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15. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years

Author

Pan, H, Gray, R, Braybrooke, J, Davies, C, Taylor, C, Mcgale, P, Peto, R, Pritchard, Ki, Bergh, J, Dowsett, M, Hayes, Df, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bartlett, J, Bergsten‐nordström, E, Bliss, J, Boccardo, F, Bradley, R, Brain, E, Cameron, D, Clarke, M, Coates, A, Coleman, R, Correa, C, Costantino, J, Cuzick, J, Davidson, N, Dodwell, D, Di Leo, A, Ewertz, M, Forbes, J, Gelber, R, Gnant, M, Goldhirsch, A, Goodwin, P, Hill, C, Ingle, J, Jagsi, R, Janni, W, Loibl, S, Mackinnon, E, Martin, M, Mukai, H, Norton, L, Ohashi, Y, Paik, S, Perez, E, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Regan, M, Robertson, J, Rutgers, E, Slamon, D, Sparano, J, Swain, S, Tutt, A, Viale, G, Von Minckwitz, G, Wang, X, Whelan, T, Wilcken, N, Winer, E, Wolmark, N, Wood, W, Zambetti, M, Alberro, Ja, Ballester, B, Deulofeu, P, Fábregas, R, Fraile, M, Gubern, Jm, Janer, J, Moral, A, De Pablo Jl, Peñalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Solà, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Garaud, P, Collett, V, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hma, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Hupperets, Psgj, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Dal, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bramwell, Vh, Chen, Be, Gelmon, K, Goss, Pe, Levine, Mn, Parulekar, W, Pater, Jl, Shepherd, Le, Tu, D, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu‐zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett‐lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec’h, J, De La Lande, B, Mouret‐fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Boddington, C, Burrett, Ja, Cutter, D, Duane, F, Evans, V, Gettins, L, Godwin, J, James, S, Kerr, A, Liu, H, Mannu, G, Mchugh, T, Morris, P, Read, S, Wang, Y, Wang, Z, Albano, J, De Oliveira Cf, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Mouridsen, Ht, Fehm, T, Trampisch, Hj, Dalesio, O, De Vries Ege, Rodenhuis, S, Van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jgm, Treurniet‐donker, Ad, Van Putten Wlj, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Van De Velde Cjh, Cunningham, Mp, Brufsky, Am, Coleman, Re, Llombart, Ha, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Carrasco, E, Segui, Ma, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Galligioni, E, Leone, B, Vallejo, Ct, Zwenger, A, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, De Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Delaloge, S, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, Van De Velde Ao, Van Dongen Ja, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Bighin, C, Bruzzi, P, Del Mastro, L, Dozin, B, Pastorino, S, Pronzato, P, Sertoli, Mr, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro Mg, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, Ah, Kohno, N, Miyashita, M, Takao, S, Ahn, Jh, Jung, Kh, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, Gj, Christiaens, R, Neven, P, Paridaens, R, Van Den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, Mg, Ro, J, Camphausen, K, Danforth, D, Lichter, A, Lippman, M, Smart, D, Steinberg, S, D’Amico, C, Lioce, M, Paradiso, A, Ohno, S, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Redmond, C, Wickerham, L, Aihara, T, Hozumi, Y, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Venturini, M, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Reinertsen, Kv, Varhaug, Je, Gundersen, S, Hauer‐jensen, M, Høst, H, Nissen‐meyer, R, Mitchell, Ak, Robertson, Jfr, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Hadji, P, A’Hern, R, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Clack, G, Van Poznak, C, Deshpande, N, Di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Ajs, Ewing, Gh, Firth, La, Krushen‐kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, Af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ahg, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Lemonnier, J, Martin, Al, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Deutsch, Gp, Kwong, Dlw, Pai, Vr, Senanayake, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Bell, R, Hinsley, S, Marshall, Hc, Pierce, Lj, Solomayer, E, Horsman, Jm, Lester, J, Winter, Mc, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Aft, R, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Other departments, CCA - Cancer Treatment and Quality of Life, Radiotherapy, Pan, Hongchao, Gray, Richard, Braybrooke, Jeremy, Davies, Christina, Taylor, Carolyn, Mcgale, Paul, Peto, Richard, Pritchard, Kathleen I, Bergh, Jona, Dowsett, Mitch, Hayes, Daniel F, De Laurentiis, Michelino, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Interne Geneeskunde

