Author: "Ganju, V." - Searchworks@Jio Institute Digital Library Search Results

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317 results on '"Ganju, V."'

1. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author: Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.
Published: 2021
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2. Prognostic gene expression signature for high-grade serous ovarian cancer

Author: Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.
Published: 2020
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3. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial

Author: Ahn, JB, Asselah, J, Badarinath, S, Baijal, S, Begbie, S, Berry, S, Canon, JL, Carbone, RG, Cervantes, A, Cha, YJ, Chang, K, Chaudhry, A, Chmielowska, E, Cho, SH, Chu, D, Couture, F, Cultrera, J, Cunningham, D, Van Cutsem, E, Cuyle, PJ, Davies, J, Dowden, S, Dvorkin, M, Ganju, V, Garcia, RV, Kerr, R, Kim, TY, King, K, Kortmansky, J, Kozloff, M, Lam, KO, Lee, J, Lee, AS, Lesperance, B, Luppi, G, Ma, B, Maiello, E, Mandanas, R, Marshall, J, Marx, G, Mullamitha, S, Nechaeva, M, Park, JO, Pavlakis, N, Ponce, CG, Potemski, P, Raouf, S, Reeves, J, Segal, N, Siena, S, Smolin, A, Streb, JO, Strickland, A, Szutowicz-Zielinska, E, Tabernero, JM, Tan, B, Valera, JS, Van den Eynde, M, Vergauwe, P, Vickers, M, Womack, M, Wroblewska, M, Young, R, Eng, Cathy, Kim, Tae Won, Bendell, Johanna, Argilés, Guillem, Tebbutt, Niall C, Di Bartolomeo, Maria, Falcone, Alfredo, Fakih, Marwan, Kozloff, Mark, Segal, Neil H, Sobrero, Alberto, Yan, Yibing, Chang, Ilsung, Uyei, Anne, Roberts, Louise, and Ciardiello, Fortunato
Published: 2019
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4. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author: Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Block, Matthew S., Vierkant, Robert A., Rambau, Peter F., Winham, Stacey J., Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G., Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H., Ramón y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B., Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M., Mack, Marie, Lubiński, Jan, Longacre, Teri A., Li, Zheng, Lester, Jenny, Kennedy, Catherine J., Kalli, Kimberly R., Jung, Audrey Y., Johnatty, Sharon E., Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P., Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y., Hartkopf, Andreas D., Harnett, Paul R., Ghatage, Prafull, García-Bueno, José M., Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P., de Sousa, Christiani B., de Andrade, Jurandyr M., Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y., Alsop, Jennifer, Whittemore, Alice S., Steed, Helen, Staebler, Annette, Moysich, Kirsten B., Menon, Usha, Koziak, Jennifer M., Kommoss, Stefan, Kjaer, Susanne K., Kelemen, Linda E., Karlan, Beth Y., Huntsman, David G., Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T., Gilks, Blake, García, María José, Fasching, Peter A., de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido dos Reis, Francisco J., Campbell, Ian G., Brenton, James D., Bowtell, David D., Benítez, Javier, Pharoah, Paul D.P., Köbel, Martin, Ramus, Susan J., and Goode, Ellen L.
Published: 2018
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5. 1028P Preliminary phase I results from a first-in-human study of EMB-02, a PD-1xLAG-3 bispecific antibody, in patients (pts) with advanced solid tumors

Author: Day, D., primary, Ganju, V., additional, Chung, K., additional, Si, L., additional, Mao, L., additional, Aghmesheh, M., additional, Hoyer, R., additional, Brewin, K., additional, Zeng, S., additional, Lu, Q., additional, Jiang, C., additional, Ren, F., additional, Wu, X., additional, and Guo, J., additional
Published: 2023
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6. 202P A phase Ib/II study of OP-1250, an oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) with palbociclib in patients (pts) with advanced or metastatic ER-positive, HER2-negative breast cancer (MBC)

Author: Chan, A., primary, Dinh, P., additional, Day, D., additional, Slancar, M., additional, Ganju, V., additional, McCarthy, N.J., additional, Lombard, J., additional, Faltaos, D., additional, Shilkrut, M., additional, Wilson, R., additional, and Murphy, C., additional
Published: 2023
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7. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author: Block, Matthew S., Vierkant, Robert A., Rambau, Peter F., Winham, Stacey J., Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G., Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H., Cajal, Teresa Ramón y, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B., Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M., Mack, Marie, Lubiński, Jan, Longacre, Teri A., Li, Zheng, Lester, Jenny, Kennedy, Catherine J., Kalli, Kimberly R., Jung, Audrey Y., Johnatty, Sharon E., Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P., Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y., Hartkopf, Andreas D., Harnett, Paul R., Ghatage, Prafull, García-Bueno, José M., Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P., de Sousa, Christiani B., de Andrade, Jurandyr M., Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y., Alsop, Jennifer, Whittemore, Alice S., Steed, Helen, Staebler, Annette, Moysich, Kirsten B., Menon, Usha, Koziak, Jennifer M., Kommoss, Stefan, Kjaer, Susanne K., Kelemen, Linda E., Karlan, Beth Y., Huntsman, David G., Hφgdall, Estrid, Gronwald, Jacek, Goodman, Marc T., Gilks, Blake, García, María José, Fasching, Peter A., de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido dos Reis, Francisco J., Campbell, Ian G., Brenton, James D., Bowtell, David D., Benítez, Javier, Pharoah, Paul D.P., Köbel, Martin, Ramus, Susan J., Goode, Ellen L., Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, Vanden T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y. E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M. K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., OʼCallaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L. F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., and Zeps, N.
Published: 2018
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8. EP08.02-109 A Drug-Drug Interaction Study of Mobocertinib and Midazolam in Patients With Advanced Non-Small Cell Lung Cancer

Author: Hanley, M.J., primary, Zhang, S., additional, Pavlakis, N., additional, Soo, R., additional, van der Wekken, A.J., additional, Ganju, V., additional, Pina, A., additional, Dong, Q., additional, and Gupta, N., additional
Published: 2022
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9. P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

Author: Pavlakis, N., Kichenadasse, G., Richardson, G., Bowyer, S., Andelkovic, V., Ganju, V., Tan, A., Samol, J., Thomas, D., Mas Fernandez, A., Paszkiewicz, K., Ingram, P., Boyd-Kirkup, J., and Kwek, K.Y.
Published: 2024
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10. 684TiP A phase I, open-label, multicenter, dose escalation and expansion study of HM97662 (EZH1/2 dual inhibitor) as a single agent in patients with advanced or metastatic solid tumors

Author: Keam, B., Ahn, J-H., Kim, K., Hong, S-H., Ganju, V., Lim, L.E., Kwatra, V., Body, A., Rhee, P.D., Jung, S., Yoon, J., Baek, E., and Noh, Y.S.
Published: 2024
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11. Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C

Author: Price, T.J., Zannino, D., Wilson, K., Simes, R.J., Cassidy, J., Van Hazel, G.A., Robinson, B.A., Broad, A., Ganju, V., Ackland, S.P., and Tebbutt, N.C.
Published: 2012
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12. Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer.

Author: Meyer B., Clifton S., Locke W., Luu P.-L., Du Q., Lam D., Armstrong N.J., Kumar B., Deng N., Harvey K., Swarbrick A., Ganju V., Clark S.J., Pidsley R., Stirzaker C., Meyer B., Clifton S., Locke W., Luu P.-L., Du Q., Lam D., Armstrong N.J., Kumar B., Deng N., Harvey K., Swarbrick A., Ganju V., Clark S.J., Pidsley R., and Stirzaker C.
Abstract: Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient's response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.Copyright © 2021, The Author(s).
Published: 2022

13. The influence of pretreatment 18F-FDG PET/CT in radiation therapy management for patients with locally advanced breast cancer: A prospective comparison with conventional imaging

Author: Ng, S, David, S, Alamgeer, M, and Ganju, V
Published: 2014

14. 1622P D-1553 in patients with KRAS G12C mutated advanced pancreatic cancer (pca)

Author: Kondo, S., Yan, D., Ganju, V., Richardson, G., Hou, X., Shan, J., Liu, X., Zhang, Y., Xie, X., Xiang, Z., Shi, Z., Wang, Y., Zhang, L., and Yamamoto, N.
Published: 2023
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15. 700P First-in-human dose-escalating study of ABSK043, a novel and oral small-molecule inhibitor of PD-L1, in patients with advanced solid tumors

Author: Cooper, A., Andelkovic, V., Wilkinson, K., Ganju, V., Lundy, J., Hong, M., Airey, S., Meng, L.L., Shen, B., Li, H., Yao, L., Zhang, M., and Coward, J.
Published: 2023
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16. 656MO The HER2-targeting ADC SHR-A1811 in HER2-expressing/mutated advanced non-breast solid tumors (STs): Results from the global phase I study

Author: Yao, H., Ryu, M.H., Park, J., Voskoboynik, M., Kim, J.H., Liu, K., Barve, M., Acuna-Villaorduna, A., Im, S-A., Roy, A.C., Bai, L-Y., Yen, C-J., Zhang, J., Ganju, V., Wu, L., Yan, M., Bao, L., Zhao, Y., Rong, S., and Song, E.
Published: 2023
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17. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses.

