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2. 84TiP Neo-CheckRay: Radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer: A randomized phase II trial

Author

De Caluwe, A., primary, Buisseret, L., additional, Poortmans, P., additional, Sotiriou, C., additional, Larsimont, D., additional, Van Gestel, D., additional, Laragione, A., additional, Desmet, A., additional, Van Den Begin, R., additional, Philippson, C., additional, Eiger, D., additional, Piccart, M., additional, Romano, E., additional, and Ignatiadis, M., additional

Published
2020
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4. 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

6. 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

7. 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

8. 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

9. 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

25. Effects of Irradiation on Facial Development in Mouse Embryos.

Author

Glineur, R., Louryan, S., Philippson, C., Evrard, L., and de Vos, L.

Subjects
IRRADIATION, FACE, MICE, EMBRYOS
Abstract

The purpose of this study was to observe the effects of irradiation on the craniofacial development of NMRI mouse embryos. Two populations of pregnant mice were irradiated with a single dose of 2 Gray on day 8 of gestation for the first population (Po. 1) and on day 9 of gestation for the second population (Po. 2). On gestational days 9 to 17, embryos were submitted to histological and scanning electron microscope examinations. The two populations of embryos presented a high percentage of centro-facial hypoplasia (74.7% for Po.1 and 75% for Po. 2) which was more pronounced in the latter one. Ocular anomalies were present in 16% of the first population. Cases of anencephaly, cleft palate and anomalies of the central nervous system were found in both populations. [ABSTRACT FROM AUTHOR]

Published
1998
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27. 334 Poster - Early invasive ductal breast cancer: Review after 5-year median follow-up of the first 681 patients treated by partial breast irradiation with intraoperative electron radiation therapy.

Author

Philippson, C., Simon, S., Vandekerkhove, C., Veys, I., Noterman, D., De Neubourg, F., Roman, M., Nogaret, J.M., Larsimont, D., and Desmet, A.

Subjects
*BREAST cancer surgery, *AESTHETICS, *BREAST cancer, *CANCER invasiveness, *CLINICAL trials, *CONFERENCES & conventions, *INTRAOPERATIVE radiotherapy, *DUCTAL carcinoma
Published
2020
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29. 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

30. First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial.

Author

De Caluwe A, Romano E, Poortmans P, Gombos A, Agostinetto E, Marta GN, Denis Z, Drisis S, Vandekerkhove C, Desmet A, Philippson C, Craciun L, Veys I, Larsimont D, Paesmans M, Van Gestel D, Salgado R, Sotiriou C, Piccart-Gebhart M, Ignatiadis M, and Buisseret L

Subjects
Humans, Adult, Middle Aged, Aged, Female, B7-H1 Antigen therapeutic use, Prognosis, Combined Modality Therapy, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Radiosurgery methods
Abstract

Background: Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in., Methods: The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery., Results: Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3., Conclusions: This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial., Trial Registration Number: NCT03875573., Competing Interests: Competing interests: ADC: institutional, AstraZeneca. ER: institutional, BMS; institutional: AstraZeneca; institutional: Replimune. Research fundings: Fondation Amgen, Fondation BMS; travel grant from Roche, BMS, Merck. Research fundings: Amgen. AG: Financial Interests, Institutional, AstraZeneca; Financial Interests, Institutional: Daiichi. EA: Consultancy fees/honoraria: Eli Lilly, Sandoz, AstraZeneca. Institutional: Gilead. Support for attending medical conferences from: Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, AstraZeneca. DVG: Advisory board/Honoraria received: Sanofi, Accuray, Merck-Pfizer, Takeda and Novartis. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, Roche, Seattle Genetics. Research grants to my Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genetech, Servier, Synthon. No stock ownership. DVG: Advisory board/Honoraria received: Sanofi, Accuray, Merck-Pfizer, Takeda and Novartis. RS: non-financial support from Merck, non-financial support from BMS, other from Puma Biotechnology, other from Roche, other from Roche, other from Merck. CS: Institutional: Astellas; Personal: Cepheid; Institutional: Vertex; Institutional: Seattle Genetics; Personal: Puma; Institutional: AMGEN; Personal: Eisai; Institutional, Other, Travel: Roche; Institutional, Other, Internal speaker: Genentech; Personal, Other, Regional speaker: Pfizer; Institutional: Inc.; Institutional: Exact Sciences; Institutional: Merck & Co; Personal: prIME Oncology, Personal: Teva. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, Roche, Seattle Genetics. Research grants to my Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genetech, Servier, Synthon. No stock ownership. MI: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics, Tesaro. Research grants to my Institute: Roche, Menarini Silicon Biosystems, Janssen Diagnostics, Pfizer. No stock ownership. Travel grants: Pfizer, Amgen. LB: institutional research grant from AstraZeneca; speaker honoraria from BMS, Novartis; travel grant from Roche, GILEAD. Advisory Board: Iteos, Domain Therapeutics. All other authors: no disclosures., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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31. Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.

