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1. IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients

Author

Kunz G, Davis JB, Huguenin PU, Studer G, Lütolf UM, and Glanzmann C

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response. The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. Results Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5–6 × 2 Gy/week to 60–70 Gy, 5 × 2.2 Gy/week to 66–68.2 Gy (according to the RTOG protocol H-0022), or 5 × 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10–44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. Conclusion SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Published
2006
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2. Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE

Author

Mamounas, E.P., Untch, M., Mano, M.S., Huang, C.-S., Geyer Jr, C.E., von Minckwitz, G., Wolmark, N., Pivot, X., Kuemmel, S., DiGiovanna, M.P., Kaufman, B., Kunz, G., Conlin, A.K., Alcedo, J.C., Kuehn, T., Wapnir, I., Fontana, A., Hackmann, J., Polikoff, J., Saghatchian, M., Brufsky, A., Yang, Y., Zimovjanova, M., Boulet, T., Liu, H., Tesarowski, D., Lam, L.H., Song, C., Smitt, M., and Loibl, S.

Published
2021
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3. Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44–GeparQuinto)

Author

von Minckwitz, G., Loibl, S., Untch, M., Eidtmann, H., Rezai, M., Fasching, P.A., Tesch, H., Eggemann, H., Schrader, I., Kittel, K., Hanusch, C., Huober, J., Solbach, C., Jackisch, C., Kunz, G., Blohmer, J.U., Hauschild, M., Fehm, T., Nekljudova, V., Gerber, B., Gnauert, K., Heinrich, B., Prätz, T., Groh, U., Tanzer, H., Villena, C., Tulusan, A., Liedtke, B., Blohmer, J.-U., Mau, C., Potenberg, J., Schilling, J., Just, M., Weiss, E., Bückner, U., Wolfgarten, M., Lorenz, R., Doering, G., Feidicker, S., Krabisch, P., Deichert, U., Augustin, D., Kast, K., Nestle-Krämling, C., Höß, C., Terhaag, J., Fasching, P., Staib, P., Aktas, B., Kühn, T., Khandan, F., Möbus, V., Stickeler, E., Heinrich, G., Wagner, H., Abdallah, A., Dewitz, T., Emons, G., Belau, A., Rethwisch, V., Lantzsch, T., Thomssen, C., Mattner, U., Nugent, A., Müller, V., Noesselt, T., Holms, F., Müller, T., Deuker, J.-U., Strumberg, D., Uleer, C., Solomayer, E., Runnebaum, I., Link, H., Tomé, O., Ulmer, H.-U., Conrad, B., Feisel-Schwickardi, G., Schumacher, C., Steinmetz, T., Bauerfeind, I., Kremers, S., Langanke, D., Kullmer, U., Ober, A., Fischer, D., Kohls, A., Weikel, W., Bischoff, J., Freese, K., Schmidt, M., Wiest, W., Sütterlin, M., Dietrich, M., Grießhammer, M., Burgmann, D.-M., Rack, B., Salat, C., Sattler, D., Tio, J., von Abel, E., Christensen, B., Burkamp, U., Köhne, C.-H., Meinerz, W., Graßhoff, S.-T., Decker, T., Overkamp, F., Thalmann, I., Sallmann, A., Beck, T., Reimer, T., Bartzke, G., Deryal, M., Weigel, M., Weder, P., Steffens, C.-C., Lemster, S., Stefek, A., Ruhland, F., Hofmann, M., Schuster, J., Simon, W., Kronawitter, U., Clemens, M., Janni, W., Latos, K., Bauer, W., Roßmann, A., Bauer, L., Lampe, D., Heyl, V., Hoffmann, G., Lorenz-Salehi, F., Hackmann, J., and Schlag, R.

Published
2014
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14. Mortality following cardiovascular and bleeding events occurring beyond 1 year after coronary stenting: A secondary analysis of the Dual Antiplatelet Therapy (DAPT) Study.