Author: Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., and Houghton R.
Abstract: TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MB
Published: 2021

18. MA06.09 Preliminary Safety, Efficacy Results of KN046 (Bispecific Anti-PD-L1/CTLA4) in Subjects With Rare Thoracic Tumors

Author: Richardson, G., primary, Kichenadasse, G., additional, Ganju, V., additional, Xu, J., additional, Van, H., additional, Kong, P., additional, Yang, F., additional, Wei, Y., additional, Lu, Y., additional, Guo, K., additional, Donato, L., additional, Xu, T., additional, and Coward, J., additional
Published: 2021
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19. Prognostic gene expression signature for high-grade serous ovarian cancer

Author: Millstein, J., primary, Budden, T., additional, Goode, E.L., additional, Anglesio, M.S., additional, Talhouk, A., additional, Intermaggio, M.P., additional, Leong, H.S., additional, Chen, S., additional, Elatre, W., additional, Gilks, B., additional, Nazeran, T., additional, Volchek, M., additional, Bentley, R.C., additional, Wang, C., additional, Chiu, D.S., additional, Kommoss, S., additional, Leung, S.C.Y., additional, Senz, J., additional, Lum, A., additional, Chow, V., additional, Sudderuddin, H., additional, Mackenzie, R., additional, George, J., additional, Fereday, S., additional, Hendley, J., additional, Traficante, N., additional, Steed, H., additional, Koziak, J.M., additional, Köbel, M., additional, McNeish, I.A., additional, Goranova, T., additional, Ennis, D., additional, Macintyre, G., additional, Silva De Silva, D., additional, Ramón y Cajal, T., additional, García-Donas, J., additional, Hernando Polo, S., additional, Rodriguez, G.C., additional, Cushing-Haugen, K.L., additional, Harris, H.R., additional, Greene, C.S., additional, Zelaya, R.A., additional, Behrens, S., additional, Fortner, R.T., additional, Sinn, P., additional, Herpel, E., additional, Lester, J., additional, Lubiński, J., additional, Oszurek, O., additional, Tołoczko, A., additional, Cybulski, C., additional, Menkiszak, J., additional, Pearce, C.L., additional, Pike, M.C., additional, Tseng, C., additional, Alsop, J., additional, Rhenius, V., additional, Song, H., additional, Jimenez-Linan, M., additional, Piskorz, A.M., additional, Gentry-Maharaj, A., additional, Karpinskyj, C., additional, Widschwendter, M., additional, Singh, N., additional, Kennedy, C.J., additional, Sharma, R., additional, Harnett, P.R., additional, Gao, B., additional, Johnatty, S.E., additional, Sayer, R., additional, Boros, J., additional, Winham, S.J., additional, Keeney, G.L., additional, Kaufmann, S.H., additional, Larson, M.C., additional, Luk, H., additional, Hernandez, B.Y., additional, Thompson, P.J., additional, Wilkens, L.R., additional, Carney, M.E., additional, Trabert, B., additional, Lissowska, J., additional, Brinton, L., additional, Sherman, M.E., additional, Bodelon, C., additional, Hinsley, S., additional, Lewsley, L.A., additional, Glasspool, R., additional, Banerjee, S.N., additional, Stronach, E.A., additional, Haluska, P., additional, Ray-Coquard, I., additional, Mahner, S., additional, Winterhoff, B., additional, Slamon, D., additional, Levine, D.A., additional, Kelemen, L.E., additional, Benitez, J., additional, Chang-Claude, J., additional, Gronwald, J., additional, Wu, A.H., additional, Menon, U., additional, Goodman, M.T., additional, Schildkraut, J.M., additional, Wentzensen, N., additional, Brown, R., additional, Berchuck, A., additional, Chenevix-Trench, G., additional, deFazio, A., additional, Gayther, S.A., additional, García, M.J., additional, Henderson, M.J., additional, Rossing, M.A., additional, Beeghly-Fadiel, A., additional, Fasching, P.A., additional, Orsulic, S., additional, Karlan, B.Y., additional, Konecny, G.E., additional, Huntsman, D.G., additional, Bowtell, D.D., additional, Brenton, J.D., additional, Doherty, J.A., additional, Pharoah, P.D.P., additional, Ramus, S.J., additional, Bowtell, D., additional, Green, A., additional, Webb, P., additional, DeFazio, A., additional, Gertig, D., additional, Moore, S., additional, Hung, J., additional, Harrap, K., additional, Sadkowsky, T., additional, Pandeya, N., additional, Malt, M., additional, Mellon, A., additional, Robertson, R., additional, Vanden Bergh, T., additional, Jones, M., additional, Mackenzie, P., additional, Maidens, J., additional, Nattress, K., additional, Chiew, Y.E., additional, Stenlake, A., additional, Sullivan, H., additional, Alexander, B., additional, Ashover, P., additional, Brown, S., additional, Corrish, T., additional, Green, L., additional, Jackman, L., additional, Ferguson, K., additional, Martin, K., additional, Martyn, A., additional, Ranieri, B., additional, White, J., additional, Jayde, V., additional, Mamers, P., additional, Bowes, L., additional, Galletta, L., additional, Giles, D., additional, Alsop, K., additional, Schmidt, T., additional, Shirley, H., additional, Ball, C., additional, Young, C., additional, Viduka, S., additional, Tran, Hoa, additional, Bilic, Sanela, additional, Glavinas, Lydia, additional, Brooks, Julia, additional, Stuart-Harris, R., additional, Kirsten, F., additional, Rutovitz, J., additional, Clingan, P., additional, Glasgow, A., additional, Proietto, A., additional, Braye, S., additional, Otton, G., additional, Shannon, J., additional, Bonaventura, T., additional, Stewart, J., additional, Begbie, S., additional, Friedlander, M., additional, Bell, D., additional, Baron-Hay, S., additional, Ferrier,a, A., additional, Gard, G., additional, Nevell, D., additional, Pavlakis, N., additional, Valmadre, S., additional, Young, B., additional, Camaris, C., additional, Crouch, R., additional, Edwards, L., additional, Hacker, N., additional, Marsden, D., additional, Robertson, G., additional, Beale, P., additional, Beith, J., additional, Carter, J., additional, Dalrymple, C., additional, Houghton, R., additional, Russell, P., additional, Links, M., additional, Grygiel, J., additional, Hill, J., additional, Brand, A., additional, Byth, K., additional, Jaworski, R., additional, Harnett, P., additional, Wain, G., additional, Ward, B., additional, Papadimos, D., additional, Crandon, A., additional, Cummings, M., additional, Horwood, K., additional, Obermair, A., additional, Perrin, L., additional, Wyld, D., additional, Nicklin, J., additional, Davy, M., additional, Oehler, M.K., additional, Hall, C., additional, Dodd, T., additional, Healy, T., additional, Pittman, K., additional, Henderson, D., additional, Miller, J., additional, Pierdes, J., additional, Blomfield, P., additional, Challis, D., additional, McIntosh, R., additional, Parker, A., additional, Brown, B., additional, Rome, R., additional, Allen, D., additional, Grant, P., additional, Hyde, S., additional, Laurie, R., additional, Robbie, M., additional, Healy, D., additional, Jobling, T., additional, Manolitsas, T., additional, McNealage, J., additional, Rogers, P., additional, Susil, B., additional, Sumithran, E., additional, Simpson, I., additional, Phillips, K., additional, Rischin, D., additional, Fox, S., additional, Johnson, D., additional, Lade, S., additional, Loughrey, M., additional, O’Callaghan, N., additional, Murray, W., additional, Waring, P., additional, Billson, V., additional, Pyman, J., additional, Neesham, D., additional, Quinn, M., additional, Underhill, C., additional, Bell, R., additional, Ng, L.F., additional, Blum, R., additional, Ganju, V., additional, Hammond, I., additional, Leung, Y., additional, McCartney, A., additional, Buck, M., additional, Haviv, I., additional, Purdie, D., additional, Whiteman, D., additional, and Zeps, N., additional
Published: 2020
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20. Phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer: double tubulin targeting

Author: Sewak, S., Kosmider, S., Ganju, V., Woollett, A., Yeow, E. G., Le, B., Henry, M., Debrincat, M. A., and Bell, R.
Published: 2010
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21. PREDICTIVE MARKERS FOR BREAST CANCER NEOADJUVANT CHEMOTHERAPY: BS12

Author: SYED, S., ROGERS, P. A. W., GANJU, V., HART, S., SUSIL, B., and CANN, L.
Published: 2007

22. Improved survival associated with prophylactic cranial irradiation (PCI) in patients with limited small cell lung cancer (SCLC). Results of an audit of single institution practice: O82

Author: BALL, D, NG, N, CHONG, J, MILNER, A, WIRTH, A, MANUS, M MAC, WHEELER, G, MICHAEL, M, and GANJU, V
Published: 2005

23. Effective treatment of leptomeningeal multiple myeloma with total craniospinal irradiation supported by second allogeneic donor stem cell infusion