Author

Philippson C, Larsen S, Simon S, Vandekerkhove C, De Caluwe A, Van Gestel D, Chintinne M, Veys I, De Neubourg F, Noterman D, Roman M, Nogaret JM, and Desmet A

Subjects
Humans, Female, Electrons, Prospective Studies, Follow-Up Studies, Neoplasm Recurrence, Local radiotherapy, Registries, Mastectomy, Segmental, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Breast Neoplasms pathology
Abstract

Background: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial., Methods: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical)., Results: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%., Conclusions: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk., (© 2022. The Author(s).)

Published
2022
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32. Unintended dose to the lower axilla in adjuvant radiotherapy for breast cancer: Differences between tangential beam and VMAT.

Author

Ahrouch I, Van Gestel D, Koshariuk O, Kirkove C, Desmet A, Philippson C, Reynaert N, and De Caluwe A

Subjects
Axilla, Female, Humans, Organs at Risk, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Adjuvant, Breast Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated
Abstract

Background and Purpose: To evaluate dosimetric differences in unintended dose to the lower axilla between 3D-standard (3DCRT), tangential beam forward intensity modulated radiotherapy (F-IMRT) and volumetric modulated arc therapy (VMAT). The objective is to evaluate whether results of clinical trials, such as the ACOSOG-Z011 trial, that evaluated omission of axillary clearance can be extrapolated towards more conformal techniques like VMAT., Materials and Methods: Twenty-five consecutive patients treated with whole breast radiotherapy alone (WBRT) using a F-IMRT technique were identified. Three additional plans were created for every patient: one plan using a single 270° arc (VMAT 1x270°), another using two small ≤90° opposing arcs (VMAT 2x < 90°) and thirdly a 3DCRT plan without F-IMRT. Axillary levels I-II were contoured after the treatment plans were made., Results: The volume of the axilla level I that was covered by the 50% isodose (V50%) was significantly higher for VMAT 2x < 90° (71.3 cm 3 , 84% of structure volume, p < 0.001) and VMAT 1x270° (68.8 cm 3 , 81%, p < 0.01) compared to 3DCRT (60.3 cm 3 , 71%) and F-IMRT (60.8 cm 3 , 72%). The V50% to the axilla level II, however, was low for all techniques: 12.3 cm 3 (12%); 8.9 cm 3 (9%); 4.3 cm 3 (4%); 4.4 cm 3 (4%) for VMAT 2x < 90°, VMAT 1x270°, 3DCRT, F-IMRT, respectively. For the higher doses (V90% and above), no clinically relevant differences were seen between the different modalities., Conclusion: WBRT treatments with VMAT do not lead to a significant reduction of the unintended axillary dose in comparison with a tangential beam setup. Hence, concerning tumor control, VMAT can be applied to clinical situations similar to the Z0011 trial. The intermediate axillary dose is higher with VMAT, but the clinical consequence of this difference on toxicity is unknown., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
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33. 3D Monte Carlo dosimetry of intraoperative electron radiation therapy (IOERT).

Author

Alhamada H, Simon S, Philippson C, Vandekerkhove C, Jourani Y, Pauly N, VanGestel D, and Reynaert N

Subjects
Intraoperative Period, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Tomography, X-Ray Computed, Electrons therapeutic use, Monte Carlo Method, Radiometry methods, Radiotherapy
Abstract

Purpose: This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images., Methods: The IOERT treatment planning was performed using the following successive steps: I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out., Results: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS)., Conclusions: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Published
2019
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34. Shielding disk position in intra-operative electron radiotherapy (IOERT): A Monte Carlo study.

