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SPECIAL FEATURES Highlights of This Issue 897 CCR Translations 899 Does TMB Impact the Effectiveness of TKIs in EGFR-Mutant NSCLC? Michael L. Cheng and Geoffrey R. Oxnard See related article, p. 1063 901 Precision Medicine Approaches When Prostate Cancer Akts Up Tian Zhang, Daniel J. George, and Andrew J. Armstrong See related article, p. 928 904 Immunotherapy and Hyperprogression: Unwanted Outcomes, Unclear Mechanism David A. Knorr and Jeffrey V. Ravetch See related article, p. 989 907 DNA Damage Response Gene Alterations in Urothelial Cancer: Ready for Practice? Petros Grivas See related article, p. 977 910 Response to Immune Checkpoint Antibodies: Not All Responses Are Created Equal Justine V. Cohen and Keith T. Flaherty See related article, p. 946 Reviews 912 The Role of Angiogenesis in Hepatocellular Carcinoma Michael A. Morse, Weijing Sun, Richard Kim, Aiwu Ruth He, Paolo B. Abada, Michelle Mynderse, and Richard S. Finn 921 Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor Immune Microenvironment Jessica L.F. Teh and Andrew E. Aplin CLINICAL TRIALS: TARGETED THERAPY 928 Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss Johann S. de Bono, Ugo De Giorgi, Daniel Nava Rodrigues, Christophe Massard, Sergio Bracarda, Albert Font, Jose Angel Arranz Arija, Kent C. Shih, George Daniel Radavoi, Na Xu, Wai Y. Chan, Han Ma, Steven Gendreau, Ruth Riisnaes, Premal H. Patel, Daniel J. Maslyar, and Viorel Jinga See related commentary, p. 901 937 Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers Maeve A. Lowery, Mikaela Bradley, Joanne F. Chou, Marinela Capanu, Scott Gerst, James J. Harding, Imane El Dika, Michael Berger, Ahmet Zehir, Ryan Ptashkin, Philip Wong, Teresa Rasalan-Ho, Kenneth H. Yu, Andrea Cercek, Ezra Morgono, Erica Salehi, Emily Valentino, Ellen Hollywood, Eileen M. O'Reilly, and Ghassan K. Abou-Alfa CLINICAL TRIALS: IMMUNOTHERAPY 946 Long-Term Survival in Patients Responding to AntiPD-1/PD-L1 Therapy and Disease Outcome upon Treatment Discontinuation Marie-L ea Gauci, Emilie Lanoy, St ephane Champiat, Caroline Caramella, Samy Ammari, Sandrine Aspeslagh, Andrea Varga, Capucine Baldini, Rastilav Bahleda, Anas Gazzah, Jean-Marie Michot, Sophie Postel-Vinay, Eric Angevin, Vincent Ribrag, Antoine Hollebecque, Jean-Charles Soria, Caroline Robert, Christophe Massard, and Aur elien Marabelle See related commentary, p. 910 PRECISION MEDICINE AND IMAGING 957 Exome Analysis Reveals Genomic Markers Associated with Better Efficacy of Nivolumab in Lung Cancer Patients Corentin Richard, Jean-David Fumet, Sandy Chevrier, Valentin Derang ere, Fanny Ledys, Aur elie Lagrange, Laure Favier, Bruno Coudert, Laurent Arnould, Caroline Truntzer, Romain Boidot, and Fran¸ cois Ghiringhelli February 1, 2019 Volume 25 Number 3 Clinical Cancer Research Table of Contents iv on January 16, 2021. © 2019 American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from

Clinical Cancer Research Table of Contents · 1063 Tumor Mutation Burden and Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with EGFR-Mutant Lung Cancers Michael Offin, Hira

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Page 1: Clinical Cancer Research Table of Contents · 1063 Tumor Mutation Burden and Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with EGFR-Mutant Lung Cancers Michael Offin, Hira

SPECIAL FEATURES

Highlights of This Issue 897

CCR Translations

899 Does TMB Impact the Effectiveness of TKIs inEGFR-Mutant NSCLC?Michael L. Cheng and Geoffrey R. OxnardSee related article, p. 1063

