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2.  Radiological imaging markers predicting clinical outcome in patients with metastatic colorectal carcinoma treated with regorafenib: post hoc analysis of the CORRECT phase III trial (RadioCORRECT study) 
ESMO Open  2017;1(6):e000111.
Objective
To identify imaging markers predicting clinical outcomes to regorafenib in metastatic colorectal carcinoma (mCRC).
Methods
The RadioCORRECT study is a post hoc analysis of a cohort of patients with mCRC treated within the phase III placebo-controlled CORRECT trial of regorafenib. Baseline and week 8 contrast-enhanced CT were used to assess response by RECIST 1.1, changes in the sum of target lesion diameters (ΔSTL), lung metastases cavitation and liver metastases density. Primary and secondary objectives were to develop ex novo univariable and multivariable models to predict overall survival (OS) and progression-free survival (PFS), respectively.
Results
202 patients were enrolled, 134 (66.3%) treated with regorafenib and 68 (33.7%) with placebo. In the univariate analysis, PFS predictors were lung metastases cavitation at baseline (HR 0.50, 95% CI 0.27 to 0.92, p=0.03) and at week 8 (HR 0.58, 95% CI 0.36 to 0.93, p=0.02). Baseline cavitation (HR 0.23, 95% CI 0.08 to 0.66, p=0.007), RECIST 1.1 (HR 0.23, 95% CI 0.14 to 0.4, p <0.0001) and ΔSTL (HR 1.16, 95% CI 1.06 to 1.27, p=0.002) predicted OS. We found an increase of 9% of diameter as the best threshold for discriminating OS (HR 2.64, 95% CI 1.61 to 4.34, p <0.001). In the multivariate analysis, baseline and week 8 cavitation remained significant PFS predictors. Baseline cavitation, RECIST 1.1 and ΔSTL remained predictors of OS in exploratory multivariable models. Assessment of liver metastases density did not predict clinical outcome.
Conclusions
RECIST 1.1 and ΔSTL predict favourable outcome to regorafenib. In contrast to liver metastases density that failed to be a predictor, lung metastases cavitation represents a novel radiological marker of favourable outcome that deserves consideration.
doi:10.1136/esmoopen-2016-000111
PMCID: PMC5548980
Regorafenib; Cavitation; Metastatic Colorectal Cancer; Radiological Predictive Factors
3.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts 
Althammer, Sonja | Steele, Keith | Rebelatto, Marlon | Tan, Tze Heng | Wiestler, Tobias | Schmidt, Guenter | Higgs, Brandon | Li, Xia | Shi, Li | Jin, Xiaoping | Antal, Joyce | Gupta, Ashok | Ranade, Koustubh | Binning, Gerd | Bellmunt, Joaquim | de Wit, Ronald | Vaughn, David J. | Fradet, Yves | Lee, Jae Lyun | Fong, Lawrence | Vogelzang, Nicholas J. | Climent, Miguel A. | Petrylak, Daniel P. | Choueiri, Toni K. | Necchi, Andrea | Gerritsen, Winald | Gurney, Howard | Quinn, David I. | Culine, Stéphane | Sternberg, Cora N. | Mai, Yabing | Puhlmann, Markus | Perini, Rodolfo F. | Bajorin, Dean F. | Sharma, Padmanee | Callahan, Margaret K. | Calvo, Emiliano | Kim, Joseph W. | de