Author

Alhamada H, Simon S, Philippson C, Vandekerkhove C, Jourani Y, Pauly N, Dubus A, and Reynaert N

Subjects
Intraoperative Period, Mechanical Phenomena, Electrons therapeutic use, Monte Carlo Method, Radiation Protection instrumentation
Abstract

Purpose: In IOERT breast treatments, a shielding disk is frequently used to protect the underlying healthy structures. The disk is usually composed of two materials, a low-Z material intended to be oriented towards the beam and a high-Z material. As tissues are repositioned around the shield before treatment, the disk is no longer visible and its correct alignment with respect to the beam is guaranteed. This paper studies the dosimetric characteristics of four possible clinical positioning scenarios of the shielding disk. A new alignment method for the shielding disk in the beam is introduced. Finally, it suggests a new design for the shielding disk., Methods: As the first step, the IOERT machine "Mobetron 1000" was modeled by using Monte Carlo simulation, tuning the MC model until an excellent match with the measured PDDs and profiles was achieved. Four possible shielding disk positioning scenarios were considered, determining the dosimetric impact. Furthermore, in our center, to prevent beam misalignment, we have developed a shielding disk equipped with guiding rods. Having ascertained a correct alignment between the disk and the beam, we can propose a new internal design of the shielding disk that can improve the dose distribution with a better coverage of the treated area., Results: All MC simulations were performed with a 12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip applicator, this applicator being the most clinically used. The simulations were compared with measurements performed in a water phantom and showed good results within 2.2% of root mean square difference (RMSD). The misplacement positions of the shielding disk have dosimetric impacts in the treatment volume and a small translation could have a significant influence on healthy tissues. The D-scenario is the worst which could happens when the shielding disk is flipped upside down, giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk. A new shielding design used, together with our alignment tool, is able to give a more homogeneous dose in the target area., Conclusions: The accuracy of shielding disk position can still be problematic in IOERT dosimetry. Any method that can ascertain the good alignment between the shielding disk and the beam is beneficial for the dose distribution and is a prerequisite for an optimized shield internal design that could improve the coverage of the treated area and the protection of healthy tissues., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Published
2018
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35. [Not Available].

Author

Fromont A, Nogaret JM, De Neubourg F, and Philippson C

Subjects
Combined Modality Therapy, Humans, Intraoperative Care, Male, Mastectomy, Segmental, Middle Aged, Breast Neoplasms, Male radiotherapy, Breast Neoplasms, Male surgery, Carcinoma, Ductal, Breast radiotherapy, Carcinoma, Ductal, Breast surgery
Abstract

Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer cases. It is often diagnosed late, at a more advanced stage than its female counterpart. Therefore, it is more commonly treated with mastectomy. In early stages, a conservative treatment associating lumpectomy, sentinel lymph node (SLN) biopsy and whole-breast external beam radiotherapy (EBRT) is possible and has been described. Recently, intra-operative radiation therapy (IORT) has been assessed as an alternative to EBRT in selected female breast cancer cases. Its use has never been described in male patients. In this article, we present the case of a 56 years old man treated with lumpectomy with the excision of the nipple-areola complex, SLN biopsy, and IORT with electron beams (IOERT), for early breast cancer disease. This case demonstrates that the IORT technique is feasible on men with early breast cancer (pT1N0).

Published
2016

36. Special focus on cardiac toxicity of different sequences of adjuvant doxorubicin/docetaxel/CMF regimens combined with radiotherapy in breast cancer patients.

Author

Magné N, Castadot P, Chargari C, Di Leo A, Philippson C, and Van Houtte P

Subjects
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms pathology, Chi-Square Distribution, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Docetaxel, Doxorubicin administration & dosage, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Heart Diseases diagnosis, Humans, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Neoplasm Staging, Pilot Projects, Prospective Studies, Radiotherapy Dosage, Taxoids administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Doxorubicin adverse effects, Heart Diseases chemically induced, Taxoids adverse effects
Abstract