Author: Quach, H, Ryan, G, Ganju, V, and Prince, H M
Published: 2005

24. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author: Gligorov, J, Ataseven, B, Verrill, M, de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Lauer, S, Shing, M, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, Van Thuan, T, Gligorov J., Ataseven B., Verrill M., de Laurentiis M., Jung K. H., Azim H. A., Al-Sakaff N., Lauer S., Shing M., Pivot X., Koroveshi D., Bouzid K., Casalnuovo M., Cascallar D., Korbenfeld E. P., Bastick P., Beith J., Colosimo M., Friedlander M., Ganju V., Green M., Patterson K., Redfern A., Richardson G., Ceric T., Gordana K., Beato C. A., Ferrari M., Hegg R., Helena V., Ismael G. F., Lessa A. E., Mano M., Morelle A., Nogueira J. A., Timcheva K., Tomova A., Tsakova M., Zlatareva-Petrova A., Asselah J., Assi H., Brezden-Masley C., Chia S., Freedman O., Harb M., Joy A. A., Kulkarni S., Prady C., Gaete A. A. A., Matamala L., Torres R., Yanez E., Franco S., Urrego M., Gugic D., Vrbanec D., Melichar B., Prausova J., Vyzula R., Pilarte R. G., Leon M. I., Munoz R., Ramos G., Azeem H. A., Aziz A. A., El Zawahry H., Osegueda F. R., Alexandre J., Artignan X., Barletta H., Beguier E., Berdah J. -F., Marty C. B., Bollet M., Bourgeois H., Bressac C., Burki F., Campone M., Coeffic D., Cojocarasu O. Z., Dagada C., Dalenc F., Del Piano F., Desauw C., Desmoulins I., Dohollou N., Egreteau J., Ferrero J. -M., Foa C., Garidi R., Gasnault L., Guardiola E., Hamizi S., Jarcau R., Jacquin J. -P., Jaubert D., Jolimoy G., Mineur H. L., Largillier R., Leduc B., Martin P., Melis A., Monge J., Moullet I., Mousseau M., Nguyen S., Orfeuvre H., Petit T., Priou F., Bach I. S., Simon H., Stefani L., Uwer L., Youssef A., Aktas B., von der Assen A., Augustin D., Balser C., Bauer L. -E., Bechtner C., Beyer G., Brucker C., Buckner U., Busch S., Christensen B., Deryal M., Farrokh A., Faust E., Friedrichs K., Graf H., Griesshammer M., Grischke E. -M., Hanle C., Heider A., Henschen S., Hesse T., Jackisch C., Kisro J., Kohler A., Kuemmel S., Lampe D., Lantzsch T., Latos K., Lex B., Liedtke C., Luedders D., Maintz C., Muller V., Overkamp F., Park-Simon T. -W., Paul M., Prechtl A., Ringsdorf U., Runnebaum I., Ruth S., Salat C., Scheffen I., Schilling J., Schmatloch S., Schmidt M., Schneeweiss A., Schrader I., Seipelt G., Simon E., Stefek A., Stickeler E., Thill M., Tio J., Tuczek A., Warm M., Weigel M., Wischnik A., Wojcinski S., Ziegler-Lohr K., Aravantinos G., Ardavanis A., Fountzilas G., Gogas H., Kakolyris S., Mavroudis D., Papadimitriou C., Papandreou C., Papazisis K., Castro H., Hernandez-Monroy C. E., Ngan R., Yeo W., Bittner N., Boer K., Csejtei A., Horvath Z., Kocsis J., Mangel L. C., Mezei K., Nagy Z., Szanto J., Atmakusuma D., Fadjari H., Kurnianda D., Prayogo N., Tanggo E. H., Coate L., Hennessy B., Kelly C., Martin M., Nasim S., O'Connor M., Aieta M., Allegrini G., Amadori D., Bidoli P., Biti G., Bordonaro R., Bottini A., Carterni G., Cavanna L., Cazzaniga M., Cognetti F., Contu A., Cruciani G., Donadio M., Falcone A., Farci D., Forcignano R. C., Frassoldati A., Gaion F., Gamucci T., Giotta F., Livi L., Lorusso V., Maiello E., Marchetti P., Mariani G., Mion M., Moscetti L., Musolino A., Pazzola A., Pedrazzoli P., Pigi A., de Placido S., Caremoli E. R., Santoro A., Tienghi A., Ahn J. -S., Lee K. S., Lee S. H., Seo J. H., Sohn J. -H., Cesas A., Juozaityte E., Cheah N. L. C., Chong F. L. T., Devi B. C. R., Phua V., Teoh D., Ching L. W., Yusof M., Corona J., Dominguez A., Mendoza R. L. G., Hernandez C. A., Ramiro A. J., Santos J. M., Espinosa P. M., Villarreal Garza C. M., Errihani H., Bakker S., van den Berkmortel F., Blaisse R. J. B., Huinink D. T. B., van den Bosch J., Braun J. J., Dercksen M. W., Droogendijk H., Erdkamp F., Haringhuizen A., de Jongh F. E., Kok T. C., Los M., Madretsma S., Terwogt J. M. M., van der Padt A., van Rossum-Schornagel Q. C., Smilde T. J., de Valk B., van der Velden A., van Warmerdam L., van de Wouw A. J., North R., Kersten C., Mjaaland I., Wist E., Aziz Z., Masood N., Rashid K., Shah M., Alcedo J. C., Aleman D., Neciosup S., Reategui R., Valdiviezo N., Vera L., Fernando G., Roque F., Strebel H. M., Krzemieniecki K., Litwiniuk M., Mruk A., Pienkowski T., Sawrycki P., Slomian G., Tomczak P., Afonso N., Cardoso F., Damasceno M., Nave M., Badulescu F., Ciule L., Curescu S., Eniu A., Filip D., Grecea D., Jinga D. -C., Lungulescu D., Oprean C. M., Stanculeanu D. L., Turdean M., Dvornichenko V., Emelyanov S., Lichinitser M., Manikhas A., Sakaeva D., Shirinkin V., Stroyakovskiy D., Abulkhair O., Zekri J., Filipovic S., Kovcin V., Nedovic J., Pesic J., Vasovic S., Ng R., Bystricky B., Leskova J., Mardiak J., Misurova E., Wagnerova M., Takac I., Demetriou G. S., Dreosti L., Govender P., Jordaan J. P., Veersamy P., Romero J. L. A., Lopez N. B., Arias C. C., Chacon J., Aramburo A. F., Morales L. A. F., Garcia M., Estevez L. G., Garcia-Palomo Perez A., Garcia Saenz J. A., Garcia Sanchis L., Cubells L. G., Cortijo L. G., Santiago S. G., De Aranguiz B. H. F., Manas J. J. I., Gallego P. J., Cussac A. L., Ferrandiz C. L., Garrido M. L., Alvarez P. L., Vega J. M. L., Del Prado P. M., Janez N. M., Murillo S. M., Rosales A. M., Jaso L. M., Fernandez I. P., Martorell A. P., Carrion R. P., Simon S. P., Alcibar A. P., Lorenzo J. P., Garcia V. Q., Asensio T. R. Y. C., Maicas M. D. T., Villanueva Silva M. J., Killander F., Svensson J. H., Fehr M., Hauser N., Muller A., Pagani O., Passmann-Kegel H., Popescu R., Rabaglio M., Rauch D., Schlatter C., Zaman K., Chang T. -W., Huang C. -S., Wang H. -C., Yu J. -C., Bandidwattanawong C., Maneechavakajorn J., Seetalarom K., Dejthevaporn T. S., Somwangprasert A., Vongsaisuwon M., Akbulut H., Altundag K., Arican A., Bozcuk H., Eralp Y., Idris M., Isikdogan A., Senol C. H., Sevinc A., Uygun K., Yucel E., Yucel I., Yumuk F., Shparyk Y., Voitko N., Jaloudi M., Adams J., Agrawal R., Ahmed S., Alhasso A., Allerton R., Anwar S., Archer C., Ashford R., Barraclough L., Bertelli G., Bishop J., Branson T., Butt M., Chakrabarti A., Chakraborti P., Churn M., Crowley C., Davis R., Dhadda A., Eldeeb H., Fraser J., Hall J., Hickish T., Hogg M., Howe T., Joffe J., Kelleher M., Kelly S., Kendall A., Kristeleit H., Lumsden G., Macmillan C., MacPherson I., Malik Z., Mithal N., Neal A., Panwar U., Proctor A., Proctor S. J., Raj S., Rehman S., Sandri I., Scatchard K., Sherwin E., Sims E., Singer J., Smith S., Tahir S., Taylor W., Tsalic M., Wardley A., Waters S., Wheatley D., Wright K., Yuille F., Alonso I., Artagaveytia N., Rodriguez R., Arbona E., Garcia Y., Lion L., Marcano D., Van Thuan T., Gligorov, J, Ataseven, B, Verrill, M, de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Lauer, S, Shing, M, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, Van Thuan, T, Gligorov J., Ataseven B., Verrill M., de Laurentiis M., Jung K. H., Azim H. A., Al-Sakaff N., Lauer S., Shing M., Pivot X., Koroveshi D., Bouzid K., Casalnuovo M., Cascallar D., Korbenfeld E. P., Bastick P., Beith J., Colosimo M., Friedlander M., Ganju V., Green M., Patterson K., Redfern A., Richardson G., Ceric T., Gordana K., Beato C. A., Ferrari M., Hegg R., Helena V., Ismael G. F., Lessa A. E., Mano M., Morelle A., Nogueira J. A., Timcheva K., Tomova A., Tsakova M., Zlatareva-Petrova A., Asselah J., Assi H., Brezden-Masley C., Chia S., Freedman O., Harb M., Joy A. A., Kulkarni S., Prady C., Gaete A. A. A., Matamala L., Torres R., Yanez E., Franco S., Urrego M., Gugic D., Vrbanec D., Melichar B., Prausova J., Vyzula R., Pilarte R. G., Leon M. I., Munoz R., Ramos G., Azeem H. A., Aziz A. A., El Zawahry H., Osegueda F. R., Alexandre J., Artignan X., Barletta H., Beguier E., Berdah J. -F., Marty C. B., Bollet M., Bourgeois H., Bressac C., Burki F., Campone M., Coeffic D., Cojocarasu O. Z., Dagada C., Dalenc F., Del Piano F., Desauw C., Desmoulins I., Dohollou N., Egreteau J., Ferrero J. -M., Foa C., Garidi R., Gasnault L., Guardiola E., Hamizi S., Jarcau R., Jacquin J. -P., Jaubert D., Jolimoy G., Mineur H. L., Largillier R., Leduc B., Martin P., Melis A., Monge J., Moullet I., Mousseau M., Nguyen S., Orfeuvre H., Petit T., Priou F., Bach I. S., Simon H., Stefani L., Uwer L., Youssef A., Aktas B., von der Assen A., Augustin D., Balser C., Bauer L. -E., Bechtner C., Beyer G., Brucker C., Buckner U., Busch S., Christensen B., Deryal M., Farrokh A., Faust E., Friedrichs K., Graf H., Griesshammer M., Grischke E. -M., Hanle C., Heider A., Henschen S., Hesse T., Jackisch C., Kisro J., Kohler A., Kuemmel S., Lampe D., Lantzsch T., Latos K., Lex B., Liedtke C., Luedders D., Maintz C., Muller V., Overkamp F., Park-Simon T. -W., Paul M., Prechtl A., Ringsdorf U., Runnebaum I., Ruth S., Salat C., Scheffen I., Schilling J., Schmatloch S., Schmidt M., Schneeweiss A., Schrader I., Seipelt G., Simon E., Stefek A., Stickeler E., Thill M., Tio J., Tuczek A., Warm M., Weigel M., Wischnik A., Wojcinski S., Ziegler-Lohr K., Aravantinos G., Ardavanis A., Fountzilas G., Gogas H., Kakolyris S., Mavroudis D., Papadimitriou C., Papandreou C., Papazisis K., Castro H., Hernandez-Monroy C. E., Ngan R., Yeo W., Bittner N., Boer K., Csejtei A., Horvath Z., Kocsis J., Mangel L. C., Mezei K., Nagy Z., Szanto J., Atmakusuma D., Fadjari H., Kurnianda D., Prayogo N., Tanggo E. H., Coate L., Hennessy B., Kelly C., Martin M., Nasim S., O'Connor M., Aieta M., Allegrini G., Amadori D., Bidoli P., Biti G., Bordonaro R., Bottini A., Carterni G., Cavanna L., Cazzaniga M., Cognetti F., Contu A., Cruciani G., Donadio M., Falcone A., Farci D., Forcignano R. C., Frassoldati A., Gaion F., Gamucci T., Giotta F., Livi L., Lorusso V., Maiello E., Marchetti P., Mariani G., Mion M., Moscetti L., Musolino A., Pazzola A., Pedrazzoli P., Pigi A., de Placido S., Caremoli E. R., Santoro A., Tienghi A., Ahn J. -S., Lee K. S., Lee S. H., Seo J. H., Sohn J. -H., Cesas A., Juozaityte E., Cheah N. L. C., Chong F. L. T., Devi B. C. R., Phua V., Teoh D., Ching L. W., Yusof M., Corona J., Dominguez A., Mendoza R. L. G., Hernandez C. A., Ramiro A. J., Santos J. M., Espinosa P. M., Villarreal Garza C. M., Errihani H., Bakker S., van den Berkmortel F., Blaisse R. J. B., Huinink D. T. B., van den Bosch J., Braun J. J., Dercksen M. W., Droogendijk H., Erdkamp F., Haringhuizen A., de Jongh F. E., Kok T. C., Los M., Madretsma S., Terwogt J. M. M., van der Padt A., van Rossum-Schornagel Q. C., Smilde T. J., de Valk B., van der Velden A., van Warmerdam L., van de Wouw A. J., North R., Kersten C., Mjaaland I., Wist E., Aziz Z., Masood N., Rashid K., Shah M., Alcedo J. C., Aleman D., Neciosup S., Reategui R., Valdiviezo N., Vera L., Fernando G., Roque F., Strebel H. M., Krzemieniecki K., Litwiniuk M., Mruk A., Pienkowski T., Sawrycki P., Slomian G., Tomczak P., Afonso N., Cardoso F., Damasceno M., Nave M., Badulescu F., Ciule L., Curescu S., Eniu A., Filip D., Grecea D., Jinga D. -C., Lungulescu D., Oprean C. M., Stanculeanu D. L., Turdean M., Dvornichenko V., Emelyanov S., Lichinitser M., Manikhas A., Sakaeva D., Shirinkin V., Stroyakovskiy D., Abulkhair O., Zekri J., Filipovic S., Kovcin V., Nedovic J., Pesic J., Vasovic S., Ng R., Bystricky B., Leskova J., Mardiak J., Misurova E., Wagnerova M., Takac I., Demetriou G. S., Dreosti L., Govender P., Jordaan J. P., Veersamy P., Romero J. L. A., Lopez N. B., Arias C. C., Chacon J., Aramburo A. F., Morales L. A. F., Garcia M., Estevez L. G., Garcia-Palomo Perez A., Garcia Saenz J. A., Garcia Sanchis L., Cubells L. G., Cortijo L. G., Santiago S. G., De Aranguiz B. H. F., Manas J. J. I., Gallego P. J., Cussac A. L., Ferrandiz C. L., Garrido M. L., Alvarez P. L., Vega J. M. L., Del Prado P. M., Janez N. M., Murillo S. M., Rosales A. M., Jaso L. M., Fernandez I. P., Martorell A. P., Carrion R. P., Simon S. P., Alcibar A. P., Lorenzo J. P., Garcia V. Q., Asensio T. R. Y. C., Maicas M. D. T., Villanueva Silva M. J., Killander F., Svensson J. H., Fehr M., Hauser N., Muller A., Pagani O., Passmann-Kegel H., Popescu R., Rabaglio M., Rauch D., Schlatter C., Zaman K., Chang T. -W., Huang C. -S., Wang H. -C., Yu J. -C., Bandidwattanawong C., Maneechavakajorn J., Seetalarom K., Dejthevaporn T. S., Somwangprasert A., Vongsaisuwon M., Akbulut H., Altundag K., Arican A., Bozcuk H., Eralp Y., Idris M., Isikdogan A., Senol C. H., Sevinc A., Uygun K., Yucel E., Yucel I., Yumuk F., Shparyk Y., Voitko N., Jaloudi M., Adams J., Agrawal R., Ahmed S., Alhasso A., Allerton R., Anwar S., Archer C., Ashford R., Barraclough L., Bertelli G., Bishop J., Branson T., Butt M., Chakrabarti A., Chakraborti P., Churn M., Crowley C., Davis R., Dhadda A., Eldeeb H., Fraser J., Hall J., Hickish T., Hogg M., Howe T., Joffe J., Kelleher M., Kelly S., Kendall A., Kristeleit H., Lumsden G., Macmillan C., MacPherson I., Malik Z., Mithal N., Neal A., Panwar U., Proctor A., Proctor S. J., Raj S., Rehman S., Sandri I., Scatchard K., Sherwin E., Sims E., Singer J., Smith S., Tahir S., Taylor W., Tsalic M., Wardley A., Waters S., Wheatley D., Wright K., Yuille F., Alonso I., Artagaveytia N., Rodriguez R., Arbona E., Garcia Y., Lion L., Marcano D., and Van Thuan T.
Abstract: Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.
Published: 2017

25. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial

Author: Eng, Cathy, primary, Kim, Tae Won, additional, Bendell, Johanna, additional, Argilés, Guillem, additional, Tebbutt, Niall C, additional, Di Bartolomeo, Maria, additional, Falcone, Alfredo, additional, Fakih, Marwan, additional, Kozloff, Mark, additional, Segal, Neil H, additional, Sobrero, Alberto, additional, Yan, Yibing, additional, Chang, Ilsung, additional, Uyei, Anne, additional, Roberts, Louise, additional, Ciardiello, Fortunato, additional, Ahn, JB, additional, Asselah, J, additional, Badarinath, S, additional, Baijal, S, additional, Begbie, S, additional, Berry, S, additional, Canon, JL, additional, Carbone, RG, additional, Cervantes, A, additional, Cha, YJ, additional, Chang, K, additional, Chaudhry, A, additional, Chmielowska, E, additional, Cho, SH, additional, Chu, D, additional, Couture, F, additional, Cultrera, J, additional, Cunningham, D, additional, Van Cutsem, E, additional, Cuyle, PJ, additional, Davies, J, additional, Dowden, S, additional, Dvorkin, M, additional, Ganju, V, additional, Garcia, RV, additional, Kerr, R, additional, Kim, TY, additional, King, K, additional, Kortmansky, J, additional, Kozloff, M, additional, Lam, KO, additional, Lee, J, additional, Lee, AS, additional, Lesperance, B, additional, Luppi, G, additional, Ma, B, additional, Maiello, E, additional, Mandanas, R, additional, Marshall, J, additional, Marx, G, additional, Mullamitha, S, additional, Nechaeva, M, additional, Park, JO, additional, Pavlakis, N, additional, Ponce, CG, additional, Potemski, P, additional, Raouf, S, additional, Reeves, J, additional, Segal, N, additional, Siena, S, additional, Smolin, A, additional, Streb, JO, additional, Strickland, A, additional, Szutowicz-Zielinska, E, additional, Tabernero, JM, additional, Tan, B, additional, Valera, JS, additional, Van den Eynde, M, additional, Vergauwe, P, additional, Vickers, M, additional, Womack, M, additional, Wroblewska, M, additional, and Young, R, additional
Published: 2019
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26. BRAF mutations in low-grade serous ovarian cancer and response to BRAF inhibition.

Author: Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., and Pavlakis N.
Abstract: Purpose Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Patients and Methods Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Results Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. Conclusion BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.Copyright © 2019 Am
Published: 2019

27. Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer.

Author: Asselin-Labat M.-L., Cain J.E., Papenfuss A.T., Cowley M.J., Watkins D.N., Leong T.L., Gayevskiy V., Steinfort D.P., De Massy M.R., Gonzalez-Rajal A., Marini K.D., Stone E., Chin V., Havryk A., Plit M., Irving L.B., Jennings B.R., McCloy R.A., Jayasekara W.S.N., Alamgeer M., Boolell V., Field A., Russell P.A., Kumar B., Gough D.J., Szczepny A., Ganju V., Rossello F.J., Asselin-Labat M.-L., Cain J.E., Papenfuss A.T., Cowley M.J., Watkins D.N., Leong T.L., Gayevskiy V., Steinfort D.P., De Massy M.R., Gonzalez-Rajal A., Marini K.D., Stone E., Chin V., Havryk A., Plit M., Irving L.B., Jennings B.R., McCloy R.A., Jayasekara W.S.N., Alamgeer M., Boolell V., Field A., Russell P.A., Kumar B., Gough D.J., Szczepny A., Ganju V., and Rossello F.J.
Abstract: Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.Copyright © 2018, The Author(s).
Published: 2019

28. Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC.

Author: Harris M., Parker B.S., Kumar B., Fox J., White M., Brockwell N.K., Rautela J., Owen K.L., Gearing L.J., Deb S., Harvey K., Spurling A., Zanker D., Chan C.-L., Cumming H.E., Deng N., Zakhour J.M., Duivenvoorden H.M., Robinson T., Ooi C., Thomson J., Potasz N., Swarbrick A., Hertzog P.J., Molloy T.J., Toole S.O., Ganju V., Harris M., Parker B.S., Kumar B., Fox J., White M., Brockwell N.K., Rautela J., Owen K.L., Gearing L.J., Deb S., Harvey K., Spurling A., Zanker D., Chan C.-L., Cumming H.E., Deng N., Zakhour J.M., Duivenvoorden H.M., Robinson T., Ooi C., Thomson J., Potasz N., Swarbrick A., Hertzog P.J., Molloy T.J., Toole S.O., and Ganju V.
Abstract: Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention.Copyright © 2019, The Author(s).
Published: 2019

29. Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC

Author: Brockwell, NK, Rautela, J, Owen, KL, Gearing, LJ, Deb, S, Harvey, K, Spurling, A, Zanker, D, Chan, C-L, Cumming, HE, Deng, N, Zakhour, JM, Duivenvoorden, HM, Robinson, T, Harris, M, White, M, Fox, J, Ooi, C, Kumar, B, Thomson, J, Potasz, N, Swarbrick, A, Hertzog, PJ, Molloy, TJ, O'Toole, S, Ganju, V, Parker, BS, Brockwell, NK, Rautela, J, Owen, KL, Gearing, LJ, Deb, S, Harvey, K, Spurling, A, Zanker, D, Chan, C-L, Cumming, HE, Deng, N, Zakhour, JM, Duivenvoorden, HM, Robinson, T, Harris, M, White, M, Fox, J, Ooi, C, Kumar, B, Thomson, J, Potasz, N, Swarbrick, A, Hertzog, PJ, Molloy, TJ, O'Toole, S, Ganju, V, and Parker, BS
Abstract: Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention.
Published: 2019

30. Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer

Author: Leong, TL, Gayevskiy, V, Steinfort, DP, De Massy, MR, Gonzalez-Rajal, A, Marini, KD, Stone, E, Chin, V, Havryk, A, Plit, M, Irving, LB, Jennings, BR, McCloy, RA, Jayasekara, WSN, Alamgeer, M, Boolell, V, Field, A, Russell, PA, Kumar, B, Gough, DJ, Szczepny, A, Ganju, V, Rossello, FJ, Cain, JE, Papenfuss, AT, Asselin-Labat, M-L, Cowley, MJ, Watkins, DN, Leong, TL, Gayevskiy, V, Steinfort, DP, De Massy, MR, Gonzalez-Rajal, A, Marini, KD, Stone, E, Chin, V, Havryk, A, Plit, M, Irving, LB, Jennings, BR, McCloy, RA, Jayasekara, WSN, Alamgeer, M, Boolell, V, Field, A, Russell, PA, Kumar, B, Gough, DJ, Szczepny, A, Ganju, V, Rossello, FJ, Cain, JE, Papenfuss, AT, Asselin-Labat, M-L, Cowley, MJ, and Watkins, DN
Abstract: Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.
Published: 2019

31. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial

Author: UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'oncologie médicale, Eng, Cathy, Kim, Tae Won, Bendell, Johanna, Argilés, Guillem, Tebbutt, Niall C, Di Bartolomeo, Maria, Falcone, Alfredo, Fakih, Marwan, Kozloff, Mark, Segal, Neil H, Sobrero, Alberto, Yan, Yibing, Chang, Ilsung, Uyei, Anne, Roberts, Louise, Ciardiello, Fortunato, Ahn, JB, Asselah, J, Badarinath, S, Baijal, S, Begbie, S, Berry, S, Canon, JL, Carbone, RG, Cervantes, A, Cha, YJ, Chang, K, Chaudhry, A, Chmielowska, E, Cho, SH, Chu, D, Couture, F, Cultrera, J, Cunningham, D, Van Cutsem, E, Cuyle, PJ, Davies, J, Dowden, S, Dvorkin, M, Ganju, V, Garcia, RV, Kerr, R, Kim, TY, King, K, Kortmansky, J, Kozloff, M, Lam, KO, Lee, J, Lee, AS, Lesperance, B, Luppi, G, Ma, B, Maiello, E, Mandanas, R, Marshall, J, Marx, G, Mullamitha, S, Nechaeva, M, Park, JO, Pavlakis, N, Ponce, CG, Potemski, P, Raouf, S, Reeves, J, Segal, N, Siena, S, Smolin, A, Streb, JO, Strickland, A, Szutowicz-Zielinska, E, Tabernero, JM, Tan, B, Valera, JS, Van den Eynde, Marc, Vergauwe, P, Vickers, M, Womack, M, Wroblewska, M, Young, R, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'oncologie médicale, Eng, Cathy, Kim, Tae Won, Bendell, Johanna, Argilés, Guillem, Tebbutt, Niall C, Di Bartolomeo, Maria, Falcone, Alfredo, Fakih, Marwan, Kozloff, Mark, Segal, Neil H, Sobrero, Alberto, Yan, Yibing, Chang, Ilsung, Uyei, Anne, Roberts, Louise, Ciardiello, Fortunato, Ahn, JB, Asselah, J, Badarinath, S, Baijal, S, Begbie, S, Berry, S, Canon, JL, Carbone, RG, Cervantes, A, Cha, YJ, Chang, K, Chaudhry, A, Chmielowska, E, Cho, SH, Chu, D, Couture, F, Cultrera, J, Cunningham, D, Van Cutsem, E, Cuyle, PJ, Davies, J, Dowden, S, Dvorkin, M, Ganju, V, Garcia, RV, Kerr, R, Kim, TY, King, K, Kortmansky, J, Kozloff, M, Lam, KO, Lee, J, Lee, AS, Lesperance, B, Luppi, G, Ma, B, Maiello, E, Mandanas, R, Marshall, J, Marx, G, Mullamitha, S, Nechaeva, M, Park, JO, Pavlakis, N, Ponce, CG, Potemski, P, Raouf, S, Reeves, J, Segal, N, Siena, S, Smolin, A, Streb, JO, Strickland, A, Szutowicz-Zielinska, E, Tabernero, JM, Tan, B, Valera, JS, Van den Eynde, Marc, Vergauwe, P, Vickers, M, Womack, M, Wroblewska, M, and Young, R
Abstract: Background Microsatellite-stable metastatic colorectal cancer is typically unresponsive to immunotherapy. This phase 3 study was designed to assess atezolizumab plus cobimetinib in metastatic colorectal cancer. Here, we report the comparison of atezolizumab plus cobimetinib or atezolizumab monotherapy versus regorafenib in the third-line setting. Methods IMblaze 370 is a multicentre, open-label, phase 3, randomised, controlled trial, done at 73 academic medical centres and community oncology practices in 11 countries. Patients aged at least 18 years with unresectable locally advanced or metastatic colorectal cancer, baseline Eastern Cooperative Oncology Group performance status of 0–1, and disease progression on or intolerance to at least two previous systemic chemotherapy regimens were enrolled. We used permuted-block randomisation (block size four) to assign patients (2:1:1) via an interactive voice and web response system to atezolizumab (840 mg intravenously every 2 weeks) plus cobimetinib (60 mg orally once daily for days 1–21 of a 28-day cycle), atezolizumab monotherapy (1200 mg intravenously every 3 weeks), or regorafenib (160 mg orally once daily for days 1–21 of a 28-day cycle). Stratification factors were extended RAS status (wild-type vs mutant) and time since diagnosis of first metastasis (<18 months vs ≥18 months). Recruitment of patients with high microsatellite instability was capped at 5%. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. IMblaze370 is ongoing and is registered with ClinicalTrials.gov, number NCT02788279. Findings Between July 27, 2016, and Jan 19, 2017, 363 patients were enrolled (183 patients in the atezolizumab plus cobimetinib group, 90 in the atezolizumab group, and 90 in the regorafenib group). At data cutoff (March 9, 2018), median follow-up was 7·3 months (IQR 3·7–13·6). Median overall su
Published: 2019

32. Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy.

Author: Boolell V., Vaghjiani V., Gonzalez-Rajal A., Hastings J.F., Chin V., Szczepny A., Kostyrko K., Marquez C., Samantha W., Jayasekara N., McCloy R.A., Han J.Z.R., Waugh T., Lee H.C., Oakes S.R., Harrison C.A., Hedger M.P., Lorensuhewa N., Kita B., Barrow R., Robinson B.W., De Kretser D.M., Wu J., Ganju V., Alejandro Sweet-Cordero E., Burgess A., Martelotto L.G., Rossello F.J., Cain J.E., Neil Watkins D., Kumar B., Alamgeer M., Marini K.D., Croucher D.R., Boolell V., Vaghjiani V., Gonzalez-Rajal A., Hastings J.F., Chin V., Szczepny A., Kostyrko K., Marquez C., Samantha W., Jayasekara N., McCloy R.A., Han J.Z.R., Waugh T., Lee H.C., Oakes S.R., Harrison C.A., Hedger M.P., Lorensuhewa N., Kita B., Barrow R., Robinson B.W., De Kretser D.M., Wu J., Ganju V., Alejandro Sweet-Cordero E., Burgess A., Martelotto L.G., Rossello F.J., Cain J.E., Neil Watkins D., Kumar B., Alamgeer M., Marini K.D., and Croucher D.R.
Abstract: Resistance to platinum chemotherapy is a long-standing problem in the management of lung adenocarcinoma. Using a whole-genome synthetic lethal RNA interference screen, we identified activin signaling as a critical mediator of innate platinum resistance. The transforming growth factor- (TGF) superfamily ligands activin A and growth differentiation factor 11 (GDF11) mediated resistance via their cognate receptors through TGF-activated kinase 1 (TAK1), rather than through the SMAD family of transcription factors. Inhibition of activin receptor signaling or blockade of activin A and GDF11 by the endogenous protein follistatin overcame this resistance. Consistent with the role of activin signaling in acute renal injury, both therapeutic interventions attenuated acute cisplatin-induced nephrotoxicity, its major dose-limiting side effect. This cancer-specific enhancement of platinum-induced cell death has the potential to dramatically improve the safety and efficacy of chemotherapy in lung cancer patients.Copyright © 2018 The Authors, some rights reserved.
Published: 2018

33. A phase IIa study of HA-irinotecan, formulation of hyaluronic acid and irinotecan targeting CD44 in extensive-stage small cell lung cancer.

Author: Neil Watkins D., Markman B., Ganju V., Alamgeer M., Kumar B., Gough D.J., Banakh I., Neil Watkins D., Markman B., Ganju V., Alamgeer M., Kumar B., Gough D.J., and Banakh I.
Abstract: Preclinical studies in small cell lung cancer (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver chemotherapy and selectively decrease CD44 expressing (stem cell-like) tumour cells. The current study aimed to replicate these findings and obtain data on safety and activity of HA-irinotecan (HA-IR). Eligible patients with extensive stage SCLC were consented. A safety cohort (n = 5) was treated with HA-IR and Carboplatin (C). Subsequently, the patients were randomised 1:1 to receive experimental (HA-IR + C) or standard (IR + C) treatment, to a maximum of 6 cycles. The second line patients were added to the study and treated with open label HA-IR + C. Tumour response was measured after every 2 cycles. Baseline tumour specimens were stained for CD44s and CD44v6 expression. Circulating tumour cells (CTCs) were enumerated before each treatment cycle. Out of 39 patients screened, 34 were evaluable for the study. The median age was 66 (range 39-83). The overall response rates were 69% and 75% for experimental and standard arms respectively. Median progression free survival was 42 and 28 weeks, respectively (p = 0.892). The treatments were well tolerated. The incidence of grade III/IV diarrhea was more common in the standard arm, while anaemia was more common in the experimental arm. IHC analysis suggested that the patients with CD44s positive tumours may gain survival benefit from HA-IR. HA-IR is well tolerated and active in ES-SCLC. The effect of HA-IR on CD44s + cancer stem-like cells provide an early hint towards a potential novel target.Copyright © 2017, Springer Science+Business Media, LLC, part of Springer Nature.
Published: 2018