Subjects
0301 basic medicine, Oncology, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Recurrence, Receptors, Neoplasm Metastasis, AMERICAN SOCIETY, Adjuvant, CLINICAL-PRACTICE GUIDELINE, Absolute risk reduction, Estrogen Antagonists, General Medicine, Estrogen Antagonist, CHEMOTHERAPY, Middle Aged, Prognosis, Neoplasm Metastasi, Local, POSTMENOPAUSAL WOMEN, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Meta-analysis, Lymphatic Metastasis, Female, Human, Estrogen Antagonists/therapeutic use, Adult, Risk, medicine.medical_specialty, Prognosi, medicine.drug_class, DISCONTINUATION, Breast Neoplasms, Article, Drug Administration Schedule, LATE DISTANT RECURRENCE, 03 medical and health sciences, Breast cancer, Breast Neoplasms/drug therapy, Internal medicine, SCORE, medicine, Humans, SURGICAL ADJUVANT BREAST, Aged, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Lymphatic Metastasi, TAMOXIFEN THERAPY, ta3122, medicine.disease, Estrogen, RANDOMIZED-TRIALS, Discontinuation, Surgery, Neoplasm Recurrence, 030104 developmental biology, Proportional Hazards Model, Neoplasm Grading, Neoplasm Recurrence, Local, business
Abstract

Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

Published
2017

16. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author

Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited

Subjects
0301 basic medicine, Oncology, Time Factors, SURGERY, medicine.medical_treatment, menopause, chemotherapy, Mastectomy, Segmental, Rate ratio, THERAPY, aromatase inhibitors, CEA, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Breast, Neoplasm Metastasis, Randomized Controlled Trials as Topic, RISK, tamoxifen, breast tumor, CA15-3, axillary dissection, mastectomy, Middle Aged, Neoadjuvant Therapy, METHOTREXATE, 3. Good health, trastuzumab, Treatment Outcome, quadrantectomy, Chemotherapy, Adjuvant, axillary lymphnodes, 030220 oncology & carcinogenesis, Meta-analysis, SURVIVAL, Disease Progression, Female, Life Sciences & Biomedicine, axillary clearance, RADIOTHERAPY, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, 3122 Cancers, Antineoplastic Agents, Breast Neoplasms, axillary nodes, sentinel node biopsy, 03 medical and health sciences, breast cancer, Breast cancer, SDG 3 - Good Health and Well-being, HER2, Internal medicine, Journal Article, medicine, cancer, Humans, Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy, Oncology & Carcinogenesis, RECURRENCE, bisphosphonates, Pathological, Neoplasm Staging, lumpectomy, Chemotherapy, Science & Technology, breast diseases, endocrine therapy, business.industry, denosumab, BRCA1, medicine.disease, BRCA2, osteoporosis, Radiation therapy, STIMULATING FACTOR, 030104 developmental biology, sentinel node, tumor marker, Methotrexate, Neoplasm Recurrence, Local, business, 1112 Oncology And Carcinogenesis, malignancy
Abstract

BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published

Published
2017
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18. Hepatic Arterial Ligation with and Without Portal Infusion in Metastatic Colorectal Cancer

Author

Gerard, A., Dalesio, O., Duez, N., Bleiberg, H., Pector, J. C., Lise, M., Nitti, D., Delvaux, G., Willems, G., Depadt, G., Arnaud, J. P., Schlag, P., Herfarth, Ch., editor, Senn, H. J., editor, Baum, M., editor, Diehl, V., editor, von Essen, C., editor, Grundmann, E., editor, Hitzig, W., editor, Rajewsky, M. F., editor, Schlag, Peter, editor, Hohenberger, Peter, editor, and Metzger, Urs, editor

Published
1988
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19. Preoperative Radiotherapy and Radical Surgery as Combined Treatment in Rectal Cancer

Author

Gerard, A., Berrod, J. L., Pene, F., Loygue, J., Laugier, A., Bruckner, R., Camelot, G., Arnaud, J. P., Metzger, U., Buyse, M., Dalesio, O., Duez, N., Herfarth, Ch., editor, Senn, H. J., editor, Baum, M., editor, Diehl, V., editor, von Essen, C., editor, Grundmann, E., editor, Hitzig, W., editor, Rajewsky, M. F., editor, Schlag, Peter, editor, Hohenberger, Peter, editor, and Metzger, Urs, editor

Published
1988
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20. Controlled Clinical Trial for the Treatment of Patients with Inoperable Esophageal Carcinoma: A Study of the EORTC Gastrointestinal Tract Cancer Cooperative Group

Author

Roussel, A., Jacob, J. H., Haegele, P., Jung, G. M., Paillot, B., Heintz, J. P., Gignoux, M., Nasca, S., Namer, A., Bleiberg, H., Buyse, M., Dalesio, O., Duez, N., Herfarth, Ch., editor, Senn, H. J., editor, Baum, M., editor, Diehl, V., editor, von Essen, C., editor, Grundmann, E., editor, Hitzig, W., editor, Rajewsky, M. F., editor, Schlag, Peter, editor, Hohenberger, Peter, editor, and Metzger, Urs, editor