Background and Purpose: Cardiac toxicity associated with anthracyclines and taxanes and/or radiotherapy (RT) can be life-threatening and can adversely affect quality of life. The aim was to evaluate treatment-related cardiac toxicity in breast cancer patients treated with doxorubicin/docetaxel/CMF sequential or combined regimens and RT., Methods and Materials: From 1996 to 1998, 64 patients with stages II-III breast cancer were included in a pilot study that investigated the efficacy/feasibility of sequential and combined doxorubicin/docetaxel/CMF regimens. No patients had any cardiovascular history or ECG abnormalities. The same RT technique was performed in all patients. LVEF measurements were obtained at baseline, during, at the end of chemotherapy, at the end of radiotherapy and subsequently during the follow-up. A cardiac event was defined as a myocardial infraction or clinical evidence of congestive heart failure., Results: Median age was 48 years (range 29-65 years). The median follow-up was 6 years. Significant drop in the post-treatment LVEF occurred in 21 patients (median decrease of 10%). Notwithstanding, all patients have preserved normal cardiac function and regained their initial LVEF value during follow-up. No cardiac events were reported., Conclusion: Sequential and combined doxorubicin/docetaxel/CMF regimens plus conventional RT in selected non high-risk cardiac patients are relatively safe without cardiac toxicity at mid-term follow-up.

Published
2009
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37. HSP110, caspase-3 and -9 expression in physiological apoptosis and apoptosis induced by in vivo embryonic exposition to all-trans retinoic acid or irradiation during early mouse eye development.

Author

Gashegu J, Ladha R, Vanmuylder N, Philippson C, Bremer F, Rooze M, and Louryan S

Subjects
Abnormalities, Drug-Induced metabolism, Abnormalities, Radiation-Induced metabolism, Animals, Apoptosis drug effects, Apoptosis radiation effects, Embryonic Development drug effects, Embryonic Development radiation effects, Eye drug effects, Eye radiation effects, Female, Gestational Age, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Animal, Pregnancy, Teratogens pharmacology, Tretinoin pharmacology, Caspase 3 analysis, Caspase 9 analysis, Embryonic Development physiology, Eye embryology, HSP110 Heat-Shock Proteins analysis
Abstract

Apoptosis is an essential physiological process in embryonic development. In the developing eye of vertebrates, three periods of developmental apoptosis can be distinguished: early, intermediate and later. Within the apoptosis pathway, caspases play a crucial role. It has also been shown that HSP110 may have a potential role in apoptosis. The aim of this research was to study the expression of HSP110, caspase-3 and -9 in physiological, retinoic- or irradiation-induced apoptosis during early eye development. Seven pregnant C57Bl/6J mice received 80 mg kg(-1) of all-trans retinoic acid mixed with sesame oil. Seven pregnant NMRI mice received 2 Gy irradiation at the same gestational day. Control mice of both strains (seven mice of each) were not submitted to any treatment. Embryos were harvested at 3, 6, 12 and 24 h after exposition, fixed, dehydrated and embedded. Coronal sections (5 microm) were made. Slide staining occurred alternatively using anti-caspase-3, anti-caspase-9 and anti-HSP110 immunohistochemistry. HSP110 and caspase-3 expression presented similar topographic and chronological patterns, whereas expression of HSP110 was more precocious in retinoic acid-treated embryos. After retinoic exposure, caspase-3- and HSP110-positive cells were increased in the region of the optic vesicle. By contrast, after irradiation, caspase-3- and HSP110-positive cells were noticeably increased in the optic vesicle, peri-optical mesoderm but less in lens placode. HSP110 was expressed before caspase-3. By contrast, caspase-9 was expressed by a very small number of cells in the optic vesicle either under physiological or under teratogenic conditions. Thus, it seems that activation of caspase-9 is dispensable in early eye developmental apoptosis.

Published
2007
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38. [Neoadjuvant radiochemotherapy and surgery of locally advanced cervical carcinoma: review of 22 patients treated at the Bordet Institute].

Author

Noterman D, Philippson C, Hertens D, Veys I, Schobbens JC, and Nogaret JM

Subjects
Adult, Aged, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma pathology, Cisplatin therapeutic use, Combined Modality Therapy, Female, Humans, Hysterectomy, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Retrospective Studies, Survival Analysis, Treatment Outcome, Uterine Cervical Neoplasms pathology, Carcinoma radiotherapy, Carcinoma surgery, Uterine Cervical Neoplasms radiotherapy, Uterine Cervical Neoplasms surgery
Abstract

