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1. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37298 women with early breast cancer in 26 randomised trials

Author

Boddington, C, Bradley, R, Braybrooke, J, Burrett, J, Clarke, M, Davies, C, Davies, L, Dodwell, D, Duane, F, Evans, V, Gettins, L, Godwin, J, Gray, R, Hills, R, James, S, Liu, H, Liu, Z, MacKinnon, E, Mannu, G, McGale, P, McHugh, T, Morris, P, Pan, H, Peto, R, Read, S, Taylor, C, Wang, Y, Wang, Z, Bergh, J, Barlow, W, Bliss, J, Bruzzi, P, Cameron, D, Fountzilas, G, Loibl, S, Mackey, J, Martin, M, Del Mastro, L, Moebus, V, Nekljudova, V, De Placido, S, Swain, S, Untch, M, Pritchard, KI, Norton, L, Fasching, P, Harbeck, N, Piedbois, P, Gnant, M, Steger, G, Di Leo, A, Dolci, S, Francis, P, Larsimont, D, Nogaret, JM, Philippson, C, Piccart-Gebhart, MJ, Linn, S, Peer, P, Tjan-Heijnen, V, Vliek, S, Slamon, D, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Rakovitch, E, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, RB, Shan, Y, Shao, YF, Wang, X, Xu, B, Zhao, DB, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Carrasco, E, Segui, MA, Blohmer, JU, Costa, SD, Gerber, B, Jackisch, C, von Minckwitz, G, Giuliano, M, De laurentiis, M, Bamia, C, Koliou, G-A, Mavroudis, D, A'Hern, R, Ellis, P, Kilburn, L, Morden, J, Yarnold, JR, Sadoon, M, Tulusan, AH, Anderson, S, Bass, G, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, EP, Paik, S, Redmond, C, Wickerham, L, Wolmark, N, Venturini, M, Bighin, C, Pastorino, S, Pronzato, P, Sertoli, MR, Foukakis, T, Albain, K, Arriagada, R, Bartlett, J, Bergsten-Nordstrom, E, Boccardo, F, Brain, E, Carey, L, Coates, A, Coleman, R, Correa, C, Cuzick, J, Davidson, N, Dowsett, M, Ewertz, M, Forbes, J, Gelber, R, Goldhirsch, A, Goodwin, P, Hayes, D, Hill, C, Ingle, J, Jagsi, R, Janni, W, Mukai, H, Ohashi, Y, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Rea, D, Regan, M, Robertson, J, Sparano, J, Tutt, A, Viale, G, Wilcken, N, Wood, W, Zambetti, M, Boddington, C, Bradley, R, Braybrooke, J, Burrett, J, Clarke, M, Davies, C, Davies, L, Dodwell, D, Duane, F, Evans, V, Gettins, L, Godwin, J, Gray, R, Hills, R, James, S, Liu, H, Liu, Z, MacKinnon, E, Mannu, G, McGale, P, McHugh, T, Morris, P, Pan, H, Peto, R, Read, S, Taylor, C, Wang, Y, Wang, Z, Bergh, J, Barlow, W, Bliss, J, Bruzzi, P, Cameron, D, Fountzilas, G, Loibl, S, Mackey, J, Martin, M, Del Mastro, L, Moebus, V, Nekljudova, V, De Placido, S, Swain, S, Untch, M, Pritchard, KI, Norton, L, Fasching, P, Harbeck, N, Piedbois, P, Gnant, M, Steger, G, Di Leo, A, Dolci, S, Francis, P, Larsimont, D, Nogaret, JM, Philippson, C, Piccart-Gebhart, MJ, Linn, S, Peer, P, Tjan-Heijnen, V, Vliek, S, Slamon, D, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Rakovitch, E, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, RB, Shan, Y, Shao, YF, Wang, X, Xu, B, Zhao, DB, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Carrasco, E, Segui, MA, Blohmer, JU, Costa, SD, Gerber, B, Jackisch, C, von Minckwitz, G, Giuliano, M, De laurentiis, M, Bamia, C, Koliou, G-A, Mavroudis, D, A'Hern, R, Ellis, P, Kilburn, L, Morden, J, Yarnold, JR, Sadoon, M, Tulusan, AH, Anderson, S, Bass, G, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, EP, Paik, S, Redmond, C, Wickerham, L, Wolmark, N, Venturini, M, Bighin, C, Pastorino, S, Pronzato, P, Sertoli, MR, Foukakis, T, Albain, K, Arriagada, R, Bartlett, J, Bergsten-Nordstrom, E, Boccardo, F, Brain, E, Carey, L, Coates, A, Coleman, R, Correa, C, Cuzick, J, Davidson, N, Dowsett, M, Ewertz, M, Forbes, J, Gelber, R, Goldhirsch, A, Goodwin, P, Hayes, D, Hill, C, Ingle, J, Jagsi, R, Janni, W, Mukai, H, Ohashi, Y, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Rea, D, Regan, M, Robertson, J, Sparano, J, Tutt, A, Viale, G, Wilcken, N, Wood, W, and Zambetti, M