Published
1988
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22. Hepatic Arterial Ligation and Portal Vein Infusion: A Clinical Trial by the Gastrointestinal Tract Cancer Group of the European Organization for Research and Treatment of Cancer

Author

Gerard, A., Dalesio, O., Duez, N., Lise, M., Pector, J. C., Bleiberg, H., Nitti, D., Willems, G., Delvaux, G., Herfarth, Ch., editor, Senn, H. J., editor, Baum, M., editor, Diehl, V., editor, von Essen, C., editor, Grundmann, E., editor, Hitzig, W., editor, Rajewsky, M. F., editor, Herfarth, Christian, editor, Schlag, Peter, editor, and Hohenberger, Peter, editor

Published
1986
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23. Interim Results of EORTC Protocol 08742: Comparison, After Irradiation of Locally Advanced Squamous Cell Bronchial Carcinoma, of Abstention, Immunotherapy, Combination Chemotherapy, or Chemoimmunotherapy

Author

Israel, L., Depiere, A., Dalesio, O., Allfrey, V. G., editor, Allgöwer, M., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Porta, G. Della, editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Kirsten, W. H., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Macbeth, R. A., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Senn, H. J., editor, Bonadonna, G., editor, and Salmon, S., editor

Published
1982
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25. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials

Author

Mcgale, P., Taylor, C., Correa, C., Cutter, D., Duane, F., Ewertz, M., Gray, R., Mannu, G., Peto, R., Whelan, T., Wang, Y., Wang, Z., Darby, S., Albain, K., Anderson, S., Arriagada, R., Barlow, W., Bergh, J., Bergsten Nordström, E., Bliss, J., Burrett, J. A., Buyse, M., Cameron, D., Carrasco, E., Clarke, M., Coleman, R., Coates, A., Collins, R., Costantino, J., Cuzick, J., Davidson, N., Davies, C., Davies, K., Delmestri, A., Di Leo, A., Dowsett, M., Elphinstone, P., Evans, V., Forbes, J., Gelber, R., Gettins, L., Geyer, C., Gianni, L., Gnant, M., Goldhirsch, A., Godwin, J., Gregory, C., Hayes, D., Hill, C., Ingle, J., Jakesz, R., James, S., Janni, W., Kaufmann, M., Kerr, A., Liu, H., Mackinnon, E., Martín, M., Mchugh, T., Morris, P., Norton, L., Ohashi, Y., Paik, S., Pan, H. C., Perez, E., Piccart, M., Pierce, L., Pritchard, K., Pruneri, G., Raina, V., Ravdin, P., Robertson, J., Rutgers, E., Shao, Y. F., Sparano, J., Swain, S., Valagussa, P., Viale, G., Von Minckwitz, G., Winer, E., Wiang, X., Wood, Abe O, W., Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Cuzick, J, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesech, J, Brain, E, de La Lande, B, Mouret-Fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Wang, X, Zhao, Db, Chen, Zm, Pan, Hc, Howell, A, Swindell, R, Burrett, Ja, Clarke, M, Collins, R, Correa, C, Cutter, D, Darby, S, Davies, K, Elphinstone, P, Evans, V, Gettins, L, Godwin, J, Gray, R, Gregory, C, Hermans, D, Hicks, C, James, S, Kerr, A, Liu, H, Mackinnon, E, Lay, M, Mcgale, P, Mchugh, T, Morris, P, Peto, R, Taylor, C, Wang, Y, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Hayes, D, Henderson, C, Shapiro, Cl, Winer, E, Christiansen, P, Ewertz, M, Møller, S, Mouridsen, Ht, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Wood, W, Cameron, D, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Rutgers, E, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Carrasco, E, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Arriagada, R, Delaloge, S, Hill, C, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Goldhirsch, A, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Abe, O, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Whelan, T, Ohno, S, Anderson, S, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Paik, S, Redmond, C, Swain, S, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Perez, E, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Reinertsen, K, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Businico, A, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Adolfsson, J, Bergh, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Janni, W, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Martin, Al, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., McGale, P, Taylor, C, Correa, C, Cutter, D, Duane, F, Ewertz, M, Gray, R, Mannu, G, Peto, R, Whelan, T, Wang, Y, Wang, Z, Darby, S, Biomedische Technologie, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Mcgale, P, DE LAURENTIIS, Michelino, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Rate ratio, Lower risk, Systemic therapy, Statistical significance, Medicine, Humans, Mastectomy, Randomized Controlled Trials as Topic, business.industry, Articles, General Medicine, Surgery, Radiation therapy, Axilla, Neoplasm Recurrence, medicine.anatomical_structure, Local, Meta-analysis, Lymphatic Metastasis, Lymph Node Excision, Female, Neoplasm Recurrence, Local, business, Breast Neoplasm, Human
Abstract

BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.