Objectives: Concomitant chemoradiation is the "new gold standard" for dealing with locally advanced cervical carcinoma, but what about surgery? We don't know yet to what extent surgery is necessary and how radical it must be when it is performed. In this study, we present the analysis of the results obtained in patients treated by concomitant chemoradiation followed by radical surgery., Materials and Methods: Twenty-two patients, median age 49 years, with I(b) - III(a) cervical tumors were enrolled to be treated by concomitant chemoradiation followed by radical surgery. The chemoradiation protocol included external radiotherapy to the pelvis: 45 Gy; Cisplatin 40 mg/m(2) in continuous intravenous infusion once a week (5 weeks) followed by brachytherapy one week later. Surgery was performed 4 to 6 weeks later and consisted in radical hysterectomy with pelvic lymphadenectomy., Results: 20/22 patients underwent surgery after chemoradiation because of a diagnosis of lung metastases in one and presence of a nonresectable metastasis for the other. A complete pathological response was demonstrated in 12/20 patients (60%), a microscopic residual tumor in 7 patients (35%), and residual disease <1cm in 1 patient (5%)., Conclusion: This study showed a particularly high rate of pathologic responses (T(0)+T(mic): 95%) and of local control. We don't know yet if surgery is a real necessity or if it could be less extended after concomitant chemoradiation.

Published
2006
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39. [Expression of caspase 3 and p53 during physiological apoptosis and apoptosis induced by three teratologic agents during early craniofacial development of the mouse embryo].

Author

Gashegu J, Vanmuylder N, Kassengera Z, Evrard L, Glineur R, Philippson C, Rooze M, and Louryan S

Subjects
Animals, Apoptosis drug effects, Apoptosis radiation effects, Caspase 3, Caspases metabolism, Embryonic Development, Immunohistochemistry, Mice, Mice, Inbred Strains, Neural Crest cytology, Neural Crest physiology, Skull cytology, Skull radiation effects, Tretinoin pharmacology, Triazenes pharmacology, Apoptosis physiology, Caspases genetics, Face embryology, Gene Expression Regulation, Developmental drug effects, Gene Expression Regulation, Developmental radiation effects, Skull embryology, Teratogens toxicity, Tumor Suppressor Protein p53 genetics
Abstract

The neural crest-derived mesectoderm gives rise to physiologic apoptosis areas in early vertebrate embryos. Certain teratologic agents increase this phenomenon. The purpose of this work was to detect caspase 3 (which is associated with the apoptosis cascade) and p53 in cell death areas, both during physiological apoptosis and during apoptosis induced by three agents (retinoic acid, methyl-triazene, irradiation). Antibody revelation was performed using the aBC peroxidase kit. Quantifications were also performed on histological sections. We observed caspase 3 uptake on some apoptotic and preapoptotic cells in control embryos, and in the embryos exposed to the three teratogens. Immunoreactivity generally preceded the development of cytological features of apoptosis. However, p53 was expressed only in the embryos exposed to ionizing radiation and methyl-triazene (an alkylating agent), but not significantly in embryos exposed to retinoic acid. The present results throw some light on apoptosis mechanisms in several teratologic conditions.

Published
2005
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40. [Why radiation for the postmastectomy patient?].

Author

Beauvois S, Philippson C, Nogaret JM, and Van Houtte P

Subjects
Breast Neoplasms surgery, Disease-Free Survival, Edema etiology, Female, Heart Diseases etiology, Humans, Lymphatic Metastasis prevention & control, Neoplasm Recurrence, Local prevention & control, Postoperative Care, Radiotherapy, Adjuvant adverse effects, Breast Neoplasms radiotherapy, Mastectomy, Radiotherapy, Adjuvant statistics & numerical data
Abstract

We can identify a subgroup of patients with a high risk of loco-regional relapse after mastectomy. When those patients are irradiated, their absolute loco-regional relapse risk drops for more than 10% with a relative risk reduction of 66% (p < 0.0001). The severe complication rate is below 1%. With earlier radiotherapy techniques, there was an excess in long term cardiac mortality among irradiated patients. Even if the breast specific survival was improved with radiotherapy, the overall survival was not better. Three recent randomised trials have shown that postmastectomy radiotherapy adds 10% survival benefit to an adjuvant systemic treatment. The impact of radiotherapy on overall survival is more pronounced for less advanced tumors.

Published
2000

41. [What is the role of radiotherapy in the treatment of breast cancer in 1995?].

