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1. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial

Author

Luft, Alexander V., Karaseva, Nina A., Kowalyszyn, Rubén Dario, Hernandez, Carlos Alberto, Csoszi, Tibor, De Vita, Ferdinando, Pfeiffer, Per, Sugimoto, Naotoshi, Kocsis, Judit, Csilla, Andràs, Bodoky, Gyorgy, Garnica Jaliffe, Georgina, Protsenko, Svetlana, Madi, Ayman, Wojcik, Elzbieta, Brenner, Baruch, Folprecht, Gunnar, Sarosiek, Tomasz, Peltola, Katriina Johanna, Bono, Peter, Ayala, Hubert, Aprile, Giuseppe, Gerardo, Cardellino Giovanni, Huitzil Melendez, Fidel David, Falcone, Alfredo, Di Costanzo, Francesco, Tehfe, Moustapha, Mineur, Laurent, García Alfonso, Pilar, Obermannova, Radka, Senellart, Hélène, Petty, Russell, Samuel, Leslie, Acs, Peter Istvan, Hussein, Maen Abdelkarim, Nechaeva, Marina N., Erdkamp, F.L.G., Won, Elizabeth, Bendell, Johanna Chock, Gallego Plazas, Javier, Lorenzen, Sylvie, Melichar, Bohuslav, Escudero, Miguel Angel, Pezet, Denis, Phelip, Jean-Marc, Kaen, Diego Lucas, Reeves, James A. Jr, Longo Muñoz, Federico, Madhusudan, Srinivasan, Barone, Carlo, Fein, Luis Enrique, Gomez Villanueva, Angel, Hebbar, Mohamed, Prausova, Jana, Visa Turmo, Laura, Vidal Barrull, Joana, Yilmaz, Mette Karen Nytoft, Beny, Alex, Van Laarhoven, H.M.W., DiCarlo, Brian Anthony, Esaki, Taito, Fujitani, Kazumasa, Geboes, Karen, Geva, Ravit, Kadowaki, Shigenori, Leong, Stephen, Machida, Nozomu, Raj, Moses Sundar, Ramirez Godinez, Francisco Javier, Ruzsa, Agnes, Ford, Hugo, Lawler, William E., Maisey, Nicolas Robert, Petera, Jiri, Shacham-Shmueli, Einat, Sinapi, Isabelle, Yamaguchi, Kensei, Hara, Hiroki, Beck, Joseph Thaddeus, Błasińska-Morawiec, Maria, Villalobos Valencia, Ricardo, Alcindor, Thierry, Bajaj, Madhuri, Berry, Scott, Gomez, Christina Maria, Dammrich, Daniel, Patel, Ravindranath, Taieb, Julien, Ten Tije, A.J., Burkes, Ronald L., Cabanillas, Fernando, Firdaus, Irfan, Chua, Cynthia Coo, Hironaka, Shuichi, Hofheinz, Ralf-Dieter, Lim, Howard J., Nordsmark, Marianne, Piko, Bela, Verma, Udit, Wadsley, Jonathan, Yukisawa, Seigo, Gutiérrez Delgado, Francisco, Denlinger, Crystal S., Kallio, Raija, Pikiel, Joanna, Wojcik-Tomaszewska, Joanna, Brezden-Masley, Christine, Jang, Raymond Woo-Jun, Pribylova, Jana, Sakai, Daisuke, Bartoli, Maria Alejandra, Cats, A., Grootscholten, M.I., Dichmann, Robert Andrew, Hool, Hugo, Shaib, Walid, Tsuji, Akihito, Van den Eynde, Marc, Velez-Cortez, Hector, Asmis, Timothy R., Fuchs, Charles S, Shitara, Kohei, Di Bartolomeo, Maria, Lonardi, Sara, Al-Batran, Salah-Eddin, Van Cutsem, Eric, Ilson, David H, Alsina, Maria, Chau, Ian, Lacy, Jill, Ducreux, Michel, Mendez, Guillermo Ariel, Alavez, Alejandro Molina, Takahari, Daisuke, Mansoor, Wasat, Enzinger, Peter C, Gorbounova, Vera, Wainberg, Zev A, Hegewisch-Becker, Susanna, Ferry, David, Lin, Ji, Carlesi, Roberto, Das, Mayukh, and Shah, Manish A

Published
2019
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2. Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies

Author

Brown, Michael, Burge, Matthew, Cardaci, Giuseppe, Clarke, Stephen, Eliadis, Paul, Ferguson, Tom, Ganju, Vinod, Gibbs, Peter, van Hazel, Guy, James, Philip, Karapetis, Chris, Liauw, Winston, Marx, Gavin, Matos, Marco, Nott, Louise, Pavlakis, Nick, Powell, Alex, Price, Timothy, Ransom, David, Segelov, Eva, Shannon, Jenny, Singhal, Nimit, Strickland, Andrew, Walpole, Euan, Craninx, Michel, Delaunoit, Thierry, Deleporte, Amélie, Ferrante, Michel, Geboes, Karen, Hendlisz, Alain, Hendrickx, Koen, De Man, Marc, Monsaert, Els, Moons, Veerle, Peeters, Marc, Polus, Marc, Boucher, Eveline, Balosso, Jacques, Chevallier, Patrick, Louafi, Samy, Pracht, Marc, Rebischung, Christine, Smith, Denis, Taieb, Julien, Terrebonne, Eric, Bruch, Harald-Robert, Gehbauer, Gerald, Heinemann, Volker, Helmberger, Thomas, Ko, Yon-Dschun, Kröning, Hendrik, Lammert, Frank, Nusch, Arnd, Pluntke, Stefan, Ridwelski, Karsten, Riera-Knorrenschild, Jorge, Riess, Hanno, Riera, Jorge Ramon, Ricke, Jens, Sauerbruch, Tilmann, Scheidhauer, Klemens, Stötzer, Oliver, Tatsch, Klaus, Vehling-Kaiser, Ursula, Vogl, Thomas, Beny, Alex, Geva, Ravit, Shacham-Shmueli, Einat, Stemmer, Salomon, Tichler, Thomas, Wolf, Ido, Angelelli, Bruna, Martoni, Andrea, Findlay, Michael P.N., Isaacs, Richard, O’Donnell, Anne, Perez, David, Robinson, Bridget A., Rodríguez, Javier, Vera-Garcia, Ruth, Amin, Pradip, Bloomgarden, Daniel, Bui, James, Carlisle, James, Chai, Seungjean, Chen, Yi-Jen, Chuong, Michael, Coveler, Andrew, Facchini, Francis, Frenette, Gary, Frick, Jacob, Garofalo, Michael, George, Benjamin, Gordon, Michael, Gulec, Seza, Hannigan, James, Holtzman, Matthew, Kaubisch, Andreas, Kaiser, Adeel, Kooy, Todd, Limentani, Steven, Margolis, Jeffrey, Martin, Robert, Ozer, Howard, Padia, Siddarth, Rilling, William, Savin, Michael, Schneiderman, Elyse, Seeger, Grant, Sharma, Navesh, Shibata, Stephen, Smith, Randall, Wang, Eric, Whiting, Samuel, Aghmesheh, Morteza, Burge, Mathew, Cooray, Prasad, Feeney, Kynan, Lim, Lionel, Singh, Madhu, Underhill, Craig, Deleporte, Amelie, Durand, Aurelie, Faivre, Sandrine, Ferru, Aurelie, Hammel, Pascal, Bremer, Christoph, De Wit, Maike, Ayala, Hubert, Heching, Norman, Shani, Adi, Granetto, Cristina, Masi, Gianluca, Mosconi, Stefania, Numico, Gianmauro, Trogu, Antonio, Kim, Yeul Hong, Sae-Won, Han, Jackson, Chris, O'Donnell, Anne, Fragoso, Maria, Tan, Iain, Casado, Ana Ruiz, Liang, Jin Tung, Liu, Jin Hwang, Ades, Steven, Auber, Miklos, Boland, Patrick, Bowers, Charles, Crain, Martin, Dowling, Kyran, Iyer, Renuka, Ratner, Lynn, Sanchez, Federico, Stoltzfus, Patricia, Westcott, Mark, Sharma, Navesh K., Findlay, Michael, Robinson, Bridget, Jackson, Christopher, Gebski, Val, Van Buskirk, Mark, and Zhao, Huaqing

Published
2018
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3. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial

Author

Lerzo, Guillermo, O'Connor, Juan Manuel, Mendez, Guillermo Ariel, Lynam, James, Tebbutt, Niall, Wong, Mark, Strickland, Andrew, Karapetis, Chris, Goldstein, David, Vasey, Paul, Van Laethem, Jean-Luc, Van Cutsem, Eric, Berry, Scott, Vincent, Mark, Muller, Bettina, Rey, Felipe, Zambrano, Angela, Guerra, Joaquin, Krogh, Merete, Baeksgaard, Lene, Yilmaz, Mette, Elme, Anneli, Magi, Andrus, Auvinen, Paivi, Alanko, Tuomo, Moehler, Markus, Kunzmann, Volker, Seufferlein, Thomas, Thuss-Patience, Peter, Goekkurt, Eray, Hoehler, Thomas, Haag, Georg, Al-Batran, Salah-Eddin, Castro, Hugo, Lopez, Karla, Aguilar Vasquez, Mynor, Sandoval, Mario, Lam, Ka On, Cuffe, Sinead, Kelly, Cathy, Geva, Ravit, Shacham-Shmueli, Einat, Hubert, Ayala, Beny, Alex, Brenner, Baruch, Giuseppe, Aprile, Falcone, Alfredo, Maiello, Evaristo, Passalacqua, Rodolfo, Montesarchio, Vincenzo, Hara, Hiroki, Chin, Keisho, Nishina, Tomohiro, Komatsu, Yoshito, Machida, Nozumo, Hironaka, Shuichi, Satoh, Taroh, Tamura, Takao, Sugimoto, Naotaoshi, Cho, Haruhiko, Omuro, Yashushi, Kato, Ken, Goto, Masahiro, Hyodo, Ichinosuke, Yoshida, Kazuhiro, Baba, Hideo, Esaki, Taito, Furuse, Junji, Wan Mohammed, Wan Zamaniah, Hernandez Hernandez, Carlos, Casas Garcia, Juan, Dominguez Andrade, Adriana, Clarke, Katriona, Hjortland, Geir, Glenjen, Nils, Kubiatowski, Tomasz, Jacek, Jassem, Wojtukiewicz, Marek, Lazarev, Sergey, Lancukhay, Yuri, Afanasayev, Sergey, Moiseyenko, Vladimir, Kostorov, Vladimir, Protsenko, Svetlana, Shirinkin, Vadim, Sakaeva, Dina, Fadeeva, Natalia, Yong, Wei Peng, Ng, Chau Hsien Matthew, Robertson, Barbara, Rapaport, Bernardo, Cohen, Graham, Dreosti, Lydia, Ruff, Paul, Jacobs, Conrad, Landers, Gregory, Szpak, Waldemar, Roh, Sang-Young, Lee, Jeeyun, Kim, Yeul Hong, Bang, Yung-Jue, Chung, Hyun Cheol, Ryu, Min-Hee, Alsina Maqueda, Maria, Longo Munoz, Federico, Cervantes Aguilar, Andres, Aranda Aguilar, Enrique, Garcia Alfonso, Pilar, Rivera, Fernando, Feliu Batle, Jaime, Pazo Cid, Roberto, Yeh, Kun-Huei, Chen, Jen-Shi, Chao, Yee, Yen, Chia-Jui, Özgüroğlu, Mustafa, Kara, Oguz, Yalcin, Suayib, Hochhauser, Daniel, Chau, Ian, Benson, Al, Shankaran, Veena, Shaib, Walid, Philip, Philip, Sharma, Vivek, Siegel, Robert, Sun, Weijing, Wainberg, Zev, George, Ben, Bullock, Andrea, Myrick, Samuel, Faruol, Josephine, Siegel, Richard, Larson, Timothy, Becerra, Carlos, Ratnam, Suresh, Richards, Donald A., Riche, Stephen L., Shitara, Kohei, Di Bartolomeo, Maria, Mandalà, Mario, Fornaro, Lorenzo, Olesiński, Tomasz, Caglevic, Christian, Chung, Hyun C, Muro, Kei, Mansoor, Wasat, McDermott, Raymond S, Chen, Xinqun, Mayo, Carlos, Kang, S Peter, Ohtsu, Atsushi, and Fuchs, Charles S