Published
2016
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31. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Author

EARLY BREAST CANCER TRIALISTS' COLLABORATIVE GROUP (EBCTCG), Darby, S., Mcgale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., Ewertz, M., Godwin, J., Gray, R., Pierce, L., Whelan, T., Wang, Y., Peto, R., Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bergh, J, Bliss, J, Buyse, M, Cameron, D, Carrasco, E, Clarke, M, Correa, C, Coates, A, Collins, R, Costantino, J, Cutter, D, Cuzick, J, Darby, S, Davidson, N, Davies, C, Davies, K, Delmestri, A, Di Leo, A, Dowsett, M, Elphinstone, P, Evans, V, Ewertz, M, Gelber, R, Gettins, L, Geyer, C, Goldhirsch, A, Godwin, J, Gray, R, Gregory, C, Hayes, D, Hill, C, Ingle, J, Jakesz, R, James, S, Kaufmann, M, Kerr, A, Mackinnon, E, Mcgale, P, Mchugh, T, Norton, L, Ohashi, Y, Paik, S, Pan, Hc, Perez, E, Peto, R, Piccart, M, Pierce, L, Pritchard, K, Pruneri, G, Raina, V, Ravdin, P, Robertson, J, Rutgers, E, Shao, Yf, Swain, S, Taylor, C, Valagussa, P, Viale, G, Whelan, T, Winer, E, Wang, Y, Wood, W, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec'h, J, Rambert, P, Mustacchi, G, Petruzelka, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Wang, X, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Burrett, Ja, Hermans, D, Hicks, C, Lay, M, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Johansen, H, Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Ejlertsen, B, Jensen, Mb, Møller, S, Carstensen, B, Palshof, T, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Tinterri, C, Bonadonna, G, Gianni, L, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, G, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Dafni, D, Fountzilas, G, Mavroudis, D, Klefstrom, P, Saarto, T, Gallen, M, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, Bourgier, C, Koscielny, S, Laplanche, A, Lê, Mg, Spielmann, M, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Janni, W, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Ohno, S, Anderson, A, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Mamounas, Ep, Redmond, C, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Martin, Al, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Ashley, S, Makris, A, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Green, S, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Adolfsson, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H, Mcgale, P, Correa, C, Taylor, C, Arriagada, R, Clarke, M, Cutter, D, Davies, C, Ewertz, M, Godwin, J, Gray, R, Pierce, L, Whelan, T, Wang, Y, Peto, R, Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, DE PLACIDO, Sabino, Carlomagno, Chiara, Darby, S, McGale, P, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
Oncology, medicine.medical_specialty, Neoplasm Recurrence, Local - epidemiology, medicine.medical_treatment, Population, Breast Neoplasms, Mastectomy, Segmental, Breast cancer, breast cancer, Internal medicine, medicine, Breast-conserving surgery, Humans, education, skin and connective tissue diseases, radiotherapy, Randomized Controlled Trials as Topic, education.field_of_study, business.industry, Estrogen Antagonists - therapeutic use, Mortality rate, Age Factors, Estrogen Antagonists, General Medicine, Breast Neoplasms - mortality - therapy, medicine.disease, Surgery, Unilateral Breast Neoplasms, Radiation therapy, Clinical trial, meta-analysis, Tamoxifen, Receptors, Estrogen, Lymphatic Metastasis, Female, Radiotherapy, Adjuvant, Neoplasm Grading, Neoplasm Recurrence, Local, business, Mastectomy
Abstract

BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35.0% to 19.3% (absolute reduction 15.7%, 95% CI 13.7-17.7, 2p/=20%), intermediate (10-19%), or lower (, link_to_OA_fulltext

Published
2011
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32. Controlled Clinical Trial for the Treatment of Patients with Inoperable Esophageal Carcinoma: A Study of the EORTC Gastrointestinal Tract Cancer Cooperative Group

Author

Roussel, A., primary, Jacob, J. H., additional, Haegele, P., additional, Jung, G. M., additional, Paillot, B., additional, Heintz, J. P., additional, Gignoux, M., additional, Nasca, S., additional, Namer, A., additional, Bleiberg, H., additional, Buyse, M., additional, Dalesio, O., additional, and Duez, N., additional

Published
1988
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37. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