Abstract

BACKGROUND: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. METHODS: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). FINDINGS: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82-0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83-0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83-0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78-0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76-0·91; p<0·0001), in the six t

Published
2019

2. 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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3. 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

4. Systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia

Author

Richards, S, Pui, C, Gayon, P, Yetgin, Z, Olcay, L, Masera, G, VALSECCHI, MARIA GRAZIA, Schrappe, M, Zimmermann, M, Henze, G, von Stackelberg, A, Gadner, H, Mann, G, Attarbarschi, A, Brandalise, SR, Carroll, WL, Gaynon, P, Boyett, JM, Sather, HN, Devidas, M, Escheriche, G, Gelber, RD, Sallan, SE, Pieters, R, Bierings, M, Kamps, WA, Otten, J, Suciu, S, Viana, MB, Stark, B, Steinberg, D, Koizumi, S, Tsurusawa, M, Eden, OB, Mitchell, C, Steinherz, PG, Ortega, JJ, Nachman, J, Appelbaum, FR, Cheng, C, Pei, D, Pui, CH, Clarke, M, Elphinstone, P, Evans, V, Gregory, C, Gettins, L, Hicks, C, James, S, MacKinnon, L, McHugh, TM, Morris, P, Wade, R., Richards, S, Pui, C, Gayon, P, Yetgin, Z, Olcay, L, Masera, G, Valsecchi, M, Schrappe, M, Zimmermann, M, Henze, G, von Stackelberg, A, Gadner, H, Mann, G, Attarbarschi, A, Brandalise, S, Carroll, W, Gaynon, P, Boyett, J, Sather, H, Devidas, M, Escheriche, G, Gelber, R, Sallan, S, Pieters, R, Bierings, M, Kamps, W, Otten, J, Suciu, S, Viana, M, Stark, B, Steinberg, D, Koizumi, S, Tsurusawa, M, Eden, O, Mitchell, C, Steinherz, P, Ortega, J, Nachman, J, Appelbaum, F, Cheng, C, Pei, D, Clarke, M, Elphinstone, P, Evans, V, Gregory, C, Gettins, L, Hicks, C, James, S, Mackinnon, L, Mchugh, T, Morris, P, and Wade, R

Subjects
Central Nervous System Neoplasms, Antineoplastic Agent, Central Nervous System, Central Nervous System Neoplasm, Humans, Antineoplastic Agents, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Child, Article, Injections, Spinal, Randomized Controlled Trials as Topic, Human
Abstract

Treatment of the central nervous system (CNS) is an essential therapy component for childhood acute lymphoblastic leukemia (ALL). Individual patient data from 47 trials addressing 16 CNS treatment comparisons were analyzed. Event-free survival (EFS) was similar for radiotherapy versus intrathecal (IT), and radiotherapy plus IT versus IV methotrexate (IV MTX) plus IT. Triple intrathecal therapy (TIT) gave similar EFS but poorer survival than intrathecal methotrexate (IT MTX), but additional IV MTX improved both outcomes. One trial resulted in similar EFS and survival with IV MTX plus IT MTX versus TIT alone. Radiotherapy can generally be replaced by IT therapy. TIT should be used with effective systemic therapy such as IV MTX.