Author

Van Houtte P, Beauvois S, and Philippson C

Subjects
Bone Neoplasms radiotherapy, Bone Neoplasms secondary, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Breast Neoplasms pathology, Breast Neoplasms surgery, Female, Humans, Neoplasm Recurrence, Local prevention & control, Palliative Care, Postoperative Period, Quality of Life, Breast Neoplasms radiotherapy
Abstract

In 1995, radiotherapy continues to remain one important component in the treatment of breast cancer both for the breast conserving approach and after a mastectomy in case of more locally advanced disease: it helps to improve the local control and so to safe more breast or to avoid a relapse in the mastectomy scar, a source of distress for the woman. Nevertheless, this modality requires a precise technique and integration with surgery and chemotherapy. Besides this curative approach, radiotherapy plays an important role in the treatment of brain or bone metastases where it is quite useful to improve the patient's quality of life.

Published
1995

42. The place for surgery in central recurrences of invasive cancer of cervix uteri.

Author

Soeiro Fidalgo de Matos C, Nogaret JM, Philippson C, Veys I, and Van Velthoven R

Subjects
Adult, Aged, Carcinoma, Squamous Cell pathology, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Quality of Life, Treatment Outcome, Uterine Cervical Neoplasms pathology, Carcinoma, Squamous Cell surgery, Neoplasm Recurrence, Local surgery, Uterine Cervical Neoplasms surgery
Abstract

Between 1988 and 1991, at the Jules Bordet Institute in Brussels, 11 patients were submitted to a surgical treatment due to an uterus cervix central recurrence. The majority were of the epidermoid type. The primary stage of the lesion at the moment of diagnosis varied from stage Ib to stage IIIb lesions. Six of the eleven patients were not submitted to an adequate initial treatment. These recurrences appeared between the 4th and the 264th month after the initial treatment. The treatments, which were determined according to the site of recurrence, consisted of: an anterior pelvic exenteration for four patients, a total exenteration for one patient, for two of them a total hysterectomy with bilateral salpingo-oophorectomy and partial cystectomy, a cervix amputation for another one and finally, for the last three ones, a laparotomy with debulking or derivation colostomy. The mortality during and after the operation was nil but there were several short term complications. After a minimal 19 months follow-up we could see that three patients survived, one was generalized and seven died. Due to the scarce number of patients and pathological disparity of them, the authors reviewed the literature concerning this problem, in order to determine some guidelines for similar cases. In spite of its consequences, surgery seems to be the only valid solution to propose to these patients, not only to give them a chance to survive but also to improve their life quality.

Published
1995

43. [Glutamic dehydrogenase activities in renal tissue during experimental and human ehronie pyelonephritis (author's transl)].

Author

Von Philippson CH

Subjects
Animals, Humans, Kidney Glomerulus enzymology, Kidney Medulla enzymology, Kidney Tubules enzymology, Male, Rabbits, Glutamate Dehydrogenase metabolism, Kidney enzymology, Pyelonephritis enzymology
Abstract

Question: These studies are one part of systemic comparative investigations concerning biochemically feasible changes of renal cells and tissues due to chronic pyelonephritis (PN) as correlated to the histological results. The experiments aim at more detailed knowledge on the pathogenesis and conditions of the progressive chronicity of PN which could be of value for the further development of therapeutic measures. In previous papers (Esp. Path., vols. 8, 9 and 10) the author reported on the acid and alkaline phosphatase as well as on the glutaminase I activities. In the present study the glutamic dehydrogenase (GIDH) activities are analyzed., Material and Methods: In 139 adult male rabbits (body weight 2.4 to 2.8 kg) unilateral pyelonephritis was experimentally induced in the left kidney. In additional 19 rabbits no PN developed despite of similar technique. 37 animals were used for controls. The animals were kept on standard diet in individual cages. Dependent on duration of the disease the 139 rabbits affected by experimental PN were divided into 6 groups: 1. Sacrification after 20 days, 2. Sacrification after 31 days, 3. Sacrification after 64 days 4. Sacrification after 100 days, 5. Sacrification after 212 days, 6. Sacrification after 261 days. The 19 rabbits which did not develop PN WERE LIKEWISE SACRIFICED AT DIFFERENT TERMS: AFTER 64 DAYS (5 ANIMALS), AFTER 100 DAYS (7 ANIMALS), AFTER 212 DAYS (7ANIMALS). These rabbits were designated "B-series". From 31 human kidneys with clinically quiescent pyelonephritic renal shrinkage wedge-shaped tissue samples were removed. Furthermore, 20 tissue samples of surgical specimens of extirpated human tumor kidneys were removed far distant from the site of the tumor. Induction of unilateral PN in the rabbits was done after the method of LEPPER (5) as modified by PRAT et al. (14). Coli of the strain O 55 K 59 were used for infection in a germ suspension of 500 millions of bacterial/ml 0.9% sterile physiological saline (control of the germ suspension by means of nephelometry). 24 hours after unilateral renal ligation each animal was i.v. administered 800-1000 millions of germs. At the end of the test the left side lesioned kidney was removed within maximally 100 sec after having been rinsed bloodless by means of cooled physiological saline (0 to 2 degrees C) during this period. On an ice-cooled glass plate the decapsulation and preparative separation of the medulla from the cortex was done using a magnifier; remnants of the capsule, hilar and fatty tissue were removed. Simultaneously tissue samples were obtained from 70 impaired kidneys and from 6 animals of the B-series (see above) for histological examination. The medullary and cortical parts were immediately swabbed with filter paper and weighed in moist state. Preparation for enzyme analysis: The renal medulla was minced and homogenized after the method of SCHMIDT, SCHMIDT and WILDHIRT (17) for 5 min at 0 degrees C...