Published
2018
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4. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials

Author

Adams, Richard, Bateman, Andrew, Blesing, Claire, Brown, Ewan, Chau, Ian, Cummins, Sebastian, Cunningham, David, Falk, Stephen, Hadaki, Maher, Hall, Marcia, Hickish, Tamas, Hornbuckle, Joanne, Lofts, Fiona, Lowndes, Sarah, Mayer, Astrid, Metcalfe, Matthew, Middleton, Gary, Mills, Jamie, Montazeri, Amir, Muirhead, Rebecca, Polychronis, Andreas, Purcell, Colin, Ross, Paul, Sharma, Ricky A, Sherwin, Liz, Smith, David, Soomal, Rubin, Swinson, Daniel, Walther, Axel, Wasan, Harpreet, Weaver, Andrew, Wilson, Charles, Wilson, Greg, Amin, Pradip, Angelelli, Bruna, Balosso, Jacques, Beny, Alex, Bloomgarden, Daniel, Boucher, Evelyn, Brown, Michael, Bruch, Harald-Robert, Bui, James, Burge, Matthew, Cardaci, Giuseppe, Carlisle, James, Chai, Seungjean, Chen, Yi-Jen, Chevallier, Patrick, Chuong, Michael, Clarke, Stephen, Coveler, Andrew, Craninx, Michael, Delanoit, Thierry, Deleporte, Amélie, Eliadis, Paul, Facchini, Francis, Ferguson, Thomas, Ferrante, Michel, Findlay, Michael, Frenette, Gary, Frick, Jacob, Ganju, Vinod, Garofalo, Michael, Geboes, Karen, Gehbauer, Gerald, George, Benjamin, Geva, Ravit, Gibbs, Peter, Gordon, Michael, Gregory, Kate, Gulec, Seza, Hannigan, James, van Hazel, Guy, Heching, Norman, Heinemann, Volker, Helmberger, Thomas, Hendlisz, Alain, Hendrickx, Koen, Holtzman, Matthew, Isaacs, Richard, Jackson, Christopher, James, Philip, Kaiser, Adeel, Karapetis, Chris, Kaubisch, Andreas, Ko, Yon-Dschun, Kröning, Hendrik, Lammert, Frank, Liauw, Winston, Limentani, Steven, Louafi, Samy, de Man, Marc, Margolis, Jeffrey, Martin, Robert, Martoni, Andrea, Marx, Gavin, Matos, Marco, Monsaert, Els, Moons, Veerle, Nott, Louise, Nusch, Arnd, O'Donnell, Anne, Ozer, Howard, Padia, Siddarth, Pavlakis, Nick, Peeters, Marc, Perez, David, Pluntke, Stefan, Polus, Marc, Powell, Alex, Pracht, Marc, Price, Timothy, Ransom, David, Rebischung, Christine, Ricke, Jens, Ridwelski, Karsten, Riera-Knorrenschild, Jorge, Riess, Hanno, Rilling, William, Robinson, Bridget, Rodríguez, Javier, Sanchez, Federico, Sauerbruch, Tilmann, Savin, Michael, Scheidhauer, Klemens, Schneiderman, Elyse, Seeger, Grant, Segelov, Eva, Schmueli, Einat Shaham, Shani, Adi, Shannon, Jenny, Sharma, Navesh, Shibata, Stephen, Singhal, Nimit, Smith, Denis, Smith, Randall, Stemmer, Salomon, Stötzer, Oliver, Strickland, Andrew, Taieb, Julien, Tatsch, Klaus, Terrebonne, Eric, Tichler, Thomas, Vehling-Kaiser, Ursula, Vera-Garcia, Ruth, Vogl, Thomas, Walpole, Euan, Wang, Eric, Whiting, Samuel, Wolf, Ido, Ades, Steven, Aghmesheh, Morteza, Auber, Miklos, Ayala, Hubert, Boland, Patrick, Bouche, Eveline, Bowers, Charles, Bremer, Christoph, Burge, Mathew, Casado, Ana Ruiz, Cooray, Prasad, Crain, Martin, De Wit, Maike, Dowling, Kyran, Durand, Aurelie, Faivre, Sandrine, Feeney, Kynan, Ferguson, Tom, Ferru, Aurelie, Fragoso, Maria, Granetto, Cristina, Hammel, Pascal, Issacs, Richard, Iyer, Renuka, Kim, Yeul Hong, Liang, Jin Tung, Lim, Lionel, Liu, Jin Hwang, Masi, Gianluca, Mosconi, Stefania, Numico, Gianmauro, Ratner, Lynn, Sae-Won, Han, Singh, Madhu, Stoltzfus, Patricia, Tan, Iain, Trogu, Antonio, Underhill, Craig, Westcott, Mark, Wasan, Harpreet S, Sharma, Navesh K, Francis, Anne, Moschandreas, Joanna, Virdee, Pradeep S, Dutton, Peter, Love, Sharon, Gebski, Val, and Gray, Alastair

