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1. CAR virus receptor mediates erythroid differentiation and migration and is downregulated in MDS

Author

Bauer, Karin, Machherndl-Spandl, Sigrid, Kazianka, Lukas, Sadovnik, Irina, Gültekin, Sinan, Suessner, Susanne, Proell, Johannes, Lauf, Jeroen, Hoermann, Gregor, Eisenwort, Gregor, Häfner, Norman, Födermayr-Mayrleitner, Mathilde, Schmolke, Ann-Sofie, van der Kouwe, Emiel, Platzbecker, Uwe, Lion, Thomas, Weltermann, Ansgar, Zach, Otto, Webersinke, Gerald, Germing, Ulrich, Gabriel, Christian, Sperr, Wolfgang R., Béné, Marie C., Staber, Philipp B., Bettelheim, Peter, and Valent, Peter

Published
2023
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3. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study

Author

Snijder, Berend, Vladimer, Gregory I, Krall, Nikolaus, Miura, Katsuhiro, Schmolke, Ann-Sofie, Kornauth, Christoph, Lopez de la Fuente, Oscar, Choi, Hye-Soo, van der Kouwe, Emiel, Gültekin, Sinan, Kazianka, Lukas, Bigenzahn, Johannes W, Hoermann, Gregor, Prutsch, Nicole, Merkel, Olaf, Ringler, Anna, Sabler, Monika, Jeryczynski, Georg, Mayerhoefer, Marius E, Simonitsch-Klupp, Ingrid, Ocko, Katharina, Felberbauer, Franz, Müllauer, Leonhard, Prager, Gerald W, Korkmaz, Belgin, Kenner, Lukas, Sperr, Wolfgang R, Kralovics, Robert, Gisslinger, Heinz, Valent, Peter, Kubicek, Stefan, Jäger, Ulrich, Staber, Philipp B, and Superti-Furga, Giulio

Published
2017
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10. Data from Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders

Author

Kornauth, Christoph, primary, Pemovska, Tea, primary, Vladimer, Gregory I., primary, Bayer, Günther, primary, Bergmann, Michael, primary, Eder, Sandra, primary, Eichner, Ruth, primary, Erl, Martin, primary, Esterbauer, Harald, primary, Exner, Ruth, primary, Felsleitner-Hauer, Verena, primary, Forte, Maurizio, primary, Gaiger, Alexander, primary, Geissler, Klaus, primary, Greinix, Hildegard T., primary, Gstöttner, Wolfgang, primary, Hacker, Marcus, primary, Hartmann, Bernd Lorenz, primary, Hauswirth, Alexander W., primary, Heinemann, Tim, primary, Heintel, Daniel, primary, Hoda, Mir Alireza, primary, Hopfinger, Georg, primary, Jaeger, Ulrich, primary, Kazianka, Lukas, primary, Kenner, Lukas, primary, Kiesewetter, Barbara, primary, Krall, Nikolaus, primary, Krajnik, Gerhard, primary, Kubicek, Stefan, primary, Le, Trang, primary, Lubowitzki, Simone, primary, Mayerhoefer, Marius E., primary, Menschel, Elisabeth, primary, Merkel, Olaf, primary, Miura, Katsuhiro, primary, Müllauer, Leonhard, primary, Neumeister, Peter, primary, Noesslinger, Thomas, primary, Ocko, Katharina, primary, Öhler, Leopold, primary, Panny, Michael, primary, Pichler, Alexander, primary, Porpaczy, Edit, primary, Prager, Gerald W., primary, Raderer, Markus, primary, Ristl, Robin, primary, Ruckser, Reinhard, primary, Salamon, Julius, primary, Schiefer, Ana-Iris, primary, Schmolke, Ann-Sofie, primary, Schwarzinger, Ilse, primary, Selzer, Edgar, primary, Sillaber, Christian, primary, Skrabs, Cathrin, primary, Sperr, Wolfgang R., primary, Srndic, Ismet, primary, Thalhammer, Renate, primary, Valent, Peter, primary, van der Kouwe, Emiel, primary, Vanura, Katrina, primary, Vogt, Stefan, primary, Waldstein, Cora, primary, Wolf, Dominik, primary, Zielinski, Christoph C., primary, Zojer, Niklas, primary, Simonitsch-Klupp, Ingrid, primary, Superti-Furga, Giulio, primary, Snijder, Berend, primary, and Staber, Philipp B., primary