Published
2013

5. Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

Author

Bauduer, M., Gribben, J., Herrmann, R., Thiel, E., Rai, K., Larson, R., Ferrara, F., Barnard, J., Pearce, H., Taylor, C., Brillant, B., Steurer, M., Weingart, O., Flinn, W., Funkhouser, A., Nallman, M., Sun, Z., Jakšić, Branimir, Suciou, S., Chevret, S., Dighiero, G., Leporrier, M., Frankel, S.R., Sirard, C., Hillmen, P., Trehu, B., Felder, M., Busch, R., Eichorst, B., Mallek, M., Stilgenbauer, S., Pangalis, G., Bezares, R., van Oers, M.H.J., van Putten, W., Gobbi, M., Spriano, M., Mabed, M., Catovsky, D., Richards, S., Wade, R., Abdelhamid, T., Dearden, C., Knauf, W., Blonski, J., Jamroziak, K., Robak, T., Mauro, F., Hiddeman, W., Johnson, S.A., Longthorne, G., Rummel, M.J., Juliusson, G., Pulluqui, P., Zinzani, P.L., Pozzato, G., Reynolds, C, Furman, R.R., Durrant, J., Elphinstone, P., Evans, V., Gettins, .L, Hicks, C., James, S., Clarke, M., MacKinnon, L., McHugh, T.M., Morris, P., Read, S., Gregory, C., Pozzato, Gabriele, Bauduer M, Gribben J, Herrmann R, Thiel E, Rai K, Larson R, Ferrara F, Barnard J, Pearce H, Taylor C, Brillant C, Steurer M, Weingart O, Flinn IW, Funkhouser A, Tallman M, Sun Z, Jaksic B, Suciu S, Chevret S, Dighiero G, Leporrier M, Frankel SR, Sirard C, Hillmen P, Trehu B, Felder M, Busch R, Eichhorst B, Hallek M, Stilgenbauer S, Pangalis G, Bezares R, van Oers MH, van Putten W, Gobbi M, Spriano M, Mabed M, Catovsky D, Richards S, Wade R, Abdelhamid T, Dearden C, Knauf W, Blonski J, Jamroziak K, Robak T, Mauro F, Hiddeman W, Johnson SA, Longthorne G, Juliusson G, Pulluqi P, Zinzani PL, Pozzato G, Oncology US, Reynolds C, Furman RR, Durrant J, Elphinstone P, Evans V, Gettins L, Hicks C, James S, Clarke M, MacKinnon L, McHugh TM, Morris P, Read S, and Gregory C. CLL Trialists’ Collaborative Group

Subjects
Oncology, medicine.medical_specialty, review, Purine analogue, chronic lymphocytic leukemia, fludarabine, clinical trial, Pharmacology, Disease-Free Survival, combination therapy, purine analog, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Progression-free survival, Cladribine, Antineoplastic Agents, Alkylating, Chlorambucil, business.industry, Hematology, Odds ratio, Leukemia, Lymphocytic, Chronic, B-Cell, Fludarabine, Clinical trial, Treatment Outcome, CLL, cyclophosphamide, Purines, Original Articles and Brief Reports, business, Untreated Chronic Lymphocytic Leukemia, medicine.drug
Abstract

Background. A systematic review of purine analogs revealed heterogeneity between trials in treatment effects on response and progression free survival, but not survival, perhaps partly due to variations in analysis methods. In addition, combination treatments required evaluation. Design and Methods. Individual patient data were sought for all randomized trials in untreated chronic lymphocytic leukemia which involved a purine analog, but not including antibody therapies. Results. Sixteen trials were found, addressing seven comparisons. Eight trials, with 2753 patients, showed that single agent purine analog improved progression free survival (Odds ratio = 0.71; 95% confidence interval =0.63-0.79). Heterogeneity remained substantial. Three trials, with 1403 patients, showed that progression free survival was further improved by the addition of cyclophosphamide (Odds ratio = 0.54; 0.47-0.62). Fewer data were available on the addition of other drugs to purine analog, and none showed clear benefit. Two trials, with 544 patients, suggested cladribine improved progression free survival compared to fludarabine (Odds ratio = 0.77; 0.63-0.95). No differences were seen in overall survival for any comparisons. Conclusions. Purine analogs, particularly combined with cyclophosphamide, significantly improve progression free survival but not survival. Some groups, such as the elderly, may not see the same benefits and maximising doses may be important for all treatments, including chlorambucil. Longer follow-up, consistent definitions and detailed reporting of trials should be encouraged.