901 Precision Medicine Approaches When ProstateCancer Akts UpTian Zhang, Daniel J. George, and Andrew J. ArmstrongSee related article, p. 928

904 Immunotherapy and Hyperprogression:Unwanted Outcomes, Unclear MechanismDavid A. Knorr and Jeffrey V. RavetchSee related article, p. 989

907 DNA Damage Response Gene Alterations inUrothelial Cancer: Ready for Practice?Petros GrivasSee related article, p. 977

910 Response to Immune Checkpoint Antibodies:Not All Responses Are Created EqualJustine V. Cohen and Keith T. FlahertySee related article, p. 946

Reviews

912 The Role of Angiogenesis in HepatocellularCarcinomaMichael A. Morse, Weijing Sun, Richard Kim,Aiwu Ruth He, Paolo B. Abada, Michelle Mynderse, andRichard S. Finn

921 Arrested Developments: CDK4/6 InhibitorResistance and Alterations in the Tumor ImmuneMicroenvironmentJessica L.F. Teh and Andrew E. Aplin

CLINICAL TRIALS: TARGETED THERAPY

928 Randomized Phase II Study Evaluating AktBlockade with Ipatasertib, in Combination withAbiraterone, in Patients with Metastatic ProstateCancer with and without PTEN LossJohann S. de Bono, UgoDeGiorgi, Daniel Nava Rodrigues,Christophe Massard, Sergio Bracarda, Albert Font,Jose Angel Arranz Arija, Kent C. Shih,George Daniel Radavoi, Na Xu, Wai Y. Chan, Han Ma,Steven Gendreau, Ruth Riisnaes, Premal H. Patel,Daniel J. Maslyar, and Viorel JingaSee related commentary, p. 901

937 Binimetinib plus Gemcitabine and CisplatinPhase I/II Trial in Patients with AdvancedBiliary CancersMaeve A. Lowery, Mikaela Bradley, Joanne F. Chou,Marinela Capanu, Scott Gerst, James J. Harding,Imane El Dika, Michael Berger, Ahmet Zehir,Ryan Ptashkin, Philip Wong, Teresa Rasalan-Ho,KennethH. Yu, Andrea Cercek, EzraMorgono, Erica Salehi,Emily Valentino, Ellen Hollywood, Eileen M. O'Reilly, andGhassan K. Abou-Alfa

CLINICAL TRIALS: IMMUNOTHERAPY

946 Long-Term Survival in Patients Responding toAnti–PD-1/PD-L1 Therapy and Disease Outcomeupon Treatment DiscontinuationMarie-L�ea Gauci, Emilie Lanoy, St�ephane Champiat,Caroline Caramella, Samy Ammari, Sandrine Aspeslagh,Andrea Varga, Capucine Baldini, Rastilav Bahleda,Anas Gazzah, Jean-Marie Michot, Sophie Postel-Vinay,Eric Angevin, Vincent Ribrag, Antoine Hollebecque,Jean-Charles Soria, Caroline Robert, Christophe Massard,and Aur�elien MarabelleSee related commentary, p. 910

PRECISION MEDICINE AND IMAGING

957 Exome Analysis Reveals Genomic MarkersAssociated with Better Efficacy of Nivolumab inLung Cancer PatientsCorentin Richard, Jean-David Fumet, Sandy Chevrier,Valentin Derang�ere, Fanny Ledys, Aur�elie Lagrange,Laure Favier, Bruno Coudert, Laurent Arnould,Caroline Truntzer, Romain Boidot, andFrancois Ghiringhelli

February 1, 2019 � Volume 25 � Number 3

Clinical Cancer Research

Table ofContents

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on January 16, 2021. © 2019 American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from

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967 Clonal Relatedness and Mutational Differencesbetween Upper Tract and Bladder UrothelialCarcinomaFrancois Audenet, Sumit Isharwal, Eugene K. Cha,Mark T.A. Donoghue, Esther N. Drill, Irina Ostrovnaya,Eugene J. Pietzak, John P. Sfakianos, Aditya Bagrodia,Paari Murugan, Guido Dalbagni, Timothy F. Donahue,Jonathan E. Rosenberg, Dean F. Bajorin, Maria E. Arcila,Jaclyn F. Hechtman, Michael F. Berger, Barry S. Taylor,Hikmat Al-Ahmadie, Gopa Iyer, Bernard H. Bochner,Jonathan A. Coleman, and David B. Solit

