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1
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Ebner R, Sheikh GT, Brendel M, Ricke J, Cyran CC. ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging. Eur Radiol 2025; 35:1894-1902. [PMID: 39384589 PMCID: PMC11914360 DOI: 10.1007/s00330-024-11094-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/05/2024] [Accepted: 09/06/2024] [Indexed: 10/11/2024]
Abstract
Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.
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Affiliation(s)
- Ricarda Ebner
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany.
| | - Gabriel T Sheikh
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Matthias Brendel
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Clemens C Cyran
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
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2
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Levis M, Oertel M. Advanced Stage Hodgkin and Diffuse Large B-Cell Lymphomas: Is There Still a Role for Consolidation Radiotherapy in the PET Era? Semin Radiat Oncol 2025; 35:16-26. [PMID: 39672638 DOI: 10.1016/j.semradonc.2024.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2024]
Abstract
The role of radiotherapy in the treatment of lymphoma is rapidly evolving. The development of modern systemic therapies and the adoption of FDG-PET-scanning as metabolic prognosticators are leading to a process of refinement of the treatment regimens. In this scenario, radiotherapy utilization is decreasing in several settings, including lower risk patients, to prevent the risk of long-term complications. Over the last decade, the most relevant changes in the treatment landscape are evident for advanced stage Hodgkin lymphoma and diffuse large B cell lymphoma. The main purpose of this paper is to review radiotherapy indications in these settings, to highlight pros and cons of a PET-guided strategy for radiotherapy recommendations, and to introduce future perspectives on the combination of radiotherapy and modern systemic therapies in both frontline and relapsed setting of advanced stage Hodgkin and diffuse large B cell lymphomas.
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Affiliation(s)
- Mario Levis
- Department of Oncology, University of Torino, Torino, Italy.
| | - Michael Oertel
- Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany
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3
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Ansell SM. Hodgkin lymphoma: 2025 update on diagnosis, risk-stratification, and management. Am J Hematol 2024; 99:2367-2378. [PMID: 39239794 DOI: 10.1002/ajh.27470] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/07/2024]
Abstract
DISEASE OVERVIEW Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8570 new patients annually and representing ~10% of all lymphomas in the United States. DIAGNOSIS HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL (also called nodular lymphocyte predominant B-cell lymphoma). Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. RISK STRATIFICATION An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. RISK-ADAPTED THERAPY Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, whereas those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. However, newer agents including brentuximab vedotin and anti-PD-1 antibodies are now standardly incorporated into frontline therapy. MANAGEMENT OF RELAPSED/REFRACTORY DISEASE High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.
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Affiliation(s)
- Stephen M Ansell
- Dorotha W. and Grant L. Sundquist Professor in Hematologic Malignancies Research Chair, Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
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4
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Milrod CJ, Pelcovits A, Ollila TA. Immune checkpoint inhibitors in advanced and relapsed/refractory Hodgkin lymphoma: current applications and future prospects. Front Oncol 2024; 14:1397053. [PMID: 38699638 PMCID: PMC11063339 DOI: 10.3389/fonc.2024.1397053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 04/08/2024] [Indexed: 05/05/2024] Open
Abstract
Classic Hodgkin lymphoma (cHL) treatment paradigms are undergoing a shift with the integration of immune checkpoint inhibitors (ICIs) into both first-line and relapsed/refractory (R/R) regimens. In first-line therapy, the synergy between ICIs and chemotherapy may surpass the previous standards of ABVD and BV-AVD established by landmark trials including RATHL and ECHELON-1. In R/R disease, the combination of ICIs with chemotherapy has begun to challenge the paradigm of chemotherapy as a bridge to consolidative autologous stem cell transplantation. The clinical advances heralded by ICI offer unique challenges to management. ICI treatment and the associated inflammatory response can make the traditional timing and modalities of treatment response assessment difficult to interpret. In contrast to ABVD and BV-AVD, pembrolizumab-AVD results in PET2 positivity rates that are higher and less predictive of treatment response even when ultimate outcomes may be superior. This suggests that the predictive value of PET2 may be less reliable in the ICI era, prompting a reevaluation of response assessment strategies. Looking forward, circulating tumor DNA (ctDNA) may be a promising tool in response-adapted therapy. Its potential to complement or even supersede PET scans in predicting response to ICIs represents a critical advancement. The integration of ctDNA analysis holds the promise of refining response-adapted approaches and enhancing precision in therapeutic decision-making for patients with cHL. This review navigates the evolving landscape of cHL therapy, emphasizing the paradigmatic shift brought about by ICIs. This article explores the impact of combining ICIs with chemotherapy in both relapsed/refractory and first-line settings, scrutinizes the challenges posed to response-adapted therapy by ICIs, and highlights the potential role of ctDNA as an adjunct in refining response-adapted strategies for cHL.
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5
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Duminuco A, Santuccio G, Chiarenza A, Figuera A, Motta G, Caruso AL, Petronaci A, Ippolito M, Cerchione C, Di Raimondo F, Romano A. Baseline IgM Amounts Can Identify Patients with Poor Outcomes: Results from a Real-Life Single-Center Study on Classical Hodgkin Lymphoma. Cancers (Basel) 2024; 16:826. [PMID: 38398216 PMCID: PMC10886525 DOI: 10.3390/cancers16040826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 02/10/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Hodgkin Lymphoma (HL) is characterized by an inflammatory background in which the reactive myeloid cells may exert an immune-suppressive effect related to the progression of the disease. Immunoglobulin M is the first antibody isotype produced during an immune response, which also plays an immunoregulatory role. Therefore, we investigated if, as a surrogate of defective B cell function, it could have any clinical impact on prognosis. In this retrospective, observational, single-center study, we evaluated 212 newly diagnosed HL patients, including 132 advanced-stage. A 50 mg/dL level of IgM at baseline resulted in 84.1% sensitivity and 45.5% specificity for predicting a complete response in the whole cohort (area under curve (AUC) = 0.62, p = 0.013). In multivariate analysis, baseline IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) were independent variables able to predict the clinical outcome, while, after two cycles of treatment, IgM ≤ 50 mg/dL at baseline and PET-2 status were independent predictors of PFS. The amount of IgM at diagnosis is a valuable prognostic factor much earlier than PET-2, and it can also provide information for PET-2-negative patients. This can help to identify different HL classes at risk of treatment failure at baseline.
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Affiliation(s)
- Andrea Duminuco
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Gabriella Santuccio
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Annalisa Chiarenza
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Amalia Figuera
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Giovanna Motta
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Anastasia Laura Caruso
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Alessandro Petronaci
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
| | - Massimo Ippolito
- Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, 95021 Catania, Italy;
| | - Claudio Cerchione
- Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Francesco Di Raimondo
- Hematology Unit with BMT, A.O.U. Policlinico “G.Rodolico-San Marco”, 95123 Catania, Italy; (G.S.); (A.C.); (A.F.); (G.M.); (A.L.C.); (A.P.); (F.D.R.)
- Department of General Surgery and Medical-Surgical Specialties, Hematology Section, University of Catania, 95123 Catania, Italy
| | - Alessandra Romano
- Department of General Surgery and Medical-Surgical Specialties, Hematology Section, University of Catania, 95123 Catania, Italy
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6
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Alderuccio JP, Kuker RA, Yang F, Moskowitz CH. Quantitative PET-based biomarkers in lymphoma: getting ready for primetime. Nat Rev Clin Oncol 2023; 20:640-657. [PMID: 37460635 DOI: 10.1038/s41571-023-00799-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2023] [Indexed: 08/20/2023]
Abstract
The use of functional quantitative biomarkers extracted from routine PET-CT scans to characterize clinical responses in patients with lymphoma is gaining increased attention, and these biomarkers can outperform established clinical risk factors. Total metabolic tumour volume enables individualized estimation of survival outcomes in patients with lymphoma and has shown the potential to predict response to therapy suitable for risk-adapted treatment approaches in clinical trials. The deployment of machine learning tools in molecular imaging research can assist in recognizing complex patterns and, with image classification, in tumour identification and segmentation of data from PET-CT scans. Initial studies using fully automated approaches to calculate metabolic tumour volume and other PET-based biomarkers have demonstrated appropriate correlation with calculations from experts, warranting further testing in large-scale studies. The extraction of computer-based quantitative tumour characterization through radiomics can provide a comprehensive view of phenotypic heterogeneity that better captures the molecular and functional features of the disease. Additionally, radiomics can be integrated with genomic data to provide more accurate prognostic information. Further improvements in PET-based biomarkers are imminent, although their incorporation into clinical decision-making currently has methodological shortcomings that need to be addressed with confirmatory prospective validation in selected patient populations. In this Review, we discuss the current knowledge, challenges and opportunities in the integration of quantitative PET-based biomarkers in clinical trials and the routine management of patients with lymphoma.
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Affiliation(s)
- Juan Pablo Alderuccio
- Department of Medicine, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
| | - Russ A Kuker
- Department of Radiology, Division of Nuclear Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Fei Yang
- Department of Radiation Oncology, Division of Medical Physics, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Craig H Moskowitz
- Department of Medicine, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
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7
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Mhlanga J, Alazraki A, Cho SY, Lai H, Nadel H, Pandit-Taskar N, Qi J, Rajderkar D, Voss S, Watal P, McCarten K. Imaging recommendations in pediatric lymphoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper. Pediatr Blood Cancer 2023; 70 Suppl 4:e29968. [PMID: 36114654 PMCID: PMC10641880 DOI: 10.1002/pbc.29968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 08/16/2022] [Indexed: 11/08/2022]
Abstract
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are both malignancies originating in the lymphatic system and both affect children, but many features differ considerably, impacting workup and management. This paper provides consensus-based imaging recommendations for evaluation of patients with HL and NHL at diagnosis and response assessment for both interim and end of therapy (follow-up).