Braud, Filipo | Ott, Patrick A. | Bono, Petri | Pillai, Rathi N. | Morse, Michael | Le, Dung T. | Taylor, Matthew | Spilliopoulou, Pavlina | Bendell, Johanna | Jaeger, Dirk | Chan, Emily | Antonia, Scott J. | Ascierto, Paolo A. | Hennicken, Delphine | Tschaika, Marina | Azrilevich, Alex | Rosenberg, Jonathan | Levy, Ofer | Chan, Christopher | Cojocaru, Gady | Liang, Spencer | Ophir, Eran | Ganguly, Sudipto | Toporik, Amir | Kotturi, Maya | Kfir, Tal Fridman | Murter, Benjamin M. | Logronio, Kathryn | Dassa, Liat | Leung, Ling | Greenwald, Shirley | Azulay, Meir | Kumar, Sandeep | Alteber, Zoya | Pan, Xiaoyu | Machlenkin, Arthur | Benita, Yair | Drake, Andrew W. | Chajut, Ayelet | Salomon, Ran | Vankin, Ilan | Safyon, Einav | Hunter, John | Levine, Zurit | White, Mark | Leidner, Rom | Kang, Hyunseok | Haddad, Robert | Segal, Neil H. | Wirth, Lori J. | Ferris, Robert L. | Hodi, F. Stephen | Sanborn, Rachel E. | Gajewski, Thomas F. | Sharfman, William | McDonald, Dan | Srivastava, Shivani | Gu, Xuemin | Phillips, Penny | Passey, Chaitali | Seiwert, Tanguy | Habtetsion, Tsadik | Zhou, Gang | Sakellariou-Thompson, Donastas | Haymaker, Cara | Creasy, Caitlin | Hurd, Mark | Uraoka, Naohiro | Canales, Jaime Rodriguez | Koptez, Scott | Hwu, Patrick | Maitra, Anirban | Bernatchez, Chantale | Coyle, Scott M. | Roybel, Kole T. | Rupp, Levi J. | Santoro, Stephen P. | Secrest, Stephanie | Spelman, Michael | Ho, Hanson | Gomes, Tina | Tse, Tiffany | Yung-Wu, Chia | Taunton, Jack | Lim, Wendell | Emtage, Peter | Moudgil, Tarsem | Ballesteros-Merino, Carmen | Hilton, Traci | Paustian, Christopher | Leidner, Rom | Page, David | Urba, Walter | Fox, Bernard | Bell, Bryan | Patel, Ashish | Olafsen, Tove | Satpayev, Daulet | Torgov, Michael | Marchioni, Filippo | Romero, Jason | Jiang, Ziyue Karen | Zamilpa, Charles | Keppler, Jennifer S. | Mascioni, Alessandro | Jia, Fang | Lee, Chen-Yu | Gudas, Jean | Sullivan, Ryan J. | Hoshida, Yujin | Logan, Theodore | Khushalani, Nikhil | Giobbie-Hurder, Anita | Margolin, Kim | Roder, Joanna | Bhatt, Rupal | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Blackmon, Shauna | Mier, James W. | Puzanov, Igor | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Signoretti, Sabina | McDermott, David F. | Anderson, Abraham A. | Puzanov, Igor | Milhem, Mohammed M. | Andtbacka, Robert H. I. | Minor, David | Gorski, Kevin S. | Baker, Daniel M. | Hamid, Omid | Kaufman, Howard L. | Akporiaye, Emmanuel | Curti, Brendan | Koguchi, Yoshinobu | Leidner, Rom | Sutcliffe, Kim | Conder, Kristie | Urba, Walter | Marron, Thomas | Bhardwaj, Nina | Hammerich, Linda | George, Fiby | Kim-Schulze, Seunghee | Keler, Tibor | Davis, Tom | Crowley, Elizabeth | Salazar, Andres | Brody, Joshua | Monjazeb, Arta | Daly, Megan E. | Riess, Jonathan | Li, Tianhong | Murphy, William J. | Kelly, Karen | Hu, Zhiwei | Shen, Rulong | Campbell, Amanda | McMichael, Elizabeth | Yu, Lianbo | Ramaswam, Bhuvaneswari | London, Cheryl