Author

Hopkins J., McGarry T., Nygaard T., Pow T., Larkin T., Caulfield T., Stys T., Lee T., Mansouri V., Srinivas V., Gupta V., Marquardt W., Ballard W., Bachinsky W., Colyer W., Dillon W., Felten W., French W., Kuehl W., Nicholas W., Nicholson W., Phillips W., Khatib Y., Al-Saghir Y., Hawa Z., Masud Z., Jafar Z., Muller D., Meredith I., Rankin J., Worthley M., Jepson N., Thompson P., Hendriks R., Whitbourn R., Duffy S., Stasek J., Novobilsky K., Naplava R., Coufal Z., Vaquette B., Bressollette E., Teiger E., Coste P., Rihani R., Darius H., Bergmann M.W., Radke P., Sebastian P., Strasser R., Hoffmann S., Behrens S., Moebius-Winkler S., Rutsch W., Lupkovics G., Horvath I., Kancz S., Forster T., Koszegi Z., Devlin G., Hart H., Elliott J., Ormiston J., Abernathy M., Fisher N., Kay P., Harding S., Jaffe W., Hoffmann A., Sosnowski C., Trebacz J., Buszman P., Dobrzycki S., Kornacewicz-Jach Z., Iancu A.C., Ginghina C.D., Matei C., Dobreanu D., Bolohan F.R., Dorobantu M., Jacques A., Jain A., Bakhai A., Gershlick A., Adamson D., Newby D., Felmeden D., Purcell I., Edmond J., Irving J., De Belder M., Pitt M., Kelly P., O'Kane P., Clifford P., Suresh V., Secemsky E.A., Yeh R.W., Kereiakes D.J., Cutlip D.E., Cohen D.J., Steg P.G., Cannon C.P., Apruzzese P.K., D'Agostino R.B., Massaro J.M., Mauri L., Kaplan A., Ahmed A., Ahmed A.-H., Albirini A., Moreyra A., Rabinowitz A., Shroff A., Moak A., Jacobs A., Kabour A., Gupta A., Irimpen A., Rosenthal A., Taussig A., Ferraro A., Chhabra A., Pucillo A., Spaedy A., White A., Pratsos A., Shakir A., Ghitis A., Agarwal A., Chawla A., Tang A., Barker B., Bertolet B., Uretsky B., Erickson B., Rama B., McLaurin B., Dearing B., Negus B., Price B., Brott B., Bhambi B., Bowers B., Watt B., Donohue B., Hassel C.D., Croft C., Lambert C., O'Shaughnessy C., Shoultz C., Kim C., Caputo C., Nielson C., Scott C., Wolfe C., McKenzie C., Brachfeld C., Thieling C., Fisher D., Simon D., Churchill D., Dobies D., Eich D., Goldberg D., Griffin D., Henderson D., Kandzari D., Lee D., Lewis D., Mego D., Paniagua D., Rizik D., Roberts D., Safley D., Abbott D., Shaw D., Temizer D., Canaday D., Myears D., Westerhausen D., Ebersole D., Netz D., Baldwin D., Letts D., Harlamert E., Kosinski E., Portnay E., Mahmud E., Korban E., Hockstad E., Rivera E., Shawl F., Shamoon F., Kiernan F., Aycock G.R., Schaer G., Kunz G., Kichura G., Myers G., Pilcher G., Tadros G., Kaddissi G.I., Ramadurai G., Eaton G., Elsner G., Mishkel G., Simonian G., Piegari G., Chen H., Liberman H., Aronow H., Tamboli H.P., Dotani I., Marin J., Fleischhauer J.F., Leggett J., Mills J., Phillips J., Revenaugh J., Mann J.T., Wilson J., Pattanayak J., Aji J., Strain J., Patel J., Carr J., Moses J., Chen J.