Published
2012

6. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis

Author

Gupta, V, Richards, S, Rowe, J, Büchner, T, Hiddemann, W, Sauerland, C, Amadori, S, Rondelli, R, Testi, Am, Attal, M, Jourdan, E, Reiffers, J, Howman, A, Patel, S, Jacobs, P, Lee, S, Brunet, S, Sierra, J, Alonzo, T, Aplenc, R, Sung, L, Cutler, C, Sun, Z, Tallman, M, Ljungman, P, Labar, B, Willemze, R, Suciu, S, Collette, S, Dombret, H, Thomas, X, Ifrah, N, Hunault-Berger, M, Mandelli, F, Vignetti, M, Tsimberidou, Am, Pagnano, K, da Souza CA, Miranda, Ec, Diaz de Heredia, C, Ortega, Jj, Cornelissen, Jj, van der Holt, B, Oh, H, Takeuchi, J, Kaizer, H, Björkholm, M, Rosenborg, A, Keating, M, Zander, A, Fielding, A, Goldstone, A, Moorman, Av, Bassan, R, Ravindranath, Y, Weinstein, H, Oriol, A, Ribera, Jm, Powles, R, Appelbaum, F, Baker, Luigi, Coltman, C, Crowley, J, Kopecky, K, Messner, H, Akan, H, Beksac, M, Hills, R, Buck, G, Davies, K, Elphinstone, T, Evans, V, Gettins, L, Gregory, C, James, S, Mackinnon, L, Mchugh, T, Morris, P, Wade, R, and Wheatley, K.

Subjects
Oncology, Homologous, Adult, medicine.medical_specialty, Adolescent, Age Factors, Aged, Aged, 80 and over, Antineoplastic Agents, Child, Hematopoietic Stem Cell Transplantation, Humans, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Randomized Controlled Trials as Topic, Transplantation, Autologous, Transplantation, Homologous, Young Adult, Hematology, Biochemistry, Cell Biology, Immunology, medicine.medical_treatment, Hematopoietic stem cell transplantation, law.invention, Randomized controlled trial, law, Acute lymphocytic leukemia, Internal medicine, 80 and over, Medicine, Young adult, Chemotherapy, Transplantation, Lymphoid Neoplasia, business.industry, Absolute risk reduction, medicine.disease, Surgery, Adult Acute Lymphoblastic Leukemia, business, Autologous
Abstract

Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard postremission strategies for adult acute lymphoblastic leukemia in first complete remission, but the optimal strategy remains controversial. There are no randomized trials of allogeneic HCT. In the present study, updated individual patient data were collected and analyzed from studies with information on availability of matched sibling donor (used to mimic randomization) and from randomized trials of autograft versus chemotherapy. Data from 13 studies including 2962 patients, excluding Philadelphia chromosome–positive patients, showed a survival benefit for having a matched sibling donor for patients < 35 years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those ≥ 35 years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03) because of the higher absolute risk of nonrelapse mortality for older patients. No differences were seen by risk group. There was a trend toward inferior survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P = .06). No beneficial effect of autografting was seen compared with chemotherapy in this analysis. We conclude that matched sibling donor myeloablative HCT improves survival only for younger patients, with an absolute benefit of approximately 10% at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality associated with allogeneic HCT may change the relative effects of these treatments in the future.

Published
2013

7. 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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8. Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia - an individual patient data meta-analysis involving 5659 children

Author

Yetgin, S, Olcay, L, Dibar, E, Conter, V, Masera, G, Valsecchi, MG, Dacou-Voutetakis, C, Henze, I, Loening, L, Schrappe, M, von Stackelberg, A, Zimmermann, M, Attarbaschi, A, Gadner, H, Mann, G, Brandalise, SR, Carroll, WL, Devidas, M, Gaynon, P, Hunger, S, Nachman, J, Janka, G, Stary, J, Gelber, RD, Bierings, M, Kamps, WA, Pieters, R, Otten, J, Suciu, S, Viana, MB, Baruchel, A, Ortega, JJ, Magyarosy, E, Perez, C, Steinberg, D, Tsurusawa, M, Zintl, F, Matsuzaki, A, Eden, TOB, Lilleyman, JS, Richards, S, Steinherz, PG, Kochupillai, V, de Toledo, JS, Appelbaum, FR, Campbell, M, Cheng, C, Pei, D, Pui, CH, Nakazawa, S, Elphinstone, T, Evans, V, Gettins, L, Hicks, C, MacKinnon, L, Morris, P, Wade, R, and Wise, C

Published
2010

9. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression:a patient-level meta-analysis of 7030 women from four randomised trials

