Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial

Christine Schmitz; Jan Rekowski; Stefan P. Müller; Bernd Hertenstein; Christiane Franzius; Arnold Ganser; Frank M. Bengel; Frank Kroschinsky; Jörg Kotzerke; Paul La Rosée; Martin Freesmeyer; Heinz Gert Hoeffkes; Andreas Hertel; Dirk Behringer; Rolf Mesters; Matthias Weckesser; Stefan Mahlmann; Uwe Haberkorn; Uwe Martens; Gabriele Prange-Krex; Winfried Brenner; Aristoteles Giagounidis; Regina Moeller; Volker Runde; Matthias Sandmann; Hubertus Hautzel; Stefan Wilop; Thomas Krohn; Heinz Dürk; Michael Heike; Ferras Alashkar; Marcus Brinkmann; Guido Trenn; Dietmar Wacker; Christiane Kreisel-Büstgens; Helga Bernhard; Gerhard Heil; Rolf Larisch; Lars Kurch; Karl Heinz Jöckel; Dieter Hoelzer; Wolfram Klapper; Ronald Boellaard; Ulrich Dührsen; Andreas Hüttmann

doi:https://doi.org/10.1002/hon.2697

Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial

Christine Schmitz, Jan Rekowski, Stefan P. Müller, Bernd Hertenstein, Christiane Franzius, Arnold Ganser, Frank M. Bengel, Frank Kroschinsky, Jörg Kotzerke, Paul La Rosée, Martin Freesmeyer, Heinz Gert Hoeffkes, Andreas Hertel, Dirk Behringer, Rolf Mesters, Matthias Weckesser, Stefan Mahlmann, Uwe Haberkorn, Uwe Martens, Gabriele Prange-KrexWinfried Brenner, Aristoteles Giagounidis, Regina Moeller, Volker Runde, Matthias Sandmann, Hubertus Hautzel, Stefan Wilop, Thomas Krohn, Heinz Dürk, Michael Heike, Ferras Alashkar, Marcus Brinkmann, Guido Trenn, Dietmar Wacker, Christiane Kreisel-Büstgens, Helga Bernhard, Gerhard Heil, Rolf Larisch, Lars Kurch, Karl Heinz Jöckel, Dieter Hoelzer, Wolfram Klapper, Ronald Boellaard, Ulrich Dührsen, Andreas Hüttmann

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

Abstract

The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV_41max) and SUV₄ thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUV_max approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm³ using SUV_41max and 460 cm³ using SUV₄. For iPET response, the respective thresholds were 46.9% SUV_max reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV_41max and SUV₄, and 29% and 25% for iPET response by ΔSUV_max and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV_41max and 3.206 (1.524-6.743) for SUV₄. At iPET, it was 3.910 (1.891-8.087) for ΔSUV_max and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.

Original language	English
Pages (from-to)	244-256
Number of pages	13
Journal	Hematological oncology
Volume	38
Issue number	3
DOIs	https://doi.org/10.1002/hon.2697
Publication status	Published - 1 Aug 2020

Keywords

T-cell
lymphoma
positron-emission tomography
prognosis
prospective studies
tumor burden

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Schmitz, C., Rekowski, J., Müller, S. P., Hertenstein, B., Franzius, C., Ganser, A., Bengel, F. M., Kroschinsky, F., Kotzerke, J., La Rosée, P., Freesmeyer, M., Hoeffkes, H. G., Hertel, A., Behringer, D., Mesters, R., Weckesser, M., Mahlmann, S., Haberkorn, U., Martens, U., ... Hüttmann, A. (2020). Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial. Hematological oncology, 38(3), 244-256. https://doi.org/10.1002/hon.2697

@article{9a485a78fea242c1b6d4ae79f175ea2f,

title = "Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial",

abstract = "The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4. For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4, and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4. At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.",

keywords = "T-cell, lymphoma, positron-emission tomography, prognosis, prospective studies, tumor burden",