-C., Williams J., Greenberg J., Cohn J., Douglas J., Gordon J., Griffin J., Hawkins J., Katopodis J., Lopez J., Marshall J., Wang J., Waltman J., Saucedo J., Galichia J., McClure M., Kozina J., Stella J., Tuma J., Kieval J., Giri K., Ramanathan K., Allen K., Atassi K., Baran K., Khaw K., Clayton K., Croce K., Skelding K., Patel K., Garratt K., Harjai K., Chandrasekhar K., Kalapatapu K., Lin L., Dean L., Barr L., MacDonald L., Cannon L., Satler L., Gruberg L., Tami L., Bikkina M., Shah M., Atieh M., Chauhan M., Litt M., Unterman M., Lechin M., Zughaib M., Fisch M., Grabarczyk M., Greenberg M., Lurie M., Rothenberg M., Stewart M., Purvis M., Hook M., Leesar M., Buchbinder M., Weiss M., Guerrero M., Abu-Fadel M., Ball M., Chang M., Cunningham M., Del Core M., Jones M., Kelberman M., Lim M., Ragosta M., Rinaldi M., Rosenberg M., Savage M., Tamberella M., Kellett M., Vidovich M., Effat M., Mirza M.A., Khan M., Dib N., Laufer N., Kleiman N., Farhat N., Amjadi N., Schechtmann N., Bladuell N., Quintana O., Gigliotti O., Best P., Flaherty P., Hall P., Gordon P., Gurbel P., Ho P., Luetmer P., Mahoney P., Mullen P., Teirstein P., Tolerico P., Ramanathan P., Kerwin P., Lee P.V., Kraft P., Wyman R.M., Gonzalez R., Kamineni R., Dave R., Sharma R., Prashad R., Aycock R., Quesada R., Goodroe R., Magorien R., Randolph R., Bach R., Kettelkamp R., Paulus R., Waters R., Zelman R., Ganim R., Bashir R., Applegate R., Feldman R., Frankel R., Hibbard R., Jobe R., Jumper R., Maholic R., Siegel R., Smith R., Stoler R., Watson R., Wheatley R., Gammon R., Hill R., Sundrani R., Caputo R., Jenkins R., Stella R., Germanwala S., Hadeed S., Ledford S., Dube S., Gupta S., Davis S., Martin S., Waxman S., Dixon S., Naidu S., Potluri S., Cook S., Crowley S., Kirkland S., McIntyre S., Thew S., Lin S., Marshalko S., Guidera S., Hearne S., Karas S., Manoukian S., Rowe S., Yakubov S., Pollock S., Banerjee S., Allaqaband S., Choi S., Mulukutla S., Papadakos S., Bajwa T., Addo T., Schreiber T., Haldis T., Mathew T., Hopkins J., McGarry T., Nygaard T., Pow T., Larkin T., Caulfield T., Stys T., Lee T., Mansouri V., Srinivas V., Gupta V., Marquardt W., Ballard W., Bachinsky W., Colyer W., Dillon W., Felten W., French W., Kuehl W., Nicholas W., Nicholson W., Phillips W., Khatib Y., Al-Saghir Y., Hawa Z., Masud Z., Jafar Z., Muller D., Meredith I., Rankin J., Worthley M., Jepson N., Thompson P., Hendriks R., Whitbourn R., Duffy S., Stasek J., Novobilsky K., Naplava R., Coufal Z., Vaquette B., Bressollette E., Teiger E., Coste P., Rihani R., Darius H., Bergmann M.W., Radke P., Sebastian P., Strasser R., Hoffmann S., Behrens S., Moebius-Winkler S., Rutsch W., Lupkovics G., Horvath I., Kancz S., Forster T., Koszegi Z., Devlin G., Hart H., Elliott J., Ormiston J., Abernathy M., Fisher N., Kay P., Harding S., Jaffe W., Hoffmann A., Sosnowski C., Trebacz J., Buszman P., Dobrzycki S., Kornacewicz-Jach Z., Iancu A.C., Ginghina C.D., Matei C., Dobreanu D., Bolohan F.R., Dorobantu M., Jacques A., Jain A., Bakhai A., Gershlick A., Adamson D., Newby D., Felmeden D., Purcell I., Edmond J., Irving J., De Belder M., Pitt M., Kelly P., O'Kane P., Clifford P., Suresh V., Secemsky E.A., Yeh R.W., Kereiakes D.J., Cutlip D.E., Cohen D.J., Steg P.G., Cannon C.P., Apruzzese P.K., D'Agostino R.B., Massaro J.M., Mauri L., Kaplan A., Ahmed A., Ahmed A.