Published
2023
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11. Supplementary Data from Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders

Author

Kornauth, Christoph, primary, Pemovska, Tea, primary, Vladimer, Gregory I., primary, Bayer, Günther, primary, Bergmann, Michael, primary, Eder, Sandra, primary, Eichner, Ruth, primary, Erl, Martin, primary, Esterbauer, Harald, primary, Exner, Ruth, primary, Felsleitner-Hauer, Verena, primary, Forte, Maurizio, primary, Gaiger, Alexander, primary, Geissler, Klaus, primary, Greinix, Hildegard T., primary, Gstöttner, Wolfgang, primary, Hacker, Marcus, primary, Hartmann, Bernd Lorenz, primary, Hauswirth, Alexander W., primary, Heinemann, Tim, primary, Heintel, Daniel, primary, Hoda, Mir Alireza, primary, Hopfinger, Georg, primary, Jaeger, Ulrich, primary, Kazianka, Lukas, primary, Kenner, Lukas, primary, Kiesewetter, Barbara, primary, Krall, Nikolaus, primary, Krajnik, Gerhard, primary, Kubicek, Stefan, primary, Le, Trang, primary, Lubowitzki, Simone, primary, Mayerhoefer, Marius E., primary, Menschel, Elisabeth, primary, Merkel, Olaf, primary, Miura, Katsuhiro, primary, Müllauer, Leonhard, primary, Neumeister, Peter, primary, Noesslinger, Thomas, primary, Ocko, Katharina, primary, Öhler, Leopold, primary, Panny, Michael, primary, Pichler, Alexander, primary, Porpaczy, Edit, primary, Prager, Gerald W., primary, Raderer, Markus, primary, Ristl, Robin, primary, Ruckser, Reinhard, primary, Salamon, Julius, primary, Schiefer, Ana-Iris, primary, Schmolke, Ann-Sofie, primary, Schwarzinger, Ilse, primary, Selzer, Edgar, primary, Sillaber, Christian, primary, Skrabs, Cathrin, primary, Sperr, Wolfgang R., primary, Srndic, Ismet, primary, Thalhammer, Renate, primary, Valent, Peter, primary, van der Kouwe, Emiel, primary, Vanura, Katrina, primary, Vogt, Stefan, primary, Waldstein, Cora, primary, Wolf, Dominik, primary, Zielinski, Christoph C., primary, Zojer, Niklas, primary, Simonitsch-Klupp, Ingrid, primary, Superti-Furga, Giulio, primary, Snijder, Berend, primary, and Staber, Philipp B., primary

Published
2023
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14. Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders

Author

Kornauth, Christoph, primary, Pemovska, Tea, additional, Vladimer, Gregory I., additional, Bayer, Günther, additional, Bergmann, Michael, additional, Eder, Sandra, additional, Eichner, Ruth, additional, Erl, Martin, additional, Esterbauer, Harald, additional, Exner, Ruth, additional, Felsleitner-Hauer, Verena, additional, Forte, Maurizio, additional, Gaiger, Alexander, additional, Geissler, Klaus, additional, Greinix, Hildegard T., additional, Gstöttner, Wolfgang, additional, Hacker, Marcus, additional, Hartmann, Bernd Lorenz, additional, Hauswirth, Alexander W., additional, Heinemann, Tim, additional, Heintel, Daniel, additional, Hoda, Mir Alireza, additional, Hopfinger, Georg, additional, Jaeger, Ulrich, additional, Kazianka, Lukas, additional, Kenner, Lukas, additional, Kiesewetter, Barbara, additional, Krall, Nikolaus, additional, Krajnik, Gerhard, additional, Kubicek, Stefan, additional, Le, Trang, additional, Lubowitzki, Simone, additional, Mayerhoefer, Marius E., additional, Menschel, Elisabeth, additional, Merkel, Olaf, additional, Miura, Katsuhiro, additional, Müllauer, Leonhard, additional, Neumeister, Peter, additional, Noesslinger, Thomas, additional, Ocko, Katharina, additional, Öhler, Leopold, additional, Panny, Michael, additional, Pichler, Alexander, additional, Porpaczy, Edit, additional, Prager, Gerald W., additional, Raderer, Markus, additional, Ristl, Robin, additional, Ruckser, Reinhard, additional, Salamon, Julius, additional, Schiefer, Ana-Iris, additional, Schmolke, Ann-Sofie, additional, Schwarzinger, Ilse, additional, Selzer, Edgar, additional, Sillaber, Christian, additional, Skrabs, Cathrin, additional, Sperr, Wolfgang R., additional, Srndic, Ismet, additional, Thalhammer, Renate, additional, Valent, Peter, additional, van der Kouwe, Emiel, additional, Vanura, Katrina, additional, Vogt, Stefan, additional, Waldstein, Cora, additional, Wolf, Dominik, additional, Zielinski, Christoph C., additional, Zojer, Niklas, additional, Simonitsch-Klupp, Ingrid, additional, Superti-Furga, Giulio, additional, Snijder, Berend, additional, and Staber, Philipp B., additional