977 ERCC2 Helicase Domain Mutations ConferNucleotide Excision Repair Deficiency andDrive Cisplatin Sensitivity in Muscle-InvasiveBladder CancerQiang Li, Alexis W. Damish, Zo€e Frazier, David Liu,Elizaveta Reznichenko, Atanas Kamburov,Andrew Bell, Huiyong Zhao, Emmet J. Jordan,S. Paul Gao, Jennifer Ma, Philip H. Abbosh,Joaquim Bellmunt, Elizabeth R. Plimack,Jean-Bernard Lazaro, David B. Solit, Dean Bajorin,Jonathan E. Rosenberg, Alan D. D'Andrea, Nadeem Riaz,Eliezer M. Van Allen, Gopa Iyer, and Kent W. MouwSee related commentary, p. 907

TRANSLATIONAL CANCER MECHANISMSAND THERAPY

989 Antibody–Fc/FcR Interaction on Macrophages asa Mechanism for Hyperprogressive Disease inNon–small Cell Lung Cancer Subsequent toPD-1/PD-L1 BlockadeGiuseppe Lo Russo, MassimoMoro, Michele Sommariva,Valeria Cancila, Mattia Boeri, Giovanni Centonze,Simona Ferro, Monica Ganzinelli, Patrizia Gasparini,Veronica Huber, Massimo Milione, Luca Porcu,Claudia Proto, Giancarlo Pruneri, Diego Signorelli,Sabina Sangaletti, Lucia Sfondrini, Chiara Storti,Elena Tassi, Alberto Bardelli, Silvia Marsoni, Valter Torri,Claudio Tripodo, Mario Paolo Colombo,Andrea Anichini, Licia Rivoltini, Andrea Balsari,Gabriella Sozzi, and Marina Chiara GarassinoSee related commentary, p. 904

1000 IND-Enabling Studies for a Clinical Trial toGenetically Program a Persistent Cancer-Targeted Immune SystemCristina Puig-Saus, Giulia Parisi, Angel Garcia-Diaz,Paige E. Krystofinski, Salemiz Sandoval, Ruixue Zhang,Ameya S. Champhekar, James McCabe,Gardenia C. Cheung-Lau, Nhat A. Truong,Agustin Vega-Crespo, Marie Desiles S. Komenan, Jia Pang,Mignonette H. Macabali, Justin D. Saco,Jeffrey L. Goodwin, Brad Bolon, Christopher S. Seet,Amelie Montel-Hagen, Gay M. Crooks, Roger P. Hollis,Beatriz Campo-Fernandez, Daniela Bischof,Kenneth Cornetta, Eric H. Gschweng, Celia Adelson,Alexander Nguyen, Lili Yang, Owen N. Witte,David Baltimore, Begonya Comin-Anduix,Donald B. Kohn, Xiaoyan Wang, Paula Cabrera,Paula J. Kaplan-Lefko, Beata Berent-Maoz, andAntoni Ribas

1012 Peripheral Stem Cell Apheresis is Feasible Post131Iodine-Metaiodobenzylguanidine-Therapy inHigh-Risk Neuroblastoma, but Results inDelayed Platelet ReconstitutionKathelijne C.J.M. Kraal, Ilse Timmerman,Hannah M. Kansen, Cor van den Bos, Jozsef Zsiros,Henk van den Berg, Sebastiaan Somers, Eric Braakman,Annemarie M.L. Peek, Max M. van Noesel,C. Ellen van der Schoot, Marta Fiocco, Huib N. Caron,Carlijn Voermans, and Godelieve A.M. Tytgat

1022 Loss of RBMS3 Confers Platinum Resistance inEpithelial Ovarian Cancer via Activation ofmiR-126-5p/b-catenin/CBP signalingGeyan Wu, Lixue Cao, Jinrong Zhu, Zhanyao Tan,Miaoling Tang, Ziwen Li, Yameng Hu, Ruyuan Yu,Shuxia Zhang, Libing Song, and Jun Li