-H., Albirini A., Moreyra A., Rabinowitz A., Shroff A., Moak A., Jacobs A., Kabour A., Gupta A., Irimpen A., Rosenthal A., Taussig A., Ferraro A., Chhabra A., Pucillo A., Spaedy A., White A., Pratsos A., Shakir A., Ghitis A., Agarwal A., Chawla A., Tang A., Barker B., Bertolet B., Uretsky B., Erickson B., Rama B., McLaurin B., Dearing B., Negus B., Price B., Brott B., Bhambi B., Bowers B., Watt B., Donohue B., Hassel C.D., Croft C., Lambert C., O'Shaughnessy C., Shoultz C., Kim C., Caputo C., Nielson C., Scott C., Wolfe C., McKenzie C., Brachfeld C., Thieling C., Fisher D., Simon D., Churchill D., Dobies D., Eich D., Goldberg D., Griffin D., Henderson D., Kandzari D., Lee D., Lewis D., Mego D., Paniagua D., Rizik D., Roberts D., Safley D., Abbott D., Shaw D., Temizer D., Canaday D., Myears D., Westerhausen D., Ebersole D., Netz D., Baldwin D., Letts D., Harlamert E., Kosinski E., Portnay E., Mahmud E., Korban E., Hockstad E., Rivera E., Shawl F., Shamoon F., Kiernan F., Aycock G.R., Schaer G., Kunz G., Kichura G., Myers G., Pilcher G., Tadros G., Kaddissi G.I., Ramadurai G., Eaton G., Elsner G., Mishkel G., Simonian G., Piegari G., Chen H., Liberman H., Aronow H., Tamboli H.P., Dotani I., Marin J., Fleischhauer J.F., Leggett J., Mills J., Phillips J., Revenaugh J., Mann J.T., Wilson J., Pattanayak J., Aji J., Strain J., Patel J., Carr J., Moses J., Chen J.-C., Williams J., Greenberg J., Cohn J., Douglas J., Gordon J., Griffin J., Hawkins J., Katopodis J., Lopez J., Marshall J., Wang J., Waltman J., Saucedo J., Galichia J., McClure M., Kozina J., Stella J., Tuma J., Kieval J., Giri K., Ramanathan K., Allen K., Atassi K., Baran K., Khaw K., Clayton K., Croce K., Skelding K., Patel K., Garratt K., Harjai K., Chandrasekhar K., Kalapatapu K., Lin L., Dean L., Barr L., MacDonald L., Cannon L., Satler L., Gruberg L., Tami L., Bikkina M., Shah M., Atieh M., Chauhan M., Litt M., Unterman M., Lechin M., Zughaib M., Fisch M., Grabarczyk M., Greenberg M., Lurie M., Rothenberg M., Stewart M., Purvis M., Hook M., Leesar M., Buchbinder M., Weiss M., Guerrero M., Abu-Fadel M., Ball M., Chang M., Cunningham M., Del Core M., Jones M., Kelberman M., Lim M., Ragosta M., Rinaldi M., Rosenberg M., Savage M., Tamberella M., Kellett M., Vidovich M., Effat M., Mirza M.A., Khan M., Dib N., Laufer N., Kleiman N., Farhat N., Amjadi N., Schechtmann N., Bladuell N., Quintana O., Gigliotti O., Best P., Flaherty P., Hall P., Gordon P., Gurbel P., Ho P., Luetmer P., Mahoney P., Mullen P., Teirstein P., Tolerico P., Ramanathan P., Kerwin P., Lee P.V., Kraft P., Wyman R.M., Gonzalez R., Kamineni R., Dave R., Sharma R., Prashad R., Aycock R., Quesada R., Goodroe R., Magorien R., Randolph R., Bach R., Kettelkamp R., Paulus R., Waters R., Zelman R., Ganim R., Bashir R., Applegate R., Feldman R., Frankel R., Hibbard R., Jobe R., Jumper R., Maholic R., Siegel R., Smith R., Stoler R., Watson R., Wheatley R., Gammon R., Hill R., Sundrani R., Caputo R., Jenkins R., Stella R., Germanwala S., Hadeed S., Ledford S., Dube S., Gupta S., Davis S., Martin S., Waxman S., Dixon S., Naidu S., Potluri S., Cook S., Crowley S., Kirkland S., McIntyre S., Thew S., Lin S., Marshalko S., Guidera S., Hearne S., Karas S., Manoukian S., Rowe S., Yakubov S., Pollock S., Banerjee S., Allaqaband S., Choi S., Mulukutla S., Papadakos S., Bajwa T., Addo T., Schreiber T., Haldis T., and Mathew T.