A. | Xu, Tian | Carson, William | Kokolus, Kathleen M. | Repasky, Elizabeth A. | Schell, Todd D. | Drabick, Joseph D. | Messenheimer, David J. | Jensen, Shawn | Fox, Bernard | Rubinstein, Mark | Andrijauskaite, Kristina | Swiderska-syn, Marzena | Lind, Kristin | Choppin, Agnes | Roell, Marina K. | Wrangle, John | Andrijauskaite, Kristina | Swiderska-syn, Marzena | Rhode, Peter | Wong, Hing | Rubinstein, Mark | Ahmad, Shamim | Webb, Mason | Abu-Eid, Rasha | Shrimali, Rajeev | Verma, Vivek | Doroodchi, Atbin | Berrong, Zuzana | Yashar, David | Samara, Raed | Mkrtichyan, Mikayel | Khleif, Samir | Powell, Steven | Gitau, Mark | Sumey, Christopher | Terrell, Andrew | Lohr, Michele | Nowak, Ryan K. | McGraw, Steven | Jensen, Ash | Blanchard, Miran | Gold, Kathryn A. | Cohen, Ezra E. W. | Ellison, Christie | Black, Lora | Lee, John | Spanos, William Chad | Wennerberg, Erik | Schwitzer, Emily | Lhuillier, Claire | Koelwyn, Graeme | Hiner, Rebecca | Jones, Lee | Demaria, Sandra | Amanda, Vandeveer | Greiner, John W. | Schlom, Jeffrey | Bookstaver, Michelle | Jewell, Christopher M. | Paustian, Christopher | Gunderson, Andrew | Boulmay, Brian | Li, Rui | Spieler, Bradley | Happel, Kyle | Moudgil, Tarsem | Feng, Zipei | Ballesteros-Merino, Carmen | Dubay, Christopher | Fisher, Brenda | Koguchi, Yoshinobu | Aung, Sandra | Mederos, Eileen | Bifulco, Carlo B. | McNamara, Michael | Bahjat, Keith | Redmond, William | Ochoa, Augusto | Hu, Hong-Ming | Mehta, Adi | Lund-Johansen, Fridtjof | Fox, Bernard | Urba, Walter | Sanborn, Rachel E. | Hilton, Traci | Bedu-Addo, Frank | Conn, Greg | King, Michael | Dutta, Panna | Shepard, Robert | Einstein, Mark | Adams, Sylvia | Wang, Ena | Jin, Ping | Novik, Yelena | Morrison, Debra | Oratz, Ruth | Marincola, Franco M. | Stroncek, David | Goldberg, Judith | Demaria, Sandra | Formenti, Silvia C. | Galon, Jérôme | Mlecnik, Bernhard | Marliot, Florence | Ou, Fang-Shu | Bifulco, Carlo B. | Lugli, Alessandro | Zlobec, Inti | Rau, Tilman T. | Nagtegaal, Iris D. | Vink-Borger, Elisa | Hartmann, Arndt | Geppert, Carol | Roehrl, Michael H. | Bavi, Prashant | Ohashi, Pamela S. | Wang, Julia Y. | Nguyen, Linh T. | Han, SeongJun | MacGregor, Heather L. | Hafezi-Bakhtiari, Sara | Wouters, Bradley G. | Kawakami, Yutaka | Papivanova, Boryana | Xu, Mingli | Fujita, Tomonobu | Hazama, Shoichi | Suzuki, Nobuaki | Nagano, Hiroaki | Okuno, Kiyotaka | Itoh, Kyogo | Zavadova, Eva | Vocka, Michal | Spacek, Jan | Petruzelka, Lubos | Konopasek, Bohuslav | Dundr, Pavel | Skalova, Helena | Torigoe, Toshihiko | Sato, Noriyuki | Furuhata, Tomohisa | Takemasa, Ichiro | Van den Eynde, Marc | Jouret-Mourin, Anne | Machiels, Jean-Pascal | Fredriksen, Tessa | Lafontaine, Lucie | Buttard, Bénédicte | Church, Sarah | Maby, Pauline | Angell, Helen | Angelova, Mihaela | Vasaturo, Angela | Bindea, Gabriela | Berger, Anne | Lagorce, Christine | Patel, Prabhu S. | Vora, Hemangini H. | Shah, Birva | Patel, Jayendrakumar B. | Rajvik, Kruti