Published
2021
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15. Blood / Core binding factor leukemia hijacks T-cell prone PU.1 antisense promoter

Author

van der Kouwe, Emiel, Heller, Gerwin, Czibere, Akos, Pulikkan, John A., Agreiter, Christiane, Castilla, Lucio H., Delwel, Ruud, Di Ruscio, Annalisa, Ebralidze, Alexander K., Forte, Maurizio, Grebien, Florian, Heyes, Elizabeth, Kazianka, Lukas, Klinger, Julian, Kornauth, Christoph, Le, Trang, Lind, Karin, Barbosa, Inês Amorim Monteiro, Pemovska, Tea, Pichler, Alexander Sebastian, Schmolke, Ann-Sofie, Schweicker, Carmen Marita, Sill, Heinz, Sperr, Wolfgang R., Spittler, Andreas, Surapally, Sridevi, Trinh, Bon Q., Valent, Peter, Vanura, Katrina, Welner, Robert S., Zuber, Johannes, Tenen, Daniel G., and Staber, Philipp B.

Published
2021

17. Functional Precision Medicine Vs Genomics Vs Clinical Experience: Feasibility Results from the Multicentric, Prospective, Randomized Controlled Exalt-2 Trial

Author

Kazianka, Lukas, Pemovska, Tea, Rohrbeck, Johannes, Kornauth, Christoph, Pichler, Alexander, Agreiter, Christiane, Lubowitzki, Simone, Prochazka, Katharina, Neumeister, Peter, Schmitt, Clemens, Greil, Richard, Willenbacher, Wolfgang, Wolf, Dominik, Jaeger, Ulrich, Simonitsch-Klupp, Ingrid, and Staber, Philipp Bernhard

Published
2023
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18. Rationale for the combination of venetoclax and ibrutinib in T-prolymphocytic leukemia

Author

Kornauth, Christoph, primary, Herbaux, Charles, additional, Boidol, Bernd, additional, Guillemette, Chantal, additional, Caron, Patrick, additional, Mayerhöfer, Marius E., additional, Poulain, Stéphanie, additional, Tournilhac, Olivier, additional, Pemovska, Tea, additional, Chong, Stephen J.F., additional, Van der Kouwe, Emiel, additional, Kazianka, Lukas, additional, Hopfinger, Georg, additional, Heintel, Daniel, additional, Jäger, Roland, additional, Raderer, Markus, additional, Jäger, Ulrich, additional, Simonitsch-Klupp, Ingrid, additional, Sperr, Wolfgang R., additional, Kubicek, Stefan, additional, Davids, Matthew S., additional, and Staber, Philipp B., additional

Published
2021
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19. CXCR4 PET imaging of mantle cell lymphoma using [68Ga]Pentixafor: comparison with [18F]FDG-PET

Author

Mayerhoefer, Marius E., primary, Raderer, Markus, additional, Lamm, Wolfgang, additional, Pichler, Verena, additional, Pfaff, Sarah, additional, Weber, Michael, additional, Kiesewetter, Barbara, additional, Hacker, Markus, additional, Kazianka, Lukas, additional, Staber, Philipp B., additional, Wester, Hans-Juergen, additional, Rohrbeck, Johannes, additional, Simonitsch-Klupp, Ingrid, additional, and Haug, Alexander, additional

Published
2021
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20. Treatment Guided By Next Generation Functional Drug Screening Provides Clinical Benefit in Advanced Aggressive Hematological Malignancies: Final Evaluation of the Open Label, Single Arm Exalt Trial