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Affiliation(s)
- Joyce Mhlanga
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, Saint Louis, Missouri, USA
| | - Adina Alazraki
- Departments of Pediatrics and Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Steve Y Cho
- Department of Radiology, Nuclear Medicine and Molecular Imaging Section, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Hollie Lai
- Department of Radiology, Children's Health of Orange County, Orange, California, USA
| | - Helen Nadel
- Department of Pediatric Radiology, Lucile Packard Children's Hospital at Stanford, Stanford University School of Medicine, Stanford, California, USA
| | - Neeta Pandit-Taskar
- Department of Radiology, Molecular imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
- Department of Radiology, Weill Cornell Medical College, New York City, New York, USA
| | - Jing Qi
- Department of Radiology, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA
| | - Dhanashree Rajderkar
- Department of Radiology, Division of Pediatric Radiology, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Stephan Voss
- Harvard Medical School, Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Pankaj Watal
- University of Central Florida College of Medicine, Nemours Children's Hospital, Orlando, Florida, USA
| | - Kathleen McCarten
- Diagnostic Imaging and Pediatrics, Imaging and Radiation Oncology Core, Lincoln, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
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8
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Al-Ibraheem A, Mottaghy FM, Juweid ME. PET/CT in Hodgkin Lymphoma: An Update. Semin Nucl Med 2023; 53:303-319. [PMID: 36369090 DOI: 10.1053/j.semnuclmed.2022.10.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 10/25/2022] [Indexed: 11/11/2022]
Abstract
18F-FDG-PET/CT is now an integral part of the workup and management of patients with Hodgkin's lymphoma (HL). PET/CT is currently routinely performed for staging and for response assessment at the end of treatment. Interim PET/CT is typically performed after 1-4 of 6-8 chemo/chemoimmunotherapy cycles ± radiation for prognostication and potential treatment escalation or de-escalation early in the course of therapy, a concept known as response-or risk-adapted treatment. Quantitative PET is an area of growing interest. Metrics such as the standardized uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and their changes with treatment are being investigated as more reproducible and, potentially, more accurate predictors of response and prognosis. Despite the progress made in standardizing the use of PET/CT in lymphoma, challenges remain, particularly with respect to its limited positive predictive value. This review highlights the most relevant applications of PET/CT in HL, its strengths and limitations, as well as recent efforts to implement PET/CT-based metrics as promising tools for precision medicine. Finally, the value of PET/CT for response assessment to immunotherapy is discussed.
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Affiliation(s)
- Akram Al-Ibraheem
- Department of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan; Division of Nuclear Medicine/Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan
| | - Felix M Mottaghy
- Department of Nuclear Medicine, University Hospital RWTH, Aachen University, Aachen, 52074, Germany, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany and Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
| | - Malik E Juweid
- Division of Nuclear Medicine/Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan
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9
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Nanni C, Kobe C, Baeßler B, Baues C, Boellaard R, Borchmann P, Buck A, Buvat I, Chapuy B, Cheson BD, Chrzan R, Cottereau AS, Dührsen U, Eikenes L, Hutchings M, Jurczak W, Kraeber-Bodéré F, Lopci E, Luminari S, MacLennan S, Mikhaeel NG, Nijland M, Rodríguez-Otero P, Treglia G, Withofs N, Zamagni E, Zinzani PL, Zijlstra JM, Herrmann K, Kunikowska J. European Association of Nuclear Medicine (EANM) Focus 4 consensus recommendations: molecular imaging and therapy in haematological tumours. Lancet Haematol 2023; 10:e367-e381. [PMID: 37142345 DOI: 10.1016/s2352-3026(23)00030-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/23/2022] [Accepted: 01/18/2023] [Indexed: 05/06/2023]
Abstract
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
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Affiliation(s)
- Cristina Nanni
- Medicina Nucleare, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Carsten Kobe
- Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Bettina Baeßler
- Institute of Diagnostic and Interventional Radiology, University Hospital Würzburg, Würzburg, Germany
| | - Christian Baues
- Department of Radiooncology, Radiotherapy and CyberKnife Center, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Ronald Boellaard
- Radiology & Nuclear Medicine, Amsterdam UMC, VUMC Cancer Center Amsterdam, Amsterdam, Netherlands; Nuclear Medicine & Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Peter Borchmann
- Department of Haematology and Oncology, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Andreas Buck
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Irène Buvat
- Laboratory of Translational Imaging in Oncology, Institut Curie, Inserm, PSL University, Orsay, France
| | - Björn Chapuy
- Department of Hematology, Oncology and Tumorimmunology, Charité University Medical Center Berlin, Benjamin Franklin Campus, Berlin, Germany
| | | | - Robert Chrzan
- Department of Radiology, Jagiellonian University Medical College, Krakow, Poland
| | | | - Ulrich Dührsen
- Klinik für Hämatologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany
| | - Live Eikenes
- Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Martin Hutchings
- Department of Haematology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Wojciech Jurczak
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Françoise Kraeber-Bodéré
- Service de Médecine Nucléaire, University Hospital Hôtel-Dieu, Nantes, France; CRCI2NA, INSERM, CNRS, Université d'Angers, Nantes Université, Nantes, France
| | - Egesta Lopci
- Nuclear Medicine, IRCCS-Humanitas Research Hospital, Milan, Italy
| | - Stefano Luminari
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine Department, University of Modena and Reggio Emilia, Reggio Emilia, Italy; Hematology Unit, Azienda USL IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Steven MacLennan
- Academic Urology Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - N George Mikhaeel
- Department of Clinical Oncology, Guy's Cancer Centre, Guy's and St Thomas' NHS Trust, London, UK; School of Cancer & Pharmaceutical Sciences, King's College, University of London, London, UK
| | - Marcel Nijland
- Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | | | - Giorgio Treglia
- Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Faculty of Biomedical sciences, Università della Svizzera italiana, Lugano, Switzerland; Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Nadia Withofs
- Division of Nuclear Medicine and Oncological Imaging, Department of Medical Physics, CHU of Liege, Liege, Belgium; GIGA-CRC In Vivo Imaging, University of Liege, Liege, Belgium
| | - Elena Zamagni
- Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
| | - Pier Luigi Zinzani
- Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
| | - Josée M Zijlstra
- Department of Hematology, Amsterdam UMC, VUMC Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Ken Herrmann
- Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany
| | - Jolanta Kunikowska
- Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland
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10
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Zeman MN, Akin EA, Merryman RW, Jacene HA. Interim FDG-PET/CT for Response Assessment of Lymphoma. Semin Nucl Med 2023; 53:371-388. [PMID: 36376131 DOI: 10.1053/j.semnuclmed.2022.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 10/25/2022] [Indexed: 11/13/2022]
Abstract
The clinical use and prognostic value of interim FDG-PET/CT (iPET/CT), which is performed after treatment initiation but prior to its completion, varies by lymphoma subtype. Evidence supporting the prognostic value of iPET/CT is more robust for classical Hodgkin lymphoma (cHL), and in this lymphoma subtype, response-adapted treatment approaches guided by iPET/CT are a widely used standard of care for first-line therapy. The data supporting use of iPET/CT among patients with non-Hodgkin lymphoma (NHL) is less well-established, but failure to achieve complete metabolic response on iPET/CT is generally considered a poor prognostic factor with likely consequences for progression free survival. This review will present the available evidence supporting use of iPET/CT in lymphoma patients, particularly as it relates to prognostication and the ability to inform response-adapted treatment strategies. The latter will be addressed through a discussion on the major iPET-response adapted clinical trials with mention of ongoing trials. Special attention will be given to cHL and a few subtypes of NHL, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T cell lymphoma (PTCL).
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Affiliation(s)
- Merissa N Zeman
- Department of Radiology, Brigham and Women's Hospital, Boston, MA
| | - Esma A Akin
- Department of Radiology, Division of Nuclear Medicine, George Washington University, Medical Faculty Associates, Washington, DC
| | - Reid W Merryman
- Harvard Medical School, Boston, MA; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA
| | - Heather A Jacene
- Department of Radiology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Department of Imaging, Dana-Farber Cancer Institute, Boston, MA.
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11
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Veziroglu EM, Farhadi F, Hasani N, Nikpanah M, Roschewski M, Summers RM, Saboury B. Role of Artificial Intelligence in PET/CT Imaging for Management of Lymphoma. Semin Nucl Med 2023; 53:426-448. [PMID: 36870800 DOI: 10.1053/j.semnuclmed.2022.11.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 03/06/2023]
Abstract
Our review shows that AI-based analysis of lymphoma whole-body FDG-PET/CT can inform all phases of clinical management including staging, prognostication, treatment planning, and treatment response evaluation. We highlight advancements in the role of neural networks for performing automated image segmentation to calculate PET-based imaging biomarkers such as the total metabolic tumor volume (TMTV). AI-based image segmentation methods are at levels where they can be semi-automatically implemented with minimal human inputs and nearing the level of a second-opinion radiologist. Advances in automated segmentation methods are particularly apparent in the discrimination of lymphomatous vs non-lymphomatous FDG-avid regions, which carries through to automated staging. Automated TMTV calculators, in addition to automated calculation of measures such as Dmax are informing robust models of progression-free survival which can then feed into improved treatment planning.