Author

EBCTCG, Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, Jl, Davies, C., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, Hma, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, Mj, Masood, Mb, Parker, D., Price, Jj, Hupperets, Psgj, Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Baum, M., Cuzick, J., Houghton, J., Riley, D., Gordon, Nh, Davis, Hl, Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, Jb, Delozier, T., Mace-Lesec H, J., Rambert, P., Andrysek, O., Barkmanova, J., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Alison, R., Boreham, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Peto, R., Wang, Y., Albano, J., Oliveira, Cf, Gervasio, H., Gordilho, J., Johansen, H., Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, Ic, Shapiro, Cl, Andersen, Kw, Axelsson, Ck, Blichert-Toft, M., Moller, S., Overgaard, J., Overgaard, M., Rose, C., Cartensen, B., Palshof, T., Trampisch, Hj, Dalesio, O., Vries, Ege, Rodenhuis, S., Tinteren, H., Comis, Rl, Davidson, Ne, Robert, N., Sledge, G., Tormey, Dc, Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, Jgm, Treurniet-Donker, Ad, Putten, Wlj, Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Hage, Ja, Velde, Cjh, Cunningham, Mp, Catalano, R., Creech, Rh, Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, Cs, Smith, Dc, Galligioni, E., Boccardo, F., Rubagotti, A., Dent, Dm, Gudgeon, Ca, Hacking, A., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Takei, H., Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D., Graeff, H., Janicke, F., Meisner, C., Scheurlen, H., Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, MR, Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Velde, Ao, Dongen, Ja, Vermorken, Jb, Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Den Boegart, W., Martin, P., Romain, S., Hakes, T., Hudis, Ca, Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., La Huerta, R., Sainz, Mg, Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O Shaughnessy, J., Pierce, Lj, Steinberg, S., Venzon, D., Zujewski, J., Paradiso, A., Lena, M., Schittulli, F., Myles, Jd, Pater, Jl, Pritchard, Ki, Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Jonsson, H., Larsson, Lg, Lythgoe, Jp, Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, Ab, Varhaug, Je, Gundersen, S., Hauer-Jensen, M., Host, H., Nissen-Meyer, R., Blamey, Rw, Mitchell, Ak, Morgan, Dal, Robertson, Jfr, Di Palma, M., Mathe, G., Misset, Jl, Clark, Rm, Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, MR, Ueo, H., Falkson, Ci, A Hern, R., Ashley, S., Powles, Tj, Smith, Ie, Yarnold, Jr, Gazet, Jc, Cocoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, Ajs, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Foster, L., George, Wd, Stewart, Hj, Stroner, P., Malmstrom, P., Moller, Tr, Ryden, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjold, B., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Glas, U., Johansson, U., Rutqvist, Le, Singnomklao, T., Wallgren, A., Maibach, R., Thurlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Shan, Y., Shao, Yf, Wang, X., Zhao, Db, Chen, Zm, Pan, Hc, Bahi, J., Reid, M., Spittle, M., Deutsch, Gp, Senanayake, F., Kwong, Dlw, Bianco, Ar, Carlomagno, C., Laurentiis, M., Placido, S., Buzdar, Au, Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, Cc, Buchanan, Rb, Cross, M., Royle, Gt, Dunn, Ja, Hills, Rk, Lee, M., Morrison, Jm, Spooner, D., Litton, A., Chlebowski, Rt, Caffier, H., Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, and DE PLACIDO, Sabino

Subjects
Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, DEATHS, Ovariectomy, Antineoplastic Agents, Breast Neoplasms, Aged, Anthracyclines, Antineoplastic Combined Chemotherapy Protocols, Cause of Death, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Ovary, Randomized Controlled Trials as Topic, Receptors, Estrogen, Survival Rate, Tamoxifen, Medicine (all), Breast cancer, MammaPrint, Internal medicine, Receptors, medicine, Chemotherapy, TAMOXIFEN, skin and connective tissue diseases, Survival rate, Adjuvant, Gynecology, Hormonal, medicine.diagnostic_test, Oncotype DX Breast Cancer Assay, business.industry, General Medicine, medicine.disease, Estrogen, Neoplasm Recurrence, Local, Hormonal therapy, Oncotype DX, business, medicine.drug, Epirubicin
Abstract

Background Quinquennial overviews (1985–2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50–69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0·0001 for recurrence, 2p For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age ( These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1–2 years of tamoxifen versus none (33 000); and about 5 years versus 1–2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.