Author

Rosie Bradley, Jeremy Braybrooke, Richard Gray, Robert K Hills, Zulian Liu, Hongchao Pan, Richard Peto, David Dodwell, Paul McGale, Carolyn Taylor, Prudence A Francis, Michael Gnant, Francesco Perrone, Meredith M Regan, Richard Berry, Clare Boddington, Mike Clarke, Christina Davies, Lucy Davies, Fran Duane, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Ewan Straiton, Raimund Jakesz, Christian Fesl, Olivia Pagani, Richard Gelber, Michelino De Laurentiis, Sabino De Placido, Ciro Gallo, Kathy Albain, Stewart Anderson, Rodrigo Arriagada, John Bartlett, Elizabeth Bergsten-Nordström, Judith Bliss, Etienne Brain, Lisa Carey, Robert Coleman, Jack Cuzick, Nancy Davidson, Lucia Del Mastro, Angelo Di Leo, James Dignam, Mitch Dowsett, Bent Ejlertsen, Matthew Goetz, Pam Goodwin, Pat Halpin-Murphy, Dan Hayes, Catherine Hill, Reshma Jagsi, Wolfgang Janni, Sibylle Loibl, Eleftherios P Mamounas, Miguel Martín, Hirofumi Mukai, Valentina Nekljudova, Larry Norton, Yasuo Ohashi, Lori Pierce, Philip Poortmans, Kathleen I Pritchard, Vinod Raina, Daniel Rea, John Robertson, Emiel Rutgers, Tanja Spanic, Joseph Sparano, Guenther Steger, Gong Tang, Masakazu Toi, Andrew Tutt, Giuseppe Viale, Xiang Wang, Tim Whelan, Nicholas Wilcken, Norman Wolmark, David Cameron, Jonas Bergh, Sandra M Swain, Bradley, R., Braybrooke, J., Gray, R., Hills, R. K., Liu, Z., Pan, H., Peto, R., Dodwell, D., Mcgale, P., Taylor, C., Francis, P. A., Gnant, M., Perrone, F., Regan, M. M., Berry, R., Boddington, C., Clarke, M., Davies, C., Davies, L., Duane, F., Evans, V., Gay, J., Gettins, L., Godwin, J., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Straiton, E., Jakesz, R., Fesl, C., Pagani, O., Gelber, R., De Laurentiis, M., De Placido, S., Gallo, C., Albain, K., Anderson, S., Arriagada, R., Bartlett, J., Bergsten-Nordstrom, E., Bliss, J., Brain, E., Carey, L., Coleman, R., Cuzick, J., Davidson, N., Del Mastro, L., Di Leo, A., Dignam, J., Dowsett, M., Ejlertsen, B., Goetz, M., Goodwin, P., Halpin-Murphy, P., Hayes, D., Hill, C., Jagsi, R., Janni, W., Loibl, S., Mamounas, E. P., Martin, M., Mukai, H., Nekljudova, V., Norton, L., Ohashi, Y., Pierce, L., Poortmans, P., Pritchard, K. I., Raina, V., Rea, D., Robertson, J., Rutgers, E., Spanic, T., Sparano, J., Steger, G., Tang, G., Toi, M., Tutt, A., Viale, G., Wang, X., Whelan, T., Wilcken, N., Wolmark, N., Cameron, D., Bergh, J., Swain, S. M., Bradbury, R, Braybrooke, J, Gray, R, Hills, R, Liu, Z, Pan, H, Peto, R, Dodwell, D, and McGale, P

Subjects
Breast Neoplasms/pathology, Antineoplastic Agents, Hormonal/therapeutic use, Antineoplastic Agents, Hormonal, Aromatase Inhibitors, Breast Neoplasms, Tamoxifen, Neoplasm Recurrence, Local/drug therapy, Tamoxifen/therapeutic use, Oncology, Receptors, Estrogen, Chemotherapy, Adjuvant, Humans, Aromatase Inhibitor, Female, Aromatase Inhibitors/adverse effects, Neoplasm Recurrence, Local, Human, Randomized Controlled Trials as Topic
Abstract