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Affiliation(s)
| | - Faraz Farhadi
- Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD; Geisel School of Medicine at Dartmouth, Hanover, NH
| | - Navid Hasani
- Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Moozhan Nikpanah
- Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD; Department of Radiology, University of Alabama at Birmingham, AL
| | - Mark Roschewski
- Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD
| | - Ronald M Summers
- Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD; Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD
| | - Babak Saboury
- Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD.
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12
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Cheriyalinkal Parambil B, Shah S, Prasad M, Vora T, Laskar S, Khanna N, Qureshi S, Ramadwar M, Kembhavi S, Sankaran H, Rangarajan V, Thakur S, Chinnaswamy G. Can 18 F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy? J Pediatr Hematol Oncol 2023; 45:e363-e369. [PMID: 36251857 DOI: 10.1097/mph.0000000000002565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 07/31/2022] [Indexed: 03/05/2023]
Abstract
BACKGROUND Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18 F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS. MATERIALS AND METHODS Children 15 years old or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18 F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors. RESULTS Sixty-three children were eligible (Group III-55, Group IV-8). 18 F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) ( P =0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) ( P =0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) ( P =0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) ( P =0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) ( P =0.011)]. CONCLUSIONS Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Seema Kembhavi
- Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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13
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Outcomes of Patients with Positive Interim Positron Emission Tomography (PET) Continuing ABVD in the Clinical Setting. Cancers (Basel) 2023; 15:cancers15061760. [PMID: 36980646 PMCID: PMC10046293 DOI: 10.3390/cancers15061760] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/20/2023] [Accepted: 03/04/2023] [Indexed: 03/17/2023] Open
Abstract
Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.
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14
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LaCasce AS, Dockter T, Ruppert AS, Kostakoglu L, Schöder H, Hsi E, Bogart J, Cheson B, Wagner-Johnston N, Abramson J, Blum K, Leonard JP, Bartlett NL. Positron Emission Tomography-Adapted Therapy in Bulky Stage I/II Classic Hodgkin Lymphoma: CALGB 50801 (Alliance). J Clin Oncol 2023; 41:1023-1034. [PMID: 36269899 PMCID: PMC9928671 DOI: 10.1200/jco.22.00947] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 08/01/2022] [Accepted: 08/10/2022] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease. METHODS Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation. RESULTS Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04). CONCLUSION Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.
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Affiliation(s)
| | - Travis Dockter
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN
| | - Amy S. Ruppert
- Alliance Statistics and Data Management Center, The Ohio State University, Columbus, OH
| | | | - Heiko Schöder
- Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eric Hsi
- Wake Forest University Health Sciences, Winston-Salem, NC
| | - Jeffrey Bogart
- State University of New York Upstate Medical University Syracuse-Health Science Center, Syracuse, NY
| | - Bruce Cheson
- Scientific Advisor, Lymphoma Research Foundation, New York, NY
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15
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Subesinghe M, Ilyas H, Dunn JT, Mir N, Duran A, Mikhaeel NG, Barrington SF. The frequency of change in five-point scale score with a Bayesian penalised likelihood PET reconstruction algorithm on interim FDG PET-CT and its potential implications for therapy decisions in Hodgkin's lymphoma. Clin Radiol 2023; 78:e89-e98. [PMID: 36333130 DOI: 10.1016/j.crad.2022.09.124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 09/21/2022] [Accepted: 09/23/2022] [Indexed: 11/07/2022]
Abstract
AIM To assess the effect of a Bayesian penalised likelihood (BPL) reconstruction algorithm on the five-point scale (5-PS) score, response categorisation, and potential implications for therapy decisions after interim 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) (iPET-CT) to guide treatment in classical Hodgkin's lymphoma (HL). MATERIALS AND METHODS The present study included new patients with HL undergoing iPET-CT from 2014-2019 after two cycles of doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD). Two reporters categorised response using the 5-PS and measured maximum standardised uptake values (SUVmax) of the most avid tumour residuum, mediastinal blood pool, and normal liver with ordered subset expected maximisation (OSEM) and BPL reconstructions. RESULTS Eighty-one iPET-CT examinations were reviewed. Compared with OSEM, BPL increased the 5-PS score by a single score in 18/81 (22.2%) patients. The frequency of potential treatment intensification by changing a score of 3-4 was 13.6% (11/81) and represented 25% (11/44) of patients with a score of 3 on OSEM. All 11 patients remained in remission without a change in therapy (mean 63 months) except one who required second-line treatment for refractory disease. Median SUVmax of tumour residuum was significantly higher with BPL compared with OSEM (2.7 versus 2.4, p<<0.0001), whilst liver SUVmax was significantly lower for both reporters (up to 6.6%, p<0.0001). CONCLUSION BPL PET reconstruction increased the 5-PS score on iPET-CT in 22% of HL patients and can potentially result in unnecessary treatment escalation in over half of these patients.
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Affiliation(s)
- M Subesinghe
- King's College London & Guy's and St Thomas' PET Centre, London, UK; Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
| | - H Ilyas
- Department of Nuclear Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - J T Dunn
- King's College London & Guy's and St Thomas' PET Centre, London, UK; Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - N Mir
- Department of Haematology, Lewisham and Greenwich NHS Trust, London, UK
| | - A Duran
- Department of Haematology, Lewisham and Greenwich NHS Trust, London, UK
| | - N G Mikhaeel
- Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK; School of Cancer & Pharmaceutical Sciences, King's College London, London, UK
| | - S F Barrington
- King's College London & Guy's and St Thomas' PET Centre, London, UK; Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
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16
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Liu Q, Yang T, Chen X, Liu Y. Clinical value of 18F-FDG PET/CT in the management of HIV-associated lymphoma. Front Oncol 2023; 13:1117064. [PMID: 36776334 PMCID: PMC9909962 DOI: 10.3389/fonc.2023.1117064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 01/10/2023] [Indexed: 01/27/2023] Open
Abstract
HIV is still a major public health problem. At present, HIV-associated lymphoma remains the leading cause of deaths among people living with HIV, which should be paid more attention to. 18F-fluorodeoxglucose (FDG) PET/CT has been recommended in the initial staging, restaging, response assessment and prognostic prediction of lymphomas in general population. HIV-associated lymphoma is, however, a different entity from lymphoma in HIV-negative with a poorer prognosis. The ability to accurately risk-stratify HIV-infected patients with lymphoma will help guide treatment strategy and improve the prognosis. In the review, the current clinical applications of 18F-FDG PET/CT in HIV-associated lymphoma will be discussed, such as diagnosis, initial staging, response evaluation, prognostic prediction, PET-guided radiotherapy decision, and surveillance for recurrence. Moreover, future perspectives will also be presented.
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Affiliation(s)
- Qi Liu
- Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, China
| | - Tao Yang
- Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Xiaoliang Chen
- Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, China,*Correspondence: Xiaoliang Chen, ; Yao Liu,
| | - Yao Liu
- Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China,*Correspondence: Xiaoliang Chen, ; Yao Liu,
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17
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Fornecker LM, Lazarovici J, Aurer I, Casasnovas RO, Gac AC, Bonnet C, Bouabdallah K, Feugier P, Specht L, Molina L, Touati M, Borel C, Stamatoullas A, Nicolas-Virelizier E, Pascal L, Lugtenburg P, Di Renzo N, Vander Borght T, Traverse-Glehen A, Dartigues P, Hutchings M, Versari A, Meignan M, Federico M, André M. Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. J Clin Oncol 2023; 41:327-335. [PMID: 35867960 DOI: 10.1200/jco.21.01281] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
PURPOSE The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979). METHODS BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD. RESULTS Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; P < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively. CONCLUSION BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.
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Affiliation(s)
- Luc-Matthieu Fornecker
- Institut de Cancérologie Strasbourg Europe (ICANS) and University of Strasbourg, Strasbourg, France
| | | | - Igor Aurer
- University Hospital Centre Zagreb, Zagreb, Croatia
| | | | | | | | | | - Pierre Feugier
- University Hospital of Nancy and University of Lorraine, Vandoeuvre les Nancy, France
| | - Lena Specht
- Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | | | | | | | | | | | | | - Pieternella Lugtenburg
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | | | | | | | | | | | | | - Michel Meignan
- LYSA Imaging and University Paris Est Créteil, Créteil, France
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18
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Taranto E, Redd R, Jeter E, McHugh K, Crombie JL, Fisher DC, Jacobsen E, Jacobson CA, Kim AI, LaCasce AS, Odejide OO, Dahi PB, Nieto Y, Joyce RM, Chen YB, Bonjoc KJC, Chaudhry A, Herrera AF, Armand P, Merryman RW. Prognostic value of minimal residual disease among patients with classical Hodgkin lymphoma undergoing autologous stem cell transplantation. Leuk Lymphoma 2022; 63:2912-2917. [PMID: 35938581 PMCID: PMC11165988 DOI: 10.1080/10428194.2022.2103808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 07/08/2022] [Indexed: 12/14/2022]
Abstract
Improved biomarkers are needed to guide patient selection for autologous stem cell transplantation (ASCT) and post-ASCT maintenance therapies in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the prognostic value of minimal residual disease (MRD) using immunoglobulin-based high-throughput sequencing (Ig-HTS), we analyzed pre- and post-ASCT peripheral blood and pre-ASCT apheresis stem cell (ASC) samples in 36 cHL patients. A tumor clonotype was detected in only 12 patients (33%). Among these patients, MRD within plasma samples was closely associated with impending relapse. All patients (n = 3) with detectable MRD in any post-ASCT plasma sample relapsed (100% specificity), and MRD was not detected in any patients in remission. MRD testing from cellular specimens (peripheral blood mononuclear cell or ASC samples) was not associated with relapse. In this small cohort, plasma-based MRD testing appeared to be a promising biomarker in cHL, but given low clonotype detection rates with Ig-HTS, alternative MRD approaches should be investigated.
