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Adapted treatment guided by interim PET scan in advanced Hodgkin’s lymphoma

Adapted treatment guided by interim PET scan in advanced Hodgkin’s lymphoma
Adapted treatment guided by interim PET scan in advanced Hodgkin’s lymphoma
Background: we tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.

Methods: patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.

Results: a total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.

Conclusions: although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).
2419-2429
Johnson, Peter
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Federico, Massimo
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Kirkwood, Amy
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Fossa, Alexander
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Berkahn, Leanne
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Carella, Angelo
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d’Amore, Francesco
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Enblad, Gunilla
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Franceschetto, Antonella
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Fulham, Michael
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Luminari, Stefano
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O’Doherty, Michael
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Patrick, Pip
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Roberts, Thomas
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Sidra, Gamal
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Stevens, Lindsey
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Smith, Paul
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Trotman, Judith
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Viney, Zaid
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Radford, John
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Barrington, Sally
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Johnson, Peter
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Federico, Massimo
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Kirkwood, Amy
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Fossa, Alexander
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Berkahn, Leanne
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Carella, Angelo
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d’Amore, Francesco
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Enblad, Gunilla
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Franceschetto, Antonella
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Fulham, Michael
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Luminari, Stefano
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O’Doherty, Michael
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Patrick, Pip
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Roberts, Thomas
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Sidra, Gamal
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Stevens, Lindsey
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Smith, Paul
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Trotman, Judith
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Viney, Zaid
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Radford, John
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Barrington, Sally
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Johnson, Peter, Federico, Massimo, Kirkwood, Amy, Fossa, Alexander, Berkahn, Leanne, Carella, Angelo, d’Amore, Francesco, Enblad, Gunilla, Franceschetto, Antonella, Fulham, Michael, Luminari, Stefano, O’Doherty, Michael, Patrick, Pip, Roberts, Thomas, Sidra, Gamal, Stevens, Lindsey, Smith, Paul, Trotman, Judith, Viney, Zaid, Radford, John and Barrington, Sally (2016) Adapted treatment guided by interim PET scan in advanced Hodgkin’s lymphoma. New England Journal of Medicine, 374, 2419-2429. (doi:10.1056/NEJMoa1510093). (PMID:27332902)

Record type: Article

Abstract

Background: we tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.

Methods: patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.

Results: a total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.

Conclusions: although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

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Accepted/In Press date: 1 April 2016
e-pub ahead of print date: 22 June 2016
Published date: 23 June 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 402114
URI: http://eprints.soton.ac.uk/id/eprint/402114
PURE UUID: f1828291-9454-441e-9952-da02ce1d4e24
ORCID for Peter Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 28 Oct 2016 08:59
Last modified: 26 Nov 2021 05:05

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Contributors

Author: Peter Johnson ORCID iD
Author: Massimo Federico
Author: Amy Kirkwood
Author: Alexander Fossa
Author: Leanne Berkahn
Author: Angelo Carella
Author: Francesco d’Amore
Author: Gunilla Enblad
Author: Antonella Franceschetto
Author: Michael Fulham
Author: Stefano Luminari
Author: Michael O’Doherty
Author: Pip Patrick
Author: Thomas Roberts
Author: Gamal Sidra
Author: Lindsey Stevens
Author: Paul Smith
Author: Judith Trotman
Author: Zaid Viney
Author: John Radford
Author: Sally Barrington

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