Background: For women with early-stage oestrogen receptor (ER)-positive breast cancer, adjuvant tamoxifen reduces 15-year breast cancer mortality by a third. Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are ineffective in premenopausal women when used without ovarian suppression. We aimed to investigate whether premenopausal women treated with ovarian suppression benefit from aromatase inhibitors. Methods: We did a meta-analysis of individual patient data from randomised trials comparing aromatase inhibitors (anastrozole, exemestane, or letrozole) versus tamoxifen for 3 or 5 years in premenopausal women with ER-positive breast cancer receiving ovarian suppression (goserelin or triptorelin) or ablation. We collected data on baseline characteristics, dates and sites of any breast cancer recurrence or second primary cancer, and dates and causes of death. Primary outcomes were breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence, and all-cause mortality. As distant recurrence invariably results in death from breast cancer several years after the occurrence, whereas locoregional recurrence and new contralateral breast cancer are not usually fatal, the distant recurrence analysis is shown separately. Standard intention-to-treat log-rank analyses estimated first-event rate ratios (RR) and their confidence intervals (CIs). Findings: We obtained data from all four identified trials (ABCSG XII, SOFT, TEXT, and HOBOE trials), which included 7030 women with ER-positive tumours enrolled between June 17, 1999, and Aug 4, 2015. Median follow-up was 8·0 years (IQR 6·1–9·3). The rate of breast cancer recurrence was lower for women allocated to an aromatase inhibitor than for women assigned to tamoxifen (RR 0·79, 95% CI 0·69–0·90, p=0·0005). The main benefit was seen in years 0–4 (RR 0·68, 99% CI 0·55–0·85; p Interpretation: Using an aromatase inhibitor rather than tamoxifen in premenopausal women receiving ovarian suppression reduces the risk of breast cancer recurrence. Longer follow-up is needed to assess any impact on breast cancer mortality.

Published
2022
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10. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Author