34. 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: Helmberger T., Findlay M.P.N., Isaacs R., O'Donnell A., Perez D., Rodriguez J., Vera-Garcia R., Amin P., Bloomgarden D., Bui J., Carlisle J., Chai S., Chen Y.-J., Chuong M., Coveler A., Facchini F., Frenette G., Frick J., Garofalo M., George B., Gordon M., Gulec S., Hannigan J., Holtzman M., Kaubisch A., Kaiser A., Kooy T., Limentani S., Margolis J., Martin R., Ozer H., Padia S., Rilling W., Savin M., Schneiderman E., Seeger G., Shibata S., Smith R., Wang E., Whiting S., Aghmesheh M., Cooray P., Feeney K., Lim L., Singh M., Underhill C., Durand A., Faivre S., Ferru A., Hammel P., Bremer C., De Wit M., Ayala H., Heching N., Shani A., Granetto C., Masi G., Mosconi S., Numico G., Trogu A., Kim Y.H., Sae-Won H., Fragoso M., Tan I., Casado A.R., Liang J.T., Liu J.H., Ades S., Auber M., Boland P., Bowers C., Crain M., Dowling K., Iyer R., Ratner L., Sanchez F., Stoltzfus P., Westcott M., Segelov E., Strickland A., Gibbs P., Heinemann V., Sharma N., Taieb J., Ricke J., Peeters M., Robinson B.A., Jackson C., Gebski V., Van Buskirk M., Zhao H., van Hazel G., Brown M., Burge M., Cardaci G., Clarke S., Eliadis P., Ferguson T., Ganju V., James P., Karapetis C., Liauw W., Marx G., Matos M., Nott L., Pavlakis N., Powell A., Price T., Ransom D., Shannon J., Singhal N., Walpole E., Craninx M., Delaunoit T., Deleporte A., Ferrante M., Geboes K., Hendlisz A., Hendrickx K., De Man M., Monsaert E., Moons V., Polus M., Boucher E., Balosso J., Chevallier P., Louafi S., Pracht M., Rebischung C., Smith D., Terrebonne E., Bruch H.-R., Gehbauer G., Ko Y.-D., Kroning H., Lammert F., Nusch A., Pluntke S., Ridwelski K., Riera-Knorrenschild J., Riess H., Riera J.R., Sauerbruch T., Scheidhauer K., Stotzer O., Tatsch K., Vehling-Kaiser U., Vogl T., Beny A., Geva R., Shacham-Shmueli E., Stemmer S., Tichler T., Wolf I., Angelelli B., Martoni A., Helmberger T., Findlay M.P.N., Isaacs R., O'Donnell A., Perez D., Rodriguez J., Vera-Garcia R., Amin P., Bloomgarden D., Bui J., Carlisle J., Chai S., Chen Y.-J., Chuong M., Coveler A., Facchini F., Frenette G., Frick J., Garofalo M., George B., Gordon M., Gulec S., Hannigan J., Holtzman M., Kaubisch A., Kaiser A., Kooy T., Limentani S., Margolis J., Martin R., Ozer H., Padia S., Rilling W., Savin M., Schneiderman E., Seeger G., Shibata S., Smith R., Wang E., Whiting S., Aghmesheh M., Cooray P., Feeney K., Lim L., Singh M., Underhill C., Durand A., Faivre S., Ferru A., Hammel P., Bremer C., De Wit M., Ayala H., Heching N., Shani A., Granetto C., Masi G., Mosconi S., Numico G., Trogu A., Kim Y.H., Sae-Won H., Fragoso M., Tan I., Casado A.R., Liang J.T., Liu J.H., Ades S., Auber M., Boland P., Bowers C., Crain M., Dowling K., Iyer R., Ratner L., Sanchez F., Stoltzfus P., Westcott M., Segelov E., Strickland A., Gibbs P., Heinemann V., Sharma N., Taieb J., Ricke J., Peeters M., Robinson B.A., Jackson C., Gebski V., Van Buskirk M., Zhao H., van Hazel G., Brown M., Burge M., Cardaci G., Clarke S., Eliadis P., Ferguson T., Ganju V., James P., Karapetis C., Liauw W., Marx G., Matos M., Nott L., Pavlakis N., Powell A., Price T., Ransom D., Shannon J., Singhal N., Walpole E., Craninx M., Delaunoit T., Deleporte A., Ferrante M., Geboes K., Hendlisz A., Hendrickx K., De Man M., Monsaert E., Moons V., Polus M., Boucher E., Balosso J., Chevallier P., Louafi S., Pracht M., Rebischung C., Smith D., Terrebonne E., Bruch H.-R., Gehbauer G., Ko Y.-D., Kroning H., Lammert F., Nusch A., Pluntke S., Ridwelski K., Riera-Knorrenschild J., Riess H., Riera J.R., Sauerbruch T., Scheidhauer K., Stotzer O., Tatsch K., Vehling-Kaiser U., Vogl T., Beny A., Geva R., Shacham-Shmueli E., Stemmer S., Tichler T., Wolf I., Angelelli B., and Martoni A.
Abstract: The primary tumor side is emerging as a prognostic factor for patients with liver metastatic colorectal cancer (mCRC). In a combined analysis of data from 2 randomized studies, the addition of selective internal radiation therapy to first-line chemotherapy in patients with mCRC was associated with statistically and clinically significant overall survival gains for patients with a right-sided primary tumor. Background(s): The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. Result(s): In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P =.810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P =.008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P =.264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P =.002). Conclusion(s): The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated
Published: 2018

35. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Author: Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., and Hill J.
Abstract: Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s).
Published: 2018

36. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma

Author: Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, Zeps, N, Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, and Zeps, N
Abstract: Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.
Published: 2018

37. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis

Author: Eichhorst, Barbara F, Fischer, Kirsten, Fink, Anna Maria, Elter, Thomas, Wendtner, Clemens M, Goede, Valentin, Bergmann, Manuela, Stilgenbauer, Stephan, Hopfinger, Georg, Ritgen, Matthias, Bahlo, Jasmin, Busch, Raymonde, Hallek, Michael, Oduncu, F, Dreyling, M, Forstpointner, R, Schneller, F, Bogner, C, Peschel, C, Ringshausen, I, Götze, K, Goebeler, Me, Rückle, Lanz, Ritgen, M, Schawitzke, A, Heydrich, B, Kern, K, Böttcher, S, Irmer, S, Strack, U, Borries, V, Klima, Km, Scholz, C, Herold, M, Härtwig, K, Dürig, J, Dührsen, U, Müller Beissenhirtz, H, Noppeney, R, Schüttrumpf, S, Hohloch, K, Binder, C, Hasenkamp, J, Trümper, L, Bäsecke, J, Rieger, M, Witzens Harig, M, Friedrichs, B, Rieger, K, Uharek, L, Kubuschok, B, Murawski, N, Held, G, Zwick, C, Pfreundschuh, M, Fingerle Rowson, G, Reiser, M, Elter, T, Eichhorst, B, Pallasch, C, Hallek, M, Borchmann, P, Hacker, U, Schinkel, S, Wieker, K, Sökler, M, Wolf, Hh, Eucker, J, Staib, P, Schlegel, F, Kropff, M, Kahl, C, Hess, G, Beck, J, Wölfel, T, Bokemeyer, C, Schilling, G, Dierlamm, J, Schüler, F, Busemann, C, Dölken, G, Trendelenburg, Tk, Bühler, A, Stilgenbauer, S, Viardot, A, Greiner, J, Zenz, T, Gaidzik, V, Langer, C, Döhner, H, Werner, I, Dienst, A, Habersang, K, Härtel, N, Leitner, A, Kehrer, G, Middeke, H, Heinisch, K, Adorf, D, Ismer, B, Hering Schubert, C, Jäckle, J, Aulmann, C, Söllner, S, Majunke, P, Fuss, H, Käfer, G, Potenberg, J, Dietrich, G, Hartung, E, Pronath, A, Riedhammer, Fj, Zehrfeld, T, Prümmer, O, Gatter, J, Meier, A, Wattad, M, Heit, W, Sauer, I, Hilgers, K, Geissler, M, Bauer, J, Stein, W, Voigtmann, R, Natt, F, Nickelsen, M, Zeis, M, Schmitz, N, Lange, E, Stoltefuss, A, Schubert, J, Dürk, Ha, Kloke, O, Fauser, A, Roemer, E, Kraut, L, Musch, E, Kohl, S, Link, H, Kirsch, Jf, Schatz, M, Mezger, J, Kempf, B, Heil, G, Derigs, Hg, Roll, C, Kettner, E, Dübbers, Hw, Lutz, L, Hentrich, M, Hoffmann, U, Ibe, M, Falge, C, Schäfer Eckart, K, Rothmann, F, Raghavachar, A, Beckmann, K, Behringer, D, Stauder, H, Hempfling, C, Matzdorff, A, Hähling, D, Kaesberger, Kj, Mück, R, Waladkhani, Ar, Clemens, M, Kraft, J, Ehlert, T, N. N., Schloen, A, Sandritter, B, Scholz, Diekmann, C, Pflüger, Kh, Hausner, G, Fetscher, S, Aulitzky, W, Brugger, W, Frickhofen, N, Fuhr, Lange, C, Lambertz, H, Schulz, L, Schmier, M, Bentz, M, Tauchmann, Gm, Schmidt, M, Meiler, J, Sandmann, M, Kürschner, D, Maier Bay, B, Lindemann, W, Diers, J, Riemeier Sievers, C, Daun, M, Mergenthaler, Hg, Hiller, S, Schirmer, V, Kirchner, H, Langer, W, Günther, B, Gassmann, W, Franke, K, Burghardt, F, Abele, U, Celikel Becker, D, von Weikersthal LF, Brög, G, Hauch, U, Heinrich, B, Brudler, O, Häcker, B, Eckart, Mj, Bolouri, H, Göttler, B, Kindler, M, Zuchold, K, Strohbach, F, Plingen, Ml, Seibt Jung, H, Kirsch, A, Herrenberger, J, Doering, G, von Grünhagen, U, Franke, H, Weniger, J, Kerzel, W, Schmalfeld, M, Rohrberg, R, Hurtz, Hj, Gehbauer, G, Hahnfeld, S, Vehling Kaiser, U, Abenhardt, W, Bosse, D, Böning, L, Schmidt, B, Schick, Hd, Jacobs, G, Stauch, M, Hoffmann, R, Müller, S, Hahn, M, Freier, W, Dietzfelbinger, H, Rassmann, I, Söling, U, Siehl, S, Rudolph, R, Weinert, R, Sauer, A, Meyer, B, Eschenburg, H, Schadeck Gressel, C, Grabenhorst, U, Perker, M, Otremba, B, Reschke, D, Hinrichs, Hf, Zirpel, I, Höring, E, Respondek, M, Köppler, H, Heymanns, J, Weide, R, Hünermund, K, Thiel, C, Reiber, T, Spohn, C, Springer, G, Fiechtner, H, Hübner, A, Kurschel, E, Weiss, J, Schlag, R, Schäfer, E, Hartwich, G, Schmitz, S, Steinmetz, T, Kim, Ts, Lerchenmüller, C, Wehmeyer, J, Laubenstein, Hp, Rendenbach, B, Lebahn, H, Kröning, H, Uhle, R, Balló, H, Gaede, B, Zumbrink, S, Eckert, R, Kamp, T, Reimann, B, Burkhard, O, Mittermüller, J, Hansen, R, Hitz, H, Schliesser, G, Schmitt, Hr, Forstbauer, H, Grundeis, M, Schulze, M, Baldus, M, Lakner, V, Haen, M, Müller, C, Dörfel, S, Göhler, T, Welslau, M, Achtzehn, V, Culmann, H, Gerhardt, S, Ulshöfer, T, Koschuth, A, Schmidt, P, Müller, L, Schneider, M, Koniczek, K, Porowski, P, Glados, M, Knoblich, J, Ben Yehuda, D, Jäger, U, Gaiger, A, Schwarzmeier, J, Nösslinger, T, Smith, M, Patton, N, Gibbons, S, Bouabdallah, R, Gandhi, M, Marlton, P, Mills, T, Angelucci, E, Sorano, Gg, Casula, P, Berneman, Z, Kohser, P, Hudcova Burgetova, A, Machová, R, Papajik, T, Kubová, Z, Fineman, R, Mayer, J, Doubek, M, Brychtova, Y, Ciceri, F, Caligaris Cappio, F, Crocchiolo, R, Dauriac, C, Bernard, M, Escoffre Barbe, M, Lamy, T, Zikesova, E, Karban, J, Salkova, J, Trnený, M, Pytlik, R, Tiley, C, Forsyth, C, Vokurka, S, Koza, V, Van Hoof, A, Selleslag, D, Sebban, C, Baker, B, Belada, D, Jebavy, L, Smolej, L, Pavel, Z, Di Ianni, M, Castaigne, S, Del Poeta, G, Amadori, S, Catalano, J, Ganju, V, Hertzberg, M, Laurenti, L, Dalseg, Am, Bron, D, Morton, J, Durrant, S, Casado, Lf, Theunissen, K, Atias, D, Berkhan, L, Seymour, J, Wolf, M, Bosly, A, Osma Cordoba MM, Portois, C, Jaubert, J, Ferrant, A, Lambert, C, Maerevoet, E, Van den Neste, E, Gadeberg, O, Carney, B, Cannell, P, Eghbali, H, Legouffe, E, Bordessoule, D, Chaury, M, Moreau, S, Pierri, I, Gobbi, M, Berrebi, A, Lishner, M, Yerushazim, R, Yermiaku, T, Kosolov, V, Ambrosetti, Achille, Andreoli, Al, Huguet, F, Laurent, G, Orsucci, L, Forconi, F, Musuraca, G, Zinzani, Pl, Loscertales, J, Mcquillan, A, Cordingley, F, Leahy, M, Cazin, B, Taylor, Mulligan, S, Herbrecht, Cull, G, Seldon, M, Rowlings, P, Ludwig, H, Zojer, N, Solal Céligny, P, Pomponi, F, Savdkova, L, Kozák, T, Christiansen, I, Pérez, I, Campbell, P, Canales Albendea, M, De Paz, R, Arthur, C, Gisselbrecht, C., Eichhorst B.F., Fischer K., Fink A.M., Elter T., Wendtner C.M., Goede V., Bergmann M., Stilgenbauer S., Hopfinger G., Ritgen M., Bahlo J., Busch R., Hallek M., and Zinzani P.L.
Subjects: Male, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, Immunology, Medizin, Antineoplastic Combined Chemotherapy Protocols, Blood Cell Count, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, Prognosis, Recurrence, Remission Induction, Tomography, X-Ray Computed, Physical examination, Biochemistry, Chemoimmunotherapy, medicine, Chronic, Tomography, Leukemia, medicine.diagnostic_test, business.industry, B-Cell, Cancer, Cell Biology, Hematology, medicine.disease, Lymphocytic, imaging techniques, X-Ray Computed, Fludarabine, Surgery, chronic lymphocytic leukemia, Radiology, business, Progressive disease, medicine.drug
Abstract: The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.
Published: 2011
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38. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

