Fiz and L. Zender$^*$ and H. Dittmann and M.
                      Hinterleitner and C. la Fougère$^*$},
      title        = {{L}ong-term prognostic factors for {PRRT} in neuroendocrine
                      tumors.},
      journal      = {Frontiers in medicine},
      volume       = {10},
      issn         = {2296-858X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01280},
      pages        = {1169970},
      year         = {2023},
      abstract     = {Peptide receptor radionuclide therapy (PRRT) is an
                      effective and well-tolerated treatment option for patients
                      with neuroendocrine tumors (NETs) that prolongs
                      progression-free survival (PFS). However, the limited
                      overall survival (OS) rates in the prospective phase III
                      study (NETTER1) highlighted the need to identify
                      patient-specific long-term prognostic markers to avoid
                      unnecessary side effects and enable better treatment
                      stratification. Therefore, we retrospectively analyzed
                      prognostic risk factors in NET patients treated with PRRT.A
                      total of 62 NET patients (G1: $33.9\%,$ G2 $62.9\%,$ and G3
                      $3.2\%)$ with at least 2 cycles of PRRT with
                      [177Lu]Lu-HA-DOTATATE (mean 4 cycles) were analyzed. Of
                      which, 53 patients had primary tumors in the
                      gastroenteropancreatic (GEP) system, 6 had bronchopulmonary
                      NET, and 3 had NET of unknown origin. [68Ga]Ga-HA-DOTATATE
                      PET/CT scans were performed before PRRT start and after the
                      second treatment cycle. Different clinical laboratory
                      parameters, as well as PET parameters, such as SUVmean,
                      SUVmax, and PET-based molecular tumor volume (MTV), were
                      collected, and their impact on the OS was investigated.
                      Patient data with a mean follow-up of 62 months (range
                      20-105) were analyzed.According to interim PET/CT, 16
                      patients $(25.8\%)$ presented with partial response (PR), 38
                      $(61.2\%)$ with stable disease (SD), and 7 $(11.3\%)$ with
                      progressive disease (PD). The 5-year OS was $61.8\%$ for all
                      patients, while bronchopulmonary NETs showed poorer OS than
                      GEP-NETs. Multivariable Cox regression analysis showed that
                      chromogranin A level and MTV together were highly
                      significant predictors of therapeutic outcome (HR 2.67;
                      $95\%$ CI 1.41-4.91; p = 0.002). Treatment response was also
                      influenced by the LDH level (HR 0.98; $95\%$ CI 0.9-1.0; p =
                      0.007) and patient age (HR 1.15; $95\%$ CI 1.08-1.23; p <
                      0.001). ROC analysis revealed baseline MTV > 112.5 ml [Sens.
                      $91\%;$ Spec. $50\%;$ AUC 0.67 $(95\%$ CI 0.51-0.84, p =
                      0.043)] and chromogranin A >1,250.75 μg/l [Sens. $87\%;$
                      Spec. $56\%;$ AUC 0.73 $(95\%$ CI 0.57-0.88, p = 0.009)] as
                      the best cutoff values for identifying patients with worse
                      5-year survival.Our retrospective analysis defined MTV and
                      chromogranin A in combination as significant prognostic
                      factors for long-term OS. Furthermore, an interim PET/CT
                      after two cycles has the potential in identifying
                      non-responders who may benefit from a change in therapy at
                      an early stage.},
      keywords     = {177Lu (Other) / DOTA-TATE (Other) / Ga-HA-DOTATATE (Other)
                      / molecular tumor volume (Other) / neuroendocrine tumor
                      (NET) (Other) / peptide receptor radionuclide therapy (PRRT)
                      (Other)},
      cin          = {TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37359009},
      pmc          = {pmc:PMC10288842},
      doi          = {10.3389/fmed.2023.1169970},
      url          = {https://inrepo02.dkfz.de/record/277115},
}