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Affiliation(s)
- Eleanor Taranto
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Robert Redd
- Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Erin Jeter
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Kristin McHugh
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Jennifer L Crombie
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - David C Fisher
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Eric Jacobsen
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Caron A Jacobson
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Austin I Kim
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Ann S LaCasce
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Oreofe O Odejide
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Parastoo B Dahi
- Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Yago Nieto
- Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robin M Joyce
- Department of Hematologic Malignancy, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Yi-Bin Chen
- Hematopoietic Cell Therapy and Transplant Program, Massachusetts General Hospital, Boston, MA, USA
| | - Kimberley-Jane C Bonjoc
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Ammar Chaudhry
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Alex F Herrera
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Philippe Armand
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Reid W Merryman
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
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19
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Ansell SM. Hodgkin lymphoma: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 2022; 97:1478-1488. [PMID: 36215668 DOI: 10.1002/ajh.26717] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 08/19/2022] [Indexed: 01/28/2023]
Abstract
DISEASE OVERVIEW Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8540 new patients annually and representing approximately 10% of all lymphomas in the United States. DIAGNOSIS HL is composed of two distinct disease entities: classical HL and nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. RISK STRATIFICATION An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. RISK-ADAPTED THERAPY Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced-stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents, including brentuximab vedotin and anti-programmed death-1 (PD-1) antibodies, are now being incorporated into frontline therapy. MANAGEMENT OF RELAPSED/REFRACTORY DISEASE High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant, or participation in a clinical trial should be considered.
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20
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Smith CP, Adefres B, Chang EM, Huang TQ, Parikh N, Raldow A. Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e992-e999. [PMID: 35963771 DOI: 10.1016/j.clml.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 06/15/2023]
Abstract
INTRODUCTION The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT. METHODS This study used a cost-effectiveness Markov model simulating 5 year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of ABVD chemotherapy ± ISRT or CMT consisting of 2 cycles of ABVD + ISRT. Patients progressed to no evidence of disease, progression of disease (PD), or death. Patients with PD underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). The primary outcome measured was the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were performed. RESULTS We found that PET-directed therapy and CMT strategies were associated with costs of $47,362 and $41,167, respectively. The CMT strategy was equally as effective as the PET-directed therapy strategy with QALYs of 3.4. On 1-way sensitivity analyses, the model was most sensitive to CMT and HDC-SCT costs. Two-way sensitivity analyses showed the model was sensitive to the relative costs of these treatments. CONCLUSION For patients with early-stage HL, CMT is the cost-effective strategy as compared with PET-directed therapy.
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Affiliation(s)
- Clayton P Smith
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
| | - Bethel Adefres
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Eric M Chang
- Department of Radiation Medicine, Oregon Health and Science University, Portland, OR
| | - Tina Q Huang
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Neil Parikh
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Ann Raldow
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
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Interim FDG-PET/CT for therapy monitoring and prognostication in Hodgkin's Lymphoma. Sci Rep 2022; 12:17702. [PMID: 36271128 PMCID: PMC9587214 DOI: 10.1038/s41598-022-22032-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 10/07/2022] [Indexed: 01/18/2023] Open
Abstract
The aim of the study was to assess the predictive value of interim FDG-PET/CT (iPET) in patients with Hodgkin's lymphoma (HL) treated with Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. A total of 245 consecutive patients with de novo HL between 12/2013 and 12/2017 were evaluated retrospectively. All patients were treated with upfront ABVD, performed PET/CT scans at baseline, after 2 cycles (interim PET, iPET2) or 4 cycles (iPET4) and at the end of therapy, and followed up for at least 6 months after therapy. The response status on iPET was defined according to the standard five-point Deauville scores (DS) as follows: complete metabolic response (CMR, DS 1-3) and non-complete metabolic response (nCMR) (DS 4 and 5). End-of-treatment (EoT) response was assessed by FDG-PET/CT and if needed biopsy confirmation of PET-positive findings. The association between iPET and EoT response was investigated using logistic regression analysis. Survival analysis was performed using the Cox regression hazard model and Kaplan-Meier methods. Sixty-nine patients underwent iPET-2 and 176 iPET-4. No association was found between the timing of iPET and iPET response status (P-value = 0.71). Two hundred and one patients (82%) had iPET-CMR and 44 (18%) iPET -nCMR. iPET was strongly associated with EoT response status: 194/201 (96 .5%) of iPET-CMR had a complete response at the EoT while only 21/44 (47.7%) of patients with iPET-nCMR presented a complete response at EoT (P-value < 0.0001). The median follow-up was 32 months (range 6-81). Patients with iPET-CMR presented a better outcome with 91% 3 y event-free-survival (EFS) and 95% 3 y overall survival (OS) than those with iPET-nCMR (41 and 86%, respectively, P-value < 0.0001). In multivariable analyses, iPET retained an independent prognostic factor of EFS and OS (P-value < 0.0001 and P-value = 0.002, respectively). iPET is highly predictive of outcome of HL patients treated with ABVD and allows to tailor therapy to the individual patient.
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22
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Guja KE, Nadel H, Iagaru A. Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma. Semin Nucl Med 2022. [DOI: 10.1053/j.semnuclmed.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer. Cancers (Basel) 2022; 14:cancers14194811. [PMID: 36230733 PMCID: PMC9563870 DOI: 10.3390/cancers14194811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/30/2022] Open
Abstract
Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.
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Abstract
Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.
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Truszkowska E, Andrzejewska M, Szymańska C, Wziątek A, Derwich K. Case Report: Brentuximab Vedotin Associated Acute Pancreatitis in a Pediatric Hodgkin Lymphoma Patient: Case Report and Literature Review. Pathol Oncol Res 2022; 28:1610445. [PMID: 36032658 PMCID: PMC9416696 DOI: 10.3389/pore.2022.1610445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 07/15/2022] [Indexed: 11/29/2022]
Abstract
Brentuximab vedotin is a conjugate drug used mainly in Hodgkin lymphoma, systemic and primary cutaneous anaplastic large cell lymphomas, and CD30-expressing peripheral T-cell lymphoma. We report a unique case of acute pancreatitis associated with brentuximab vedotin in a 17-year-old male patient suffering from classical Hodgkin lymphoma. Diagnosed in 2020, the patient was classified to an intermediate therapeutic group and disease’s grade was IIIAE. The patient was treated with brentuximab vedotin and bendamustine in the third line. Two weeks after the drug administration, the patient developed acute epigastric pain. Laboratory and radiological findings confirmed the clinical suspicion of acute pancreatitis that was managed with opioid pain medications, meropenem, parenteral nutrition, ondansetron and omeprazole. This is the first case report of brentuximab vedotin-associated acute pancreatitis in the pediatric patient reported in the literature to the best of our knowledge.
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Affiliation(s)
| | - Marta Andrzejewska
- Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Cyntia Szymańska
- Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Agnieszka Wziątek
- Department of Pediatric Oncology, Hematology and Transplantology, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, Poland
| | - Katarzyna Derwich
- Department of Pediatric Oncology, Hematology and Transplantology, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, Poland
- *Correspondence: Katarzyna Derwich,
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Baseline 18 F-FDG PET/CT May Portend the Prognosis of Patients With Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma After First-Line Treatment. Clin Nucl Med 2022; 47:954-960. [PMID: 35961637 DOI: 10.1097/rlu.0000000000004362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE The outcome of patients with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is variable. We aim to study if baseline 18 F-FDG PET/CT has some prognostic significance in WM/LPL. METHODS Thirty-three patients with newly diagnosed WM/LPL who underwent baseline 18 F-FDG PET/CT and received active treatment thereafter were recruited in this retrospective study. Semiquantitative indices of baseline 18 F-FDG PET/CT were measured as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and SUV max . The patients were followed up for at least 3 years or until reaching the endpoint, which were defined as progression-free survival (PFS) and the time to next treatment (TTNT). RESULTS The overall response rate of the first-line treatment in the recruited patients was 84.8% (28/33). The 3-year PFS and overall survival rates were 56.3% and 89.3%, respectively. Patients with PFS <36 months and TTNT <36 months showed TLG and MTV significantly higher than those with PFS ≥36 months and TTNT ≥36 months ( P < 0.05). SUV max in patients with PFS <36 months was significantly higher than those with PFS ≥36 months ( P = 0.033). Receiver operating characteristic analysis demonstrated that cutoff values of TLG >291.28 SUVbw * mL, MTV >108.78 mL, and SUV max >3.16 were optimal for predicting PFS <36 months. Kaplan-Meier analysis showed that TLG >291.28 SUVbw * mL and MTV >108.78 mL were predictive for shorter PFS ( P = 0.003) and TTNT ( P = 0.002). In multivariate analysis, TLG >291.28 SUVbw * mL and MTV >108.78 mL were independent predictors for shorter PFS (hazard ratio, 3.06; 95% confidence interval, 1.09-8.57; P = 0.033) and TTNT (hazard ratio, 10.01; 95% confidence interval, 2.56-39.22; P = 0.001). CONCLUSIONS The metabolic indices of TLG and MTV in baseline 18 F-FDG PET/CT were independent prognostic factors to predict PFS and TTNT in patients with WM/LPL.