Published
2005

38. A Randomized Phase Ii Study of Paclitaxel-Carboplatin-Bevacizumab (Pcb) with or Without Nitroglycerin Patches (Ntg) in Patients (Pts) with Stage Iv Non-Squamous-Non-Small Cell Lung Cancer (Ns-Nsclc)(Nvalt 12), Impact of Circulating Vascular Endothelial Growth Factor (Vegf) Levels

Author

Dingemans, A.C., primary, Groen, H.J.M., additional, Herder, G., additional, Smit, E.F., additional, Burgers, S., additional, Stigt, J., additional, De Goeije, P., additional, Dalesio, O., additional, Biesma, B., additional, van der Noort, V., additional, and Aerts, J.G., additional

Published
2014
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39. Novel insights into pathological changes in muscular arteries of radiotherapy patients.

Author

Russell, N.S., Hoving, S., Heeneman, S., Hage, J.J., Woerdeman, L.A., Bree, R. de, Lohuis, P.J., Smeele, L., Cleutjens, J., Valenkamp, A., Dorresteijn, L.D.A., Dalesio, O., Daemen, M.J., Stewart, F.A., Russell, N.S., Hoving, S., Heeneman, S., Hage, J.J., Woerdeman, L.A., Bree, R. de, Lohuis, P.J., Smeele, L., Cleutjens, J., Valenkamp, A., Dorresteijn, L.D.A., Dalesio, O., Daemen, M.J., and Stewart, F.A.

Abstract

Contains fulltext : 81320.pdf (publisher's version ) (Closed access), BACKGROUND AND PURPOSE: Vascular disease is increased after radiotherapy and is an important determinant of late treatment-induced morbidity and excess mortality. This study evaluates the nature of underlying pathologic changes occurring in medium-sized muscular arteries following irradiation. MATERIALS AND METHODS: Biopsies of irradiated medium-sized arteries and unirradiated control arteries were taken from 147 patients undergoing reconstructive surgery with a vascularised free flap following treatment for head and neck (H&N) or breast cancer (BC). Relative intimal thickening was derived from the ratio of the thickness of the intima to the thickness of the media (IMR) on histological sections. Proteoglycan, collagen and inflammatory cell content were also scored. RESULTS: Intimal thickness was significantly increased in irradiated vessels: in the H&N group the IMR was 1.5-fold greater without correction for the control artery (p=0.018); in the BC group the IMR increased 1.4-fold after correction for the control artery (p=0.056) at a mean of 4 years following irradiation. There was an increase in the proteoglycan content of the intima of the irradiated IMA vessels, from 65% to 73% (p=0.024). Inflammatory cell content was increased in the intima of the irradiated H&N vessels (p=0.014). CONCLUSIONS: Radiation-induced vascular pathology differs quantitatively and qualitatively from age-related atherosclerosis.

Published
2009

40. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Author

Tol, J., Koopman, M., Cats, A., Rodenburg, C.J., Creemers, G.J., Schrama, J.G., Erdkamp, F.L., Vos, A.H., Groeningen, C.J. van, Sinnige, H.A.M., Richel, D.J., Voest, E.E., Dijkstra, J.R., Vink-Borger, M.E., Antonini, N.F., Mol, L., Krieken, J.H.J.M. van, Dalesio, O., Punt, C.J.A., Tol, J., Koopman, M., Cats, A., Rodenburg, C.J., Creemers, G.J., Schrama, J.G., Erdkamp, F.L., Vos, A.H., Groeningen, C.J. van, Sinnige, H.A.M., Richel, D.J., Voest, E.E., Dijkstra, J.R., Vink-Borger, M.E., Antonini, N.F., Mol, L., Krieken, J.H.J.M. van, Dalesio, O., and Punt, C.J.A.

Abstract

Contains fulltext : 79995.pdf (publisher's version ) (Open Access), BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)

Published
2009

41. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.

Author

Koopman, M., Antonini, N., Douma, J., Wals, J., Honkoop, A.H., Erdkamp, F.L., Jong, R.S. de, Rodenburg, C.J., Vreugdenhil, G.R., Loosveld, O.J., Bochove, A. van, Sinnige, H.A.M., Creemers, G.J., Tesselaar, M.E., Slee, P.H., Werter, M.J., Mol, L., Dalesio, O., Punt, C.J.A., Koopman, M., Antonini, N., Douma, J., Wals, J., Honkoop, A.H., Erdkamp, F.L., Jong, R.S. de, Rodenburg, C.J., Vreugdenhil, G.R., Loosveld, O.J., Bochove, A. van, Sinnige, H.A.M., Creemers, G.J., Tesselaar, M.E., Slee, P.H., Werter, M.J., Mol, L., Dalesio, O., and Punt, C.J.A.

