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1. The Role of the Amino Acid (Methionine) Protected on the Productivity Performance of the Dairy Cow

Author

Khasraw M. Hassan

Subjects
RPMeth, methionine, milk yield, dairy cattle, performance, lactation, Agriculture
Abstract

One of the most important aspects of livestock is the supply of essential quantities of balanced nutrients manufacture. In several physiological functions of nutrients, concerning organisms, protein has an important role. Ruminants are not wholly protected of amino acids by microflora degradation of animal feed sources and by maintaining proteins from the breakdown in the rumen where both high and medium yielding ruminant amino acids are required, they must be met; therefore, rumen-protected protein (RPP) dietary supplementation, including primarily rumen-protected protein (RPP), methionine (RPMeth), protected from rumen flora, it was necessary. Numerous scientists are attracted in the study of the character of (RPMeth) in a dairy cow about it’s an impact on milk produce, growth rate, N- efficiency, coefficient digestibility, intake of DM. Unluckily, the findings obtained from many RPMeth investigations showed excessive fluctuation results in ruminant nutrition between its helpful and useless influence, specifically during early and late lactation periods. Thus, for ruminants, when they use this review post, farm owners may be careful when they are plan to apply RPMeth to the diet of animals. In summary, supplementation RPMeth also has a positive balanced effect, even with no detrimental effect on the yield of milk, animal productivity and hemato-biochemical parameters, especially during the early lactation when used with a ruminant diet low in crude protein

Published
2022
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7. Validation of cancer-type-dependent benefit from immune checkpoint blockade in TMB-H tumors identified by the FoundationOne CDx assay

Author

McGrail, D.J., primary, Pilié, P.G., additional, Rashid, N.U., additional, Voorwerk, L., additional, Slagter, M., additional, Kok, M., additional, Jonasch, E., additional, Khasraw, M., additional, Heimberger, A.B., additional, Ueno, N.T., additional, Ferrarotto, R., additional, Chang, J.T., additional, and Lin, S.-Y., additional

Published
2022
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9. P11.65.B GBM AGILE: A global, phase 2/3 adaptive platform trial to evaluate multiple treatment regimens in newly diagnosed and recurrent glioblastoma

Author

Weller, M, primary, Ellingson, B, additional, Alexander, B, additional, Wen, P, additional, Sulman, E, additional, Colman, H, additional, Berry, D, additional, Tanner, K, additional, Khasraw, M, additional, Lim, M, additional, Perry, J, additional, Lassman, A, additional, Cloughesy, T, additional, Yung, W K A, additional, Lee, E Q, additional, Mellinghoff, I, additional, Gordon, G, additional, de Groot, J, additional, Mikkelsen, T, additional, Cavenee, W, additional, Nelli, A, additional, Buxton, M, additional, and Li, W, additional

Published
2022
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11. Barriers and potential solutions to international collaboration in neuro-oncology clinical trials: Challenges from the Australian perspective

Author

Kong, BY, Carter, C, Nowak, AK, Hovey, E, Lwin, Z, Haghighi, N, Gan, Hui, Sim, HW, Ziegler, DS, Barton, K, Parkinson, J, Leonard, R, Khasraw, M, and Foote, M

Subjects
education, health care economics and organizations, Uncategorized
Abstract

Aim: The neuro-oncology community in Australia is well positioned to collaborate internationally, with a motivated trials group, strong regulatory bodies and an attractive fiscal environment. We sought to identify gaps in the Australian neuro-oncology clinical trials landscape and describe strategies to increase international trial access in Australia. Methods: We searched clinical trial registries to identify active adult primary brain cancer trials. We compared the participation rate and phase of these trials between tumour types and countries. A survey was distributed to the Cooperative Trials Group for Neuro-Oncology membership to identify barriers and solutions to effective international collaboration. Results: Globally, 307 trials for adult primary brain cancers were identified. These included 50% pharmaceutical agents, 18% cellular therapies and 9% radiation therapy. Twelve adult primary brain cancer trials were actively recruiting in Australia at the time the survey was sent out. There were more early phase brain cancer trials (34%) compared with colorectal and breast cancer (21% and 24%, respectively). In Australia, 92% of brain cancer trials were involving pharmaceutical agents. The most commonly cited barrier was lack of funding for international trials (86%) and insufficient research time (75%). High ranking solutions included increasing the availability of funding for international trials and creating opportunities to develop personal relationships with collaborators. Accreditation of clinical research key performance indicators into practice (88%) and hospital accreditation (73%) also ranked highly. Conclusions: Participation in international research in Australia could be improved by embedding clinical research targets into institutional funding, provision of funding for early phase studies and streamlining mutual ethics schemes.

Published
2022
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18. Phase I study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumours

Author

Luke, J.J., primary, Fong, L., additional, Chung, K., additional, Tolcher, A.W., additional, Kelly, K., additional, Hollebecque, A., additional, Le Tourneau, C., additional, Subbiah, V., additional, Tsai, F., additional, Kao, S., additional, Cassier, P., additional, Khasraw, M., additional, Allaire, K., additional, Fan, F., additional, Fang, H., additional, Patel, M., additional, Henner, W., additional, Hayflick, J., additional, McDevitt, M., additional, and Barlesi, F., additional

Published
2019
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22. Rezidivmuster bei Patienten mit anaplastischem Glioma mit einer IDH1/2-Mutation.

Author

Back, M., Jayamanne, D., Brazier, D., Newey, A., Bailey, D., Schembri, G., Hsiao, E., Khasraw, M., Wong, M., Kastelan, M., Brown, C., and Wheeler, H.

Abstract

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2020
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24. 1220P - Phase I study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumours

Author

Luke, J.J., Fong, L., Chung, K., Tolcher, A.W., Kelly, K., Hollebecque, A., Le Tourneau, C., Subbiah, V., Tsai, F., Kao, S., Cassier, P., Khasraw, M., Allaire, K., Fan, F., Fang, H., Patel, M., Henner, W., Hayflick, J., McDevitt, M., and Barlesi, F.