N. | Pandya, Shashank J. | Shukla, Shilin N. | Wang, Yili | Zhang, Guanjun | Masucci, Giuseppe V. | Andersson, Emilia K. | Grizzi, Fabio | Laghi, Luigi | Botti, Gerardo | Tatangelo, Fabiana | Delrio, Paolo | Cilberto, Gennaro | Ascierto, Paolo A. | Marincola, Franco | Sargent, Daniel J. | Fox, Bernard A. | Algazi, Alain | Tsai, Katy | Rosenblum, Michael | Nandoskar, Prachi | Andtbacka, Robert H. I. | Li, Amy | Nonomura, John | Takamura, Kathryn | Dwyer, Mary | Browning, Erica | Talia, Reneta | Twitty, Chris | Gargosky, Sharron | Campbell, Jean | Ballesteros-Merino, Carmen | Bifulco, Carlo B. | Fox, Bernard | Le, Mai | Pierce, Robert H. | Daud, Adil | Gartrell, Robyn | Marks, Douglas | Stack, Edward | Lu, Yan | Izaki, Daisuke | Beck, Kristen | Jia, Dan Tong | Armenta, Paul | White-Stern, Ashley | Fu, Yichun | Blake, Zoe | Kaufman, Howard L. | Taback, Bret | Horst, Basil | Saenger, Yvonne M. | Leonardo, Steven | Gorden, Keith | Fulton, Ross B. | Fraser, Kathryn | Kangas, Takashi O. | Walsh, Richard | Ertelt, Kathleen | Graff, Jeremy | Uhlik, Mark | Sims, Jennifer S. | Lei, Liang | Tsujiuchi, Takashi | Bruce, Jeffrey N. | Canoll, Peter | Tolcher, Anthony W | Alley, Evan W | Chichili, Gurunadh | Canoll, Jan E | Moore, Paul | Bonvini, Ezio | Johnson, Syd | Shankar, Sadhna | Vasselli, James | Wigginton, Jon | Powderly, John
doi:10.1186/s40425-016-0191-4
PMCID: PMC5260784
4.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one 
Lundqvist, Andreas | van Hoef, Vincent | Zhang, Xiaonan | Wennerberg, Erik | Lorent, Julie | Witt, Kristina | Sanz, Laia Masvidal | Liang, Shuo | Murray, Shannon | Larsson, Ola | Kiessling, Rolf | Mao, Yumeng | Sidhom, John-William | Bessell, Catherine A. | Havel, Jonathan | Schneck, Jonathan | Chan, Timothy A. | Sachsenmeier, Eliot | Woods, David | Berglund, Anders | Ramakrishnan, Rupal | Sodre, Andressa | Weber, Jeffrey | Zappasodi, Roberta | Li, Yanyun | Qi, Jingjing | Wong, Philip | Sirard, Cynthia | Postow, Michael | Newman, Walter | Koon, Henry | Velcheti, Vamsidhar | Callahan, Margaret K. | Wolchok, Jedd D. | Merghoub, Taha | Lum, Lawrence G. | Choi, Minsig | Thakur, Archana | Deol, Abhinav | Dyson, Gregory | Shields, Anthony | Haymaker, Cara | Uemura, Marc | Murthy, Ravi | James, Marihella | Wang, Daqing | Brevard, Julie | Monaghan, Catherine | Swann, Suzanne | Geib, James | Cornfeld, Mark | Chunduru, Srinivas | Agrawal, Sudhir | Yee, Cassian | Wargo, Jennifer | Patel, Sapna P. | Amaria, Rodabe | Tawbi, Hussein | Glitza, Isabella | Woodman, Scott | Hwu, Wen-Jen | Davies, Michael A. | Hwu, Patrick | Overwijk, Willem W. | Bernatchez, Chantale | Diab, Adi | Massarelli, Erminia | Segal, Neil H. | Ribrag, Vincent | Melero, Ignacio | Gangadhar, Tara C. | Urba, Walter | Schadendorf, Dirk | Ferris, Robert L. | Houot, Roch | Morschhauser, Franck | Logan, Theodore | Luke, Jason J. | Sharfman, William | Barlesi, Fabrice | Ott, Patrick A. | Mansi, Laura | Kummar, Shivaani | Salles, Gilles | Carpio, Cecilia | Meier, Roland | Krishnan, Suba | McDonald, Dan | Maurer, Matthew | Gu, Xuemin | Neely, Jaclyn | Suryawanshi, Satyendra | Levy, Ronald | Khushalani, Nikhil | Wu, Jennifer | Zhang, Jinyu | Basher, Fahmin | Rubinstein, Mark | Bucsek, Mark | Qiao, Guanxi | MacDonald, Cameron | Hylander, Bonnie | Repasky, Elizabeth | Chatterjee, Shilpak | Daenthanasanmak, Anusara | Chakraborty, Paramita | Toth, Kyle | Meek, Megan | Garrett-Mayer, Elizabeth | Nishimura, Michael | Paulos, Chrystal | Beeson, Craig | Yu, Xuezhong | Mehrotra, Shikhar | Zhao, Fei | Evans, Kathy | Xiao, Christine | Holtzhausen, Alisha | Hanks, Brent A. | Scharping, Nicole | Menk, Ashley V. | Moreci, Rebecca | Whetstone, Ryan | Dadey, Rebekah | Watkins, Simon | Ferris, Robert | Delgoffe, Greg M. | Peled, Jonathan | Devlin, Sean | Staffas, Anna | Lumish, Melissa | Rodriguez, Kori Porosnicu | Ahr, Katya | Perales, Miguel | Giralt, Sergio | Taur, Ying | Pamer, Eric | van den Brink, Marcel R. M. | Jenq, Robert | Annels, Nicola | Pandha, Hardev | Simpson, Guy | Mostafid, Hugh | Harrington, Kevin | Melcher, Alan | Grose, Mark | Davies, Bronwyn | Au, Gough | Karpathy, Roberta | Shafren, Darren | Ricca, Jacob | Merghoub, Taha | Wolchok, Jedd D. | Zamarin, Dmitriy | Batista, Luciana | Marliot, Florence | Vasaturo, Angela | Carpentier, Sabrina | Poggionovo, Cécile | Frayssinet, Véronique | Fieschi, Jacques | Van den Eynde, Marc | Pagès, Franck | Galon, Jérôme | Hermitte, Fabienne | Smith, Sean G. | Nguyen, Khue | Ravindranathan, Sruthi | Koppolu, Bhanu | Zaharoff, David | Schvartsman, Gustavo | Bassett, Roland | McQuade, Jennifer L. | Haydu, Lauren E. | Davies, Michael A. | Tawbi, Hussein | Glitza, Isabella | Kline, Douglas | Chen, Xiufen | Fosco, Dominick | Kline, Justin | Overacre, Abigail | Chikina, Maria | Brunazzi, Erin | Shayan, Gulidanna | Horne, William | Kolls, Jay | Ferris, Robert L. | Delgoffe, Greg M. | Bruno, Tullia C. | Workman, Creg | Vignali, Dario | Adusumilli, Prasad S. | Ansa-Addo, Ephraim A | Li, Zihai | Gerry, Andrew | Sanderson, Joseph P. | Howe, Karen | Docta, Roslin | Gao, Qian | Bagg, Eleanor A. L. | Tribble, Nicholas | Maroto, Miguel | Betts, Gareth | Bath, Natalie | Melchiori, Luca | Lowther, Daniel E. | Ramachandran, Indu | Kari, Gabor | Basu, Samik | Binder-Scholl, Gwendolyn | Chagin, Karen | Pandite, Lini | Holdich, Tom | Amado, Rafael | Zhang, Hua | Glod, John | Bernstein, Donna | Jakobsen, Bent | Mackall, Crystal | Wong, Ryan | Silk, Jonathan D. | Adams, Katherine | Hamilton, Garth | Bennett, Alan D. | Brett, Sara | Jing, Junping | Quattrini, Adriano | Saini, Manoj | Wiedermann, Guy | Gerry, Andrew | Jakobsen, Bent | Binder-Scholl, Gwendolyn | Brewer, Joanna | Duong, MyLinh | Lu, An | Chang, Peter | Mahendravada, Aruna | Shinners, Nicholas | Slawin, Kevin | Spencer, David M. | Foster, Aaron E. | Bayle, J. 