Richard Gray, Rosie Bradley, Jeremy Braybrooke, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, William Barlow, Judith Bliss, Paolo Bruzzi, David Cameron, George Fountzilas, Sibylle Loibl, John Mackey, Miguel Martin, Lucia Del Mastro, Volker Möbus, Valentina Nekljudova, Sabino De Placido, Sandra Swain, Michael Untch, Kathleen I Pritchard, Jonas Bergh, Larry Norton, Clare Boddington, Julie Burrett, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Lucy Gettins, Jon Godwin, Robert Hills, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Yaochen Wang, Zhe Wang, Peter Fasching, Nadia Harbeck, Pascal Piedbois, Michael Gnant, Guenther Steger, Angelo Di Leo, Stella Dolci, Prue Francis, Denis Larsimont, Jean Marie Nogaret, Catherine Philippson, Martine Piccart, Sabine Linn, Petronella Peer, Vivianne Tjan-Heijnen, Sonja Vliek, Dennis Slamon, John Bartlett, Vivien H Bramwell, Bingshu Chen, Stephen Chia, Karen Gelmon, Paul Goss, Mark Levine, Wendy Parulekar, Joseph Pater, Eileen Rakovitch, Lois Shepherd, Dongsheng Tu, Tim Whelan, Don Berry, Gloria Broadwater, Constance Cirrincione, Hyman Muss, Raymond Weiss, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Harry Bartelink, Nina Bijker, Jan Bogaerts, Fatima Cardoso, Tanja Cufer, Jean-Pierre Julien, Philip Poortmans, Emiel Rutgers, Cornelis van de Velde, Eva Carrasco, Miguel Angel Segui, Jens Uwe Blohmer, Serban Costa, Bernd Gerber, Christian Jackisch, Gunter von Minckwitz, Mario Giuliano, Michele De Laurentiis, Christina Bamia, Georgia-Angeliki Koliou, Dimitris Mavroudis, Roger A'Hern, Paul Ellis, Lucy Kilburn, James Morden, John Yarnold, Mohammad Sadoon, Augustinus H Tulusan, Stewart Anderson, Gordon Bass, Joe Costantino, James Dignam, Bernard Fisher, Charles Geyer, Eleftherios P Mamounas, Soon Paik, Carol Redmond, D Lawrence Wickerham, Marco Venturini, Claudia Bighin, Simona Pastorino, Paolo Pronzato, Mario Roberto Sertoli, Theodorus Foukakis, Kathy Albain, Rodrigo Arriagada, Elizabeth Bergsten Nordström, Francesco Boccardo, Etienne Brain, Lisa Carey, Alan Coates, Robert Coleman, Candace Correa, Jack Cuzick, Nancy Davidson, Mitch Dowsett, Marianne Ewertz, John Forbes, Richard Gelber, Aron Goldhirsch, Pamela Goodwin, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Wolfgang Janni, Hirofumi Mukai, Yasuo Ohashi, Lori Pierce, Vinod Raina, Peter Ravdin, Daniel Rea, Meredith Regan, John Robertson, Joseph Sparano, Andrew Tutt, Giuseppe Viale, Nicholas Wilcken, Norman Wolmark, Wiliam Wood, Milvia Zambetti, Gray, R., Bradley, R., Braybrooke, J., Liu, Z., Peto, R., Davies, L., Dodwell, D., Mcgale, P., Pan, H., Taylor, C., Barlow, W., Bliss, J., Bruzzi, P., Cameron, D., Fountzilas, G., Loibl, S., Mackey, J., Martin, M., Del Mastro, L., Mobus, V., Nekljudova, V., De Placido, S., Swain, S., Untch, M., Pritchard, K. I., Bergh, J., Norton, L., Boddington, C., Burrett, J., Clarke, M., Davies, C., Duane, F., Evans, V., Gettins, L., Godwin, J., Hills, R., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Wang, Y., Wang, Z., Fasching, P., Harbeck, N., Piedbois, P., Gnant, M., Steger, G., Di Leo, A., Dolci, S., Francis, P., Larsimont, D., Nogaret, J. M., Philippson, C., Piccart, M., Linn, S., Peer, P., Tjan-Heijnen, V., Vliek, S., Slamon, D., Bartlett, J., Bramwell, V. H., Chen, B., Chia, S., Gelmon, K., Goss, P., Levine, M., Parulekar, W., Pater, J., Rakovitch, E., Shepherd, L., Tu, D., Whelan, T., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Weiss, R., Shan, Y., Shao, Y. F., Wang, X., Xu, B., Zhao, D. -B., Bartelink, H., Bijker, N., Bogaerts, J., Cardoso, F., Cufer, T., Julien, J. -P., Poortmans, P., Rutgers, E., van de Velde, C., Carrasco, E., Segui, M. A., Blohmer, J. U., Costa, S., Gerber, B., Jackisch, C., von Minckwitz, G., Giuliano, M., De Laurentiis, M., Bamia, C., Koliou, G. -A., Mavroudis, D., A'Hern, R., Ellis, P., Kilburn, L., Morden, J., Yarnold, J., Sadoon, M., Tulusan, A. H., Anderson, S., Bass, G., Costantino, J., Dignam, J., Fisher, B., Geyer, C., Mamounas, E. P., Paik, S., Redmond, C., Wickerham, D. L., Venturini, M., Bighin, C., Pastorino, S., Pronzato, P., Sertoli, M. R., Foukakis, T., Albain, K., Arriagada, R., Bergsten Nordstrom, E., Boccardo, F., Brain, E., Carey, L., Coates, A., Coleman, R., Correa, C., Cuzick, J., Davidson, N., Dowsett, M., Ewertz, M., Forbes, J., Gelber, R., Goldhirsch, A., Goodwin, P., Hayes, D., Hill, C., Ingle, J., Jagsi, R., Janni, W., Mukai, H., Ohashi, Y., Pierce, L., Raina, V., Ravdin, P., Rea, D., Regan, M., Robertson, J., Sparano, J., Tutt, A., Viale, G., Wilcken, N., Wolmark, N., Wood, W., and Zambetti, M.

Subjects
Oncology, treatment schedule, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, novotvorbe dojk, Antineoplastic Agents, Breast Neoplasms, režim zdravljenja, Disease, randomized trials, 030204 cardiovascular system & hematology, chemotherapy, meta-analiza, klinični protokoli, Drug Administration Schedule, randomizirane raziskave, Antineoplastic Agent, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Internal medicine, breast neoplasms, medicine, Humans, clinical protocols, terapija z zdravili, 030212 general & internal medicine, Early breast cancer, Chemotherapy, Taxane, business.industry, rak dojk, kemoterapija, General Medicine, medicine.disease, Dose intensity, udc:618.19-006, drug therapy, meta-analysis, Meta-analysis, Female, women, ženske, business, Breast Neoplasm
Abstract

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

Published
2019
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11. Global and regional genetic diversity of HIV-1 in 2010-21: systematic review and analysis of prevalence.