Published
2019
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25. AGITG NABNEC: A randomised phase II study of nab-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas

Author

Khasraw, M., primary, Hofman, M.S., additional, Chantrill, L., additional, Pavlakis, N., additional, Gebski, V., additional, Gill, A.J., additional, Markman, B., additional, Yip, S., additional, Gibbs, E., additional, Karapetis, C., additional, Wong, S.F., additional, Ransom, D.T., additional, Michael, M., additional, Wilson, K., additional, Simes, J., additional, and Lipton, L., additional

Published
2017
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26. Accuracy and prognostic significance of oncologists’ estimates and scenarios for survival time in a randomised Phase 2 trial of regorafenib in advanced gastric cancer

Author

Vasista, A., primary, Martin, A., additional, Pavlakis, N., additional, Sjoquist, K., additional, Snow, S., additional, Jonker, D., additional, Chua, Y.J., additional, Epstein, R., additional, Bonaventura, A., additional, Khasraw, M., additional, Varma, S.C., additional, Singhal, N., additional, Ransom, D.T., additional, Aubin, F., additional, Burkes, R., additional, Lim, H., additional, Lemay, F., additional, Begbie, S., additional, Stockler, M.R., additional, and Kiely, B., additional

Published
2017
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28. A randomized phase 2, single-blind study of temozolomide (TMZ) and radiotherapy (RT) combined with nivolumab or placebo (PBO) in newly diagnosed adult patients (pts) with tumor O6-methylguanine DNA methyltransferase (MGMT)-methylated glioblastoma (GBM)—CheckMate-548

Author

Weller, M., primary, Vlahovic, G., additional, Khasraw, M., additional, Brandes, A.A., additional, Zwirtes, R., additional, Tatsuoka, K., additional, Carpentier, A.F., additional, Reardon, D.A., additional, and Bent, Mvanden, additional

Published
2016
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30. 32LBA The AGITG ICECREAM Study: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Amongst Patients with a G13D Mutation – analysis of outcomes in patients with refractory metastatic colorectal cancer harbouring the KRAS G13D mutation

Author

Segelov, E., primary, Thavaneswaran, S., additional, Waring, P., additional, Desai, J., additional, Mann, K., additional, Elez, E., additional, Chantrill, L., additional, Pavlakis, N., additional, Nott, L., additional, Underhill, C., additional, Khasraw, M., additional, Wasan, H., additional, Ciardiello, F., additional, Jefford, M., additional, Joubert, W., additional, Haydon, A., additional, Karapetis, C., additional, Price, T., additional, Wilson, K., additional, and Shapiro, J., additional

Published
2015
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34. MEDICAL AND NEURO-ONCOLOGY