Author: Nordlinger, B, Sorbye, H, Glimelius, B, Poston, Gj, Schlag, Pm, Rougier, P, Bechstein, Wo, Primrose, Jn, Walpole, Et, FINCH JONES, M, Jaeck, D, Mirza, D, Parks, Rw, Collette, L, Praet, M, Bethe, U, VAN CUTSEM, E, Scheithauer, W, Gruenberger, T, Hohenberger, W, Iveson, T, Karner, J, Levi, J, Hugh, T, DE GREVE, J, Chan, A, Davidson, B, Lindner, P, Peeters, M, Stein, B, Diamond, T, Ducreux, M, Lasser, P, Graeven, U, Paillot, B, Doran, J, Gouillat, C, Iesalnieks, I, Jauch, Kw, JAGOT LACOUSSIERE, P, Jansen, Rl, Koehne, H, Konopke, R, Otto, F, Sherlock, D, VAN HAZEL, G, Ackland, S, Bedenne, L, Bories, E, CLAVERO FABRI MC, Conroy, T, KAMINSKY FORRETT MC, Husseini, F, Karapetis, C, Mãœller, L, Price, T, Rosenberg, R, Schott, J, Tschmelitsch, J, VAN LAETHEM JL, Wals, J, Weimann, A, Arnaud, Jp, Arsene, D, Auby, D, Bhattacharya, S, Cebon, E, Cherqui, D, Confente, C, Dousset, B, Frickhofen, N, Frilling, A, Evan, P, Ganju, V, Hã–ffken, K, Lazorthes, F, Letoublon, C, Madroszyk, A, Nitti, Donato, Orr, B, Pariente, Ea, Pector, Jc, Raoul, Jl, Rees, M, Ridwelski, K, Rouanet, P, Toogood, Gj, Vergauwe, P, Wilke, Hj, Kaplan, R, Horiot, Jc, Littbrand, B, Awada, A, Stenning, S, Lejeune, F., Haukeland University Hospital, University of Bergen (UiB), Uppsala Universitet [Uppsala], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Chirurgie Viscérale, Hépatique et de Transplantation Multiorganes, Université Louis Pasteur - Strasbourg I, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), University Hospitals Leuven [Leuven], Centre Énergétique et Procédés (CEP), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
Subjects: Adult, Male, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, [SDV]Life Sciences [q-bio], 030230 surgery, Perioperative Care, 03 medical and health sciences, 0302 clinical medicine, Hepatic arterial infusion, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, business.industry, Liver Neoplasms, Hazard ratio, Cancer, General Medicine, Perioperative, Middle Aged, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Oxaliplatin, Clinical trial, 030220 oncology & carcinogenesis, Female, Fluorouracil, Colorectal Neoplasms, Liver cancer, business, medicine.drug
Abstract: Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
Published: 2008
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39. The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer

Author: Szczepny, A, primary, Rogers, S, additional, Jayasekara, W S N, additional, Park, K, additional, McCloy, R A, additional, Cochrane, C R, additional, Ganju, V, additional, Cooper, W A, additional, Sage, J, additional, Peacock, C D, additional, Cain, J E, additional, Burgess, A, additional, and Watkins, D N, additional
Published: 2017
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40. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53mutation status in ovarian mucinous tumors: implications for outcome analyses

Author: Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Anglesio, Michael S., Au-Yeung, George, Böhm, Maret, Bowtell, David D.L., Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Gilks, C. Blake, Gourley, Charlie, Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Huntsman, David G., Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mes-Masson, Anne-Marie, Mileshkin, Linda, Provencher, Diane M., Pyman, Jan, Rahimi, Kurosh, Samimi, Goli, Sharma, Ragwha, Stephens, Andrew N., Traficante, Nadia, Antill, Yoland C., Scott, Clare L., Campbell, Ian G., and Gorringe, Kylie L.
Abstract: TP53mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53mutation status in ovarian mucinous tumors and to evaluate the association of TP53mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5–14.3, p= 0.0087). Within MOC, 61.1% (259/424) harbored a TP53mutation, but this was not associated with survival (overall survival, p= 0.77). TP53 IHC is an accurate proxy for TP53mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
Published: 2021
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41. Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

Author: Beer, T.M., Kwon, E.D., Drake, C.G., Fizazi, K., Logothetis, C., Gravis, G., Ganju, V., Polikoff, J., Saad, F., Humanski, P., Piulats, J.M., Mella, P. Gonzalez, Ng, S.S., Jaeger, D., Parnis, F.X., Franke, F.A., Puente, J., Carvajal, R., Sengelov, L., McHenry, M.B., Varma, A., Eertwegh, A.J. van den, Gerritsen, W.R., Beer, T.M., Kwon, E.D., Drake, C.G., Fizazi, K., Logothetis, C., Gravis, G., Ganju, V., Polikoff, J., Saad, F., Humanski, P., Piulats, J.M., Mella, P. Gonzalez, Ng, S.S., Jaeger, D., Parnis, F.X., Franke, F.A., Puente, J., Carvajal, R., Sengelov, L., McHenry, M.B., Varma, A., Eertwegh, A.J. van den, and Gerritsen, W.R.
Abstract: Item does not contain fulltext, Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in >/= 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.
Published: 2017

42. Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.

Author: Swanton C., Chitapanarux I., Ganju V., Im S.-A., Kim S.-B., Dechaphunkul A., Maneechavakajorn J., Spector N., Yau T., Afrit M., Ahmed S.B., Johnston S.R., Gibson N., Uttenreuther-Fischer M., Herrero J., Goh G., Schmid R., Guiver K., Arpornwirat W., Swanton C., Chitapanarux I., Ganju V., Im S.-A., Kim S.-B., Dechaphunkul A., Maneechavakajorn J., Spector N., Yau T., Afrit M., Ahmed S.B., Johnston S.R., Gibson N., Uttenreuther-Fischer M., Herrero J., Goh G., Schmid R., Guiver K., and Arpornwirat W.
Abstract: Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. Methods and Findings: HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naive patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naive patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naive patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p
Published: 2017

43. Investigating phenotypic and genomic heterogeneity in malignant pleural mesothelioma.

Author: Watkins N., Alamgeer M., Prodanovic Z., Ramdave S., Kumar B., Pick A., Joshi P., Ganju V., Watkins N., Alamgeer M., Prodanovic Z., Ramdave S., Kumar B., Pick A., Joshi P., and Ganju V.
Abstract: Background: Phenotypic and genomic heterogeneity may contribute to the pathogenesis of Malignant Mesothelioma (MM). We have implemented a novel clinical study in which multiple samples of tumor and normal pleura are obtained from individual patients undergoing surgery for the management of MM. Method(s): Patients undergoing routine video-assisted thoracoscopic surgery (VATS) undergo a baseline FDGPET scan. Extra samples are taken from both PET positive and PET negative areas of pleura, along with normal pleural samples. Corresponding fresh and formalin fixed tissue samples are obtained. Patients are subsequently treated as per standard of care practice, along with detailed clinical follow up and serial PET imaging. Standard H&E will be performed on formalin fixed samples to look for morphological heterogeneity in tumor cells and stroma and the findings will be correlated with PET imaging. Result(s): Six (6) patients (4 epithelioid, 1 sarcomatoid and 1 biphasic subtype) with median age of 70 (62-81) have been recruited into the project so far. All patients underwent an FGD-PET scan prior to VATS procedure. Multiple samples from PET avid and PET non-avid areas were collected and stored from 5 out of 6 patients. Preliminary results show that high quality samples were obtained. The H&E analysis shows that tumors from PET avid area are morphologically different to PET not avid areas (Figure 1). Further IHC analysis of various MM specific markers is underway. Conclusion(s): This preliminary data demonstrate the feasibility of our clinical approach. We therefore propose to create a unique research platform in which MM samples from multiple sites from each patient will be integrated with clinical, imaging and therapeutic response. Further proof-of-principle studies will explore: (i) regional heterogeneity and the response to therapies; (ii) variability in the detection of predictive biomarkers within the same patient; (iii) genomic heterogeneity within MM, and its relations
Published: 2017

44. The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.

Author: Park K., McCloy R.A., Cochrane C.R., Ganju V., Cooper W.A., Sage J., Watkins D.N., Burgess A., Cain J.E., Peacock C.D., Szczepny A., Rogers S., Jayasekara W.S.N., Park K., McCloy R.A., Cochrane C.R., Ganju V., Cooper W.A., Sage J., Watkins D.N., Burgess A., Cain J.E., Peacock C.D., Szczepny A., Rogers S., and Jayasekara W.S.N.
Abstract: Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.Copyright © The Autor(s) 2017.
Published: 2017

45. RAD51B in familial breast cancer.

Author: Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Anderson L., Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., and Anderson L.
Abstract: Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
Published: 2017

46. Updated analysis of Phase II study of HA-Irinotecan, a CD44-targeting formulation of hyaluronic acid and irinotecan, in small cell lung cancer.

