SPECIAL FEATURES

Highlights of This Issue 1439

CCR Translations

1441 Predicting Outcome in Head and Neck Cancer:miRNAs with Potentially Big EffectsDavid A. Clump, Curtis R. Pickering, and Heath D. SkinnerSee related article, p. 1505

1443 Predicting Treatment Response Based on RNAExpression in Large DatasetsAaron S. Mansfield and Jin JenSee related article, p. 1564

1446 Virus, Vessel, Victory: A Novel Approach to TumorKillingYonina Bykov and Dmitriy ZamarinSee related article, p. 1624

1449 Tumor-Infiltrating Lymphocytes—Location forPrognostic EvaluationMichael Peled, Amir Onn, and Roy S. HerbstSee related article, p. 1526

1452 Biomarkers for Immunotherapy Toxicity: AreCytokines the Answer?Douglas B. Johnson and Justin M. BalkoSee related article, p. 1557

CCR Perspectives in Regulatory Science andPolicy

1455 Clinical Development of Novel Drug–Radiotherapy CombinationsSaif S. Ahmad, Marka R. Crittenden, Phuoc T. Tran,Paul G. Kluetz, Gideon M. Blumenthal, Helen Bulbeck,Richard D. Baird, Kaye J. Williams, Tim Illidge,StephenM. Hahn, Theodore S. Lawrence, Patricia A. Spears,Amanda J. Walker, and Ricky A. Sharma

Review

1462 Reimagining IDO Pathway Inhibition in CancerImmunotherapy via Downstream Focus on theTryptophan–Kynurenine–Aryl HydrocarbonAxisBrian W. Labadie, Riyue Bao, and Jason J. Luke

CLINICAL TRIALS: TARGETED THERAPY

1472 Phase IB Dose Escalation and Expansion Studyof AKT Inhibitor Afuresertib with Carboplatinand Paclitaxel in Recurrent Platinum-resistantOvarian CancerSarah P. Blagden, Anne L. Hamilton, Linda Mileshkin,Shirley Wong, Agnieszka Michael, Marcia Hall,Jeffrey C. Goh, Alla S. Lisyanskaya, Michelle DeSilvio,Eleni Frangou, Euan A. Stronach, Prashanth Gopalakrishna,Tarek M. Meniawy, and Hani Gabra

1479 Impact of Concomitant Administration of GastricAcid–Suppressive Agents and Pazopanib onOutcomes in Soft-Tissue Sarcoma Patients Treatedwithin the EORTC 62043/62072 TrialsOlivier Mir, Nathan Touati, Michela Lia, Saskia Liti�ere,Axel Le Cesne, Stefan Sleijfer, Jean-Yves Blay, Michael Leahy,Robin Young, Ron H.J. Mathijssen, Nielka P. Van Erp,Hans Gelderblom, Winette T. Van der Graaf, andAlessandro Gronchi

CLINICAL TRIALS: IMMUNOTHERAPY

1486 A Phase II Study of Tumor-infiltrating LymphocyteTherapy for Human Papillomavirus–associatedEpithelial CancersSanja Stevanovi�c, Sarah R. Helman, John R. Wunderlich,Michelle M. Langhan, Stacey L. Doran, Mei Li M. Kwong,Robert P.T. Somerville, Christopher A. Klebanoff,Udai S. Kammula, Richard M. Sherry, James C. Yang,Steven A. Rosenberg, and Christian S. Hinrichs

1494 Autologous Dendritic Cell-Cytokine InducedKiller Cell Immunotherapy Combined with S-1Plus Cisplatin in Patients with Advanced GastricCancer: A Prospective StudyGuoliang Qiao, Xiaoli Wang, Lei Zhou, Xinna Zhou,Yuguang Song, Shuo Wang, Lei Zhao, Michael A. Morse,Amy Hobeika, Jin Song, Xin Yi, Xuefeng Xia, Jun Ren, andHerbert Kim Lyerly

March 1, 2019 � Volume 25 � Number 5

Clinical Cancer Research

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PRECISION MEDICINE AND IMAGING