Author

Prithviraj, G. K., primary, Sommers, S. R., additional, Jump, R. L., additional, Halmos, B., additional, Chambless, L. B., additional, Parker, S. L., additional, Hassam-Malani, L., additional, McGirt, M. J., additional, Thompson, R. C., additional, Hunter, K., additional, Chamberlain, M. C., additional, Le, E. M., additional, Lee, E. L. T., additional, Sadighi, Z. S., additional, Pearlman, M. L., additional, Slopis, J. M., additional, Vats, T. S., additional, Khatua, S., additional, DeVito, N. C., additional, Yu, M., additional, Chen, R., additional, Pan, E., additional, Cloughesy, T., additional, Raizer, J., additional, Drappatz, J., additional, Gerena-Lewis, M., additional, Rogerio, J., additional, Yacoub, S., additional, Desjardin, A., additional, Groves, M. D., additional, DeGroot, J., additional, Loghin, M., additional, Conrad, C. A., additional, Hess, K., additional, Ni, J., additional, Ictech, S., additional, Yung, W. A., additional, Porter, A. B., additional, Dueck, A. C., additional, Karlin, N. J., additional, Olson, J., additional, Silber, J., additional, Reiner, A. S., additional, Panageas, K. S., additional, Iwamoto, F. M., additional, Cloughesy, T. F., additional, Aldape, K. D., additional, Rivera, A. L., additional, Eichler, A. F., additional, Louis, D. N., additional, Paleologos, N. A., additional, Fisher, B. J., additional, Ashby, L. S., additional, Cairncross, J. G., additional, Roldan, G. B., additional, Wen, P. Y., additional, Ligon, K. L., additional, Shiff, D., additional, Robins, H. I., additional, Rocque, B. G., additional, Mason, W. P., additional, Weaver, S. A., additional, Green, R. M., additional, Kamar, F. G., additional, Abrey, L. E., additional, DeAngelis, L. M., additional, Jhanwar, S. C., additional, Rosenblum, M. K., additional, Lassman, A. B., additional, Cachia, D., additional, Alderson, L., additional, Moser, R., additional, Smith, T., additional, Yunus, S., additional, Saito, K., additional, Mukasa, A., additional, Narita, Y., additional, Tabei, Y., additional, Shinoura, N., additional, Shibui, S., additional, Saito, N., additional, Flechl, B., additional, Ackerl, M., additional, Sax, C., additional, Dieckmann, K., additional, Crevenna, R., additional, Widhalm, G., additional, Preusser, M., additional, Marosi, C., additional, Ay, C., additional, Dunkler, D., additional, Pabinger, I., additional, Zielinski, C., additional, Belongia, M., additional, Jogal, S., additional, Schlingensiepen, K.-H., additional, Bogdahn, U., additional, Stockhammer, G., additional, Mahapatra, A. K., additional, Venkataramana, N. K., additional, Oliushine, V., additional, Parfenov, V., additional, Poverennova, I., additional, Hau, P., additional, Jachimczak, P., additional, Heinrichs, H., additional, Mammoser, A. G., additional, Shonka, N. A., additional, de Groot, J. F., additional, Shibahara, I., additional, Sonoda, Y., additional, Kumabe, T., additional, Saito, R., additional, Kanamori, M., additional, Yamashita, Y., additional, Watanabe, M., additional, Ishioka, C., additional, Tominaga, T., additional, Silvani, A., additional, Gaviani, P., additional, Lamperti, E., additional, Botturi, A., additional, DiMeco, F., additional, Broggi, G., additional, Fariselli, L., additional, Solero, C. L., additional, Salmaggi, A., additional, Woyshner, E. A., additional, Shu, F., additional, Oh, Y. S., additional, Iganej, S., additional, Singh, G., additional, Vemuri, S. L., additional, Theeler, B. J., additional, Ellezam, B., additional, Gilbert, M. R., additional, Aoki, T., additional, Kobayashi, H., additional, Takano, S., additional, Nishikawa, R., additional, Nagane, M., additional, Muragaki, Y., additional, Sugiyama, K., additional, Kuratsu, J., additional, Matsutani, M., additional, Langford, L. A., additional, Puduvalli, V. K., additional, Shen, D., additional, Chen, Z.-p., additional, Zhang, J.-p., additional, Bedekar, D., additional, Rand, S., additional, Connelly, J., additional, Malkin, M., additional, Paulson, E., additional, Mueller, W., additional, Schmainda, K., additional, Gallego, O., additional, Benavides, M., additional, Segura, P. P., additional, Balana, C., additional, Gil, M., additional, Berrocal, A., additional, Reynes, G., additional, Garcia, J. L., additional, Murata, P., additional, Bague, S., additional, Quintana, M. J., additional, Vasishta, V. G., additional, Kobayashi, K., additional, Tanaka, M., additional, Tsuchiya, K., additional, Shiokawa, Y., additional, Bavle, A. A., additional, Ayyanar, K., additional, Prado, M. P., additional, Hess, K. R., additional, Liu, V., additional, de Groot, J., additional, Loghin, M. E., additional, Colman, H., additional, Levin, V. A., additional, Alfred Yung, W. K., additional, Hackney, J. R., additional, Palmer, C. A., additional, Markert, J. M., additional, Cure, J., additional, Riley, K. O., additional, Fathallah-Shaykh, H., additional, Nabors, L. B., additional, Saria, M. G., additional, Corle, C., additional, Hu, J., additional, Rudnick, J., additional, Phuphanich, S., additional, Mrugala, M. M., additional, Lee, L. K., additional, Fu, B. D., additional, Bota, D. A., additional, Kim, R. Y., additional, Brown, T., additional, Feely, H., additional, Hu, A., additional, Lee, J. W., additional, Carter, B., additional, Kesari, S., additional, Kong, X.-T., additional, Sparagana, S., additional, Belousova, E., additional, Jozwiak, S., additional, Korf, B., additional, Frost, M., additional, Kuperman, R., additional, Kohrman, M., additional, Witt, O., additional, Wu, J., additional, Flamini, R., additional, Jansen, A., additional, Curtalolo, P., additional, Thiele, E., additional, Whittemore, V., additional, De Vries, P., additional, Ford, J., additional, Shah, G., additional, Cauwel, H., additional, Edrich, P., additional, Sahmoud, T., additional, Franz, D., additional, Khasraw, M., additional, Brown, C., additional, Ashley, D. M., additional, Rosenthal, M. A., additional, Jiang, X., additional, Mou, Y. g., additional, Chen, Z. p., additional, Oh, M., additional, kim, E., additional, Chang, J., additional, Juratli, T. A., additional, Kirsch, M., additional, Schackert, G., additional, Krex, D., additional, Wang, M., additional, Stupp, R., additional, Hegi, M., additional, Jaeckle, K. A., additional, Armstrong, T. S., additional, Wefel, J. S., additional, Won, M., additional, Blumenthal, D. T., additional, Mahajan, A., additional, Schultz, C. J., additional, Erridge, S. C., additional, Brown, P. D., additional, Chakravarti, A., additional, Curran, W. J., additional, Mehta, M. P., additional, Hofland, K. F., additional, Hansen, S., additional, Sorensen, M., additional, Schultz, H., additional, Muhic, A., additional, Engelholm, S., additional, Ask, A., additional, Kristiansen, C., additional, Thomsen, C., additional, Poulsen, H. S., additional, Lassen, U. N., additional, Zalatimo, O., additional, Weston, C., additional, Zoccoli, C., additional, Glantz, M., additional, Rahmanuddin, S., additional, Shiroishi, M. S., additional, Cen, S. Y., additional, Jones, J., additional, Chen, T., additional, Pagnini, P., additional, Go, J., additional, Lerner, A., additional, Gomez, J., additional, Law, M., additional, Ram, Z., additional, Wong, E. T., additional, Gutin, P. H., additional, Bobola, M. S., additional, Alnoor, M., additional, Silbergeld, D. L., additional, Rostomily, R. C., additional, Silber, J. R., additional, Martha, N., additional, Jacqueline, S., additional, Thaddaus, G., additional, Daniel, P., additional, Hans, M., additional, Armin, M., additional, Eugen, T., additional, Gunther, S., additional, Hutterer, M., additional, Tseng, H.