Published
2017
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10. The Predictive Role of ERCC1 Status in Oxaliplatin Based Neoadjuvant Therapy for Metastatic Colorectal Cancer (mCRC) to the Liver

Author

Elaine C. Johnstone, Eli Brazowsky, Ravit Geva, Einat Shacham-Shmueli, Mendi Ben-Haim, Sivan Shamai, Michael Paoulas, and Beny Alex

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Metastasis, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Neoadjuvant therapy, Aged, Aged, 80 and over, Chemotherapy, Predictive marker, business.industry, Liver Neoplasms, General Medicine, Middle Aged, Endonucleases, medicine.disease, Primary tumor, Neoadjuvant Therapy, digestive system diseases, Oxaliplatin, DNA-Binding Proteins, Liver, Female, ERCC1, Colorectal Neoplasms, business, medicine.drug
Abstract

Increased expression of excision repair cross-complementing 1 (ERCC1) in mCRC patients could be related to their response to Oxaliplatin based chemotherapy. We evaluated ERCC1 mRNA expression levels in primary bowel and liver metastases of 51 patients, and correlated with pathologic parameters and clinical outcomes. A significant negative correlation was detected between primary tumor ERCC1 and both the extent of clear surgical margins (P = 0.0011) and the percent of liver metastasis necrosis (P = 0.0167). No relationship was observed between ERCC1 expression and survival. Further study is needed to assess the promising role of ERCC1 expression as a predictive marker benefiting subgroups for Oxaliplatin.

Published
2015
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11. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial

Author

Fuchs, Charles S, primary, Shitara, Kohei, additional, Di Bartolomeo, Maria, additional, Lonardi, Sara, additional, Al-Batran, Salah-Eddin, additional, Van Cutsem, Eric, additional, Ilson, David H, additional, Alsina, Maria, additional, Chau, Ian, additional, Lacy, Jill, additional, Ducreux, Michel, additional, Mendez, Guillermo Ariel, additional, Alavez, Alejandro Molina, additional, Takahari, Daisuke, additional, Mansoor, Wasat, additional, Enzinger, Peter C, additional, Gorbounova, Vera, additional, Wainberg, Zev A, additional, Hegewisch-Becker, Susanna, additional, Ferry, David, additional, Lin, Ji, additional, Carlesi, Roberto, additional, Das, Mayukh, additional, Shah, Manish A, additional, Luft, Alexander V., additional, Karaseva, Nina A., additional, Kowalyszyn, Rubén Dario, additional, Hernandez, Carlos Alberto, additional, Csoszi, Tibor, additional, De Vita, Ferdinando, additional, Pfeiffer, Per, additional, Sugimoto, Naotoshi, additional, Kocsis, Judit, additional, Csilla, Andràs, additional, Bodoky, Gyorgy, additional, Garnica Jaliffe, Georgina, additional, Protsenko, Svetlana, additional, Madi, Ayman, additional, Wojcik, Elzbieta, additional, Brenner, Baruch, additional, Folprecht, Gunnar, additional, Sarosiek, Tomasz, additional, Peltola, Katriina Johanna, additional, Bono, Peter, additional, Ayala, Hubert, additional, Aprile, Giuseppe, additional, Gerardo, Cardellino Giovanni, additional, Huitzil Melendez, Fidel David, additional, Falcone, Alfredo, additional, Di Costanzo, Francesco, additional, Tehfe, Moustapha, additional, Mineur, Laurent, additional, García Alfonso, Pilar, additional, Obermannova, Radka, additional, Senellart, Hélène, additional, Petty, Russell, additional, Samuel, Leslie, additional, Acs, Peter Istvan, additional, Hussein, Maen Abdelkarim, additional, Nechaeva, Marina N., additional, Erdkamp, F.L.G., additional, Won, Elizabeth, additional, Bendell, Johanna Chock, additional, Gallego Plazas, Javier, additional, Lorenzen, Sylvie, additional, Melichar, Bohuslav, additional, Escudero, Miguel Angel, additional, Pezet, Denis, additional, Phelip, Jean-Marc, additional, Kaen, Diego Lucas, additional, Reeves, James A. Jr, additional, Longo Muñoz, Federico, additional, Madhusudan, Srinivasan, additional, Barone, Carlo, additional, Fein, Luis Enrique, additional, Gomez Villanueva, Angel, additional, Hebbar, Mohamed, additional, Prausova, Jana, additional, Visa Turmo, Laura, additional, Vidal Barrull, Joana, additional, Yilmaz, Mette Karen Nytoft, additional, Beny, Alex, additional, Van Laarhoven, H.M.W., additional, DiCarlo, Brian Anthony, additional, Esaki, Taito, additional, Fujitani, Kazumasa, additional, Geboes, Karen, additional, Geva, Ravit, additional, Kadowaki, Shigenori, additional, Leong, Stephen, additional, Machida, Nozomu, additional, Raj, Moses Sundar, additional, Ramirez Godinez, Francisco Javier, additional, Ruzsa, Agnes, additional, Ford, Hugo, additional, Lawler, William E., additional, Maisey, Nicolas Robert, additional, Petera, Jiri, additional, Shacham-Shmueli, Einat, additional, Sinapi, Isabelle, additional, Yamaguchi, Kensei, additional, Hara, Hiroki, additional, Beck, Joseph Thaddeus, additional, Błasińska-Morawiec, Maria, additional, Villalobos Valencia, Ricardo, additional, Alcindor, Thierry, additional, Bajaj, Madhuri, additional, Berry, Scott, additional, Gomez, Christina Maria, additional, Dammrich, Daniel, additional, Patel, Ravindranath, additional, Taieb, Julien, additional, Ten Tije, A.J., additional, Burkes, Ronald L., additional, Cabanillas, Fernando, additional, Firdaus, Irfan, additional, Chua, Cynthia Coo, additional, Hironaka, Shuichi, additional, Hofheinz, Ralf-Dieter, additional, Lim, Howard J., additional, Nordsmark, Marianne, additional, Piko, Bela, additional, Verma, Udit, additional, Wadsley, Jonathan, additional, Yukisawa, Seigo, additional, Gutiérrez Delgado, Francisco, additional, Denlinger, Crystal S., additional, Kallio, Raija, additional, Pikiel, Joanna, additional, Wojcik-Tomaszewska, Joanna, additional, Brezden-Masley, Christine, additional, Jang, Raymond Woo-Jun, additional, Pribylova, Jana, additional, Sakai, Daisuke, additional, Bartoli, Maria Alejandra, additional, Cats, A., additional, Grootscholten, M.I., additional, Dichmann, Robert Andrew, additional, Hool, Hugo, additional, Shaib, Walid, additional, Tsuji, Akihito, additional, Van den Eynde, Marc, additional, Velez-Cortez, Hector, additional, and Asmis, Timothy R., additional