1505 A Five-MicroRNA Signature Predicts Survival andDisease Control of Patients with Head and NeckCancer Negative for HPV InfectionJulia Hess, Kristian Unger, Cornelius Maihoefer,Lars Sch€uttrumpf, Ludmila Wintergerst, Theresa Heider,Peter Weber, Sebastian Marschner, Herbert Braselmann,Daniel Samaga, Sebastian Kuger, Ulrike Pflugradt,Philipp Baumeister, Axel Walch, Christine Woischke,Thomas Kirchner, Martin Werner, Kristin Werner,Michael Baumann, Volker Budach, Stephanie E. Combs,J€urgen Debus, Anca-Ligia Grosu, Mechthild Krause,Annett Linge, Claus R€odel, Martin Stuschke, Daniel Zips,Horst Zitzelsberger, Ute Ganswindt, Michael Henke, andClaus BelkaSee related commentary, p. 1441

1517 Rare, Pathogenic Germline Variants in FanconiAnemia Genes Increase Risk for SquamousLung CancerMyvizhi Esai Selvan, Robert J. Klein, and ZeynepH. G€um€us

1526 Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for PredictingLikelihood of Recurrence in Early-Stage Non–Small Cell Lung CancerGerm�an Corredor, Xiangxue Wang, Yu Zhou, Cheng Lu,Pingfu Fu, Konstantinos Syrigos, David L. Rimm,Michael Yang, Eduardo Romero, Kurt A. Schalper,Vamsidhar Velcheti, and Anant MadabhushiSee related commentary, p. 1449

1535 NK Cell Infiltrates and HLA Class I Expressionin Primary HER2þ Breast Cancer Predict andUncouple Pathological Response and Disease-free SurvivalAura Muntasell, Federico Rojo, Sonia Servitja,Carlota Rubio-Perez, Mariona Cabo, David Tamborero,Marcel Costa-García, María Martínez-Garcia,Sílvia Men�endez, Ivonne Vazquez, Ana Lluch,Abel Gonzalez-Perez, Ana Rovira, Miguel L�opez-Botet, andJoan Albanell

1546 Development and Validation of a Novel Signatureto Predict Overall Survival in "Driver Gene–negative" Lung Adenocarcinoma (LUAD):Results of a Multicenter StudyYongmei Cui, Wenfeng Fang, Chaofeng Li, Kejing Tang,Jian Zhang, Yiyan Lei, Weiling He, Sui Peng, Ming Kuang,Hui Zhang, Lili Chen, Di Xu, Cuilan Tang, Wenhui Zhang,Yuxin Zhu, Wenting Jiang, Neng Jiang, Yu Sun,Yangshan Chen, Han Wang, Yingrong Lai, Shuhua Li,Qiong He, Jianwen Zhou, Yang Zhang, Millicent Lin,Honglei Chen, Chenzhi Zhou, Chunlin Wang,Jianhong Wang, Xuenong Zou, Liantang Wang, andZunfu Ke

TRANSLATIONAL CANCER MECHANISMSAND THERAPY

1557 Circulating Cytokines Predict Immune-RelatedToxicity in Melanoma Patients Receiving Anti-PD-1–Based ImmunotherapySu Y. Lim, Jenny H. Lee, Tuba N. Gide,Alexander M. Menzies, Alexander Guminski,Matteo S. Carlino, Edmond J. Breen, Jean Y.H. Yang,Shila Ghazanfar, Richard F. Kefford, Richard A. Scolyer,Georgina V. Long, and Helen RizosSee related commentary, p. 1452

1564 Molecular Profiling of Cohorts of Tumor Samplesto Guide Clinical Development ofPembrolizumab as MonotherapyMark Ayers, Michael Nebozhyn, Razvan Cristescu,Terrill K. McClanahan, Rodolfo Perini, Eric Rubin,Jonathan D. Cheng, David R. Kaufman, andAndrey LobodaSee related commentary, p. 1443

1574 AKT/mTORC2 Inhibition Activates FOXO1Function in CLL Cells Reducing B-Cell Receptor-Mediated SurvivalEmilio Cosimo, Anuradha Tarafdar, Michael W. Moles,Ailsa K. Holroyd, Natasha Malik, Mark A. Catherwood,Jodie Hay, Karen M. Dunn, Alan M. Macdonald,Sylvie M. Guichard, Declan O'Rourke, Michael T. Leach,Owen J. Sansom, Sabina C. Cosulich, Alison M. McCaig,and Alison M. Michie

1588 Ablation of Cancer Stem Cells by TherapeuticInhibition of the MDM2–p53 Interaction inMucoepidermoid CarcinomaApril Andrews, Kristy Warner, Christie Rodriguez-Ramirez,Alexander T. Pearson, Felipe N€or, Zhaocheng Zhang,Samuel Kerk, Aditi Kulkarni, Joseph I. Helman,J. Chad Brenner, Max S. Wicha, Shaomeng Wang, andJacques E. N€or