Author: Midolo P., Markman B., Watkins N., Ganju V., Kumar B., Alamgeer M., Briggs P., Midolo P., Markman B., Watkins N., Ganju V., Kumar B., Alamgeer M., and Briggs P.
Abstract: Background: Preclinical studies in small cell lung cancer cell (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan and selectively decrease CD44 expressing (stem cell-like) tumor cells. The current "proof of principle" study was aimed to replicate these findings by investigating the effect on clinical outcome according to CD44 expression. Final efficacy and bio-marker data on the study is presented. Method(s): Patients with ESLC, having measurable disease, suitable for safe biopsy and able to give informed consent were screened for this study. First 5 patients were treated with HA-irinotecan (150mg/m2) and carboplatin (AUC 5), every 3 weeks to evaluate safety data. Subsequent patients were stratified as first line or second line. All second line patients receive open label HA-irinotecan, while first line patients are randomized to receive either HAirinotecan/carboplatin or irinotecan/carboplatin. The response was measured by CT/PET at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumor samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood samples for circulating tumor cells (CTCs) were also obtained at the baseline and before each treatment cycle till progression of disease. Result(s): Forty (40) patients, median age 66 (range 39-83) were enrolled treated on this study. Seven (7) patients either died or progressed before the first evaluation scan. Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%) complete and 13 (38%) partial responses. Four patients (12%) achieved stable disease while 7 patients (20%) progressed during the treatment. There was no PFS difference in the two first line treatment arms (median 28 weeks in experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity profile was similar to standard irinotecan, with the incidence of grade III/IV diarrhea seen in the experime
Published: 2017

47. SIRFLOX: Differences in site of first progression between mFOLFOX6 +/- bevacizumab (bev) versus mFOLFOX6 +/- bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).

Author: Ganju V., Gibbs P., Heinemann V., Sharma N.K., Findlay M.P.N., Ricke J., Peeters M., Perez D., Robinson B.A., Ferguson T., Rodriguez J., Kroening H., Wolf I., Walpole E.T., Strickland A., Van Hazel G.A., Van Buskirk M., Gebski V., Tichler T.E., Boucher E., Ganju V., Gibbs P., Heinemann V., Sharma N.K., Findlay M.P.N., Ricke J., Peeters M., Perez D., Robinson B.A., Ferguson T., Rodriguez J., Kroening H., Wolf I., Walpole E.T., Strickland A., Van Hazel G.A., Van Buskirk M., Gebski V., Tichler T.E., and Boucher E.
Abstract: Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (+/- bev) chemotherapy alone [arm A] FOLFOX (+/- bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77-1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55-0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Method(s): Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Result(s): From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (+/- other sites) in arm A v B (92.1% v 72.3%; p < 0.001). Conversely, site of first progression was less frequent in the lung (+/- other sites) in arm A v B (19.1% v 42.8%; p < 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p < 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p < 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (+/- extrahepatic sites) in arm A v B (72.5% v48.2%; p < 0.001). Conclusion(s): The addition of SIRT to FOLFOX chemotherapy alone (+/- bev) reduced the frequency at which first disease progression oc
Published: 2016

48. A randomized controlled trial (RCT) of a nurse-led supportive care package (survivor care) for survivors of colorectal cancer.

Author: Ganju V., Franco M., Strickland A., Ugalde A., King D., Blum R., Johnson C., Shapiro J., Schofield P., Charlton J., Chong G., Jefford M., Gough K., Drsodowsky A., Russell L., Aranda S., Butow P., Phipps-Nelson J., Young J., Krishnasamy M., Ganju V., Franco M., Strickland A., Ugalde A., King D., Blum R., Johnson C., Shapiro J., Schofield P., Charlton J., Chong G., Jefford M., Gough K., Drsodowsky A., Russell L., Aranda S., Butow P., Phipps-Nelson J., Young J., and Krishnasamy M.
Abstract: Background: Colorectal cancer (CRC) and its treatments can cause distressing long-term side effects and significant functional consequences. Current models of follow-up fail to address these issues. We conducted amulti-center RCT of an innovative program (Survivor Care (SC)); designed to have a beneficial effect on psychological distress, supportive care needs (SCN) and quality of life (QOL). Method(s): At the end of active treatment for stage I-III CRC, eligible patients (>=18 years, adequate English) were randomized 1:1 to usual care (UC) or to UC+SC. SC comprised educational materials, an individualized survivorship care plan, nurse-led end-of-treatment session and 3 follow up (FU) phone calls. Distress (BSI-18), SCN (CaSUN) and QOL (EORTC QLQ-C30, CR29) were assessed at baseline, 2 (FU1) and 6 (FU2)months. Primary hypothesis: SC would have a beneficial effect on distress at FU1. Secondary hypotheses: SC would have a beneficial effect on (1) SCN and QOL at FU1; and(2) distress, SCN and QO Lat FU2. 15 items assessed satisfaction with survivorship care. Sample size of 180 (90/arm) was based on 80% power, 2-sided alpha of 0.05, to detect a between groups difference of 3.6 on BSI-18 at FU1. Outcome analysis was ITT. Result(s): Of 221 patients randomized (111 UC, 110 SC), 4were ineligible and 1 lost to FU, leaving 110 UC, 106 SC. Groups appeared well balanced. Median age was 64, 52% male, 56% colon, 35% rectal cancer, 10% overlap. Stage I 7%, II 22%, III 71%. Intervention fidelity was acceptable. Baseline distress and QOL were similar to population norms. Between groups differences in distress at FU1 (primary outcome), distress at FU2 and SCN and QOL at FU1 and FU2 were small and non-significant. SC patients were more satisfied with survivorship care than UC patients (significant differences on 10 of 15 items). Conclusion(s): The addition of SC to UC did not have a beneficial effect on distress, SCN or QOL outcomes but SC patients were more satisfied with survivorship
Published: 2016

49. Panitumumab added to docetaxel, cisplatin and fluoropyrimidine in oesophagogastric cancer: ATTAX3 phase II trial.

Author: Ganju V., Underhill C., Shannon J.A., Gebski V., Tebbutt N.C., Price T.J., Ferraro D.A., Wong N., Veillard A.-S., Hall M., Sjoquist K.M., Pavlakis N., Strickland A., Varma S.C., Cooray P., Young R., Ganju V., Underhill C., Shannon J.A., Gebski V., Tebbutt N.C., Price T.J., Ferraro D.A., Wong N., Veillard A.-S., Hall M., Sjoquist K.M., Pavlakis N., Strickland A., Varma S.C., Cooray P., and Young R.
Abstract: Background:This randomised phase II study evaluated the efficacy and safety of panitumumab added to docetaxel-based chemotherapy in advanced oesophagogastric cancer. Method(s):Patients with metastatic or locally recurrent cancer of the oesophagus, oesophagogastric junction or stomach received docetaxel and a fluoropyrimidine with or without panitumumab for 8 cycles or until progression. The primary end point was response rate (RECIST1.1). We planned to enrol 100 patients, with 50% expected response rate for combination therapy. Result(s):A total of 77 patients were enrolled. A safety alert from the REAL3 trial prompted a review of data that found no evidence of adverse outcomes associated with panitumumab but questionable efficacy, and new enrolment was ceased. Enrolled patients were treated according to protocol. Response rates were 49% (95% CI 34-64%) in the chemotherapy arm and 58% (95% CI 42-72%) in the combination arm. Common grade 3 and 4 toxicities included infection, anorexia, vomiting, diarrhoea and fatigue. At 23.7 months of median follow-up, median progression-free survival was 6.9 months vs 6.0 months and median overall survival was 11.7 months vs 10.0 months in the chemotherapy arm and the combination arm, respectively. Conclusion(s):Adding panitumumab to docetaxel-based chemotherapy for advanced oesophagogastric cancer did not improve efficacy and increased toxicities.Copyright © 2016 Cancer Research UK.
Published: 2016

50. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (Plus or Minus Bevacizumab) versus mFOLFOX6 (Plus or Minus Bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer.

Author: Eliadis P., Rodriguez J., Kroning H., Wolf I., Ganju V., Walpole E., Boucher E., Tichler T., Shacham-Shmueli E., Powell A., Ferguson T., Isaacs R., Price D., Moeslein F., Taieb J., Bower G., Gebski V., Van Buskirk M., Cade D.N., Thurston K., Gibbs P., Van Hazel G.A., Heinemann V., Sharma N.K., Findlay M.P.N., Ricke J., Peeters M., Perez D., Robinson B.A., Strickland A.H., Eliadis P., Rodriguez J., Kroning H., Wolf I., Ganju V., Walpole E., Boucher E., Tichler T., Shacham-Shmueli E., Powell A., Ferguson T., Isaacs R., Price D., Moeslein F., Taieb J., Bower G., Gebski V., Van Buskirk M., Cade D.N., Thurston K., Gibbs P., Van Hazel G.A., Heinemann V., Sharma N.K., Findlay M.P.N., Ricke J., Peeters M., Perez D., Robinson B.A., and Strickland A.H.
Abstract: Purpose: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. Patients and Methods: Chemotherapy-naive patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. Result(s): Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267).Median PFS at any site was 10.2 v 10.7months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95%CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4%in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8%v 78.7% in control v SIRT; P = .042). Grade >= 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. Conclusion(s): The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liveronly metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.Copyright © 2016 by American Society of Clinical Oncology.
Published: 2016

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