Abstract

Importance: Early cardiovascular and bleeding events after coronary stenting are associated with high risk of morbidity and mortality. Objective(s): To assess the prognosis of cardiovascular and bleeding events occurring beyond 1 year after coronary stenting. Design, Setting, and Participant(s): This secondary analysis is derived from data from the Dual Antiplatelet Therapy (DAPT) Study, a multi center trial involving 220 US and in ternational clinical sites from 11 countries. The study dateswere August 2009 to May 2014. Individuals who underwent coronary stenting and completed 12 months of thienopyridine plus aspirin therapy without ischemic or bleeding events remained on an aspirin regimen and were randomized to continued thienopyridine therapy vs placebo for 18 additional months. Individuals were then followed up for 3 additional months while receiving aspirin therapy alone. The analysis began in August 2015. Exposures: Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries [GUSTO] classification moderate or severe bleeding). Main Outcomes and Measures: Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (GUSTO classification moderate or severe bleeding). Death at 21 months after randomization (33 months after coronary stenting). Result(s): Intotal, 25 682 individuals older than 18 years with an indication for coronarystentingwere enrolled, and 11 648(meanage,61.3 years; 25.1%female)were randomized. After randomization, 478 individuals (4.1%) had 502 ischemic events (306 with myocardial infarction, 113 with stent thrombosis, and 83 with ischemic stroke), and 232 individuals (2.0%) had 235 bleeding events (155 with moderate and 80 with severe bleeding). Among individuals with ischemic events, 52(10.9%) died. The annualize

Published
2017

15. Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44)†

Author

Gerber, B., Loibl, S., Eidtmann, H., Rezai, M., Fasching, P. A., Tesch, H., Eggemann, H., Schrader, I., Kittel, K., Hanusch, C., Kreienberg, R., Solbach, C., Jackisch, C., Kunz, G., Blohmer, J. U., Huober, J., Hauschild, M., Nekljudova, V., Untch, M., von Minckwitz, G., Gerber, B., Loibl, S., Eidtmann, H., Rezai, M., Fasching, P. A., Tesch, H., Eggemann, H., Schrader, I., Kittel, K., Hanusch, C., Kreienberg, R., Solbach, C., Jackisch, C., Kunz, G., Blohmer, J. U., Huober, J., Hauschild, M., Nekljudova, V., Untch, M., and von Minckwitz, G.

Abstract

Background We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). Patients and methods Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m2; q3w) followed by four cycles docetaxel (100 mg/m2; q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. Results TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. Conclusions The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates

Published
2017

17. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial

Author

Baselga, J, Bradbury, I, Eidtmann, H, Di Cosimo, S, de Azambuja, E, Aura, C, Gómez, H, Dinh, P, Fauria, K, Van Dooren, V, Aktan, G, Goldhirsch, A, Chang, T, Horváth, Z, Coccia-Portugal, M, Domont, J, Tseng, L, Kunz, G, Sohn, J, Semiglazov, V, Lerzo, G, Palacova, M, Probachai, V, Pusztai, L, Untch, M, Gelber, R, Piccart-Gebhart, M, Bidoli, P, Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, Bidoli P, Baselga, J, Bradbury, I, Eidtmann, H, Di Cosimo, S, de Azambuja, E, Aura, C, Gómez, H, Dinh, P, Fauria, K, Van Dooren, V, Aktan, G, Goldhirsch, A, Chang, T, Horváth, Z, Coccia-Portugal, M, Domont, J, Tseng, L, Kunz, G, Sohn, J, Semiglazov, V, Lerzo, G, Palacova, M, Probachai, V, Pusztai, L, Untch, M, Gelber, R, Piccart-Gebhart, M, Bidoli, P, Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, and Bidoli P