1036 Targeting PIM Kinase with PD1 InhibitionImproves Immunotherapeutic Antitumor T-cellResponseShilpak Chatterjee, Paramita Chakraborty,Anusara Daenthanasanmak, Supinya Iamsawat,Gabriela Andrejeva, Libia A. Luevano, Melissa Wolf,Uday Baliga, Carsten Krieg, Craig C. Beeson,Meenal Mehrotra, Elizabeth G. Hill, Jeffery C. Rathmell,Xue-Zhong Yu, Andrew S. Kraft, and Shikhar Mehrotra

1050 Transcription Factor Myeloid Zinc-Finger 1Suppresses Human Gastric Carcinogenesis byInteracting with Metallothionein 2AShuye Lin, Xiaoyue Wang, Yuanming Pan,Rongmeng Tian, Bonan Lin, Guosheng Jiang,Keqiang Chen, Yuqi He, Lulu Zhang, Wanli Zhai, Peng Jin,Lang Yang, Guoqiang Li, Yun Wu, Jiang Hu,Wanghua Gong, Zhijie Chang, Jian-qiu Sheng,Youyong Lu, Ji Ming Wang, and Jiaqiang Huang

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1063 Tumor Mutation Burden and Efficacy ofEGFR-Tyrosine Kinase Inhibitors in Patientswith EGFR-Mutant Lung CancersMichael Offin, Hira Rizvi, Megan Tenet, Andy Ni,Francisco Sanchez-Vega, Bob T. Li, Alexander Drilon,Mark G. Kris, Charles M. Rudin, Nikolaus Schultz,Maria E. Arcila, Marc Ladanyi, Gregory J. Riely, Helena Yu,and Matthew D. HellmannSee related commentary, p. 899

1070 Targeting an Autocrine Regulatory Loop inCancer Stem-like Cells Impairs the Progressionand Chemotherapy Resistance of Bladder CancerKai-Jian Wang, Chao Wang, Li-He Dai, Jun Yang,Hai Huang, Xiao-Jing Ma, Zhe Zhou, Ze-Yu Yang,Wei-Dong Xu, Mei-Mian Hua, Xin Lu, Shu-Xiong Zeng,Hui-Qing Wang, Zhen-Sheng Zhang, Yan-Qiong Cheng,Dan Liu, Qin-Qin Tian, Ying-Hao Sun, andChuan-Liang Xu

1087 Frequent Homologous RecombinationDeficiency in High-grade EndometrialCarcinomasMarthe M. de Jonge, Aur�elie Auguste,Lise M. van Wijk, Philip C. Schouten, Matty Meijers,Natalja T. ter Haar, Vincent T.H.B.M. Smit,Remi A. Nout, Mark A. Glaire, David N. Church,Harry Vrieling, Bastien Job, Yannick Boursin,Cor D. de Kroon, Etienne Rouleau, Alexandra Leary,Maaike P.G. Vreeswijk, and Tjalling Bosse

1098 Targeting Cancer Cells and TumorMicroenvironment in Preclinical and ClinicalModels of Hodgkin Lymphoma Using the DualPI3Kd/g Inhibitor RP6530Silvia L. Locatelli, Giuseppa Careddu, Simone Serio,Francesca M. Consonni, Akihiro Maeda,Srikant Viswanadha, Swaroop Vakkalanka, Luca Castagna,Armando Santoro, Paola Allavena, Antonio Sica, andCarmelo Carlo-Stella

1113 SMAC Mimetic Debio 1143 and AblativeRadiation Therapy Synergize to EnhanceAntitumor Immunity against Lung CancerZhen Tao, Neal S. McCall, Norbert Wiedemann,Gr�egoire Vuagniaux, Zhiyong Yuan, and Bo Lu

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ABOUT THE COVER

The cover shows an immunofluorescence panel from prototypical hyperprogressive diseaseinfiltrates in non-small cell lung cancer patients treated with immune checkpoint inhibitor,showing the colocalization of CD33 and PD-L1 in clustered macrophages with epithelioidmorphology. For details, see the article by Lo Russo and colleagues on page 989 of this issue.

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