-M., additional, Zoccoli, C. M., additional, Patel, A., additional, Rizzo, K., additional, Sheehan, J. M., additional, Sumrall, A. L., additional, Vredenburgh, J. J., additional, Desjardins, A., additional, Reardon, D. A., additional, Friiedman, H. S., additional, Peters, K. B., additional, Taylor, L. P., additional, Stewart, M., additional, Blondin, N. A., additional, Baehring, J. M., additional, Foote, T., additional, Laack, N., additional, Call, J., additional, Hamilton, M. G., additional, Walling, S., additional, Eliasziw, M., additional, Easaw, J., additional, Shirsat, N. V., additional, Kundar, R., additional, Gokhale, A., additional, Goel, A., additional, Moiyadi, A. A., additional, Wang, J., additional, Mutlu, E., additional, Oyan, A., additional, Yan, T., additional, Tsinkalovsky, O., additional, Jacobsen, H. K., additional, Talasila, K. M., additional, Sleire, L., additional, Pettersen, K., additional, Miletic, H., additional, Andersen, S., additional, Mitra, S., additional, Weissman, I., additional, Li, X., additional, Kalland, K.-H., additional, Enger, P. O., additional, Sepulveda, J., additional, Belda, C., additional, Sitt, R., additional, Phishniak, L., additional, Bokstein, F., additional, Philippe, M., additional, Carole, C., additional, Andre, M. d. P., additional, Marylin, B., additional, Olivier, C., additional, L'Houcine, O., additional, Dominique, F.-B., additional, Isabelle, N.-M., additional, Frederic, F., additional, Stephane, F., additional, Henry, D., additional, Errico, M. A., additional, Kunschner, L. J., additional, Soffietti, R., additional, Trevisan, E., additional, Ruda, R., additional, Bertero, L., additional, Bosa, C., additional, Fabrini, M. G., additional, Lolli, I., additional, Jalali, R., additional, Julka, P. K., additional, Anand, A. K., additional, Bhavsar, D., additional, Singhal, N., additional, Naik, R., additional, John, S., additional, Mathew, B. S., additional, Thaipisuttikul, I., additional, Graber, J., additional, Shirinian, M., additional, Fontebasso, A. M., additional, Jacob, K., additional, Gerges, N., additional, Montpetit, A., additional, Nantel, A., additional, Albrecht, S., additional, Jabado, N., additional, Shah, K., additional, Di, K., additional, Linskey, M., additional, Thon, N., additional, Eigenbrod, S., additional, Kreth, S., additional, Lutz, J., additional, Tonn, J.-C., additional, Kretzschmar, H., additional, Peraud, A., additional, Kreth, F.-W., additional, Muggeri, A. D., additional, Alderuccio, J. P., additional, Diez, B. D., additional, Jiang, P., additional, Chao, Y., additional, Gallagher, M., additional, Kim, R., additional, Pastorino, S., additional, Fogal, V., additional, Rudnick, J. D., additional, Bresee, C., additional, Rogatko, A., additional, Sakowsky, S., additional, Franco, M., additional, Lim, S., additional, Lopez, A., additional, Yu, L., additional, Ryback, K., additional, Tsang, V., additional, Lill, M., additional, Steinberg, A., additional, Sheth, R., additional, Grimm, S., additional, Helenowski, I., additional, Rademaker, A., additional, Nunes, F. P., additional, Merker, V., additional, Jennings, D., additional, Caruso, P., additional, Muzikansky, A., additional, Stemmer-Rachamimov, A., additional, Plotkin, S., additional, Spalding, A. C., additional, Vitaz, T. W., additional, Sun, D. A., additional, Parsons, S., additional, Welch, M. R., additional, Omuro, A., additional, Beal, K., additional, Correa, D., additional, Chan, T., additional, DeAngelis, L., additional, Gavrilovic, I., additional, Nolan, C., additional, Hormigo, A., additional, Kaley, T., additional, Mellinghoff, I., additional, Grommes, C., additional, Panageas, K., additional, Reiner, A., additional, Barradas, R., additional, Abrey, L., additional, Gutin, P., additional, Lee, S. Y., additional, Slagle-Webb, B., additional, Glantz, M. J., additional, Connor, J. R., additional, Schlimper, C. A., additional, Schlag, H., additional, Stoffels, G., additional, Weber, F., additional, Krueger, D. A., additional, Care, M. M., additional, Holland, K., additional, Agricola, K., additional, Tudor, C., additional, Byars, A., additional, Franz, D. N., additional, Rice, L., additional, Chandler, J., additional, Levy, R., additional, Muro, K., additional, Nayak, L., additional, Norden, A. D., additional, Kaley, T. J., additional, Thomas, A. A., additional, Fadul, C. E., additional, Meyer, L. P., additional, Lallana, E. C., additional, Gilbert, M., additional, Aldape, K., additional, De Groot, J., additional, Conrad, C., additional, Levin, V., additional, Groves, M., additional, Chris, P., additional, Puduvalli, V., additional, Nagpal, S., additional, Feroze, A., additional, Recht, L., additional, Rangarajan, H. G., additional, Kieran, M. W., additional, Scott, R. M., additional, Lew, S. M., additional, Firat, S. Y., additional, Segura, A. D., additional, Jogal, S. A., additional, Kumthekar, P. U., additional, Grimm, S. A., additional, Avram, M., additional, Patel, J., additional, Kaklamani, V., additional, McCarthy, K., additional, Cianfrocca, M., additional, Gradishar, W., additional, Mulcahy, M., additional, Von Roenn, J., additional, Galanis, E., additional, Anderson, S. K., additional, Lafky, J. M., additional, Kaufmann, T. J., additional, Uhm, J. H., additional, Giannini, C., additional, Kumar, S. K., additional, Northfelt, D. W., additional, Flynn, P. J., additional, Buckner, J. C., additional, Omar, A. I., additional, Schiff, D., additional, Delios, A., additional, Jakubowski, A., additional, Melguizo-Gavilanes, I., additional, Qiao, W., additional, Wang, X., additional, Hashemi-Sadraei, N., additional, Bawa, H., additional, Rahmathulla, G., additional, Patel, M., additional, Elson, P., additional, Stevens, G., additional, Peereboom, D., additional, Vogelbaum, M., additional, Weil, R., additional, Barnett, G., additional, Ahluwalia, M. S., additional, Alvord, E. C., additional, Rockne, R. C., additional, Rockhill, J. K., additional, Rostomily, R., additional, Lai, A., additional, Wardlaw, J., additional, Spence, A. M., additional, Swanson, K. R., additional, Zadeh, G., additional, Alahmadi, H., additional, Wilson, J., additional, Gentili, F., additional, Beumer, J. J., additional, Wright, J., additional, Takebe, N., additional, Gaur, R., additional, Werner-Wasik, M., additional, Gupta, A. J., additional, Campos-Gines, A., additional, Le, K., additional, Arango, C., additional, Richards, M., additional, Landeros, M., additional, Juan, H., additional, Chang, J. H., additional, Kim, J. S., additional, Cho, J. H., additional, Seo, C. O., additional, Baldock, A. L., additional, Rockne, R., additional, Canoll, P., additional, Born, D., additional, Yagle, K., additional, Alexandru, D., additional, Bota, D., additional, Linskey, M. E., additional, Nabeel, S., additional, Raval, S. N., additional, Rosenow, J., additional, Bredel, M., additional, New, P. Z., additional, Plotkin, S. R., additional, Supko, J. G., additional, Curry, W. T., additional, Chi, A. S., additional, Gerstner, E. R., additional, Batchelor, T. T., additional, Hashemi, N., additional, Chao, S. T., additional, Weil, R. J., additional, Suh, J. H., additional, Vogelbaum, M. A., additional, Stevens, G. H., additional, Barnett, G. H., additional, Corwin, D., additional, Holdsworth, C., additional, Stewart, R., additional, Swanson, K., additional, Graber, J. J., additional, Anderson, A. R., additional, Jeyapalan, S., additional, Goldman, M., additional, Boxerman, J., additional, Donahue, J., additional, Elinzano, H., additional, Evans, D., additional, O'Connor, B., additional, Puthawala, M. Y., additional, Oyelese, A., additional, Cielo, D., additional, Blitstein, M., additional, Dargush, M., additional, Santaniello, A., additional, Constantinou, M., additional, DiPetrillo, T., additional, Safran, H., additional, Halpin, C., additional, Barker, F. G., additional, Maher, E. A., additional, Ganji, S., additional, DeBerardinis, R., additional, Hatanpaa, K., additional, Rakheja, D., additional, Yang, X.-L., additional, Mashimo, T., additional, Raisanen, J., additional, Madden, C., additional, Mickey, B., additional, Malloy, C., additional, Bachoo, R., additional, Choi, C., additional, Ranjan, T., additional, Yono, N., additional, Han, S. J., additional, Sun, M., additional, Berger, M. S., additional, Aghi, M., additional, Gupta, N., additional, and Parsa, A. T., additional