Abstract

Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. Methods: In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/m 2, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m 2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358. Findings: 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3; 95 CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5; 22·4-37·5]; difference 21·1, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7, 18·1-32·3]) and the trastuzumab (difference -4·8, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4]) and lapatinib plus trastuzumab (32 [21·1]) than with trastuzumab (t

Published
2012

19. Os Modos de vida da População em Situação de Rua: narrativas de andanças nas ruas de Vitórias/ES

Author

KUNZ, G. S., CARVALHO, S. V., TAVARES, G. M., and Heckert, A.L.

Abstract

Made available in DSpace on 2016-08-29T14:09:49Z (GMT). No. of bitstreams: 1 tese_6192_Gilderlandia Kunz.pdf: 2117813 bytes, checksum: 3a9ed4f83c20c9d56b969405d2ee0e4b (MD5) Previous issue date: 2012-09-27 Os Modos de vida da População em Situação de Rua: narrativas de andanças nas ruas de Vitórias/ES

Published
2012

20. Verbreitung und Biologie der Wiesenknopf-Feuerzikade Zygina frauenfeldi LETHIERRY in REIBER & PUTON 1880 (Insecta: Auchenorrhyncha: Cicadellidae: Typhlocybinae)

Author

W.E, Kunz, G., and Seljak, G.

Subjects
Biodiversity, Taxonomy
Abstract

W.E, Kunz, G., Seljak, G. (2011): Verbreitung und Biologie der Wiesenknopf-Feuerzikade Zygina frauenfeldi LETHIERRY in REIBER & PUTON 1880 (Insecta: Auchenorrhyncha: Cicadellidae: Typhlocybinae). Linzer biologische Beiträge 43 (2): 1465-1474, DOI: http://doi.org/10.5281/zenodo.5326928

Published
2011
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22. Insecta Hemiptera collected in the Mont Avic Natural Park (Aosta Valley, Northwest Italy)

Author

Alma, A, Bocca, M, Ermak, V, Chen, P, D'Urso, Vera, Exnerová, A, Goula, A, Guglielmino, A, Kunz, G, Lauterer, P, Malenovský, I, Mazzoglio, P. J., NICOLI ALDINI, R, Ouvrard, D, Remane, R, Rintala, T, Seljak, G, Söderman, G, SOULIER PERKINS, A, Tys, P, Tavella, L, Tedeschi, R, and Wilson, M.

Subjects
Hemiptera, Italy, Settore AGR/11 - ENTOMOLOGIA GENERALE E APPLICATA, Hemiptera, Western Alps, Western Alps, faunistics, Aosta Valley
Abstract

The results are given of the Hemiptera collection exscursions in the Monte Avic Natural Park (Aosta Valley, NW Italy) that took place during the 4th European Hemiptera Congress held in Ivrea in September 2007. Altogether 126 species of Heteroptera, belonging to 89 genera, 108 species of Auchenorrhyncha, belonging to 75 genera, and 30 species of Sternorrhyncha Psyllomorpha, belonging to 8 genera were collected at the four different elevation sites of Capoluogo-Tendeur (500-600m a.s.l.), Chevrère (1200-1400m a.s.l.), Dondena (2100-2300m a.s.l.), and Miserin (2588m a.s.l.). Of these species, 2 were new records for Italy: the Mirid Lygus maritimus and Cicadellid Edwardsiana ishidai. New records for Italy are also the Pipunculid Dipteran Tomosvarjella freidbergi and the Halictophagid Strepsipteran Halictophagus languedoci, parasitoids of Auchenorrhyncha.