Published
2019
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12. Intratumoral HLA-DR−/CD33+/CD11b+ Myeloid-Derived Suppressor Cells Predict Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Author

Hasnis, Erez, Dahan, Aviva, Khoury, Wissam, Duek, Daniel, Fisher, Yael, Beny, Alex, Shaked, Yuval, Chowers, Yehuda, and Half, Elizabeth E.

Subjects
RECTAL cancer, SUPPRESSOR cells, CHEMORADIOTHERAPY, COLON cancer, BIOMARKERS, DRUG resistance
Abstract

Capecitabine-based neoadjuvant chemoradiation therapy (nCRT) is currently the mainstay of treatment for locally advanced rectal cancer (LARC), prior to surgical tumor removal. While response to this treatment is partial, it carries significant risk of side effects. As of today, there is no accepted model to predict tumor response, and allow for patient stratification. The level of circulating Myeloid-derived suppressor cells (MDSCs), a subpopulation of early myeloid cells (EMCs), has been shown to correlate with prognosis and response to therapy in advanced colon cancer, but their role in LARC is not clear. We sought to study the effect of intratumoral and circulating levels of different EMCs subpopulations including MDSCs on response to nCRT. We analyzed tumor, normal mucosa, and peripheral blood samples from 25 LARC patients for their different EMCs subpopulation before and after nCRT, and correlated them with degree of pathologic response, as determined postoperatively. In addition, we compared LARC patient to 10 healthy donors and 6 metastatic patients. CD33+HLA-DR−CD16−CD11b+EMCs in the circulation of LARC patients were found to inhibit T-cell activation. Furthermore, elevated levels of CD33+HLA-DR− myeloid cells were found in the tumor relative to normal mucosa, but not in the circulation when compared to healthy subjects. Moreover, intratumoral, but not circulating levels of MDSCs correlated with clinical stage and response to therapy in patients treated with nCRT, with high levels of MDSCs significantly predicting poor response to nCRT. Importantly, therapy by itself, had significant differential effects on MDSC levels, leading to increased circulating MDSCs, concomitantly with decreasing intratumoral MDSCs. Our results suggest that high levels of intratumoral, but not circulating MDSCs may confer drug resistance due to immunomodulatory effects, and serve as a biomarker for patient stratification and decision-making prior to nCRT. [ABSTRACT FROM AUTHOR]

Published
2020
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13. Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies

Author

Gibbs, Peter, primary, Heinemann, Volker, additional, Sharma, Navesh K., additional, Taieb, Julien, additional, Ricke, Jens, additional, Peeters, Marc, additional, Findlay, Michael, additional, Robinson, Bridget, additional, Jackson, Christopher, additional, Strickland, Andrew, additional, Gebski, Val, additional, Van Buskirk, Mark, additional, Zhao, Huaqing, additional, van Hazel, Guy, additional, Brown, Michael, additional, Burge, Matthew, additional, Cardaci, Giuseppe, additional, Clarke, Stephen, additional, Eliadis, Paul, additional, Ferguson, Tom, additional, Ganju, Vinod, additional, Gibbs, Peter, additional, James, Philip, additional, Karapetis, Chris, additional, Liauw, Winston, additional, Marx, Gavin, additional, Matos, Marco, additional, Nott, Louise, additional, Pavlakis, Nick, additional, Powell, Alex, additional, Price, Timothy, additional, Ransom, David, additional, Segelov, Eva, additional, Shannon, Jenny, additional, Singhal, Nimit, additional, Walpole, Euan, additional, Craninx, Michel, additional, Delaunoit, Thierry, additional, Deleporte, Amélie, additional, Ferrante, Michel, additional, Geboes, Karen, additional, Hendlisz, Alain, additional, Hendrickx, Koen, additional, De Man, Marc, additional, Monsaert, Els, additional, Moons, Veerle, additional, Polus, Marc, additional, Boucher, Eveline, additional, Balosso, Jacques, additional, Chevallier, Patrick, additional, Louafi, Samy, additional, Pracht, Marc, additional, Rebischung, Christine, additional, Smith, Denis, additional, Terrebonne, Eric, additional, Bruch, Harald-Robert, additional, Gehbauer, Gerald, additional, Helmberger, Thomas, additional, Ko, Yon-Dschun, additional, Kröning, Hendrik, additional, Lammert, Frank, additional, Nusch, Arnd, additional, Pluntke, Stefan, additional, Ridwelski, Karsten, additional, Riera-Knorrenschild, Jorge, additional, Riess, Hanno, additional, Riera, Jorge Ramon, additional, Sauerbruch, Tilmann, additional, Scheidhauer, Klemens, additional, Stötzer, Oliver, additional, Tatsch, Klaus, additional, Vehling-Kaiser, Ursula, additional, Vogl, Thomas, additional, Beny, Alex, additional, Geva, Ravit, additional, Shacham-Shmueli, Einat, additional, Stemmer, Salomon, additional, Tichler, Thomas, additional, Wolf, Ido, additional, Angelelli, Bruna, additional, Martoni, Andrea, additional, Findlay, Michael P.N., additional, Isaacs, Richard, additional, O’Donnell, Anne, additional, Perez, David, additional, Robinson, Bridget A., additional, Rodríguez, Javier, additional, Vera-Garcia, Ruth, additional, Amin, Pradip, additional, Bloomgarden, Daniel, additional, Bui, James, additional, Carlisle, James, additional, Chai, Seungjean, additional, Chen, Yi-Jen, additional, Chuong, Michael, additional, Coveler, Andrew, additional, Facchini, Francis, additional, Frenette, Gary, additional, Frick, Jacob, additional, Garofalo, Michael, additional, George, Benjamin, additional, Gordon, Michael, additional, Gulec, Seza, additional, Hannigan, James, additional, Holtzman, Matthew, additional, Kaubisch, Andreas, additional, Kaiser, Adeel, additional, Kooy, Todd, additional, Limentani, Steven, additional, Margolis, Jeffrey, additional, Martin, Robert, additional, Ozer, Howard, additional, Padia, Siddarth, additional, Rilling, William, additional, Savin, Michael, additional, Schneiderman, Elyse, additional, Seeger, Grant, additional, Sharma, Navesh, additional, Shibata, Stephen, additional, Smith, Randall, additional, Wang, Eric, additional, Whiting, Samuel, additional, Aghmesheh, Morteza, additional, Burge, Mathew, additional, Cooray, Prasad, additional, Feeney, Kynan, additional, Lim, Lionel, additional, Singh, Madhu, additional, Underhill, Craig, additional, Deleporte, Amelie, additional, Durand, Aurelie, additional, Faivre, Sandrine, additional, Ferru, Aurelie, additional, Hammel, Pascal, additional, Bremer, Christoph, additional, De Wit, Maike, additional, Ayala, Hubert, additional, Heching, Norman, additional, Shani, Adi, additional, Granetto, Cristina, additional, Masi, Gianluca, additional, Mosconi, Stefania, additional, Numico, Gianmauro, additional, Trogu, Antonio, additional, Kim, Yeul Hong, additional, Sae-Won, Han, additional, Jackson, Chris, additional, O'Donnell, Anne, additional, Fragoso, Maria, additional, Tan, Iain, additional, Casado, Ana Ruiz, additional, Liang, Jin Tung, additional, Liu, Jin Hwang, additional, Ades, Steven, additional, Auber, Miklos, additional, Boland, Patrick, additional, Bowers, Charles, additional, Crain, Martin, additional, Dowling, Kyran, additional, Iyer, Renuka, additional, Ratner, Lynn, additional, Sanchez, Federico, additional, Stoltzfus, Patricia, additional, and Westcott, Mark, additional

Published
2018
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14. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial

Author

Shitara, Kohei, primary, Özgüroğlu, Mustafa, additional, Bang, Yung-Jue, additional, Di Bartolomeo, Maria, additional, Mandalà, Mario, additional, Ryu, Min-Hee, additional, Fornaro, Lorenzo, additional, Olesiński, Tomasz, additional, Caglevic, Christian, additional, Chung, Hyun C, additional, Muro, Kei, additional, Goekkurt, Eray, additional, Mansoor, Wasat, additional, McDermott, Raymond S, additional, Shacham-Shmueli, Einat, additional, Chen, Xinqun, additional, Mayo, Carlos, additional, Kang, S Peter, additional, Ohtsu, Atsushi, additional, Fuchs, Charles S, additional, Lerzo, Guillermo, additional, O'Connor, Juan Manuel, additional, Mendez, Guillermo Ariel, additional, Lynam, James, additional, Tebbutt, Niall, additional, Wong, Mark, additional, Strickland, Andrew, additional, Karapetis, Chris, additional, Goldstein, David, additional, Vasey, Paul, additional, Van Laethem, Jean-Luc, additional, Van Cutsem, Eric, additional, Berry, Scott, additional, Vincent, Mark, additional, Muller, Bettina, additional, Rey, Felipe, additional, Zambrano, Angela, additional, Guerra, Joaquin, additional, Krogh, Merete, additional, Baeksgaard, Lene, additional, Yilmaz, Mette, additional, Elme, Anneli, additional, Magi, Andrus, additional, Auvinen, Paivi, additional, Alanko, Tuomo, additional, Moehler, Markus, additional, Kunzmann, Volker, additional, Seufferlein, Thomas, additional, Thuss-Patience, Peter, additional, Hoehler, Thomas, additional, Haag, Georg, additional, Al-Batran, Salah-Eddin, additional, Castro, Hugo, additional, Lopez, Karla, additional, Aguilar Vasquez, Mynor, additional, Sandoval, Mario, additional, Lam, Ka On, additional, Cuffe, Sinead, additional, Kelly, Cathy, additional, Geva, Ravit, additional, Hubert, Ayala, additional, Beny, Alex, additional, Brenner, Baruch, additional, Giuseppe, Aprile, additional, Falcone, Alfredo, additional, Maiello, Evaristo, additional, Passalacqua, Rodolfo, additional, Montesarchio, Vincenzo, additional, Hara, Hiroki, additional, Chin, Keisho, additional, Nishina, Tomohiro, additional, Komatsu, Yoshito, additional, Machida, Nozumo, additional, Hironaka, Shuichi, additional, Satoh, Taroh, additional, Tamura, Takao, additional, Sugimoto, Naotaoshi, additional, Cho, Haruhiko, additional, Omuro, Yashushi, additional, Kato, Ken, additional, Goto, Masahiro, additional, Hyodo, Ichinosuke, additional, Yoshida, Kazuhiro, additional, Baba, Hideo, additional, Esaki, Taito, additional, Furuse, Junji, additional, Wan Mohammed, Wan Zamaniah, additional, Hernandez Hernandez, Carlos, additional, Casas Garcia, Juan, additional, Dominguez Andrade, Adriana, additional, Clarke, Katriona, additional, Hjortland, Geir, additional, Glenjen, Nils, additional, Kubiatowski, Tomasz, additional, Jacek, Jassem, additional, Wojtukiewicz, Marek, additional, Lazarev, Sergey, additional, Lancukhay, Yuri, additional, Afanasayev, Sergey, additional, Moiseyenko, Vladimir, additional, Kostorov, Vladimir, additional, Protsenko, Svetlana, additional, Shirinkin, Vadim, additional, Sakaeva, Dina, additional, Fadeeva, Natalia, additional, Yong, Wei Peng, additional, Ng, Chau Hsien Matthew, additional, Robertson, Barbara, additional, Rapaport, Bernardo, additional, Cohen, Graham, additional, Dreosti, Lydia, additional, Ruff, Paul, additional, Jacobs, Conrad, additional, Landers, Gregory, additional, Szpak, Waldemar, additional, Roh, Sang-Young, additional, Lee, Jeeyun, additional, Kim, Yeul Hong, additional, Chung, Hyun Cheol, additional, Alsina Maqueda, Maria, additional, Longo Munoz, Federico, additional, Cervantes Aguilar, Andres, additional, Aranda Aguilar, Enrique, additional, Garcia Alfonso, Pilar, additional, Rivera, Fernando, additional, Feliu Batle, Jaime, additional, Pazo Cid, Roberto, additional, Yeh, Kun-Huei, additional, Chen, Jen-Shi, additional, Chao, Yee, additional, Yen, Chia-Jui, additional, Kara, Oguz, additional, Yalcin, Suayib, additional, Hochhauser, Daniel, additional, Chau, Ian, additional, Benson, Al, additional, Shankaran, Veena, additional, Shaib, Walid, additional, Philip, Philip, additional, Sharma, Vivek, additional, Siegel, Robert, additional, Sun, Weijing, additional, Wainberg, Zev, additional, George, Ben, additional, Bullock, Andrea, additional, Myrick, Samuel, additional, Faruol, Josephine, additional, Siegel, Richard, additional, Larson, Timothy, additional, Becerra, Carlos, additional, Ratnam, Suresh, additional, Richards, Donald A., additional, and Riche, Stephen L., additional

Published
2018
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15. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials

Author

Wasan, Harpreet S, Gibbs, Peter, Sharma, Navesh K, Taieb, Julien, Heinemann, Volker, Ricke, Jens, Peeters, Marc, Findlay, Michael, Weaver, Andrew, Mills, Jamie, Wilson, Charles, Adams, Richard, Francis, Anne, Moschandreas, Joanna, Virdee, Pradeep S, Dutton, Peter, Love, Sharon, Gebski, Val, Gray, Alastair, Bateman, Andrew, Blesing, Claire, Brown, Ewan, Chau, Ian, Cummins, Sebastian, Cunningham, David, Falk, Stephen, Hadaki, Maher, Hall, Marcia, Hickish, Tamas, Hornbuckle, Joanne, Lofts, Fiona, Lowndes, Sarah, Mayer, Astrid, Metcalfe, Matthew, Middleton, Gary, Montazeri, Amir, Muirhead, Rebecca, Polychronis, Andreas, Purcell, Colin, Ross, Paul, Sharma, Ricky A, Sherwin, Liz, Smith, David, Soomal, Rubin, Swinson, Daniel, Walther, Axel, Wasan, Harpreet, Wilson, Greg, Amin, Pradip, Angelelli, Bruna, Balosso, Jacques, Beny, Alex, Bloomgarden, Daniel, Boucher, Evelyn, Brown, Michael, Bruch, Harald-Robert, Bui, James, Burge, Matthew, Cardaci, Giuseppe, Carlisle, James, Chai, Seungjean, Chen, Yi-Jen, Chevallier, Patrick, Chuong, Michael, Clarke, Stephen, Coveler, Andrew, Craninx, Michael, Delanoit, Thierry, Deleporte, Amã©lie, Eliadis, Paul, Facchini, Francis, Ferguson, Thomas, Ferrante, Michel, Frenette, Gary, Frick, Jacob, Ganju, Vinod, Garofalo, Michael, Geboes, Karen, Gehbauer, Gerald, George, Benjamin, Geva, Ravit, Gordon, Michael, Gregory, Kate, Gulec, Seza, Hannigan, James, van Hazel, Guy, Heching, Norman, Helmberger, Thomas, Hendlisz, Alain, Hendrickx, Koen, Holtzman, Matthew, Isaacs, Richard, Jackson, Christopher, MORRISON JR, PHILIP JAMES, Kaiser, Adeel, Karapetis, Chris, Kaubisch, Andreas, Yon-Dschun, Ko, Krã¶ning, Hendrik, Lammert, Frank, Liauw, Winston, Limentani, Steven, Louafi, Samy, de Man, Marc, Margolis, Jeffrey, Martin, Robert, Martoni, Andrea, Marx, Gavin, Matos, Marco, Monsaert, Els, Moons, Veerle, Nott, Louise, Nusch, Arnd, O'Donnell, Anne, Ozer, Howard, Padia, Siddarth, Pavlakis, Nick, Perez, David, Pluntke, Stefan, Polus, Marc, Powell, Alex, Pracht, Marc, Price, Timothy, Ransom, David, Rebischung, Christine, Ridwelski, Karsten, Riera-Knorrenschild, Jorge, Riess, Hanno, Rilling, William, Robinson, Bridget, Rodrã­guez, Javier, Sanchez, Federico, Sauerbruch, Tilmann, Savin, Michael, Scheidhauer, Klemens, Schneiderman, Elyse, Seeger, Grant, Segelov, Eva, Schmueli, Einat Shaham, Shani, Adi, Shannon, Jenny, Sharma, Navesh, Shibata, Stephen, Singhal, Nimit, Smith, Denis, Smith, Randall, Stemmer, Salomon, Stã¶tzer, Oliver, Strickland, Andrew, Tatsch, Klaus, Terrebonne, Eric, Tichler, Thomas, Vehling-Kaiser, Ursula, Vera-Garcia, Ruth, Vogl, Thomas, Walpole, Euan, Wang, Eric, Whiting, Samuel, Wolf, Ido, Ades, Steven, Aghmesheh, Morteza, Auber, Miklos, Ayala, Hubert, Boland, Patrick, Bouche, Eveline, Bowers, Charles, Bremer, Christoph, Burge, Mathew, Casado, Ana Ruiz, Cooray, Prasad, Crain, Martin, De Wit, Maike, Deleporte, Amelie, Dowling, Kyran, Durand, Aurelie, Faivre, Sandrine, Feeney, Kynan, Ferguson, Tom, Ferru, Aurelie, Fragoso, Maria, Granetto, Cristina, Hammel, Pascal, Issacs, Richard, Iyer, Renuka, Kim, Yeul Hong, Liang, Jin Tung, Lim, Lionel, Liu, Jin Hwang, Masi, Gianluca, Mosconi, Stefania, Numico, Gianmauro, Ratner, Lynn, Sae-Won, Han, Singh, Madhu, Stoltzfus, Patricia, Tan, Iain, Trogu, Antonio, Underhill, Craig, Westcott, Mark, FOXFIRE Trial Investigators, SIRFLOX Trial Investigators, and FOXFIRE-Global Trial Investigators