Published
2011
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40. Ongoing Clinical Trials

Author

Clarke, J. L., primary, Ennis, M. M., additional, Lamborn, K. R., additional, Prados, M. D., additional, Puduvalli, V. K., additional, Penas-Prado, M., additional, Gilbert, M. R., additional, Groves, M. D., additional, Hess, K. R., additional, Levin, V. A., additional, de Groot, J., additional, Colman, H., additional, Conrad, C. A., additional, Loghin, M. E., additional, Hunter, K., additional, Yung, W. K., additional, Chen, C., additional, Damek, D., additional, Liu, A., additional, Gaspar, L. E., additional, Waziri, A., additional, Lillehei, K., additional, Kavanagh, B., additional, Finlay, J. L., additional, Haley, K., additional, Dhall, G., additional, Gardner, S., additional, Allen, J., additional, Cornelius, A., additional, Olshefski, R., additional, Garvin, J., additional, Pradhan, K., additional, Etzl, M., additional, Goldman, S., additional, Atlas, M., additional, Thompson, S., additional, Hirt, A., additional, Hukin, J., additional, Comito, M., additional, Bertolone, S., additional, Torkildson, J., additional, Joyce, M., additional, Moertel, C., additional, Letterio, J., additional, Kennedy, G., additional, Walter, A., additional, Ji, L., additional, Sposto, R., additional, Dorris, K., additional, Wagner, L., additional, Hummel, T., additional, Drissi, R., additional, Miles, L., additional, Leach, J., additional, Chow, L., additional, Turner, R., additional, Gragert, M. N., additional, Pruitt, D., additional, Sutton, M., additional, Breneman, J., additional, Crone, K., additional, Fouladi, M., additional, Friday, B. B., additional, Buckner, J., additional, Anderson, S. K., additional, Giannini, C., additional, Kugler, J., additional, Mazurczac, M., additional, Flynn, P., additional, Gross, H., additional, Pajon, E., additional, Jaeckle, K., additional, Galanis, E., additional, Badruddoja, M. A., additional, Pazzi, M. A., additional, Stea, B., additional, Lefferts, P., additional, Contreras, N., additional, Bishop, M., additional, Seeger, J., additional, Carmody, R., additional, Rance, N., additional, Marsella, M., additional, Schroeder, K., additional, Sanan, A., additional, Swinnen, L. J., additional, Rankin, C., additional, Rushing, E. J., additional, Hutchins, L. F., additional, Damek, D. M., additional, Barger, G. R., additional, Norden, A. D., additional, Lesser, G., additional, Hammond, S. N., additional, Drappatz, J., additional, Fadul, C. E., additional, Batchelor, T. T., additional, Quant, E. C., additional, Beroukhim, R., additional, Ciampa, A., additional, Doherty, L., additional, LaFrankie, D., additional, Ruland, S., additional, Bochacki, C., additional, Phan, P., additional, Faroh, E., additional, McNamara, B., additional, David, K., additional, Rosenfeld, M. R., additional, Wen, P. Y., additional, Phuphanich, S., additional, Reardon, D., additional, Wong, E. T., additional, Plotkin, S. R., additional, Mintz, A., additional, Raizer, J. J., additional, Kaley, T. J., additional, Smith, K. H., additional, Chamberlain, M. C., additional, Graham, C., additional, Mrugala, M., additional, Johnston, S., additional, Kreisl, T. N., additional, Smith, P., additional, Iwamoto, F., additional, Sul, J., additional, Butman, J. A., additional, Fine, H. A., additional, Westphal, M., additional, Heese, O., additional, Warmuth-Metz, M., additional, Pietsch, T., additional, Schlegel, U., additional, Tonn, J.-C., additional, Schramm, J., additional, Schackert, G., additional, Melms, A., additional, Mehdorn, H. M., additional, Seifert, V., additional, Geletneky, K., additional, Reuter, D., additional, Bach, F., additional, Khasraw, M., additional, Abrey, L. E., additional, Lassman, A. B., additional, Hormigo, A., additional, Nolan, C., additional, Gavrilovic, I. T., additional, Mellinghoff, I. K., additional, Reiner, A. S., additional, DeAngelis, L., additional, Omuro, A. M., additional, Burzynski, S. R., additional, Weaver, R. A., additional, Janicki, T. J., additional, Burzynski, G. S., additional, Szymkowski, B., additional, Acelar, S. S., additional, Mechtler, L. L., additional, O'Connor, P. C., additional, Kroon, H.-A., additional, Vora, T., additional, Kurkure, P., additional, Arora, B., additional, Gupta, T., additional, Dhamankar, V., additional, Banavali, S., additional, Moiyadi, A., additional, Epari, S., additional, Merchant, N., additional, Jalali, R., additional, Moller, S., additional, Grunnet, K., additional, Hansen, S., additional, Schultz, H., additional, Holmberg, M., additional, Sorensen, M. M., additional, Poulsen, H. S., additional, Lassen, U., additional, Reardon, D. A., additional, Vredenburgh, J. J., additional, Desjardins, A., additional, Janney, D. E., additional, Peters, K., additional, Sampson, J., additional, Gururangan, S., additional, Friedman, H. S., additional, Jeyapalan, S., additional, Constantinou, M., additional, Evans, D., additional, Elinzano, H., additional, O'Connor, B., additional, Puthawala, M. Y., additional, Goldman, M., additional, Oyelese, A., additional, Cielo, D., additional, Dipetrillo, T., additional, Safran, H., additional, Anan, M., additional, Seyed Sadr, M., additional, Alshami, J., additional, Sabau, C., additional, Seyed Sadr, E., additional, Siu, V., additional, Guiot, M.-C., additional, Samani, A., additional, Del Maestro, R., additional, Bogdahn, U., additional, Stockhammer, G., additional, Mahapatra, A. K., additional, Venkataramana, N. K., additional, Oliushine, V. E., additional, Parfenov, V. E., additional, Poverennova, I. E., additional, Hau, P., additional, Jachimczak, P., additional, Heinrichs, H., additional, Schlingensiepen, K.-H., additional, Shibui, S., additional, Kayama, T., additional, Wakabayashi, T., additional, Nishikawa, R., additional, de Groot, M., additional, Aronica, E., additional, Vecht, C. J., additional, Toering, S. T., additional, Heimans, J. J., additional, Reijneveld, J. C., additional, Batchelor, T., additional, Mulholland, P., additional, Neyns, B., additional, Nabors, L. B., additional, Campone, M., additional, Wick, A., additional, Mason, W., additional, Mikkelsen, T., additional, Ashby, L. S., additional, DeGroot, J. F., additional, Gattamaneni, H. R., additional, Cher, L. M., additional, Rosenthal, M. A., additional, Payer, F., additional, Xu, J., additional, Liu, Q., additional, van den Bent, M., additional, Nabors, B., additional, Fink, K., additional, Chan, M., additional, Trusheim, J., additional, Raval, S., additional, Hicking, C., additional, Henslee-Downey, J., additional, Picard, M., additional, Schiff, D., additional, Karimi, S., additional, DeAngelis, L. M., additional, Nolan, C. P., additional, Omuro, A., additional, Gavrilovic, I., additional, Norden, A., additional, Purow, B. W., additional, Lieberman, F. S., additional, Hariharan, S., additional, Perez-Larraya, J. G., additional, Honnorat, J., additional, Chinot, O., additional, Catry-Thomas, I., additional, Taillandier, L., additional, Guillamo, J. S., additional, Campello, C., additional, Monjour, A., additional, Tanguy, M. L., additional, Delattre, J. Y., additional, Franz, D. N., additional, Krueger, D. A., additional, Care, M. M., additional, Holland-Bouley, K., additional, Agricola, K., additional, Tudor, C., additional, Mangeshkar, P., additional, Byars, A. W., additional, Sahmoud, T., additional, Alonso-Basanta, M., additional, Lustig, R. A., additional, Dorsey, J. F., additional, Lai, R. K., additional, Recht, L. D., additional, Paleologos, N., additional, Groves, M., additional, Meech, S., additional, Davis, T., additional, Pavlov, D., additional, Marshall, M. A., additional, Slot, M., additional, Peerdeman, S. M., additional, Beauchesne, P. D., additional, Faure, G., additional, Noel, G., additional, Schmitt, T., additional, Kerr, C., additional, Jadaud, E., additional, Martin, L., additional, Carnin, C., additional, Peters, K. B., additional, Herndon, J. E., additional, Kirkpatrick, J. P., additional, Nayak, L., additional, Panageas, K. S., additional, and Deangelis, L. M., additional