author = "Christine Schmitz and Jan Rekowski and M{\"u}ller, {Stefan P.} and Bernd Hertenstein and Christiane Franzius and Arnold Ganser and Bengel, {Frank M.} and Frank Kroschinsky and J{\"o}rg Kotzerke and {La Ros{\'e}e}, Paul and Martin Freesmeyer and Hoeffkes, {Heinz Gert} and Andreas Hertel and Dirk Behringer and Rolf Mesters and Matthias Weckesser and Stefan Mahlmann and Uwe Haberkorn and Uwe Martens and Gabriele Prange-Krex and Winfried Brenner and Aristoteles Giagounidis and Regina Moeller and Volker Runde and Matthias Sandmann and Hubertus Hautzel and Stefan Wilop and Thomas Krohn and Heinz D{\"u}rk and Michael Heike and Ferras Alashkar and Marcus Brinkmann and Guido Trenn and Dietmar Wacker and Christiane Kreisel-B{\"u}stgens and Helga Bernhard and Gerhard Heil and Rolf Larisch and Lars Kurch and J{\"o}ckel, {Karl Heinz} and Dieter Hoelzer and Wolfram Klapper and Ronald Boellaard and Ulrich D{\"u}hrsen and Andreas H{\"u}ttmann",

year = "2020",

month = aug,

day = "1",

doi = "https://doi.org/10.1002/hon.2697",

language = "English",

volume = "38",

pages = "244--256",

journal = "Hematological oncology",

issn = "0278-0232",

publisher = "John Wiley and Sons Ltd",

number = "3",

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Schmitz, C, Rekowski, J, Müller, SP, Hertenstein, B, Franzius, C, Ganser, A, Bengel, FM, Kroschinsky, F, Kotzerke, J, La Rosée, P, Freesmeyer, M, Hoeffkes, HG, Hertel, A, Behringer, D, Mesters, R, Weckesser, M, Mahlmann, S, Haberkorn, U, Martens, U, Prange-Krex, G, Brenner, W, Giagounidis, A, Moeller, R, Runde, V, Sandmann, M, Hautzel, H, Wilop, S, Krohn, T, Dürk, H, Heike, M, Alashkar, F, Brinkmann, M, Trenn, G, Wacker, D, Kreisel-Büstgens, C, Bernhard, H, Heil, G, Larisch, R, Kurch, L, Jöckel, KH, Hoelzer, D, Klapper, W, Boellaard, R, Dührsen, U & Hüttmann, A 2020, 'Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial', Hematological oncology, vol. 38, no. 3, pp. 244-256. https://doi.org/10.1002/hon.2697

TY - JOUR

T1 - Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma

T2 - A subgroup analysis of the PETAL trial

AU - Schmitz, Christine

AU - Rekowski, Jan

AU - Müller, Stefan P.

AU - Hertenstein, Bernd

AU - Franzius, Christiane

AU - Ganser, Arnold

AU - Bengel, Frank M.

AU - Kroschinsky, Frank

AU - Kotzerke, Jörg

AU - La Rosée, Paul

AU - Freesmeyer, Martin

AU - Hoeffkes, Heinz Gert

AU - Hertel, Andreas

AU - Behringer, Dirk

AU - Mesters, Rolf

AU - Weckesser, Matthias

AU - Mahlmann, Stefan

AU - Haberkorn, Uwe

AU - Martens, Uwe

AU - Prange-Krex, Gabriele

AU - Brenner, Winfried

AU - Giagounidis, Aristoteles

AU - Moeller, Regina

AU - Runde, Volker

AU - Sandmann, Matthias

AU - Hautzel, Hubertus

AU - Wilop, Stefan

AU - Krohn, Thomas

AU - Dürk, Heinz

AU - Heike, Michael

AU - Alashkar, Ferras

AU - Brinkmann, Marcus

AU - Trenn, Guido

AU - Wacker, Dietmar

AU - Kreisel-Büstgens, Christiane

AU - Bernhard, Helga

AU - Heil, Gerhard

AU - Larisch, Rolf

AU - Kurch, Lars

AU - Jöckel, Karl Heinz

AU - Hoelzer, Dieter

AU - Klapper, Wolfram

AU - Boellaard, Ronald

AU - Dührsen, Ulrich

AU - Hüttmann, Andreas

PY - 2020/8/1

Y1 - 2020/8/1

N2 - The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4. For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4, and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4. At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.

AB - The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4. For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4, and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4. At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.

KW - T-cell

KW - lymphoma

KW - positron-emission tomography

KW - prognosis

KW - prospective studies

KW - tumor burden

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U2 - https://doi.org/10.1002/hon.2697

DO - https://doi.org/10.1002/hon.2697

M3 - Article

C2 - 32067259

SN - 0278-0232

VL - 38

SP - 244

EP - 256

JO - Hematological oncology

JF - Hematological oncology

IS - 3

ER -

Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial

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Keywords

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