Published
2009

25. PARFORCE: Objectives and Achievements

Author

Becker, E., Hoell, C., Kulmala, M., Hameri, K., Pirjola, L., Aalto, P., Geever, M., Kunz, G., Hansson, H-C, Strom, J., Jennings, M., O'Dowd, C.D., Makela, J.M., Vakeva, M., Leeuw, G. de, and TNO Fysisch en Elektronisch Laboratorium

Subjects
Physics, Coastal environment, Aerosol growth, Particle formation, Aerosol paricles, Coastal nucleation, Boundary layer structure
Abstract

Understanding the formation of natural particles in the atmosphere, and their growth to radiatively active sizes, is critical to quantifying the role of anthropogenic emissions on cloud formation, climate change and public health. Only a few regions have been identified as strong natural sources of aerosols in the boundary layer: in particular, the coastal region seems to be the strongest natural source of these new particles. The PARFORCE program was designed to elucidate and understand the underlying processes leading to observed coastal nucleation and to quantify the factors promoting coastal nucleation. Initial results indicate that nucleation rates in the coastal environment are of the order of 107 cm-3 s-1 and can be explained by ternary nucleation of sulphuric acid, water vapor and ammonia; however, growth to detectable sizes can only be explained by additional condensation of, probably, organic vapor-otherwise these new stable embryos are lost due to coagulation. The primary biogenic condensing species leading to the observed particle concentrations is thought to be a halocarbon derivative. Peak concentration of particles at sizes >3 nm can reach 1,000,000 cm-3 after a coastal nucleation event and these events occur almost on a daily basis over considerable spatial scales

Published
2000

26. IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients

Author

Studer, G, Huguenin, P U, Davis, J B, Kunz, G, Lütolf, U M, Glanzmann, C, Studer, G, Huguenin, P U, Davis, J B, Kunz, G, Lütolf, U M, and Glanzmann, C

Abstract

BACKGROUND: Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. RESULTS: Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5-6 x 2 Gy/week to 60-70 Gy, 5 x 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 x 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients. Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. CONCLUSION: SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to

Published
2006

27. Pathological Complete Response to Trastuzumab Subcutaneous Fixed-Dose Formulation in the Hannah Study: Subgroup Analysis of Patient Demographics and Tumor Characteristics and Influence of Body Weight (BW) and Serum Trough Concentration (Ctrough) of Trastuzumab

Author

Melichar, B., primary, Stroyakovskiy, D., additional, Ahn, J.S., additional, Kopp, M.V., additional, Srimuninnimit, V., additional, Kunz, G., additional, Li, J., additional, van der Horst, T., additional, Muehlbauer, S., additional, and Jackisch, C., additional

Published
2012
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28. Abstract S4-6: Neoadjuvant Chemotherapy with or without Bevacizumab: Primary Efficacy Endpoint Analysis of the GEPARQUINTO Study (GBG 44)

Author

von Minckwitz, G, primary, Eidtmann, H, additional, Rezai, M, additional, Fasching, PA, additional, Tesch, H, additional, Eggemann, H, additional, Schrader, I, additional, Kittel, K, additional, Hanusch, C, additional, Kreienberg, R, additional, Solbach, C, additional, Gerber, B, additional, Jackisch, C, additional, Kunz, G, additional, Blohmer, J-U, additional, Huober, J, additional, Hauschild, M, additional, Fehm, T, additional, Loibl, S, additional, Nekljudova, V, additional, and Untch, M., additional

Published
2010
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34. Parforce:Objectives and achievements

Author

Hale, Barbara, Kulmala, Markku, O'Dowd, C. D., Becker, E., Hoell, C., Mäkelä, J. M., Kulmala, M., Hämeri, K., Väkevä, M., Pirjola, L., Aalto, P., Hansson, H. C., Strom, J., Jennings, S. G., Geever, M., De Leeuw, G., Kunz, G., Berresheim, H., Hewitt, C. N., Sartin, J., Harrison, R. M., Allen, A. G., Viisanen, Y., Korhonen, P., Rapsomanikis, S., Hoffman, T., Hale, Barbara, Kulmala, Markku, O'Dowd, C. D., Becker, E., Hoell, C., Mäkelä, J. M., Kulmala, M., Hämeri, K., Väkevä, M., Pirjola, L., Aalto, P., Hansson, H. C., Strom, J., Jennings, S. G., Geever, M., De Leeuw, G., Kunz, G., Berresheim, H., Hewitt, C. N., Sartin, J., Harrison, R. M., Allen, A. G., Viisanen, Y., Korhonen, P., Rapsomanikis, S., and Hoffman, T.