Published
2010
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43. Using lithium as a neuroprotective agent in patients with cancer

Author

Khasraw Mustafa, Ashley David, Wheeler Greg, and Berk Michael

Subjects
Medicine
Abstract

Abstract Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect. This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.

Published
2012
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44. Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma

Author

William H. Tomaszewski, Jessica Waibl-Polania, Molly Chakraborty, Jonathan Perera, Jeremy Ratiu, Alexandra Miggelbrink, Donald P. McDonnell, Mustafa Khasraw, David M. Ashley, Peter E. Fecci, Luigi Racioppi, Luis Sanchez-Perez, Michael D. Gunn, John H. Sampson, Tomaszewski, W. H., Waibl-Polania, J., Chakraborty, M., Perera, J., Ratiu, J., Miggelbrink, A., Mcdonnell, D. P., Khasraw, M., Ashley, D. M., Fecci, P. E., Racioppi, L., Sanchez-Perez, L., Gunn, M. D., and Sampson, J. H.

Subjects
Immunosuppression Therapy, Neurons, Multidisciplinary, Tumor Microenvironment, Humans, General Physics and Astronomy, Calcium-Calmodulin-Dependent Protein Kinase Kinase, General Chemistry, CD8-Positive T-Lymphocytes, Glioblastoma, General Biochemistry, Genetics and Molecular Biology
Abstract

Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly expressed in pro-tumor cells and is associated with worsened survival in patients with GBM. Host CaMKK2, specifically, reduces survival and promotes ICB resistance. Multimodal profiling of the TME reveals that CaMKK2 is associated with several ICB resistance-associated immune phenotypes. CaMKK2 promotes exhaustion in CD8+ T cells and reduces the expansion of effector CD4+ T cells, additionally limiting their tumor penetrance. CaMKK2 also maintains myeloid cells in a disease-associated microglia-like phenotype. Lastly, neuronal CaMKK2 is required for maintaining the ICB resistance-associated myeloid phenotype, is deleterious to survival, and promotes ICB resistance. Our findings reveal CaMKK2 as a contributor to ICB resistance and identify neurons as a driver of immunotherapeutic resistance in GBM.