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Zhang X, Jiang H, Wu S, Wang J, Zhou R, He X, Qian S, Zhao S, Zhang H, Civelek AC, Tian M. Positron Emission Tomography Molecular Imaging for Phenotyping and Management of Lymphoma. PHENOMICS (CHAM, SWITZERLAND) 2022; 2:102-118. [PMID: 36939797 PMCID: PMC9590515 DOI: 10.1007/s43657-021-00042-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 12/18/2021] [Accepted: 12/21/2021] [Indexed: 10/19/2022]
Abstract
Positron emission tomography (PET) represents molecular imaging for non-invasive phenotyping of physiological and biochemical processes in various oncological diseases. PET imaging with 18F-fluorodeoxyglucose (18F-FDG) for glucose metabolism evaluation is the standard imaging modality for the clinical management of lymphoma. One of the 18F-FDG PET applications is the detection and pre-treatment staging of lymphoma, which is highly sensitive. 18F-FDG PET is also applied during treatment to evaluate the individual chemo-sensitivity and accordingly guide the response-adapted therapy. At the end of the therapy regiment, a negative PET scan is indicative of a good prognosis in patients with advanced Hodgkin's lymphoma and diffuse large B-cell lymphoma. Thus, adjuvant radiotherapy may be alleviated. Future PET studies using non-18F-FDG radiotracers, such as 68Ga-labeled pentixafor (a cyclic pentapeptide that enables sensitive and high-contrast imaging of C-X-C motif chemokine receptor 4), 68Ga-labeled fibroblast activation protein inhibitor (FAPI) that reflects the tumor microenvironment, and 89Zr-labeled atezolizumab that targets the programmed cell death-ligand 1 (PD-L1), may complement 18F-FDG and offer essential tools to decode lymphoma phenotypes further and identify the mechanisms of lymphoma therapy.
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Affiliation(s)
- Xiaohui Zhang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Han Jiang
- grid.411176.40000 0004 1758 0478PET-CT Center, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Shuang Wu
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Jing Wang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Rui Zhou
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Xuexin He
- grid.412465.0Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
| | - Shufang Qian
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Shuilin Zhao
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Hong Zhang
- grid.412465.0Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XInstitute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, 310009 Zhejiang China
- grid.13402.340000 0004 1759 700XKey Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310027 Zhejiang China
- grid.13402.340000 0004 1759 700XCollege of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310027 Zhejiang China
| | - Ali Cahid Civelek
- grid.469474.c0000 0000 8617 4175Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD 21287 USA
| | - Mei Tian
- grid.8547.e0000 0001 0125 2443Human Phenome Institute, Fudan University, Shanghai, 201203 China
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Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, Dupuis J, Gac AC, Gastinne T, Joly B, Bouabdallah K, Nicolas-Virelizier E, Feugier P, Morschhauser F, Sibon D, Bonnet C, Berriolo-Riedinger A, Edeline V, Parrens M, Damotte D, Coso D, André M, Meignan M, Rossi C. Positron Emission Tomography-Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study. J Clin Oncol 2022; 40:1091-1101. [PMID: 34990281 DOI: 10.1200/jco.21.01777] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
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Affiliation(s)
- René-Olivier Casasnovas
- Department of Hematology, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, France
| | - Reda Bouabdallah
- Department of Hematology, Institut P. Calmette, Marseille, France.,Department of Hematology, Hopital privé de Provence, Aix en Provence, France
| | - Pauline Brice
- Department of Hematology, APHP, Hopital Saint Louis, Paris, France
| | | | - Hervé Ghesquieres
- Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, et Université Claude Bernard Lyon-1, Pierre Bénite, France
| | | | - Jehan Dupuis
- Lymphoid Malignancies Unit, Henri Mondor University Hospital, Créteil, France
| | - Anne-Claire Gac
- Department of Hematology, Institut d'hématologie de basse normandie, Caen, France
| | - Thomas Gastinne
- Department of Hematology, University Hospital of Nantes, Nantes, France
| | - Bertrand Joly
- Department of Hematology, Hospital Sud Francilien, Corbeille-Essonnes, France
| | - Krimo Bouabdallah
- Department of Hematology, University Hospital of Bordeaux, Bordeaux, France
| | | | - Pierre Feugier
- Department of Hematology, University Hospital of Nancy, Vandoeuvre les Nancy, France
| | - Franck Morschhauser
- Department of Hematology, CHU Lille, Unité GRITA, Université de Lille 2, Lille, France
| | - David Sibon
- Department of Hematology, Hopital Necker, Paris, France
| | | | | | - Véronique Edeline
- Department of Nuclear Medicine, Hopital R. Huguenin, Institut Curie, St-Cloud, France
| | - Marie Parrens
- Department of Pathology, University Hospital of Bordeaux and Inserm UMR 1053, Bordeaux, France
| | - Diane Damotte
- Department of Pathology, Université de Paris et GH Paris Centre APHP, Paris, France
| | - Diane Coso
- Department of Hematology, Institut P. Calmette, Marseille, France
| | - Marc André
- Department of Hematology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium.,Pole Mont, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Michel Meignan
- Department of Nuclear Medicine, University Hospital H. Mondor, Creteil, France
| | - Cédric Rossi
- Department of Hematology, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, France
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Tao Y, Zhou Y, Chen H, Qin Y, He X, Liu P, Zhou S, Yang J, Zhou L, Zhang C, Yang S, Gui L, Shi Y. Prognostic role of red blood cell distribution width and platelet/lymphocyte ratio in early-stage classical Hodgkin lymphoma. Future Oncol 2022; 18:1817-1827. [PMID: 35179068 DOI: 10.2217/fon-2021-1398] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background: To investigate the prognostic role of red blood cell distribution width (RDW) and platelet/lymphocyte ratio (PLR) in early-stage classical Hodgkin lymphoma (cHL). Materials & methods: Data from 402 patients with newly diagnosed early-stage cHL were retrospectively collected. The impact of factors on complete response (CR) rate and freedom from progression (FFP) was analyzed. Results: High PLR was associated with lower CR, but high RDW was not. The univariate analysis showed that RDW and PLR were predictive of FFP. On multivariate analysis, high PLR was an independent risk factor for inferior FFP. Subgroup analysis and a prognostic model for FFP based on PLR validated the prognostic role of PLR. Conclusion: PLR was a robust prognostic factor for newly diagnosed early-stage cHL.
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Affiliation(s)
- Yunxia Tao
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Yu Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Haizhu Chen
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Yan Qin
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Xiaohui He
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Peng Liu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Shengyu Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Jianliang Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Liqiang Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Changgong Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Sheng Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Lin Gui
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
| | - Yuankai Shi
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China
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30
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Hasani N, Paravastu SS, Farhadi F, Yousefirizi F, Morris MA, Rahmim A, Roschewski M, Summers RM, Saboury B. Artificial Intelligence in Lymphoma PET Imaging:: A Scoping Review (Current Trends and Future Directions). PET Clin 2022; 17:145-174. [PMID: 34809864 PMCID: PMC8735853 DOI: 10.1016/j.cpet.2021.09.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Malignant lymphomas are a family of heterogenous disorders caused by clonal proliferation of lymphocytes. 18F-FDG-PET has proven to provide essential information for accurate quantification of disease burden, treatment response evaluation, and prognostication. However, manual delineation of hypermetabolic lesions is often a time-consuming and impractical task. Applications of artificial intelligence (AI) may provide solutions to overcome this challenge. Beyond segmentation and detection of lesions, AI could enhance tumor characterization and heterogeneity quantification, as well as treatment response prediction and recurrence risk stratification. In this scoping review, we have systematically mapped and discussed the current applications of AI (such as detection, classification, segmentation as well as the prediction and prognostication) in lymphoma PET.
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Affiliation(s)
- Navid Hasani
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA; University of Queensland Faculty of Medicine, Ochsner Clinical School, New Orleans, LA 70121, USA
| | - Sriram S Paravastu
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA
| | - Faraz Farhadi
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA
| | - Fereshteh Yousefirizi
- Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada
| | - Michael A Morris
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA; Department of Computer Science and Electrical Engineering, University of Maryland-Baltimore Country, Baltimore, MD, USA
| | - Arman Rahmim
- Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada; Department of Radiology, BC Cancer Research Institute, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada
| | - Mark Roschewski
- Lymphoid Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA
| | - Ronald M Summers
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA.
| | - Babak Saboury
- Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1C455, Bethesda, MD 20892, USA; Department of Computer Science and Electrical Engineering, University of Maryland-Baltimore Country, Baltimore, MD, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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31
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PET imaging of lymphomas. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00047-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Phillips EH, Iype R, Wirth A. PET-guided treatment for personalised therapy of Hodgkin lymphoma and aggressive non-Hodgkin lymphoma. Br J Radiol 2021; 94:20210576. [PMID: 34520242 DOI: 10.1259/bjr.20210576] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
FDG-PET scanning has a central role in lymphoma staging and response assessment. There is a growing body of evidence that PET response assessment during and after initial systemic therapy can provide useful prognostic information, and PET response has an evolving role in guiding patient care. This review provides a perspective on the role of PET response assessment for individualised management of patients with the most common aggressive lymphomas, Hodgkin lymphoma and diffuse large B-cell lymphoma.