Author

Kornauth, Christoph, primary, Pemovska, Tea, additional, Vladimer, Gregory Ian, additional, Bayer, Günther, additional, Bergmann, Michael, additional, Eder, Sandra, additional, Eichner, Ruth, additional, Esterbauer, Harald, additional, Exner, Ruth, additional, Felsleitner-Hauer, Verena, additional, Forte, Maurizio, additional, Gaiger, Alexander, additional, Greinix, Hildegard T., additional, Gstöttner, Wolfgang, additional, Hacker, Marcus, additional, Hauswirth, Alexander, additional, Heinemann, Tim, additional, Heintel, Daniel, additional, Hoda, Mir Ali Reza, additional, Jaeger, Ulrich, additional, Kazianka, Lukas, additional, Kenner, Lukas, additional, Kiesewetter, Barbara, additional, Krall, Nikolaus, additional, Le, Trang, additional, Lubowitzki, Simone, additional, Mayerhoefer, Marius E, additional, Menschel, Elisabeth, additional, Merkel, Olaf, additional, Miura, Katsuhiro, additional, Muellauer, Leonhard, additional, Neumeister, Peter, additional, Noesslinger, Thomas, additional, Ocko, Katharina, additional, Öhler, Leopold, additional, Panny, Michael, additional, Pichler, Alexander, additional, Porpaczy, Edit Anna, additional, Prager, Gerald, additional, Raderer, Markus, additional, Ristl, Robin, additional, Ruckser, Reinhard, additional, Salamon, Julius, additional, Schiefer, Ana-Iris, additional, Schmolke, Ann-Sofie, additional, Schwarzinger, Ilse, additional, Selzer, Edgar, additional, Skrabs, Cathrin, additional, Sperr, Wolfgang R., additional, Srndic, Ismet, additional, Thalhammer, Renate, additional, Valent, Peter, additional, van der Kouwe, Emiel, additional, Vanura, Katrina, additional, Vogt, Stefan, additional, Waldstein, Cora, additional, Wolf, Dominik, additional, Zielinski, Christoph, additional, Simonitsch-Klupp, Ingrid, additional, Superti-Furga, Giulio, additional, Snijder, Berend, additional, and Staber, Philipp B., additional

Published
2020
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21. Core Binding Factor Leukemias Utilize a Physiologic Sense/Antisense Promoter Switch Employed By T-Cells

Author

van der Kouwe, Emiel, primary, Heller, Gerwin, additional, Czibere, Akos, additional, Castilla, Lucio H., additional, Delwel, Ruud, additional, Di Ruscio, Annalisa, additional, Ebralidze, Alexander, additional, Forte, Maurizio, additional, Kazianka, Lukas, additional, Kornauth, Christoph, additional, Le, Trang, additional, Lind, Karin, additional, Barbosa, Ines, additional, Pichler, Alexander, additional, Pulikkan, John, additional, Schmolke, Ann-Sofie, additional, Sill, Heinz, additional, Sperr, Wolfgang R., additional, Spittler, Andreas, additional, Trinh, Bon Q., additional, Valent, Peter, additional, Vanura, Katrina, additional, Welner, Robert, additional, Zuber, Johannes, additional, Tenen, Daniel G., additional, and Staber, Philipp B., additional

Published
2020
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24. First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia

Author

Boidol, Bernd, Kornauth, Christoph, van der Kouwe, Emiel, Prutsch, Nicole, Kazianka, Lukas, Gültekin, Sinan, Hoermann, Gregor, Mayerhoefer, Marius E., Hopfinger, Georg, Hauswirth, Alexander, Panny, Michael, Aretin, Marie-Bernadette, Hilgarth, Bernadette, Sperr, Wolfgang R., Valent, Peter, Simonitsch-Klupp, Ingrid, Moriggl, Richard, Merkel, Olaf, Kenner, Lukas, Jäger, Ulrich, Kubicek, Stefan, and Staber, Philipp B.

Published
2017
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27. The relationship between cholecystokinin secretion and pancreatic [11C]methionine uptake in patients after partial pancreaticoduodenectomy.