Published
2022

45. ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours

Author

Chris Karapetis, Sabine Tejpar, Lorraine A. Chantrill, Fiona Day, Jayesh Desai, Eva Segelov, Jeremy Shapiro, Warren Joubert, Nick Pavlakis, Kate Wilson, Timothy J. Price, Paul Waring, Niall C. Tebbutt, Elena Elez, Harpreet Wasan, Guy van Hazel, Mustafa Khasraw, Andrew Haydon, Louise M. Nott, Subotheni Thavaneswaran, Val Gebski, Fortunato Ciardiello, Michael Jefford, Craig Underhill, Segelov, E, Waring, P, Desai, J, Wilson, K, Gebski, V, Thavaneswaran, S, Elez, E, Underhill, C, Pavlakis, N, Chantrill, L, Nott, L, Jefford, M, Khasraw, M, Day, F, Wasan, H, Ciardiello, Fortunato, Karapetis, C, Joubert, W, van Hazel, G, Haydon, A, Price, T, Tejpar, S, Tebbutt, N, and Shapiro, J. 2. 3.

Subjects
0301 basic medicine, Oncology, Cancer Research, Colorectal cancer, medicine.medical_treatment, Cetuximab, Colorectal tumour, medicine.disease_cause, GTP Phosphohydrolases, Targeted therapy, Study Protocol, 0302 clinical medicine, Clinical endpoint, Prospective Studies, Clinical trial, Basic-Leucine Zipper Transcription Factors, Research Design, 030220 oncology & carcinogenesis, Colorectal tumours, KRAS, Colorectal Neoplasms, medicine.drug, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Antineoplastic Agents, Irinotecan, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Tumour mutations, neoplasms, business.industry, Membrane Proteins, medicine.disease, digestive system diseases, Activating Transcription Factor 6, Oxaliplatin, 030104 developmental biology, Mutation, Camptothecin, business
Abstract

Background Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are “wild type”). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a “quadruple wild type” tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. Methods and design ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with “quadruple wild type” or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. Discussion This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the “quadruple wild type”, which may ‘superselect’ for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups. Trial registration Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808, registered 16 August 2012.

Published
2016

46. Response to Cetuximab With or Without Irinotecan in Patients With Refractory Metastatic Colorectal Cancer Harboring the KRAS G13D Mutation: Australasian Gastro-Intestinal Trials Group ICECREAM Study

Author

Louise M. Nott, Sebastian Lunke, Craig Underhill, Jeremy Shapiro, Guy van Hazel, Eva Segelov, Kate Wilson, Timothy J. Price, Jayesh Desai, Michael Jefford, Subotheni Thavaneswaran, Nick Pavlakis, John Simes, Val Gebski, Fortunato Ciardiello, Lorraine A. Chantrill, Kristy P. Robledo, Mustafa Khasraw, Andrew Haydon, Paul Waring, Christos S. Karapetis, Elena Elez, Harpreet Wasan, Segelov, E, Thavaneswaran, S, Waring, Pm, Desai, J, Robledo, Kp, Gebski, Vj, Elez, E, Nott, Lm, Karapetis, C, Lunke, S, Chantrill, La, Pavlakis, N, Khasraw, M, Underhill, C, Ciardiello, Fortunato, Jefford, M, Wasan, H, Haydon, A, Price, Tj, van Hazel, G, Wilson, K, Simes, J, and Shapiro, J. d. 2.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Cetuximab, medicine.disease_cause, Irinotecan, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Panitumumab, Humans, Epidermal growth factor receptor, Neoplasm Metastasis, neoplasms, Monoclonal antibody therapy, Aged, Aged, 80 and over, Chemotherapy, biology, business.industry, Middle Aged, medicine.disease, digestive system diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, biology.protein, Quality of Life, Camptothecin, Female, KRAS, business, Colorectal Neoplasms, medicine.drug
Abstract

Purpose RAS mutations predict lack of response to epidermal growth factor receptor monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC), but preclinical studies and retrospective clinical data suggest that patients with tumors harboring the exon 2 KRAS G13D mutation may benefit from cetuximab. We aimed to assess cetuximab monotherapy and cetuximab plus irinotecan in patients with molecularly selected (G13D mutation) chemotherapy-refractory mCRC in a randomized phase II trial of this rare molecular subtype. Patients and Methods Patients with chemotherapy-refractory KRAS G13D mutation–positive mCRC who had progressed within 6 months of irinotecan therapy were randomly assigned to cetuximab 400 mg/m2 loading dose and then 250 mg/m2 once per week with or without irinotecan 180 mg/m2 once every 2 weeks. The primary end point was 6-month progression-free survival; secondary end points were response rate, overall survival, quality of life, and toxicity. Results Fifty-one of 53 patients recruited over 2 years were eligible. The 6-month progression-free survival rate was 10% (95% CI, 2% to 26%) for cetuximab versus 23% (95% CI, 9% to 40%) for cetuximab plus irinotecan with a hazard ratio of 0.74 (95% CI, 0.42 to 1.32). Response and stable disease rates were 0% and 58% for monotherapy versus 9% and 70% for combination treatment, respectively. Overall survival and quality of life were similar; toxicities were higher with combination therapy. Conclusion In patients with G13D-mutated chemotherapy-refractory mCRC, there was no statistically significant improvement in disease control at 6 months with either cetuximab monotherapy or cetuximab plus irinotecan. No responses were seen with single-agent cetuximab. The responses observed with the combination of cetuximab and irinotecan may reflect true drug synergy or persistent irinotecan sensitivity. The ICECREAM (Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Among Patients with a G13D Mutation) study demonstrates the need to prospectively evaluate hypotheses that were previously supported by retrospective analyses and exemplifies the value of international collaboration in trials of rare molecular subtypes.