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Affiliation(s)
- Elizabeth H Phillips
- Division of Cancer Sciences, University of Manchester, Manchester, UK.,Department of Medical Oncology, The Christie Hospital NHS Foundation Trust, Manchester, UK
| | - Rohan Iype
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Andrew Wirth
- Department of Clinical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia
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Buglione M, Guerini AE, Filippi AR, Spiazzi L, Pasinetti N, Magli A, Toraci C, Borghetti P, Triggiani L, Alghisi A, Costantino G, Bertagna F, Giaj Levra N, Pegurri L, Magrini SM. A Systematic Review on Intensity Modulated Radiation Therapy for Mediastinal Hodgkin's Lymphoma. Crit Rev Oncol Hematol 2021; 167:103437. [PMID: 34358649 DOI: 10.1016/j.critrevonc.2021.103437] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 05/20/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Secondary malignant neoplasms (SMNs) and cardiovascular diseases induced by chemotherapy and radiotherapy represent the main cause of excess mortality for early-stage Hodgkin lymphoma patients, especially when the mediastinum is involved. Conformal radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) could allow a reduction of the dose to the organs-at-risk (OARs) and therefore limit long-term toxicity. METHODS We performed a systematic review of the current literature regarding comparisons between IMRT and conventional photon beam radiotherapy, or between different IMRT techniques, for the treatment of mediastinal lymphoma. RESULTS AND CONCLUSIONS IMRT allows a substantial reduction of the volumes of OARs exposed to high doses, reducing the risk of long-term toxicity. This benefit is conterbalanced by the increase of volumes receiving low doses, that could potentially increase the risk of SMNs. Treatment planning should be personalized on patient and disease characteristics. Dedicated techniques such as "butterfly" VMAT often provide the best trade-off.
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Affiliation(s)
- Michela Buglione
- Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Andrea Emanuele Guerini
- Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Andrea Riccardo Filippi
- Radiation Oncology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy.
| | - Luigi Spiazzi
- Department of Radiation Oncology, ASST Spedali Civili di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Nadia Pasinetti
- Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, P.le Spedali Civili 1, 25123 Brescia, Italy; Radiation Oncology Service, ASST Valcamonica Esine, Italy.
| | - Alessandro Magli
- Department of Radiation Oncology, Udine General Hospital, Udine, Italy.
| | - Cristian Toraci
- Department of Radiation Oncology, ASST Spedali Civili di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Paolo Borghetti
- Department of Radiation Oncology, ASST Spedali Civili di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Luca Triggiani
- Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Alessandro Alghisi
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco, Italy.
| | | | - Francesco Bertagna
- Nuclear Medicine Department, University of Brescia and Spedali Civili of Brescia, Brescia, Italy.
| | - Niccolò Giaj Levra
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Italy.
| | - Ludovica Pegurri
- Department of Radiation Oncology, ASST Spedali Civili di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy.
| | - Stefano Maria Magrini
- Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, P.le Spedali Civili 1, 25123 Brescia, Italy.
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Al Tabaa Y, Bailly C, Kanoun S. FDG-PET/CT in Lymphoma: Where Do We Go Now? Cancers (Basel) 2021; 13:cancers13205222. [PMID: 34680370 PMCID: PMC8533807 DOI: 10.3390/cancers13205222] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/11/2021] [Accepted: 10/15/2021] [Indexed: 01/06/2023] Open
Abstract
18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is an essential part of the management of patients with lymphoma at staging and response evaluation. Efforts to standardize PET acquisition and reporting, including the 5-point Deauville scale, have enabled PET to become a surrogate for treatment success or failure in common lymphoma subtypes. This review summarizes the key clinical-trial evidence that supports PET-directed personalized approaches in lymphoma but also points out the potential place of innovative PET/CT metrics or new radiopharmaceuticals in the future.
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Affiliation(s)
- Yassine Al Tabaa
- Scintidoc Nuclear Medicine Center, 25 rue de Clémentville, 34070 Montpellier, France
- Correspondence:
| | - Clement Bailly
- CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, 44093 Nantes, France;
- Nuclear Medicine Department, University Hospital, 44093 Nantes, France
| | - Salim Kanoun
- Nuclear Medicine Department, Institute Claudius Regaud, 31100 Toulouse, France;
- Cancer Research Center of Toulouse (CRCT), Team 9, INSERM UMR 1037, 31400 Toulouse, France
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Ribeiro T, Marques A, Ferreira G, Castro C, Tavares M, Espírito-Santo A, Moreira C, Mariz J. Semiquantitative analysis of interim 18F-FDG PET is superior in predicting outcome in Hodgkin lymphoma patients compared to visual analysis. Rev Esp Med Nucl Imagen Mol 2021; 40:281-286. [PMID: 34425968 DOI: 10.1016/j.remnie.2020.06.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 06/14/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. MATERIAL AND METHODS Retrospective analysis of Hodgkin's lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-hematology Department of Instituto Português de Oncologia - Porto (median follow-up: 46.5 months [2.6-66.4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analyzed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. RESULTS Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value >92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p<0.05), ΔSUVpeak (55.9% vs. 88.1%, p<0.05), ΔMTV (35.3% vs. 88.7%, p<0.05), and ΔTLG (42.4% vs. 88.1%, p<0.05). Statistical significance was not reached when considering 5-PS results. DISCUSSION PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity.
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Affiliation(s)
- T Ribeiro
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
| | - A Marques
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - G Ferreira
- Nuclear Medicine Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - C Castro
- Epidemiology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - M Tavares
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - A Espírito-Santo
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - C Moreira
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - J Mariz
- Onco-Hematology Department, Instituto Português de Oncologia do Porto FG, Street Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
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Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study. Biomedicines 2021; 9:biomedicines9080971. [PMID: 34440175 PMCID: PMC8393404 DOI: 10.3390/biomedicines9080971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/01/2021] [Accepted: 08/02/2021] [Indexed: 11/16/2022] Open
Abstract
Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97-60). RESULTS Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan-Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.
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Santoro A, Mazza R, Spina M, Califano C, Specchia G, Carella M, Consoli U, Palombi F, Musso M, Pulsoni A, Kovalchuk S, Bonfichi M, Ricci F, Fabbri A, Liberati AM, Rodari M, Giordano L, Chimienti E, Balzarotti M, Sorasio R, Gallamini A, Ghiggi C, Ciammella P, Ricardi U, Chauvie S, Carlo-Stella C, Merli F. Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi. Ann Hematol 2021; 100:2547-2556. [PMID: 34327561 DOI: 10.1007/s00277-021-04604-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 07/04/2021] [Indexed: 11/28/2022]
Abstract
We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.
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Affiliation(s)
- Armando Santoro
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Italy. .,IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
| | - Rita Mazza
- IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Michele Spina
- Medical Oncology Division, Centro Riferimento Oncologico, Aviano, Italy
| | - Catello Califano
- Onco-Hematology Department, A. Tortora Hospital, Pagani, Salerno, Italy
| | - Giorgina Specchia
- Emergency and Transplantation Department, Hematology Section, University of Bari Medical School, Bari, Italy
| | - Michele Carella
- Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.,Clinica La Madonnina, Milan, Italy.,Clinica Villa Pia, Rome, Italy
| | - Ugo Consoli
- Hematology Department, Garibaldi Nesima Hospital, Catania, Italy
| | | | - Maurizio Musso
- Onco-Hematology Unit, Casa Di Cura "La Maddalena", Palermo, Italy
| | - Alessandro Pulsoni
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | | | - Francesca Ricci
- IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | | | - Anna Marina Liberati
- Onco-Hematology Division, S. Maria Hospital, Università Degli Studi Di Perugia, Terni, Italy
| | - Marcello Rodari
- IRCCS Humanitas Clinical and Research Hospital, Department of Diagnostic Imaging, Via Manzoni 56, Milano, Rozzano, Italy
| | - Laura Giordano
- Biostatistic Unit, Humanitas Clinical and Research Hospital, Rozzano, Milano, Italy
| | | | - Monica Balzarotti
- IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Roberto Sorasio
- Division of Hematology, S. Croce E Carle Hospital, Cuneo, Italy
| | - Andrea Gallamini
- Division of Hematology, S. Croce E Carle Hospital, Cuneo, Italy.,Research and Clinical Innovation Department, Centre Antoine-Lacassagne, Nice, France
| | - Chiara Ghiggi
- Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Patrizia Ciammella
- Radiation Oncology Unit, Azienda Unità Sanitaria Locale IRCCS Di Reggio Emilia, Reggio Emilia, Italy
| | - Umberto Ricardi
- Oncology Department, Radiation Oncology, University of Torino, Torino, Italy
| | - Stephane Chauvie
- Medical Physics Department, S. Croce E Carle Hospital, Cuneo, Italy
| | - Carmelo Carlo-Stella
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Italy.,IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Francesco Merli
- Hematology Department, Azienda Unità Sanitaria Locale IRCCS Di Reggio Emilia, Reggio Emilia, Italy
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Vellemans H, André MPE. Review of Treatment Options for the Management of Advanced Stage Hodgkin Lymphoma. Cancers (Basel) 2021; 13:cancers13153745. [PMID: 34359646 PMCID: PMC8345175 DOI: 10.3390/cancers13153745] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 07/20/2021] [Accepted: 07/23/2021] [Indexed: 11/23/2022] Open
Abstract
Simple Summary The cure rate of Hodgkin lymphoma is currently higher than 80% for almost all stages at diagnosis. Despite the particularly good efficacy of chemotherapy and radiotherapy, some late complications such as cardiovascular disease and second malignancies can occur in a small proportion of patients. A major concern nowadays is, therefore, to find the balance between remission and toxicity in the development of new treatments for classical Hodgkin lymphoma. This review focuses on how to best treat first-line advanced Hodgkin lymphomas, considering the acute and long-term consequences of chemotherapy and radiotherapy treatments. New drugs such as brentuximab vedotin and checkpoint inhibitors are also a field of interest. Abstract Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPPesc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.