1601 Eradication of Central Nervous System Leukemiaof T-Cell Origin with a Brain-Permeable LSD1InhibitorShiori Saito, Jiro Kikuchi, Daisuke Koyama, Shin Sato,Hiroo Koyama, Naoki Osada, Yoshiaki Kuroda,Koshi Akahane, Takeshi Inukai, Takashi Umehara, andYusuke Furukawa

1612 Tumor Microenvironment Remodeling byIntratumoral Oncolytic Vaccinia Virus Enhancesthe Efficacy of Immune-Checkpoint BlockadeHong Jae Chon,Won Suk Lee, Hannah Yang, So Jung Kong,Na Keum Lee, Eun Sang Moon, Jiwon Choi,Eun Chun Han, Joo Hoon Kim, Joong Bae Ahn,Joo Hang Kim, and Chan Kim

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1624 Combining Vascular Normalization with anOncolytic Virus Enhances Immunotherapy in aPreclinical Model of Advanced-Stage OvarianCancerKathy Matuszewska, Lisa A. Santry, Jacob P. van Vloten,Amanda W.K. AuYeung, Pierre P. Major, Jack Lawler,Sarah K. Wootton, Byram W. Bridle, and Jim PetrikSee related commentary, p. 1446

1639 NRF2 through RPS6 Activation Is Related toAnti-HER2 Drug Resistance in HER2-AmplifiedGastric CancerValentina Gambardella, Francisco Gimeno-Valiente,Noelia Tarazona, Carolina Martinez Ciarpaglini,Desamparados Roda, Tania Fleitas, Pablo Tolosa,Juan Miguel Cejalvo, Marisol Huerta, Susana Rosell�o,Josefa Castillo, and Andr�es Cervantes

1650 The COX2 Effector Microsomal PGE2 Synthase 1is a Regulator of Immunosuppression inCutaneous MelanomaSun-Hee Kim, Jason Roszik, Sung-Nam Cho, Dai Ogata,Den�ai R. Milton, Weiyi Peng, David G. Menter,Suhendan Ekmekcioglu, and Elizabeth A. Grimm

1664 The Ewing Family of Tumors Relies on BCL-2and BCL-XL to Escape PARP Inhibitor ToxicityDaniel A.R. Heisey, Timothy L. Lochmann,Konstantinos V. Floros, Colin M. Coon, Krista M. Powell,Sheeba Jacob, Marissa L. Calbert, Maninderjit S. Ghotra,Giovanna T. Stein, Yuki Kato Maves, Steven C. Smith,Cyril H. Benes, Joel D. Leverson, Andrew J. Souers,Sosipatros A. Boikos, and Anthony C. Faber

1676 Anagrelide for Gastrointestinal Stromal TumorOlli-Pekka Pulkka, Yemarshet K. Gebreyohannes,

Agnieszka Wozniak, John-Patrick Mpindi, Olli Tynninen,Katherine Icay, Alejandra Cervera, Salla Keskitalo,Astrid Murum€agi, Evgeny Kulesskiy, Maria Laaksonen,Krister Wennerberg, Markku Varjosalo, Pirjo Laakkonen,Rainer Lehtonen, Sampsa Hautaniemi, Olli Kallioniemi,Patrick Sch€offski, Harri Sihto, and Heikki Joensuu

LETTERS TO THE EDITOR

1688 DICER1 and Associated Conditions:Identification of At-risk Individuals andRecommended Surveillance Strategies—LetterLeeyan S. Gilmour, Penny J. Hunt, Karen E. Mackenzie,and Martin de Bock

1689 DICER1 and Associated Conditions:Identification of At-risk Individuals andRecommended Surveillance Strategies—ResponseAndrew J. Bauer, Douglas R. Stewart, Junne Kamihara,Anne K. Harris, Joyce Turner, Rachana Shah,Kami Wolfe Schneider, Katherine Schneider,Ann Garrity Carr, Laura A. Harney, A. Lindsay Frazier,Daniel Orbach, Dominik T. Schneider, David Malkin,Louis P. Dehner, Yoav H. Messinger, D. Ashley Hill, andKris Ann P. Schultz

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ABOUT THE COVER

The cover shows how intratumoral oncolytic virus treatment induces dramatic remodeling oftumor microenvironment by facilitating the accumulation of CD8þ T cells. Left panel:pretreatment; right panel: post-treatment. For details, see the article by Chon and colleagues onpage 1612 of this issue.

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