Abstract

Understanding the formation of natural particles in the atmosphere, and their growth to radiatively active sizes, is critical to quantifying the role of anthropogenic emissions on cloud formation, climate change and public health. Only a few regions have been identified as strong natural sources of aerosols in the boundary layer: in particular, the coastal region seems to be the strongest natural source of these new particles. The PARFORCE program was designed to elucidate and understand the underlying processes leading to observed coastal nucleation and to quantify the factors promoting coastal nucleation. Initial results indicate that nucleation rates in the coastal environment are of the order of 107 cm−3 s−1 and can be explained by ternary nucleation of sulphuric acid, water vapor and ammonia; however, growth to detectable sizes can only be explained by additional condensation of, probably, organic vapor—otherwise these new stable embryos are lost due to coagulation. The primary biogenic condensing species leading to the observed particle concentrations is thought to be a halocarbon derivative. Peak concentration of particles at sizes >3 nm can reach 1,000,000 cm−3 after a coastal nucleation event and these events occur almost on a daily basis over considerable spatial scales.

Published
2000

37. A Bulk Model to Predict Optical Turbulence in the Marine Surface Layer

Author

FYSISCH EN ELEKTRONISCH LAB TNO THE HAGUE (NETHERLANDS), Kunz, G. J., FYSISCH EN ELEKTRONISCH LAB TNO THE HAGUE (NETHERLANDS), and Kunz, G. J.

Abstract

A model for turbulence in the marine atmospheric surface layer has been developed and evaluated. The model uses only standard meteorological parameters and is suited to become part of a technical decision aid to predict optical turbulence and refractivity effects. In addition, the model provides all the basic tools to calculate the vertical profiles of wind speed, air temperature and air humidity, the micrometeorological parameters such as stability, roughness lengths, exchange coefficients and the fluxes of momentum, heat, water vapor. These results are used to estimate the structure function parameters for the refractive index, C(2)(sub n), which is the controlling parameter for the prediction of scintillation, blurring and beam wander., Text in English and Dutch.

Published
1996

39. PARFORCE: Objectives and achievements

Author

O'Dowd, C.D., primary, Becker, E., additional, Hoell, C., additional, Mäkela, J.M., additional, Kulmala, M., additional, Hämeri, K., additional, Väkevä, M., additional, Pirjola, L., additional, Aalto, P., additional, Hansson, H.-C., additional, Strom, J., additional, Jennings, S.G., additional, Geever, M., additional, de Leeuw, G., additional, Kunz, G., additional, Berresheim, H., additional, Hewitt, C.N., additional, Sartin, J., additional, Harrison, R.M., additional, Allen, A.G., additional, Viisanen, Y., additional, Korhonen, P., additional, Rapsomanikis, S., additional, and Hoffman, T., additional

Published
2000
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45. A High Repetition Rate LIDAR (En LIDAR met een Hoge Herhalingsfrequentie)

Author

FYSISCH EN ELEKTRONISCH LAB TNO THE HAGUE (NETHERLANDS), Kunz, G. J., FYSISCH EN ELEKTRONISCH LAB TNO THE HAGUE (NETHERLANDS), and Kunz, G. J.

Abstract

Using optical radar (LIDAR) techniques, properties of the atmosphere can be determined by remote sensing. Examples are, e.g., the horizontal visibility or the extinction coefficient, the vertical extinction or visibility profile and the cloud base altitude. Because the time scales in the atmosphere are much shorter than the maximum sample rate or the LIDAR available at the start of this project, a need existed of a system with a repetition rate of at least 10 pulses per second. With such a system it is possible to measure the dynamics of the atmosphere on a sub-second time scale and to map smoke and dust clouds. This report describes the properties of such a system designed and developed at the physics and electronics laboratory TNO. Some typical examples of results obtained with this system are presented., Original contains color plates: All DTIC and NTIS reproductions will be in black and white. Abstract in English and Dutch.

Published
1991

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