Author

Steiner, Emanuel, Kazianka, Lukas, Breuer, Robert, Hacker, Marcus, Wadsak, Wolfgang, Mitterhauser, Markus, Rehfeld, Jens F., Karanikas, Georgios, and Miholic, Johannes

Abstract

Objective: The pancreatic uptake of [11C]methionine ([11C]MET) is associated with beta-cell function and insulin secretion, but [11C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [11C]MET in the residual pancreas following pancreaticoduodenectomy. Methods: Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56–67 years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8–26 years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180 min after ingestion. Simultaneously, 800 MBq of [11C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60 min after injection. Results: Integrated CCK (AUC30) correlated with SUVmax (AUC60, R2 = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC60) and CCK concentrations and young age as significant independent predictors of [11C] methionine uptake. Conclusion: The association between CCK concentrations and pancreatic [11C]MET uptake might indicate a causal relationship. Further research should assess whether [11C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Next-Generation Functional Drug Screening for Patients with Aggressive Hematologic Malignancies

Author

Staber, Philipp Bernhard, primary, Snijder, Berend, additional, Vladimer, Gregory Ian, additional, Krall, Nikolaus, additional, Miura, Katsuhiro, additional, Schmolke, Ann-Sofie, additional, Kornauth, Christoph, additional, Lopez de la Fuente, Oscar, additional, Choi, Hye-Soo, additional, van der Kouwe, Emiel, additional, Kazianka, Lukas, additional, Bigenzahn1, Johannes, additional, Hoermann, Gregor, additional, Prutsch, Nicole, additional, Merkel, Olaf, additional, Ringler, Anna, additional, Jeryczynski, Georg, additional, Mayerhoefer, Marius, additional, Simonitsch-Klupp, Ingrid, additional, Felberbauer, Franz X, additional, Muellauer, Leonhard, additional, Prager, Gerald W, additional, Korkmaz, Belgin, additional, Kenner, Lukas, additional, Sperr, Wolfgang R., additional, Kralovics, Robert, additional, Gisslinger, Heinz, additional, Valent, Peter, additional, Kubicek, Stefan, additional, Jaeger, Ulrich, additional, and Superti-Furga, Giulio, additional

Published
2017
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32. Ristocetin-Induced Platelet Aggregation for Monitoring of Bleeding Tendency in Ibrutinib-Treated Patients with Chronic Lymphocytic Leukemia

Author

Kazianka, Lukas, primary, Drucker, Christa, additional, Skrabs, Cathrin, additional, Staber, Philipp Bernhard, additional, Porpaczy, Edit Anna, additional, Einberger, Christine, additional, Heinz, Marion, additional, Hauswirth, Alexander, additional, Pabinger, Ingrid, additional, Quehenberger, Peter, additional, Jilma, Bernd, additional, and Jaeger, Ulrich, additional

Published
2015
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36. **-Postprandial pancreatic [C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release.

Author

Steiner, Emanuel, Kazianka, Lukas, Breuer, Robert, Hacker, Marcus, Wadsak, Wolfgang, Mitterhauser, Markus, Stimpfl, Thomas, Reiter, Birgit, Karanikas, Georgios, and Miholic, Johannes

Subjects
PANCREATIC tumors, PANCREATICODUODENECTOMY, METHIONINE, INSULIN regulation, PANCREATIC beta cells, PANCREATIC surgery, TUMOR treatment
Abstract

Purpose: [ S-methyl-C]-L-methionine ([C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [C]MET uptake. Methods: Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. Results: The uptake of [C]MET in the pancreas was significantly higher ( p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects ( p < 0.0001). Paracetamol AUC correlated with the SUVmax increment between 15 and 30 minutes (R = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [C]MET. Total integrated SUVmax correlated with insulin AUC (R = 0.66, p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R = 0.78, p < 0.0001). Conclusion: Postprandial [C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function. [ABSTRACT FROM AUTHOR]

Published
2017
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37. Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.

Author

Kornauth C, Pemovska T, Vladimer GI, Bayer G, Bergmann M, Eder S, Eichner R, Erl M, Esterbauer H, Exner R, Felsleitner-Hauer V, Forte M, Gaiger A, Geissler K, Greinix HT, Gstöttner W, Hacker M, Hartmann BL, Hauswirth AW, Heinemann T, Heintel D, Hoda MA, Hopfinger G, Jaeger U, Kazianka L, Kenner L, Kiesewetter B, Krall N, Krajnik G, Kubicek S, Le T, Lubowitzki S, Mayerhoefer ME, Menschel E, Merkel O, Miura K, Müllauer L, Neumeister P, Noesslinger T, Ocko K, Öhler L, Panny M, Pichler A, Porpaczy E, Prager GW, Raderer M, Ristl R, Ruckser R, Salamon J, Schiefer AI, Schmolke AS, Schwarzinger I, Selzer E, Sillaber C, Skrabs C, Sperr WR, Srndic I, Thalhammer R, Valent P, van der Kouwe E, Vanura K, Vogt S, Waldstein C, Wolf D, Zielinski CC, Zojer N, Simonitsch-Klupp I, Superti-Furga G, Snijder B, and Staber PB