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Peter | Shankaran, Veena | Piha-Paul, Sarina A. | Yearley, Jennifer | Seiwert, Tanguy | Ribas, Antoni | McClanahan, Terrill K. | Cristescu, Razvan | Mogg, Robin | Ayers, Mark | Albright, Andrew | Murphy, Erin | Yearley, Jennifer | Sher, Xinwei | Liu, Xiao Qiao | Nebozhyn, Michael | Lunceford, Jared | Joe, Andrew | Cheng, Jonathan | Plimack, Elizabeth | Ott, Patrick A. | McClanahan, Terrill K. | Loboda, Andrey | Kaufman, David R. | Forrest-Hay, Alex | Guyre, Cheryl A. | Narumiya, Kohei | Delcommenne, Marc | Hirsch, Heather A. | Deshpande, Amit | Reeves, Jason | Shu, Jenny | Zi, Tong | Michaelson, Jennifer | Law, Debbie | Trehu, Elizabeth | Sathyanaryanan, Sriram | Hodkinson, Brendan P. | Hutnick, Natalie A. | Schaffer, Michael E. | Gormley, Michael | Hulett, Tyler | Jensen, Shawn | Ballesteros-Merino, Carmen | Dubay, Christopher | Afentoulis, Michael | Reddy, Ashok | David, Larry | Fox, Bernard | Jayant, Kumar | Agrawal, Swati | Agrawal, Rajendra | Jeyakumar, Ghayathri | Kim, Seongho | Kim, Heejin | Silski, Cynthia | Suisham, Stacey | Heath, Elisabeth | Vaishampayan, Ulka | Vandeven, Natalie | Viller, Natasja Nielsen | O’Connor, Alison | Chen, Hui | Bossen, Bolette | Sievers, Eric | Uger, Robert | Nghiem, Paul | Johnson, Lisa | Kao, Hsiang-Fong | Hsiao, Chin-Fu | Lai, Shu-Chuan | Wang, Chun-Wei | Ko, Jenq-Yuh | Lou, Pei-Jen | Lee, Tsai-Jan | Liu, Tsang-Wu | Hong, Ruey-Long | Kearney, Staci J. | Black, Joshua C. | Landis, Benjamin J. | Koegler, Sally | Hirsch, Brooke | Gianani, Roberto | Kim, Jeffrey | He, Ming-Xiao | Zhang, Bingqing | Su, Nan | Luo, Yuling | Ma, Xiao-Jun | Park, Emily | Kim, Dae Won | Copploa, Domenico | Kothari, Nishi | doo Chang, Young | Kim, Richard | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Knaus, Hanna A. | Berglund, Sofia | Hackl, Hubert | Karp, Judith E. | Gojo, Ivana | Luznik, Leo | Hong, Henoch S. | Koch, Sven D. | Scheel, Birgit | Gnad-Vogt, Ulrike | Kallen, Karl-Josef | Wiegand, Volker | Backert, Linus | Kohlbacher, Oliver | Hoerr, Ingmar | Fotin-Mleczek, Mariola | Billingsley, James M. | Koguchi, Yoshinobu | Conrad, Valerie | Miller, William | Gonzalez, Iliana | Poplonski, Tomasz | Meeuwsen, Tanisha | Howells-Ferreira, Ana | Rattray, Rogan | Campbell, Mary | Bifulco, Carlo | Dubay, Christopher | Bahjat, Keith | Curti, Brendan | Urba, Walter | Vetsika, E-K | Kallergi, G. | Aggouraki, Despoina | Lyristi, Z. | Katsarlinos, P. | Koinis, Filippos | Georgoulias, V. | Kotsakis, Athanasios | Martin, Nathan T. | Aeffner, Famke | Kearney, Staci J. | Black, Joshua C. | Cerkovnik, Logan | Pratte, Luke | Kim, Rebecca | Hirsch, Brooke | Krueger, Joseph | Gianani, Roberto | Martínez-Usatorre, Amaia | Jandus, Camilla | Donda, Alena | Carretero-Iglesia, Laura | Speiser, Daniel E. | Zehn, Dietmar | Rufer, Nathalie | Romero, Pedro | Panda, Anshuman | Mehnert, Janice | Hirshfield, Kim M. | Riedlinger, Greg | Damare, Sherri | Saunders, Tracie | Sokol, Levi | Stein, Mark | Poplin, Elizabeth | Rodriguez-Rodriguez, Lorna | Silk, Ann | Chan, Nancy | Frankel, Melissa | Kane, Michael | Malhotra, Jyoti | Aisner, Joseph | Kaufman, Howard L. | Ali, Siraj | Ross, Jeffrey | White, Eileen | Bhanot, Gyan | Ganesan, Shridar | Monette, Anne | Bergeron, Derek | Amor, Amira Ben | Meunier, Liliane | Caron, Christine | Morou, Antigoni | Kaufmann, Daniel | Liberman, Moishe | Jurisica, Igor | Mes-Masson, Anne-Marie | Hamzaoui, Kamel | Lapointe, Rejean | Mongan, Ann | Ku, Yuan-Chieh | Tom, Warren | Sun, Yongming | Pankov, Alex | Looney, Tim | Au-Young, Janice | Hyland, Fiona | Conroy, Jeff | Morrison, Carl | Glenn, Sean | Burgher, Blake | Ji, He | Gardner, Mark | Mongan, Ann | Omilian, Angela R. | Conroy, Jeff | Bshara, Wiam | Angela, Omilian | Burgher, Blake | Ji, He | Glenn, Sean | Morrison, Carl | Mongan, Ann | Obeid, Joseph M. | Erdag, Gulsun | Smolkin, Mark E. | Deacon, Donna H. | Patterson, James W. | Chen, Lieping | Bullock, Timothy N. | Slingluff, Craig L. | Obeid, Joseph M. | Erdag, Gulsun | Deacon, Donna H. | Slingluff, Craig L. | Bullock, Timothy N. | Loffredo, John T. | Vuyyuru, Raja | Beyer, Sophie | Spires, Vanessa M. | Fox, Maxine | Ehrmann, Jon M. | Taylor, Katrina A. | Korman, Alan J. | Graziano, Robert F. | Page, David | Sanchez, Katherine | Ballesteros-Merino, Carmen | Martel, Maritza | Bifulco, Carlo | Urba, Walter | Fox, Bernard | Patel, Sapna P. | De Macedo, Mariana Petaccia | Qin, Yong | Reuben, Alex | Spencer, Christine | Guindani, Michele | Bassett, Roland | Wargo, Jennifer | Racolta, Adriana | Kelly, Brian | Jones, Tobin | Polaske, Nathan | Theiss, Noah | Robida, Mark | Meridew, Jeffrey | Habensus, Iva | Zhang, Liping | Pestic-Dragovich, Lidija | Tang, Lei | Sullivan, Ryan J. | Logan, Theodore | Khushalani, Nikhil | Margolin, Kim | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Roder, Joanna | Blackmon, Shauna | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Weber, Jeffrey | McDermott, David F. | Weber, Jeffrey | Kluger, Harriet | Halaban, Ruth | Snzol, Mario | Roder, Heinrich | Roder, Joanna | Asmellash, Senait | Steingrimsson, Arni | Blackmon, Shauna | Sullivan, Ryan J. | Wang, Chichung | Roman, Kristin | Clement, Amanda | Downing, Sean | Hoyt, Clifford | Harder, Nathalie | Schmidt, Guenter | Schoenmeyer, Ralf | Brieu, Nicolas | Yigitsoy, Mehmet | Madonna, Gabriele | Botti, Gerardo | Grimaldi, Antonio | Ascierto, Paolo A. | Huss, Ralf | Athelogou, Maria | Hessel, Harald | Harder, Nathalie | Buchner, Alexander | Schmidt, Guenter | Stief, Christian | Huss, Ralf | Binnig, Gerd | Kirchner, Thomas | Sellappan, Shankar | Thyparambil, Sheeno | Schwartz, Sarit | Cecchi, Fabiola | Nguyen, Andrew | Vaske, Charles | Hembrough, Todd
Journal for Immunotherapy of Cancer  2016;4(Suppl 1):1-106.
doi:10.1186/s40425-016-0172-7
PMCID: PMC5123387
5.  Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer 
Introduction
The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient’s unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine.
Methods
