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000148366 1001_ $$0P:(DE-He78)8f7c3bc1451193551c2458d93222536a$$aMock, Andreas$$b0$$eFirst author
000148366 245__ $$aCommunity-driven development of a modified progression-free survival ratio for precision oncology.
000148366 260__ $$aLondon$$bBMJ$$c2019
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000148366 520__ $$aMeasuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint is an intra-patient progression-free survival (PFS) ratio, defined as the PFS interval associated with molecularly guided therapy (PFS2) divided by the PFS interval associated with the last prior systemic therapy (PFS1), above 1.3 or, in some studies, above 1.33 or 1.5.To investigate if the concept of PFS ratios is in agreement with actual response evaluations by physicians, we conducted a survey among members of the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Programme of the German Cancer Consortium who were asked to classify the success of molecularly guided therapies in 194 patients enrolled in the MOSCATO 01 trial based on PFS1 and PFS2 times.A comparison of classification profiles revealed three distinct clusters of PFS benefit assessments. Only 29% of assessments were consistent with a PFS ratio threshold of 1.3, whereas the remaining 71% of participants applied a different classification scheme that did not rely on the relation between PFS times alone, but also took into account absolute PFS1 intervals. Based on these community-driven insights, we developed a modified PFS ratio that incorporates the influence of absolute PFS1 intervals on the judgement of clinical benefit by physicians. Application of the modified PFS ratio to outcome data from two recent precision oncology trials, MOSCATO 01 and WINTHER, revealed significantly improved concordance with physician-perceived clinical benefit and identified comparable proportions of patients who benefited from molecularly guided therapies.The modified PFS ratio may represent a meaningful clinical endpoint that could aid in the design and interpretation of future precision oncology trials.
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000148366 7001_ $$0P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aHeilig, Christoph E$$b1
000148366 7001_ $$0P:(DE-He78)e5972dddc3c8d1412db29ba54fed83ba$$aKreutzfeldt, Simon$$b2
000148366 7001_ $$0P:(DE-He78)a5218e4871866cd5ab2312e594ca403d$$aHuebschmann, Daniel$$b3
000148366 7001_ $$0P:(DE-He78)1464357f7ec5faf677a390a414e50c88$$aHeining, Christoph$$b4
000148366 7001_ $$0P:(DE-HGF)0$$aSchröck, Evelin$$b5
000148366 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b6
000148366 7001_ $$0P:(DE-HGF)0$$aStenzinger, Albrecht$$b7
000148366 7001_ $$0P:(DE-He78)ed0321409c9cde20b380ae663dbcefd1$$aJäger, Dirk$$b8
000148366 7001_ $$0P:(DE-He78)d8a0e60e5e095f3161ee0de3712409bc$$aSchlenk, Richard$$b9
000148366 7001_ $$0P:(DE-He78)157277fe62f07df1732f9d126a51d1b9$$aGlimm, Hanno$$b10
000148366 7001_ $$0P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aFröhling, Stefan$$b11$$eLast author
000148366 7001_ $$0P:(DE-He78)5ea1944c122bc098a81df27a05572719$$aHorak, Peter$$b12$$eLast author
000148366 7001_ $$aNetwork, DKTK MASTER$$b13$$eCollaboration Author
000148366 7001_ $$aApostolidis, Leonidas$$b14
000148366 7001_ $$aAugustin, Marinela$$b15
000148366 7001_ $$aAust, Daniela$$b16
000148366 7001_ $$aBhatti, Irfan Ahmed$$b17
000148366 7001_ $$aBloehdorn, Johannes$$b18
000148366 7001_ $$aBrendel, Cornelia$$b19
000148366 7001_ $$aBritschgi, Christian$$b20