Author

Nair M, Gettins L, Fuller M, Kirtley S, and Hemelaar J

Subjects
Humans, Prevalence, Global Health, HIV-1 genetics, HIV-1 classification, HIV Infections epidemiology, HIV Infections virology, Genetic Variation genetics
Abstract

Background: The extensive global genetic diversity of HIV-1 poses a major challenge to HIV vaccine development. We aimed to determine recent estimates of and changes in the global and regional distributions of HIV-1 genetic variants., Methods: We conducted a systematic literature review by searching PubMed, Embase, Global Health, and CINAHL for studies containing country-specific HIV-1 subtyping data, published between Jan 1, 2010 and Sep 16, 2022. The proportions of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each country were weighted by UNAIDS estimates of the numbers of people living with HIV (PLHIV) in each country to obtain regional and global prevalence estimates of HIV-1 subtypes, CRFs, and URFs with 95% CIs for the time periods 2010-15 and 2016-21. The protocol is registered with PROSPERO, CRD42017067164., Findings: We obtained 1044 datasets, containing HIV-1 subtyping data from 653 013 PLHIV from 122 countries in 2010-2021. In 2016-2021, subtype C accounted for 50·4% (95% CI 50·2-50·7; n=18 570 462 of 36 823 798) of global HIV infections, subtype A for 12·4% (12·2-12·6; n=4 571 250), subtype B for 11·3% (11·1-11·5; n=4 157 686), subtype G for 2·9% (2·9-3·0; n=1 083 568), subtype D for 2·6% (2·5-2·7; n=945 815), subtype F for 0·9% (0·8-0·9; n=316 724), CRFs for 15·1% (14·9-15·3; n=5 564 566), and URFs for 2·0% (1·9-2·1; n=733 374). Subtypes H, J, and K each accounted for 0·1% or less of infections. Compared with 2010-15, we observed significant (p<0·0001) increases in global proportions of subtype A (0·9%, 95% CI 0·7 to 1·1) and subtype C (3·4%, 3·0 to 3·7) and decreases in subtype D (-0·5%, -0·6 to -0·4), subtype G (-0·8%, -1·0 to -0·7), CRFs (-1·0%, -1·3 to -0·8), and URFs (-1·8%, -1·9 to -1·7), with no changes for subtypes B and F. The global proportion of infections attributed to recombinants decreased from 21·6% (95% CI 21·4 to 21·7; n=7 099 252 of 32 622 808) in 2010-15 to 19·3% (19·1 to 19·5; n=7 094 694 of 36 823 798) in 2016-21 (-2·3%, 95% CI -2·6 to -2·0; p<0·0001). Regional distributions of HIV-1 variants were complex and evolving, with global trends in the prevalence of HIV-1 variants supported by trends across the regions., Interpretation: Global and regional HIV-1 genetic diversity are complex and continue to evolve. Continued and improved surveillance of HIV-1 variants remains vital for HIV vaccine development and implementation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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12. The human FK506-binding proteins: characterization of human FKBP19.

Author

Rulten SL, Kinloch RA, Tateossian H, Robinson C, Gettins L, and Kay JE

Subjects
Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Western, Cattle, Cloning, Molecular, Escherichia coli genetics, Humans, Immunoenzyme Techniques, Immunosuppressive Agents metabolism, Mice, Mice, Inbred C3H, Molecular Sequence Data, Protein Biosynthesis, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Sequence Homology, Amino Acid, Tacrolimus metabolism, Tacrolimus Binding Protein 1A metabolism, Tacrolimus Binding Proteins isolation & purification, Tacrolimus Binding Proteins metabolism, Transcription, Genetic, Recombinant Proteins genetics, Tacrolimus Binding Proteins genetics
Abstract

Analysis of the human repertoire of the FK506-binding protein (FKBP) family of peptidyl-prolyl cis/trans isomerases has identified an expansion of genes that code for human FKBPs in the secretory pathway. There are distinct differences in tissue distribution and expression levels of each variant. In this article we describe the characterization of human FKBP19 (Entrez Gene ID: FKBP11), an FK506-binding protein predominantly expressed in vertebrate secretory tissues. The FKBP19 sequence comprises a cleavable N-terminal signal sequence followed by a putative peptidyl-prolyl cis/trans isomerase domain with homology to FKBP12. This domain binds FK506 weakly in vitro. FKBP19 mRNA is abundant in human pancreas and other secretory tissues and high levels of FKBP19 protein are detected in the acinar cells of mouse pancreas.

Published
2006
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