Subjects
Aged, 80 and over, Adult, Male, Radiotherapy, Brachytherapy, Liver Neoplasms, Aged, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms, Disease-Free Survival, Female, Humans, Middle Aged, Radiotherapy, Adjuvant, Treatment Outcome, Oncology, Articles, digestive system diseases, Editorial, Colonic Neoplasms, 80 and over, Human medicine, Adjuvant
Abstract

Background Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. Methods FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1: 1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m(2) oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m(2) bolus fluorouracil followed by a 2400 mg/m(2) continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m(2) oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m(2) bolus fluorouracil followed by a 2400 mg/m(2) continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global). Findings Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43.3 months (IQR 31.6-58.4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1.04, 95% CI 0.90-1.19; p=0.61). The median survival time in the FOLFOX plus SIRT group was 22.6 months (95% CI 21.0-24.5) compared with 23.3 months (21.8-24.7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3-4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group. Interpretation Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Published
2017

18. Management of Inguinal Involvement of Peritoneal Surface Malignancies by Cytoreduction and HIPEC with Inguinal Perfusion

Author

Shachar, Yair, primary, Adileh, Mohamed, additional, Keidar, Assaf, additional, Eid, Luminita, additional, Hubert, Ayalah, additional, Temper, Mark, additional, Azam, Salah, additional, Beny, Alex, additional, Grednader, Tal, additional, Khalaileh, Abed, additional, Yuval, Jonathan B., additional, Stojadinovic, Alexander, additional, Avital, Itzhak, additional, and Nissan, Aviram, additional

Published
2015
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22. Intratumoral HLA-DR - /CD33 + /CD11b + Myeloid-Derived Suppressor Cells Predict Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Author

Hasnis E, Dahan A, Khoury W, Duek D, Fisher Y, Beny A, Shaked Y, Chowers Y, and Half EE

Abstract

Capecitabine-based neoadjuvant chemoradiation therapy (nCRT) is currently the mainstay of treatment for locally advanced rectal cancer (LARC), prior to surgical tumor removal. While response to this treatment is partial, it carries significant risk of side effects. As of today, there is no accepted model to predict tumor response, and allow for patient stratification. The level of circulating Myeloid-derived suppressor cells (MDSCs), a subpopulation of early myeloid cells (EMCs), has been shown to correlate with prognosis and response to therapy in advanced colon cancer, but their role in LARC is not clear. We sought to study the effect of intratumoral and circulating levels of different EMCs subpopulations including MDSCs on response to nCRT. We analyzed tumor, normal mucosa, and peripheral blood samples from 25 LARC patients for their different EMCs subpopulation before and after nCRT, and correlated them with degree of pathologic response, as determined postoperatively. In addition, we compared LARC patient to 10 healthy donors and 6 metastatic patients. CD33 + HLA-DR - CD16 - CD11b + EMCs in the circulation of LARC patients were found to inhibit T-cell activation. Furthermore, elevated levels of CD33 + HLA-DR - myeloid cells were found in the tumor relative to normal mucosa, but not in the circulation when compared to healthy subjects. Moreover, intratumoral, but not circulating levels of MDSCs correlated with clinical stage and response to therapy in patients treated with nCRT, with high levels of MDSCs significantly predicting poor response to nCRT. Importantly, therapy by itself, had significant differential effects on MDSC levels, leading to increased circulating MDSCs, concomitantly with decreasing intratumoral MDSCs. Our results suggest that high levels of intratumoral, but not circulating MDSCs may confer drug resistance due to immunomodulatory effects, and serve as a biomarker for patient stratification and decision-making prior to nCRT., (Copyright © 2020 Hasnis, Dahan, Khoury, Duek, Fisher, Beny, Shaked, Chowers and Half.)

Published
2020
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