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Juweid ME, Mueller M, Alhouri A, A-Risheq MZ, Mottaghy FM. Positron emission tomography/computed tomography in the management of Hodgkin and B-cell non-Hodgkin lymphoma: An update. Cancer 2021; 127:3727-3741. [PMID: 34286864 DOI: 10.1002/cncr.33772] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 06/06/2021] [Accepted: 06/07/2021] [Indexed: 01/20/2023]
Abstract
18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is now an integral part of lymphoma staging and management. Because of its greater accuracy compared with CT alone, PET/CT is currently routinely performed for staging and for response assessment at the end of treatment in the vast majority of FDG-avid lymphomas and is the cornerstone of response classification for these lymphomas according to the Lugano classification. Interim PET/CT, typically performed after 2 to 4 of 6 to 8 chemotherapy/chemoimmunotherapy cycles with or without radiation, is commonly performed for prognostication and potential treatment escalation or de-escalation early in the course of therapy, a concept known as response-adapted or risk-adapted treatment. Quantitative PET is an area of growing interest. Metrics, such as the standardized uptake value, changes (Δ) in the standardized uptake value, metabolic tumor volume, and total lesion glycolysis, are being investigated as more reproducible and potentially more accurate predictors of response and prognosis. Despite the progress made in standardizing the use of PET/CT in lymphoma, challenges remain, particularly with respect to its limited positive predictive value, emphasizing the need for more specific molecular probes. This review highlights the most relevant applications of PET/CT in Hodgkin and B-cell non-Hodgkin lymphoma, its strengths and limitations, as well as recent efforts at implementing PET/CT-based metrics as promising tools for precision medicine.
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Affiliation(s)
- Malik E Juweid
- Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan
| | - Marguerite Mueller
- Department of Nuclear Medicine, University Hospital Rheinish-Westphalian Technical University, Aachen University, Aachen, Germany
| | - Abdullah Alhouri
- Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan
| | - M Ziad A-Risheq
- Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan
| | - Felix M Mottaghy
- Department of Nuclear Medicine, University Hospital Rheinish-Westphalian Technical University, Aachen University, Aachen, Germany.,Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
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Kedmi M, Khaustov P, Ribakovsy E, Benjamini O, Avigdor A. Outcomes Related to FDG-PET-CT Response in Patients With Hodgkin Lymphoma Treated With Brentuximab-Vedotin at Relapse or Consolidation. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 21:e929-e937. [PMID: 34366266 DOI: 10.1016/j.clml.2021.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/29/2021] [Accepted: 07/02/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Brentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting. PATIENTS AND METHODS Records of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.4%) or consolidation (28.6%) post-ASCT were analyzed. Patients who did not reach complete response (CR) on PET/CT after 4 cycles (non-responders) discontinued BV and received the next treatment line. Overall survival (OS) and progression-free survival (PFS) were compared between responders and non-responders. RESULTS After a median follow-up of 19.1 months, all consolidation patients were alive and none progressed. Median OS in 23 relapsed patients that did not achieve CR after 4 cycles and continued to the next treatment was 55.0 months, while all those in CR (n = 24) were alive (P = .0120). No statistically significant differences in OS were observed between responders and non-responders with relapsed HL (P = .1072). Median PFS evaluated after 4 BV cycles was significantly longer in responders compared to non-responders (47.9 vs. 1.5 months, P < .0001). Neuropathy and neutropenia were the main toxicities observed. CONCLUSIONS HL patients treated with BV for relapse or consolidation who achieved CR by PET-CT after 4 cycles showed improved PFS and OS compared to non-responders. Non-responders treated for relapsed HL who proceeded to the next treatment line demonstrated comparable OS to responders.
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Affiliation(s)
- Meirav Kedmi
- Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv university, Tel-Aviv, Israel; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
| | - Pavel Khaustov
- Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Elena Ribakovsy
- Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Ohad Benjamini
- Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv university, Tel-Aviv, Israel
| | - Abraham Avigdor
- Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv university, Tel-Aviv, Israel
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Mohty R, Dulery R, Bazarbachi AH, Savani M, Hamed RA, Bazarbachi A, Mohty M. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J 2021; 11:126. [PMID: 34244478 PMCID: PMC8270913 DOI: 10.1038/s41408-021-00518-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/16/2021] [Accepted: 06/21/2021] [Indexed: 12/16/2022] Open
Abstract
Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody-drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.
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Affiliation(s)
- Razan Mohty
- Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rémy Dulery
- Department of Hematology, Saint Antoine Hospital, AP-HP, Paris, France
- Sorbonne University, INSERM UMRs 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France
| | - Abdul Hamid Bazarbachi
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY, USA
| | - Malvi Savani
- Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA
| | - Rama Al Hamed
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY, USA
| | - Ali Bazarbachi
- Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mohamad Mohty
- Department of Hematology, Saint Antoine Hospital, AP-HP, Paris, France.
- Sorbonne University, INSERM UMRs 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France.
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Wijetunga NA, Imber BS, Caravelli JF, Mikhaeel NG, Yahalom J. A picture is worth a thousand words: a history of diagnostic imaging for lymphoma. Br J Radiol 2021; 94:20210285. [PMID: 34111961 DOI: 10.1259/bjr.20210285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The journey from early drawings of Thomas Hodgkin's patients to deep learning with radiomics in lymphoma has taken nearly 200 years, and in many ways, it parallels the journey of medicine. By tracing the history of imaging in clinical lymphoma practice, we can better understand the motivations for current imaging practices. The earliest imaging modalities of the 2D era each had varied, site-dependent sensitivity, and the improved accuracy of imaging studies allowed new diagnostic and therapeutic techniques. First, we review the initial imaging technologies that were applied to understand lymphoma spread and achieve practical guidance for the earliest lymphoma treatments. Next, in the 3D era, we describe how anatomical imaging advances replaced and complemented conventional modalities. Afterward, we discuss how the PET era scans were used to understand response of tumors to treatment and risk stratification. Finally, we discuss the emergence of radiomics as a promising area of research in personalized medicine. We are now able to identify involved lymph nodes and body sites both before and after treatment to offer patients improved treatment outcomes. As imaging methods continue to improve sensitivity, we will be able to use personalized medicine approaches to give targeted and highly focused therapies at even earlier time points, and ideally, we can obtain long-term disease control and cures for lymphomas.
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Affiliation(s)
- N Ari Wijetunga
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Brandon Stuart Imber
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - James F Caravelli
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - N George Mikhaeel
- Department of Clinical Oncology, Guy's and St. Thomas' Hospital, London, UK
| | - Joachim Yahalom
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Jachimowicz RD, Pieper L, Reinke S, Gontarewicz A, Plütschow A, Haverkamp H, Frauenfeld L, Fend F, Overkamp M, Jochims F, Thorns C, Leo Hansmann M, Möller P, Rosenwald A, Stein H, Reinhardt HC, Borchmann P, von Tresckow B, Engert A, Klapper W. Whole-slide image analysis of the tumor microenvironment identifies low B-cell content as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP. Haematologica 2021; 106:1684-1692. [PMID: 32381573 PMCID: PMC8168506 DOI: 10.3324/haematol.2019.243287] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Indexed: 01/18/2023] Open
Abstract
Asubset of patients with advanced-stage classical Hodgkin lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and validated in this high-risk group are still lacking. Here, we applied wholeslide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on pre-treatment biopsies from 340 patients with advanced-stage cHL enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin and Reed-Sternberg cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B-cell count was associated with significantly reduced progression-free survival and overall survival, while the content of T cells, macrophages and Hodgkin and Reed-Sternberg cells was not associated with the risk of progression or relapse in the study cohort. We further validated low Bcell content as a prognostic factor for progression-free survival and overall survival in the validation cohort and demonstrated the good interobserver agreement of WSI. WSI may represent a key tool for risk stratification of advanced-stage cHL and can easily be added to the standard diagnostic histopathology work-up.
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Affiliation(s)
| | - Luise Pieper
- University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
| | - Sarah Reinke
- University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
| | - Artur Gontarewicz
- University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
| | - Annette Plütschow
- University of Cologneand University Hospital Cologne, German Hodgkin Study Group, Germany
| | - Heinz Haverkamp
- University of Cologneand University Hospital Cologne, German Hodgkin Study Group, Germany
| | | | - Falko Fend
- Department of Pathology, University of Tübingen, Germany
| | | | - Franziska Jochims
- University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
| | - Christoph Thorns
- Department of Pathology, University Hospital Schleswig-Holstein, University of Lübeck, Germany
| | | | - Peter Möller
- Department of Pathology, University Hospital Ulm, Germany
| | - Andreas Rosenwald
- Institute of Pathology, University of Würzburg, Comprehensive Cancer Center Mainfranken, Germany
| | | | | | - Peter Borchmann
- University of Cologne, German Hodgkin Study Group, Cologne, Germany
| | | | - Andreas Engert
- University of Cologne, German Hodgkin Study Group, Cologne, Germany
| | - Wolfram Klapper
- University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
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Zanoni L, Mattana F, Calabrò D, Paccagnella A, Broccoli A, Nanni C, Fanti S. Overview and recent advances in PET/CT imaging in lymphoma and multiple myeloma. Eur J Radiol 2021; 141:109793. [PMID: 34148014 DOI: 10.1016/j.ejrad.2021.109793] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 03/18/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023]
Abstract
Imaging in hematological diseases has evolved extensively over the past several decades. Positron emission tomography/computed tomography (PET/CT) with of 2-[18 F]-fluoro-2-deoxy-d-glucose ([18 F] FDG) is currently essential for accurate staging and for early and late therapy response assessment for all FDG-avid lymphoproliferative histologies. The widely adopted visual Deauville 5-point scale and Lugano Classification recommendations have recently standardized PET scans interpretation and improved lymphoma patient management. In addition [18 F] FDG-PET is routinely recommended for initial evaluation and treatment response assessment of Multiple Myeloma (MM) with significant contribution in risk-stratification and prognostication, although magnetic resonance imaging remains the Gold Standard for the assessment of bone marrow involvement. In this review, an overview of the role of [18 F] FDG-PET, in hematological malignancies is provided, particularly focusing on Hodgkin lymphoma (HL) and Diffuse Large B Cell Lymphoma (DLBCL), both in adult and pediatric populations, and MM, at each point of patient management. Potential alternative molecular imaging applications in this field, such as non-[18 F] FDG-tracers, whole body magnetic resonance imaging (WB-MRI), hybrid PET/MRI and emerging radiomics research are briefly presented.
