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      Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study

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          Abstract

          PURPOSE

          Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) –adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes.

          PATIENTS AND METHODS

          Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS).

          RESULTS

          High PET score was associated with inferior EFS, before ( P < .001) and after adjustment ( P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4).

          CONCLUSION

          In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.

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          Most cited references32

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          Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.

          The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.
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            Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group.

            Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.
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              Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma.

              To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials. An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted. PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.
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                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                July 10 2019
                July 10 2019
                : 37
                : 20
                : 1732-1741
                Affiliations
                [1 ]King’s College London and Guy’s and St Thomas’ PET Centre, Kings College London, King’s Health Partners, London, United Kingdom
                [2 ]Cancer Research UK and University College London Cancer Trials Centre, University College London, London, United Kingdom
                [3 ]University of Sheffield and Weston Park Hospital, Sheffield, United Kingdom
                [4 ]St George’s, University of London, London, United Kingdom
                [5 ]Cancer Research UK Centre, University of Southampton, Southampton, United Kingdom
                [6 ]University College Hospital London, London, United Kingdom
                [7 ]Aberdeen Royal Infirmary, Aberdeen, United Kingdom
                [8 ]Nottingham City Hospitals National Health Service (NHS) Trust, Nottingham, United Kingdom
                [9 ]Mount Vernon Hospital, Middlesex, United Kingdom
                [10 ]Institute of Cancer Sciences and the Christie NHS Foundation Trust, University of Manchester, Manchester, United Kingdom
                Article
                10.1200/JCO.18.01799
                6638600
                31112475
                c6f84f35-b2ac-4131-97e3-f8aa5a47d52c
                © 2019
                History

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