This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding.
Results
On baseline FDG PET-CT, 124 measurable “target” lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis.
Conclusions
Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.
doi:10.1007/s00259-016-3365-x
PMCID: PMC4969337  PMID: 27072811
Early metabolic response assessment; FDG PET-CT; Tumoral heterogeneity; Metastatic colorectal cancer; Targeted therapy
6.  The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer 
PLoS ONE  2015;10(9):e0138341.
Background
Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC).
Methods
Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions.
Results
Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS.
Conclusion
The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC.
Trial Registration
ClinicalTrials.gov NCT01290926
doi:10.1371/journal.pone.0138341
PMCID: PMC4589397  PMID: 26421426
7.  Hemoglobin level significantly impacts the tumor cell survival fraction in humans after internal radiotherapy 
EJNMMI Research  2012;2:20.
Background
Anemia is usually not taken into account in internal radiotherapy. We investigated whether the hemoglobin (Hb) level could have an impact on the tumor response, as observed in external beam radiotherapy (EBRT).
Methods
Absorbed doses of 25 hepatic metastatic sites in eight patients who underwent a liver selective internal radiotherapy (SIRT) were computed by a 3D convolution of a dose deposition kernel with the 90Y time-of-flight positron emission tomography (TOF-PET) images acquired following therapy. Early tumor response was assessed by comparing a follow-up FDG TOF-PET scan with a baseline scan. Hb level was measured on the day of the SIRT procedure.
Results
All patients displayed early tumor response increasing with the tumor-absorbed dose. Significant differences between patients were noted, the response slope correlating with the Hb level. After applying a global fit on all metastases using a tumor radiosensitivity modulated by a Hb enhancement factor (HEF) linearly dependent on the Hb level, a strong correlation (R = 0.96) was observed between the early response and the absorbed dose. Hb level had a major impact on tumor response by modulating HEF by a factor 6.
Conclusions
These results prove the significant impact of Hb level on the tumor response and support the study of methods for correcting tumor hypoxia, such as intensively performed in EBRT. The quantitative analysis of the relationship between tumor doses and early response has the power to allow fast screening of such correction methods in limited patient series. Internal radiotherapy could be more efficient if performed earlier in the therapy line, when the disease- and treatment-related anemia remains limited.
doi:10.1186/2191-219X-2-20
PMCID: PMC3413597  PMID: 22608186
Liver SIRT; Internal radiotherapy; Dosimetry; Hemoglobin; Anemia; Dose-response.

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