Abstract

Contains fulltext : 52831.pdf (publisher's version ) (Closed access), BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS: We randomly assigned 820 patients with advanced colorectal cancer to receive either first-line treatment with capecitabine, second-line irinotecan, and third-line capecitabine plus oxaliplatin (sequential treatment; n=410) or first-line treatment capecitabine plus irinotecan and second-line capecitabine plus oxaliplatin (combination treatment; n=410). The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov with the number NCT00312000. FINDINGS: 17 patients (nine in the sequential treatment group, eight in the combination group) were found to be ineligible and were excluded from the analysis. 675 (84%) patients died during the study: 336 in the sequential group and 339 in the combination group. Median overall survival was 16.3 (95% CI 14.3-18.1) months for sequential treatment and 17.4 (15.2-19.2) months for combination treatment (p=0.3281). The hazard ratio for combination versus sequential treatment was 0.92 (95% CI 0.79-1.08; p=0.3281). The frequency of grade 3-4 toxicity over all lines of treatment did not differ significantly between the two groups, except for grade 3 hand-foot syndrome, which occurred more often with sequential treatment than with combination treatment (13%vs 7%; p=0.004). INTERPRETATION: Combination treatment does not significantly improve overall survival compared with the sequential use of cytotoxic drugs in advanced colorectal cancer. Thus sequential treatment remains a valid option for patients with advanced colorectal cancer.

Published
2007

42. Prognostic value of different metabolic measurements with fluorine-18 fluorodeoxyglucose positron emission tomography in resectable non-small cell lung cancer: a two-center study.

Author

Jong, W.K. de, Heijden, H.F.M. van der, Pruim, J., Dalesio, O., Oyen, W.J.G., Groen, H.J., Jong, W.K. de, Heijden, H.F.M. van der, Pruim, J., Dalesio, O., Oyen, W.J.G., and Groen, H.J.

Abstract

Contains fulltext : 53268.pdf (publisher's version ) (Closed access), INTRODUCTION: Standard uptake value (SUV) is a quantitative measure for the preferential uptake of a radiopharmaceutical in a tumor compared with the homogeneous distribution in the body. SUV can be based on the maximal value of one pixel (SUVmax) or on the mean value in a region outlined by isodensity contours. The prognostic value of different SUVs in non-small cell lung cancer (NSCLC) is not established. We evaluated this value for SUVmax, SUV70%, and SUV50% among patients with resectable NSCLC. METHODS: All consecutive patients with resectable NSCLC who underwent an attenuation-corrected whole-body fluorine-18 fluorodeoxyglucose positron emission tomography scan from two university hospitals were selected. By adjusting the isocontour in the region of interest on the scan, SUVmax, SUV70%, and SUV50% of the primary tumor were calculated. RESULTS: Sixty-six patients (50 male, median age 63 years) were included. Of the tumors, 16 were pathological stage IA, 23 were IB, 4 were IIA, 14 were IIB, and 9 were IIIA. Median (range) values for SUVmax, SUV70%, and SUV50% were 6.4 (1.6-19.1), 5.1 (1.0-15.7), and 4.0 (0.9-13.4), respectively. SUVs were associated with survival. Analysis of residuals of SUVmax as a continuous variable in a Cox's proportional hazard model for survival suggested no cutoff point and no indication of time-dependency. Patients with a SUV higher than the median value had a worse survival than patients with a SUV lower than median (hazard ratios for SUVmax, SUV70%, and SUV50% all were 2.9; p = 0.02). CONCLUSIONS: SUVmax, SUV70%, and SUV50% measured with fluorine-18 fluorodeoxyglucose positron emission tomography have a similar prognostic value, and no "natural" cutoff point for SUVmax in resectable NSCLC was identified.

Published
2007

43. Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC lung cancer cooperative group

Author

Nico van Zandwijk, Groen, Hjm, Postmus, Pe, Burghouts, Jtw, Tenvelde, Gpm, Ardizzoni, A., Smith, Ie, Baas, P., Sahmoud, T., Kirkpatrick, A., Dalesio, O., Giaccone, G., Faculteit Medische Wetenschappen/UMCG, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
ALPHA, CARCINOMA, maintenance therapy, ONCOLOGY-GROUP, small cell lung cancer, CHEMOTHERAPY, interferon type II, rIFN-gamma, THERAPY, CLINICAL-TRIAL
Abstract