Published
2016

47. The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Author

Martin MV, Aguilar-Rosas S, Franke K, Pieterse M, Langelaar JV, Schreurs R, Bijlsma MF, Besselink MG, Koster J, Timens W, Khasraw M, Ashley DM, Keir ST, Ottensmeier CH, King EV, Verheij J, Waasdorp C, Valk PJM, Engels SAG, Oostenbach E, van Dinter JT, Hofman DA, Mok JY, van Esch WJE, Wilmink H, Monkhorst K, Verheul HMW, Poel D, Hiltermann TJN, Kempen LCLTV, Groen HJM, Aerts JGJV, Heesch SV, Löwenberg B, Plasterk R, and Kloosterman WP

Subjects
Humans, Peptides immunology, Antigens, Neoplasm immunology, Antigens, Neoplasm genetics, Immunotherapy methods, Open Reading Frames, Neoplasms immunology, Neoplasms therapy
Abstract

Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of noncoding regions of the genome downstream of a rearrangement breakpoint, i.e., where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for the detection of NOPs., (©2024 American Association for Cancer Research.)

Published
2024
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48. Immune Checkpoint Inhibitors in Geriatric Oncology.

Author

Cook SL, Al Amin M, Bari S, Poonnen PJ, Khasraw M, and Johnson MO

Subjects
Humans, Aged, Aging immunology, Geriatrics methods, Medical Oncology methods, Immunotherapy methods, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors adverse effects, Neoplasms drug therapy, Neoplasms immunology
Abstract

Purpose of Review: This manuscript will update prior reviews of immune checkpoint inhibitors (ICIs) in light of basic science, translational, and clinical discoveries in the field of cancer immunology and aging., Recent Findings: ICIs have led to significant advancements in the treatment of cancer. Landmark trials of ICIs have cited the efficacy and toxicity experienced by older patients, but most trials are not specifically designed to address outcomes in older patients. Underlying mechanisms of aging, like cellular senescence, affect the immune system and may ultimately alter the host's response to ICIs. Validated tools are currently used to identify older adults who may be at greater risk of developing complications from their cancer treatment. We review changes in the aging immune system that may alter responses to ICIs, report outcomes and toxicities in older adults from recent ICI clinical trials, and discuss clinical tools specific to older patients with cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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49. Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic Alterations: A Systematic Literature Review.

Author

Khasraw M, Yalamanchili P, Santhanagopal A, Wu C, Salas M, Meng J, Karnoub M, Esker S, and Felip E

Subjects
Humans, Genomics, Anaplastic Lymphoma Kinase genetics, Mutation, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Brain Neoplasms secondary, Brain Neoplasms genetics, Brain Neoplasms therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
Abstract

Introduction: Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During the disease course, 25-50% of patients will develop BrMs. Despite available treatments, survival rates for patients with NSCLC and BrMs remain low, and their overall prognosis is poor. Even with newer agents for NSCLC, options for treating BrMs can be limited by their ineffective transport across the blood-brain barrier (BBB) and the unique brain tumor microenvironment. The presence of actionable genomic alterations (AGAs) is a key determinant of optimal treatment selection, which aims to maximize responses and minimize toxicities. The objective of this systematic literature review (SLR) was to understand the current landscape of the clinical management of patients with NSCLC and BrMs, particularly those with AGAs., Method: A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant SLR was conducted to identify studies in patients with BrMs in NSCLC. Searches used the EMBASE and MEDLINE ® databases, and articles published between January 1, 2017 and September 26, 2022 were reviewed., Results: Overall, 179 studies were included in the SLR. This subset review focused on 80 studies that included patients with NSCLC, BrMs, and AGAs (19 randomized controlled trials [RCTs], two single-arm studies, and 59 observational studies). Sixty-four of the 80 studies reported on epidermal growth factor receptor (EGFR) mutations, 14 on anaplastic lymphoma kinase (ALK) alterations, and two on both alterations. Ninety-five percent of studies evaluated targeted therapy. All RCTs allowed patients with previously treated, asymptomatic, or neurologically stable BrMs; the percentage of asymptomatic BrMs varied across observational studies., Conclusions: Although targeted therapies demonstrate systemic benefits for patients with NSCLC, BrMs, and AGAs, there remains a continued need for effective therapies to treat and prevent BrMs in this population. Increased BBB permeability of emerging therapies may improve outcomes for this population., (© 2024. The Author(s).)

Published
2024
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50. Local hero: A phase II study of local therapy only (stereotactic radiosurgery and / or surgery) for treatment of up to five brain metastases from HER2+ breast cancer. (TROG study 16.02).

Author

Phillips C, Pinkham MB, Moore A, Sia J, Jeffree RL, Khasraw M, Kam A, Bressel M, and Haworth A

Subjects
Adult, Humans, Female, Brain surgery, Salvage Therapy methods, Radiosurgery methods, Breast Neoplasms surgery, Brain Neoplasms secondary
Abstract

Introduction, A decade ago, stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) was emerging as preferred treatment for oligometastatic brain metastases. Studies of cavity SRS after neurosurgery were underway. Data specific to metastatic HER2 breast cancer (MHBC), describing intracranial, systemic and survival outcomes without WBRT, were lacking. A Phase II study was designed to address this gap. Method, Adults with MHBC, performance status 0-2, ≤ five BrM, receiving/planned to receive HER2-targeted therapy were eligible. Exclusions included leptomeningeal disease and prior WBRT. Neurosurgery allowed ≤6 weeks before registration and required for BrM >4 cm. Primary endpoint was 12-month requirement for WBRT. Secondary endpoints; freedom from (FF-) local failure (LF), distant brain failure (DBF), extracranial disease failure (ECDF), overall survival (OS), cause of death, mini-mental state examination (MMSE), adverse events (AE). Results, Twenty-five patients accrued Decembers 2016-2020. The study closed early after slow accrual. Thirty-seven BrM and four cavities received SRS. Four cavities and five BrM were observed. At 12 months: one patient required WBRT (FF-WBRT 95 %, 95 % CI 72-99), FFLF 91 % (95 % CI 69-98), FFDBF 57 % (95 % CI 34-74), FFECDF 64 % (95 % CI 45-84), OS 96 % (95 % CI 74-99). Two grade 3 AE occurred. MMSE was abnormal for 3/24 patients at baseline and 1/17 at 12 months. Conclusion, At 12 months, SRS and/or neurosurgery provided good control with low toxicity. WBRT was not required in 95 % of cases. This small study supports the practice change from WBRT to local therapies for MHBC BrM., Competing Interests: Declaration of competing interest No conflicting relationship exists for any author., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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