Subjects
Adult, Aged, Aged, 80 and over, Austria, Cohort Studies, Female, Hematologic Neoplasms mortality, Humans, Male, Middle Aged, Molecular Targeted Therapy, Precision Medicine, Progression-Free Survival, Young Adult, Hematologic Neoplasms drug therapy
Abstract

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290 . This article is highlighted in the In This Issue feature, p. 275 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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38. CXCR4 PET imaging of mantle cell lymphoma using [ 68 Ga]Pentixafor: comparison with [ 18 F]FDG-PET.

Author

Mayerhoefer ME, Raderer M, Lamm W, Pichler V, Pfaff S, Weber M, Kiesewetter B, Hacker M, Kazianka L, Staber PB, Wester HJ, Rohrbeck J, Simonitsch-Klupp I, and Haug A

Subjects
Aged, Aged, 80 and over, Female, Humans, Lymphoma, Mantle-Cell diagnostic imaging, Lymphoma, Mantle-Cell metabolism, Male, Middle Aged, Coordination Complexes metabolism, Fluorodeoxyglucose F18 metabolism, Lymphoma, Mantle-Cell pathology, Peptides, Cyclic metabolism, Positron-Emission Tomography methods, Radiopharmaceuticals metabolism, Receptors, CXCR4 metabolism
Abstract

For PET imaging of mantle cell lymphoma (MCL), [ 18 F]FDG (2-deoxy-2-[ 18 F]fluoro-D-glucose) is the currently recommended radiotracer, although uptake is variable and bone marrow evaluation is limited. In this prospective study, we evaluated the novel CXCR4 (G-protein-coupled C-X-C chemokine receptor type 4) tracer [ 68 Ga]Pentixafor in MCL patients, and compared it to [ 18 F]FDG. Methods: MCL patients underwent [ 68 Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [ 18 F]FDG-PET/MRI, before treatment. PET was evaluated separately for 23 anatomic regions (12 lymph node stations and 11 organs/tissues), using MRI as the main reference standard. Standardized uptake values (SUV max and SUV mean ) and tumor-to-background ratios (TBR blood and TBR liver ) were calculated. General Estimation Equations (GEE) were used to compare [ 68 Ga]Pentixafor-PET and [ 18 F]FDG-PET sensitivities and positive predictive values (PPV). For bone marrow involvement, where biopsy served as the main reference standard, and splenic involvement, receiver operating characteristic curves were used to determine the optimal SUV and TBR cut-off values, and areas under the curve (AUC) were calculated. Results: Twenty-two MCL patients were included. [ 68 Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [ 18 F]FDG-PET (75.2%) ( P <0.001), and PPV was slightly, but not significantly lower (94.0%.vs. 96.5%; P =0.21). SUVs and TBRs were significantly higher for [ 68 Ga]Pentixafor-PET than for [ 18 F]FDG-PET ( P <0.001 in all cases); the greatest difference was observed for mean TBR blood , with 4.9 for [ 68 Ga]Pentixafor-PET and 2.0 for [ 18 F]FDG-PET. For bone marrow involvement, [ 68 Ga]Pentixafor-PET SUV mean showed an AUC of 0.92; and for splenic involvement, TBR blood showed an AUC of 0.81. Conclusion: [ 68 Ga]Pentixafor-PET may become an alternative to [ 18 F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast., Competing Interests: Competing Interests: M.E.M. received speaker honoraria and research support from Siemens, and speaker honoraria from Bristol Myers Squibb. M.R. received speaker honoraria from Celgene, Ipsen, Novartis, and Eisai. P.B.S. received speaker and advisory board honoraria from Janssen und Abbvie. H.-J.W. is a founder and shareholder of Scintomics. All author authors report no competing interests., (© The author(s).)

Published
2021
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