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@ARTICLE{Mock:148366,
author = {A. Mock$^*$ and C. E. Heilig$^*$ and S. Kreutzfeldt$^*$ and
D. Huebschmann$^*$ and C. Heining$^*$ and E. Schröck$^*$
and B. Brors$^*$ and A. Stenzinger$^*$ and D. Jäger$^*$ and
R. Schlenk$^*$ and H. Glimm$^*$ and S. Fröhling$^*$ and P.
Horak$^*$ and L. Apostolidis and M. Augustin and D. Aust and
I. A. Bhatti and J. Bloehdorn and C. Brendel and C.
Britschgi and J. Braess and S. Burdach and E. Busch and J.
Casuscelli and A. Desuki and T. Deutsch and M. Dietrich and
U. Ehmer and T. J. Ettrich and J. Falkenhorst and T. Fehm
and A. Flörcken and A. Forschner and S. Fuxius and M.
Gonzales-Carmona and F. Griesinger and S. Grill and S.
Gröschel and G. M. Haag and U. Haag and N. Halama and H.
Hebart and N. Heidger and B. Hermes and G. Hess and S.
Hettmer and M. Hoechstetter and M. Hoffmann and F. J.
Hüttner and A. L. Illert and M. Jenzer and B. Kasper and S.
Kasper-Virchow and T. Kindler and E. Koscielniak and J.
Krönke and M. Kühn and V. Kunzmann and A. Lang and J.
Leichsenring and E. Livingstone and L. Liotta and K. Luley
and E. Mack and U. M. Martens and K. Metzeler and J. M.
Middeke and L. Möhrmann and R. Jayarama-Naidu and U.-F.
Pape and L. Perkhofer and A. Pfeufer and C. Pixberg and M.
Quante and B. Rendenbach and D. Rieke and C. Rothermundt and
A. N. Sagerer and M. Salzmann and D. Saur and B. Schilling
and J. Schleicher and A. Schlenska-Lange and T. Schmidt and
S. Schmitz and S. Schölch and R. Shah and K. Shoumariyeh
and A. Siebenhüner and M. Singh and J. Siveke and C.
Springfeld and H. Starke and S. Strobel and V. Teleanu and
N. Thon and S. Wagner and T. Walle and B. Westphalen and B.
Whitlock and E. Winkler and N. M. Wirsik and L. Woydack and
A. Z. Bois and S. Zschäbitz},
collaboration = {D. M. Network},
title = {{C}ommunity-driven development of a modified
progression-free survival ratio for precision oncology.},
journal = {ESMO open},
volume = {4},
number = {6},
issn = {2059-7029},
address = {London},
publisher = {BMJ},
reportid = {DKFZ-2019-02922},
pages = {e000583},
year = {2019},
abstract = {Measuring the success of molecularly guided therapies is a
major challenge in precision oncology trials. A commonly
used endpoint is an intra-patient progression-free survival
(PFS) ratio, defined as the PFS interval associated with
molecularly guided therapy (PFS2) divided by the PFS
interval associated with the last prior systemic therapy
(PFS1), above 1.3 or, in some studies, above 1.33 or 1.5.To
investigate if the concept of PFS ratios is in agreement
with actual response evaluations by physicians, we conducted
a survey among members of the MASTER (Molecularly Aided
Stratification for Tumor Eradication Research) Programme of
the German Cancer Consortium who were asked to classify the
success of molecularly guided therapies in 194 patients
enrolled in the MOSCATO 01 trial based on PFS1 and PFS2
times.A comparison of classification profiles revealed three
distinct clusters of PFS benefit assessments. Only $29\%$ of
assessments were consistent with a PFS ratio threshold of
1.3, whereas the remaining $71\%$ of participants applied a
different classification scheme that did not rely on the
relation between PFS times alone, but also took into account
absolute PFS1 intervals. Based on these community-driven
insights, we developed a modified PFS ratio that
incorporates the influence of absolute PFS1 intervals on the
judgement of clinical benefit by physicians. Application of
the modified PFS ratio to outcome data from two recent
precision oncology trials, MOSCATO 01 and WINTHER, revealed
significantly improved concordance with physician-perceived
clinical benefit and identified comparable proportions of
patients who benefited from molecularly guided therapies.The
modified PFS ratio may represent a meaningful clinical
endpoint that could aid in the design and interpretation of
future precision oncology trials.},
cin = {B340 / L101 / V960 / L301 / D120 / B330},
ddc = {610},
cid = {I:(DE-He78)B340-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)V960-20160331 / I:(DE-He78)L301-20160331 /
I:(DE-He78)D120-20160331 / I:(DE-He78)B330-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31798980},
pmc = {pmc:PMC6863673},
doi = {10.1136/esmoopen-2019-000583},
url = {https://inrepo02.dkfz.de/record/148366},
}