This study was undertaken to determine if recombinant interferon-gamma (rIFN-gamma) given every other day as maintenance therapy could prolong the survival of patients with small cell lung cancer (SCLC) who achieved a complete or nearly-complete response to induction therapy. A secondary endpoint was to assess the toxicity of alternate day doses of this treatment. One hundred and seventy seven patients in complete or nearly-complete response following chemotherapy with or without thoracic radiotherapy were studied. Patients were randomised to receive either rIFN-gamma 4 million units (0.2 mg) subcutaneously every other day for 4 months or observation. One hundred and twenty of the 127 registered patients were eligible; 59 patients received IFN and 61 patients without maintenance therapy were followed. Alternate day IFN was reasonably well tolerated by the majority of patients, but in 12% substantial non-haematological toxicity (including flu-like syndrome) occurred. One of 3 patients with pneumonitis died after having received 3.6 mg IFN. The median survival time from the date of randomisation was 8.9 months for the IFN arm and 9.9 months for the observation arm. rIFN-gamma at the dose and schedule used in this study failed to prolong response duration and survival in SCLC patients in complete or nearly-complete response. The toxicity seen with every other day doses of IFN was less than that reported with daily dosing. The hypothesis that this agent may increase the deleterious effects of radiation on normal lung tissue was supported by the development of pneumonitis in 3 cases of whom 1 had a fatal outcome. The results do not warrant further studies with rIFN-gamma on maintaining response in SCLC. (C) 1997 Elsevier Science Ltd.

Published
1997

46. Mobilisation of blood progenitor cells with ifosfamide and etoposide (VP-16) in combination with recombinant human G-CSF (Filgrastim) in patients with malignant lymphomas or solid tumours

Author

Baars, J. W., Holtkamp, M. J., Nooyen, W. J., Walll, E. V., te Velde, A., Dalesio, O., Slaper-Cortenbach, I. C., Schoot, E. V., Richel, D. J., Gerritsen, W. R., Schornagel, J. H., Rodenhuis, S., and Other departments

Abstract

The mobilisation characteristics of ifosfamide and etoposide followed by Granulocyte Colony-Stimulating Factor fGCSF, filgrastim) were analysed in 17 patients with malignant lymphoma and 24 patients with solid tumours, with respect to the optimum time to harvest progenitor cells and to the yields of progenitor cells that could be achieved. In addition, we analysed patient characteristics which could influence the size of the progenitor cell harvest. Clinical parameters which were co-related with the size of the circulating progenitor cells (CPC) harvests were: the dose of G-CSF, dose of if osfamide, sex, age, diagnosis and extent of pretreatment. CPC were mobilised with 3 g/m2 (n = 11) or 4 g/m2 (n = 30) ifosfamide on day 1 and etoposide 100 mg/m2/day, on days 1-3 i.v., followed by daily s.c. injections with filgrastim 5 micrograms/kg (n = 26) or 10 micrograms/kg (n = 15) from day 4. The maximal progenitor cell harvest was achieved on either day 12 or day 13 after the start of the ifosfamide/etoposide course. The median number of leukaphereses necessary to harvest the target quantity of 3 x 10(6) CD34+ cells/kg body weight was 1 (range 1-9). Thirteen/41 (32%) of the patients did not achieve the target yield of 3 x 10(6) CD34+ cells/kg. By multivariate analysis, the dose of GCSF and prior irradiation were associated with the number of progenitor cells harvested, while all other parameters, induding the dose of if osfamide and number of previous chemotherapy courses, were not. Sixteen patients received two or more mobilisation courses. Despite the fact that the same mobilisation schedule was used, the progenitor cell yields after the first mobilisation course did not predict the results after the subsequent mobilisation courses, indicating that unknown transient factors may significantly influence the CPC yield

Published
1996

49. A randomized two-arm phase III study to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) versus CAPOX alone in post radical resection of patients with liver metastases of colorectal cancer.

Author

Voest, E. E., primary, Snoeren, N., additional, Schouten, S. B., additional, Bergman, A. M., additional, van Werkhoven, E., additional, Loosveld, O. J. L., additional, van Gulik, T. M., additional, Smit, J. M., additional, Cats, A., additional, Boven, E., additional, Hesselink, E., additional, Rijken, A., additional, Tol, M., additional, Dalesio, O., additional, Verheul, H. M., additional, Tollenaar, R. A., additional, van der Sijp, J., additional, Borel Rinkes, I., additional, and van Hillegersberg, R., additional

Published
2011
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50. Randomized phase III study of docetaxel with or without risedronate in patients with bone metastases from castration-resistant prostate cancer (CRPC): The Netherlands Prostate Study (NePro).

Author

Meulenbeld, H. J., primary, van Werkhoven, E. D., additional, Coenen, J. L. L. M., additional, Creemers, G., additional, Loosveld, O. J. L., additional, De Jong, P. C., additional, Ten Tije, A. J., additional, Fossa, S. D., additional, Polee, M., additional, Gerritsen, W. R., additional, Dalesio, O., additional, and De Wit, R., additional

Published
2011
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