Published
1976

44. [Aspartate aminotransferase activities in renal tissue during experimental and human chronic pyelonephritis].

Author

Philippson C

Subjects
Animals, Humans, Kidney Cortex enzymology, Kidney Glomerulus enzymology, Kidney Medulla enzymology, Male, Rabbits, Time Factors, Aspartate Aminotransferases metabolism, Kidney enzymology, Pyelonephritis enzymology
Abstract

This study belongs to a series of comparative biochemical and semiquantitative-histological investigations in renal tissue fractions of pyelonephritis patients (human PN) and of different types of experimental pyelonephritis (experimental PN). The experiments aim at more detailed knowledge on the interrelationship of intermediary cell metabolism and histopathological changes during the different phases of human and experimental PN. The results concerning acid and alkaline phosphatase activities as well as concerning glutaminase I and glutamic dehydrogenase activities were earlier reported (Exp. Path. vols. 8, 9, 10 and 12). In the present study the author has analyzed the activities of aspartate aminotransferase (E.C.2.6.1.1. AspAT) the synonym of which is glutamic oxaloacetic transaminase (GOT).

Published
1977

45. Citrate-synthase activities in the renal tissue during experimental and chronic human pyelonephritis.

Author

Philippson C

Subjects
Animals, Chronic Disease, Humans, Kidney Glomerulus enzymology, Kidney Medulla enzymology, Male, Rabbits, Citrate (si)-Synthase metabolism, Kidney enzymology, Oxo-Acid-Lyases metabolism, Pyelonephritis enzymology
Abstract

In chronic experimental and human pyelonephritis (PN) renal enzyme and phosphatide analyses and quantitative histological examinations were performed. The results reported in this study only refer to citrate-synthase activities (= condensing enzyme = CE). 139 rabbits developed unilateral experimental pyelonephritis, in further 19 rabbits the experimental PN did not settle or "healed up spontaneously". 31 samples of human pyelonephritic nephrocirrhotic kidneys and 20 samples of healthy human kidneys were examined in the same manner. The glomerular CE-activities in the rabbit increased steeply in the 20- and 31-days-series, remained at a high level up to the 100-days-series, showed normal values in the 213-days-series, and permitted a marked decrease to be seen in the 261-days-series only. The corticotubular CE-activities increased steeply in the 20- and 31-day-series, still being above the normal values in the 64-days-series. Thereafter, only reduced and strongly reduced values were observed. In the pyelonephritic medulla of rabbits the CE-activities increased very steeply during the 20-days-series, were still above the level of the normal values up to the 100-days-series, dropping then to pathologically reduced data in the 212-days-series. Thus the CE-activities showed a similar type of behaviour to that of the corresponding glomeruli. Chronically pyelonephritic contracted renal tissue in human beings also showed major reductions in CE-activities in all three tissue fractions studies. The significance calculations (universally applied t-test) showed an overwhelming majority of significant values (p less than 0.001).

Published
1981
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46. The phosphatidylcholine metabolism in the renal tissue during experimental acute and chronic pyelonephritis in the rabbit.