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Affiliation(s)
- Lucia Zanoni
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy.
| | - Francesco Mattana
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Diletta Calabrò
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Andrea Paccagnella
- Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
| | - Alessandro Broccoli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
| | - Cristina Nanni
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy.
| | - Stefano Fanti
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Nuclear Medicine, via Massarenti 9, 40138, Bologna, Italy; Nuclear Medicine, DIMES, Alma Mater studiorum, Università di Bologna, Bologna, Italy.
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Semiquantitative analysis of interim 18F-FDG PET is superior in predicting outcome in Hodgkin lymphoma patients compared to visual analysis. Rev Esp Med Nucl Imagen Mol 2021. [PMID: 33947644 DOI: 10.1016/j.remn.2020.06.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
PURPOSE To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. MATERIAL AND METHODS Retrospective analysis of Hodgkin's Lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-Hematology Department of Instituto Português de Oncologia - Porto (median follow-up: 46.5 months [2,6-66,4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analysed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. RESULTS Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value > 92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p < 0.05), ΔSUVpeak (55.9% vs 88.1%, p< 0.05), ΔMTV (35.3% vs. 88.7%, p< 0.05), and ΔTLG (42.4% vs. 88.1%, p< 0.05). Statistical significance wasn't reached when considering 5-PS results. DISCUSSION PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity.
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Chen X, Zhao S, Wang H, Fu C, Tian R, Zou L. Assessment of the prognostic value of interim fluorodeoxyglucose positron emission tomography/computed tomography in nasal-type extranodal natural killer/T-cell lymphoma. Quant Imaging Med Surg 2021; 11:1220-1233. [PMID: 33816162 DOI: 10.21037/qims-20-620] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background The prognostic value of interim positron emission tomography/computed tomography (PET/CT) for nasal-type extranodal natural killer/T-cell lymphoma (ENKTL) is controversial. We evaluated the prognostic value of interim PET/CT in ENKTL patients to facilitate risk stratification and guide clinical treatment. Methods Patients with ENKTL who received first-line chemotherapy based on L-asparaginase/pegaspargase with/without involved-field radiotherapy were recruited for this study. Pretreatment and interim PET/CT evaluations were performed. Interim PET/CT was evaluated via the maximum standardized uptake value (SUVmax) and the Deauville 5-point scale (DS); and the capacity to predict progression-free survival (PFS) and overall survival (OS) was evaluated. Receiver operating characteristic (ROC) curves were used to determine the optimal SUVmax cutoff. Fisher's exact test was used to analyze relationships between interim PET/CT results and clinical characteristics. Univariate and multivariate analyses were performed to examine the independent effects of interim PET/CT. The Cochran-Mantel-Haenszel test was used to assess the prognostic value of interim PET/CT at different timepoints. Results Overall, 129 ENKTL patients were enrolled. The optimal interim PET/CT SUVmax cut-off was 4.95. The median follow-up was 34 [2-90] months, in the low SUVmax group (≤4.95), the 2-year PFS and OS rates were 76.3% and 88.0%, respectively; in the high SUVmax group (>4.95), the PFS and OS rates were 15.6% and 44.5%, respectively. Likewise, for the DS 1-3 group, the PFS and OS rates were 78.9% and 91.2%, respectively; and in the DS 4 or 5 group, the rates of PFS and OS were 49.7% and 69.0%, respectively. In univariate analysis, interim PET/CT evaluation based on SUVmax and DS scores were both PFS and OS predictors. In multivariate analysis, SUVmax was independently significantly associated with PFS (P<0.001) and OS (P=0.002), and DS was independently significantly associated with PFS (P=0.004) but not OS (P=0.204). In the Cochran-Mantel-Haenszel testing, the SUVmax and DS were significantly associated with PFS and OS after adjustments for the interim PET/CT timing. Conclusions Interim PET/CT was of prognostic value concerning ENKTL. The SUVmax is an independent prognostic indicator of PFS and OS, while the DS is an independent prognostic indicator of PFS but not OS. The SUVmax is of greater prognostic value than DS.
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Affiliation(s)
- Xi Chen
- Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Shengnan Zhao
- Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hongxi Wang
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Chunxi Fu
- Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Rong Tian
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Liqun Zou
- Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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Camus V, Jardin F. Cell-Free DNA for the Management of Classical Hodgkin Lymphoma. Pharmaceuticals (Basel) 2021; 14:ph14030207. [PMID: 33801462 PMCID: PMC7998645 DOI: 10.3390/ph14030207] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 12/12/2022] Open
Abstract
Cell-free DNA (cfDNA) testing, is an emerging “liquid biopsy” tool for noninvasive lymphoma detection, and an increased amount of data are now available to use this technique with accuracy, especially in classical Hodgkin lymphoma (cHL). The advantages of cfDNA include simplicity of repeated blood sample acquisition over time; dynamic, noninvasive, and quantitative analysis; fast turnover time; reasonable cost; and established consistency with results from tumor genomic DNA. cfDNA analysis offers an easy method for genotyping the overall molecular landscape of pediatric and adult cHL and may help in cases of diagnostic difficulties between cHL and other lymphomas. cfDNA levels are correlated with clinical, prognostic, and metabolic features, and may serve as a therapeutic response evaluation tool and as a minimal residual disease (MRD) biomarker in complement to positron emission tomography (PET). Indeed, cfDNA real-time monitoring by fast high-throughput techniques enables the prompt detection of refractory disease or may help to address PET residual hypermetabolic situations during or at the end of treatment. The major recent works presented and described here demonstrated the clinically meaningful applicability of cfDNA testing in diagnostic and theranostic settings, but also in disease risk assessment, therapeutic molecular response, and monitoring of cHL treatments.
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Affiliation(s)
- Vincent Camus
- Correspondence: ; Tel.: +33(0)-2-32-08-29-47; Fax: +33-(0)-2-32-08-22-83
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Dynamic evaluation of the prognostic value of 18F-FDG PET/CT in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol 2021; 100:1039-1047. [PMID: 33634350 DOI: 10.1007/s00277-021-04466-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 02/18/2021] [Indexed: 10/22/2022]
Abstract
Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.
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Camus V, Viennot M, Lequesne J, Viailly PJ, Bohers E, Bessi L, Marcq B, Etancelin P, Dubois S, Picquenot JM, Veresezan EL, Cornic M, Burel L, Loret J, Becker S, Decazes P, Lenain P, Lepretre S, Lemasle E, Lanic H, Ménard AL, Contentin N, Tilly H, Stamatoullas A, Jardin F. Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study. Haematologica 2021; 106:154-162. [PMID: 32079702 PMCID: PMC7776248 DOI: 10.3324/haematol.2019.237719] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 02/12/2020] [Indexed: 11/28/2022] Open
Abstract
The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq® technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow-up at diagnosis and after two cycles (C2) of chemotherapy. Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients]) were assessed in this noninterventional study. The median age of the patients was 33.5 years (range: 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype were correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, not available [NA] =6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). The mean of DeltaSUVmax after C2 was -78.8%. ctDNA after C2 was analysed in 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.
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Affiliation(s)
- Vincent Camus
- Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen
| | - Mathieu Viennot
- INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen
| | | | | | - Elodie Bohers
- INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen
| | - Lucile Bessi
- INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France
| | - Bénédicte Marcq
- Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen
| | | | - Sydney Dubois
- University of Rouen and Department of Genetic Oncology, Centre Henri Becquerel, Rouen
| | | | | | - Marie Cornic
- Clinical Research Unit, Centre Henri Becquerel, Rouen
| | - Lucie Burel
- Clinical Research Unit, Centre Henri Becquerel, Rouen, France
| | - Justine Loret
- Clinical Research Unit, Centre Henri Becquerel, Rouen, France
| | - Stéphanie Becker
- Department of Nuclear Medicine and Radiology, Centre Henri Becquerel and QuantIF, Rouen, France
| | - Pierre Decazes
- Department of Nuclear Medicine and Radiology, Centre Henri Becquerel and QuantIF, Rouen
| | - Pascal Lenain
- Department of Hematology, Centre Henri Becquerel, Rouen
| | - Stéphane Lepretre
- Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen
| | - Emilie Lemasle
- Department of Hematology, Centre Henri Becquerel, Rouen, France
| | - Hélène Lanic
- Department of Hematology, Centre Henri Becquerel, Rouen, France
| | | | | | - Hervé Tilly
- Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen, France
| | | | - Fabrice Jardin
- Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen, France
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Trotman J, Barrington SF. The role of PET in first-line treatment of Hodgkin lymphoma. LANCET HAEMATOLOGY 2021; 8:e67-e79. [DOI: 10.1016/s2352-3026(20)30357-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/05/2020] [Accepted: 10/08/2020] [Indexed: 11/30/2022]
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