000148366 7001_ $$aBraess, Jan$$b21
000148366 7001_ $$aBurdach, Stefan$$b22
000148366 7001_ $$aBusch, Elena$$b23
000148366 7001_ $$aCasuscelli, Jozefina$$b24
000148366 7001_ $$aDesuki, Alexander$$b25
000148366 7001_ $$aDeutsch, Thomas$$b26
000148366 7001_ $$aDietrich, Mareike$$b27
000148366 7001_ $$aEhmer, Ursula$$b28
000148366 7001_ $$aEttrich, Thomas J$$b29
000148366 7001_ $$aFalkenhorst, Johanna$$b30
000148366 7001_ $$aFehm, Tanja$$b31
000148366 7001_ $$aFlörcken, Anne$$b32
000148366 7001_ $$aForschner, Andrea$$b33
000148366 7001_ $$aFuxius, Stefan$$b34
000148366 7001_ $$aGonzales-Carmona, Maria$$b35
000148366 7001_ $$aGriesinger, Frank$$b36
000148366 7001_ $$aGrill, Sabine$$b37
000148366 7001_ $$aGröschel, Stefan$$b38
000148366 7001_ $$aHaag, Georg Martin$$b39
000148366 7001_ $$aHaag, Ulrich$$b40
000148366 7001_ $$aHalama, Niels$$b41
000148366 7001_ $$aHebart, Holger$$b42
000148366 7001_ $$aHeidger, Nina$$b43
000148366 7001_ $$aHermes, Barbara$$b44
000148366 7001_ $$aHess, Georg$$b45
000148366 7001_ $$aHettmer, Simone$$b46
000148366 7001_ $$aHoechstetter, Manuela$$b47
000148366 7001_ $$aHoffmann, Martin$$b48
000148366 7001_ $$aHüttner, Felix J$$b49
000148366 7001_ $$aIllert, Anna L$$b50
000148366 7001_ $$aJenzer, Maximilian$$b51
000148366 7001_ $$aKasper, Bernd$$b52
000148366 7001_ $$aKasper-Virchow, Stefan$$b53
000148366 7001_ $$aKindler, Thomas$$b54
000148366 7001_ $$aKoscielniak, Ewa$$b55
000148366 7001_ $$aKrönke, Jan$$b56
000148366 7001_ $$aKühn, Michael$$b57
000148366 7001_ $$aKunzmann, Volker$$b58
000148366 7001_ $$aLang, Alois$$b59
000148366 7001_ $$aLeichsenring, Jonas$$b60
000148366 7001_ $$aLivingstone, Elisabeth$$b61
000148366 7001_ $$aLiotta, Lucia$$b62
000148366 7001_ $$aLuley, Kim$$b63
000148366 7001_ $$aMack, Elisabeth$$b64
000148366 7001_ $$aMartens, Uwe M$$b65
000148366 7001_ $$aMetzeler, Klaus$$b66
000148366 7001_ $$aMiddeke, Jan Moritz$$b67
000148366 7001_ $$aMöhrmann, Lino$$b68
000148366 7001_ $$aJayarama-Naidu, Roopa$$b69
000148366 7001_ $$aPape, Ulrich-Frank$$b70
000148366 7001_ $$aPerkhofer, Lukas$$b71
000148366 7001_ $$aPfeufer, Arne$$b72
000148366 7001_ $$aPixberg, Constantin$$b73
000148366 7001_ $$aQuante, Michael$$b74
000148366 7001_ $$aRendenbach, Bernhard$$b75
000148366 7001_ $$aRieke, Damian$$b76
000148366 7001_ $$aRothermundt, Christian$$b77
000148366 7001_ $$aSagerer, Andre Norbert$$b78
000148366 7001_ $$aSalzmann, Martin$$b79
000148366 7001_ $$aSaur, Dieter$$b80
000148366 7001_ $$aSchilling, Bastian$$b81
000148366 7001_ $$aSchleicher, Jan$$b82
000148366 7001_ $$aSchlenska-Lange, Anke$$b83
000148366 7001_ $$aSchmidt, Thomas$$b84
000148366 7001_ $$aSchmitz, Sophia$$b85
000148366 7001_ $$aSchölch, Sebastian$$b86
000148366 7001_ $$aShah, Rajiv$$b87
000148366 7001_ $$aShoumariyeh, Khalid$$b88
000148366 7001_ $$aSiebenhüner, Alexander$$b89
000148366 7001_ $$aSingh, Martin$$b90
000148366 7001_ $$aSiveke, Jens$$b91
000148366 7001_ $$aSpringfeld, Christoph$$b92
000148366 7001_ $$aStarke, Helen$$b93
000148366 7001_ $$aStrobel, Sophia$$b94
000148366 7001_ $$aTeleanu, Veronica$$b95
000148366 7001_ $$aThon, Niklas$$b96
000148366 7001_ $$aWagner, Sebastian$$b97
000148366 7001_ $$aWalle, Thomas$$b98
000148366 7001_ $$aWestphalen, Benedikt$$b99
000148366 7001_ $$aWhitlock, Bettina$$b100
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000148366 7001_ $$aWirsik, Naita Maren$$b102
000148366 7001_ $$aWoydack, Lena$$b103
000148366 7001_ $$aBois, Angelika Zabel-du$$b104
000148366 7001_ $$aZschäbitz, Stefanie$$b105
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