Author

Philippson C

Subjects
Animals, Kidney Cortex metabolism, Kidney Medulla metabolism, Male, Rabbits, Kidney metabolism, Phosphatidylcholines metabolism, Pyelonephritis metabolism
Abstract

In 139 adult male rabbits unilateral pyelonephritis (PN) was induced. In a broad spectrum of enzymes and phospholipids also the content of phosphatidylcholine (PC) was determined. Only these latter values are reported here. PC showed markedly increased levels up to the 20-d-, and to the 31-d-series in the cortex. After 64 and 100 d of experimental PN the content of PC was less than the half of the normal values, and after 261 d of disease, it was only about 1/16 of the normal value (= 22.58 +/- 1.55 micrograms P/g wet weight). In the medulla the PC increased only till the 20-d-series, but showed a marked decrease in the 31-d-series already, which is in contrast to the corresponding cortical situation. Thereafter the medullary PC decreased successively, so that only about 5 per cent of the normal value were found in the contracted kidneys of the 261-d-series (n = 13.58 +/- 1.24 microgramsP/g wet weight). The increased PC-concentrations should be due mainly to the increased cell contents, the following reductions being due to the lower cell contents of this interstitium. Other factors (induced synthesis and/or reduced decomposition) may be responsible to a lesser degree of probability. The strongly decreased PC concentrations in the chronic and late-chronic series are caused by the low cell-contents, increasing vascular changes, the augmented connective tissue, and the general epithelial damage of the remaining nephrons.

Published
1986
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47. [The maximum adsorptive capacities of three activated carbons produced in the GDR for barbiturates, other hypnotics and tranquilizers from aqueous and low-percentage ethanolic solutions (author's transl)].

Author

Philippson C and Schmiedel R

Subjects
Adsorption, Ethanol, Salicylates, Solutions, Water, Barbiturates, Carbon, Hypnotics and Sedatives
Abstract

A standardized stirred-batch experiment has been performed to determine the maximum adsorptive capacities of three activated carbons (R4, ASO and walnut coal) produced in the GDR for acetylsalicylic acid, methylsalicylate, phenobarbital, crotylbarbital, hexobarbital, pentobarbital, glutethimide, chlorophenethazine and methaqualone from aqueous and low-percentage ethanolic solutions. The activated carbon ASO and the walnut coal have always been found to be markedly superior to the activeated coal R 4. The maximum adsorptive capacities so far determined compare with data on activated carbons produced abroad, so that further developmental work seems worthwhile.20

Published
1980

48. [Significance of physical-chemistry procedures and of biochemical technics for the uremia detoxication and for the construction of modern artificial kidneys. II. Electrochemical oxidation; description of various adsorbents related to uremic detoxication and other intoxications; additional possibilities of urea adsorption].

Author

Philippson C

Subjects
Acrolein, Adsorption, Electrochemistry, Histocytochemistry methods, Humans, Ion Exchange Resins, Starch, Urea metabolism, Kidneys, Artificial, Uremia therapy
Published
1978

50. Alanine-aminotransferase activities in the renal tissue during experimental and chronic human pyelonephritis.

Author

Philippson C

Subjects
Animals, Chronic Disease, Humans, Male, Rabbits, Alanine Transaminase metabolism, Kidney Glomerulus enzymology, Kidney Medulla enzymology, Kidney Tubules enzymology, Pyelonephritis enzymology
Abstract

In chronic experimental and human pyelonephritis (PN) simultaneously renal enzyme and phosphatide analyses and quantitative histological examinations were performed. The results reported in this study refer only to alanine-aminotransferase (AlAT) activities. 139 rabbits developed unilateral experimental pyelonephritis, in further 19 rabbits the experimental PN did not settle or "healed up spontaneously". 31 samples of human pyelonephritis nephrocirrhotic kidneys and 20 samples of healthy human kidneys were examined. Glomerular AlAT-activities increased initially up to the 31-days series, thereafter they decreased without any exception. In the cortical tubules of the rabbit kidneys the enzyme activities increased also up to the 31-days-series, later on they decreased extremely. The medullary AlAT-activities similarly showed increasing values till the 31-days-series, which were followed by sharply depressed data. In the "spontaneously healed up" tissue the glomerular AlAT was increased more than 100%, the cortico-tubular one nearly 100%, and the AlAT of the medulla paralleled the increased values of the 20-days series nearly. The human samples of pyelonephritic nephrocirrhosis showed in all 3 fractions (glomerula, cortical tubules and medulla) extremely depressed AlAT-activities. The significance calculations (universally applied t-test) showed an overhelming majority of the values with significance (p less than 0.001). The measured enzyme activities correlate well with the quantitative histological examinations.

Published
1979
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