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      Pulmonary lesions in early response assessment in pediatric Hodgkin lymphoma: prevalence and possible implications for initial staging

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          Abstract

          Background

          Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification.

          Objective

          This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging.

          Materials and methods

          A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes.

          Results

          Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common.

          Conclusion

          New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.

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          Most cited references46

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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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            Fleischner Society: glossary of terms for thoracic imaging.

            Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for the majority of terms. (c) RSNA, 2008.
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              Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017.

              The Fleischner Society Guidelines for management of solid nodules were published in 2005, and separate guidelines for subsolid nodules were issued in 2013. Since then, new information has become available; therefore, the guidelines have been revised to reflect current thinking on nodule management. The revised guidelines incorporate several substantive changes that reflect current thinking on the management of small nodules. The minimum threshold size for routine follow-up has been increased, and recommended follow-up intervals are now given as a range rather than as a precise time period to give radiologists, clinicians, and patients greater discretion to accommodate individual risk factors and preferences. The guidelines for solid and subsolid nodules have been combined in one simplified table, and specific recommendations have been included for multiple nodules. These guidelines represent the consensus of the Fleischner Society, and as such, they incorporate the opinions of a multidisciplinary international group of thoracic radiologists, pulmonologists, surgeons, pathologists, and other specialists. Changes from the previous guidelines issued by the Fleischner Society are based on new data and accumulated experience. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 13, 2017.
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                Author and article information

                Contributors
                dietrich.stoevesandt@medizin.uni-halle.de
                Journal
                Pediatr Radiol
                Pediatr Radiol
                Pediatric Radiology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0301-0449
                1432-1998
                31 January 2024
                31 January 2024
                2024
                : 54
                : 5
                : 725-736
                Affiliations
                [1 ]GRID grid.461820.9, ISNI 0000 0004 0390 1701, Department of Radiology, , University Hospital Halle, ; Ernst-Grube-Straße 40, 06120 Halle/Salle, Germany
                [2 ]GRID grid.461820.9, ISNI 0000 0004 0390 1701, Department of Internal Medicine, , University Hospital Halle, ; Halle/Saale, Germany
                [3 ]GRID grid.411067.5, ISNI 0000 0000 8584 9230, Department of Pediatric Hematology and Oncology, , University Hospital Giessen-Marburg, ; Giessen, Germany
                [4 ]Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany
                [5 ]Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, ( https://ror.org/03s7gtk40) Leipzig, Germany
                [6 ]Diagnostic Imaging and Pediatrics, Warren Alpert Medical School, Brown University, ( https://ror.org/05gq02987) Providence, RI USA
                [7 ]Pediatric Radiology, IROCRI (Imaging and Radiation Oncology Core - Rhode Island), Lincoln, RI USA
                [8 ]Department of Oncology, St. Jude Children’s Research Hospital, ( https://ror.org/02r3e0967) Memphis, TN USA
                [9 ]Department of Nuclear Medicine, University of Leipzig, ( https://ror.org/03s7gtk40) Leipzig, Germany
                [10 ]GRID grid.413776.0, ISNI 0000 0004 1937 1098, Hôpital Armand-Trousseau Sorbonne Université, ; Paris, France
                [11 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Department of Paediatric Haematology and Oncology, Royal Hospital for Children and Young People and University of Edinburgh, ; Edinburgh, UK
                [12 ]Department of Medical Oncology and Radiotherapy, Oslo University Hospital, ( https://ror.org/00j9c2840) Oslo, Norway
                [13 ]GRID grid.9018.0, ISNI 0000 0001 0679 2801, Department of Radiation Oncology, Medical Faculty of the Martin-Luther-University, ; Halle (Saale), Germany
                [14 ]Karolinska University Hospital, Astrid Lindgrens Children’s Hospital, ( https://ror.org/00m8d6786) Stockholm, Sweden
                [15 ]GRID grid.4491.8, ISNI 0000 0004 1937 116X, Department of Pediatric Hematology and Oncology, , University Hospital Motol and Second Medical Faculty of Charles University, ; Prague, Czech Republic
                [16 ]Department of Pediatric Oncology and Hematology, University Children’s Hospital of Krakow, ( https://ror.org/009x1kj44) Kraków, Poland
                [17 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Pediatric Hematology and Oncology, , St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria and St. Anna Children’s Cancer Research Institute, ; Vienna, Austria
                [18 ]GRID grid.470095.f, ISNI 0000 0004 0608 5535, Department of Pediatric Hematology and Oncology, , University Children’s Hospital, ; Bratislava, Slovakia
                [19 ]GRID grid.410569.f, ISNI 0000 0004 0626 3338, Department of Pediatric Hematology and Oncology, , University Hospitals Leuven, ; Louvain, Belgium
                [20 ]GRID grid.487647.e, Princess Máxima Center for Pediatric Oncology, ; Utrecht, The Netherlands
                [21 ]Department of Radio-Oncology, Medical University Vienna, ( https://ror.org/05n3x4p02) Vienna, Austria
                [22 ]Service d’Hématologie Et d’Immunologie Pédiatrique, Hôpital Robert-Debré, ( https://ror.org/02dcqy320) Paris, France
                [23 ]GRID grid.439749.4, ISNI 0000 0004 0612 2754, Department of Pediatric Hematology and Oncology, , University College London Hospitals, ; London, UK
                Author information
                http://orcid.org/0000-0001-5105-4488
                Article
                5859
                10.1007/s00247-024-05859-y
                11056341
                38296856
                32842d1a-0e0f-437e-bd13-8f24e81632e4
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 September 2023
                : 11 January 2024
                : 12 January 2024
                Funding
                Funded by: Universitätsklinikum Halle (Saale) (8960)
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Pediatrics
                cancer,computed tomography,hodgkin lymphoma,immunosuppression,lung,pediatric
                Pediatrics
                cancer, computed tomography, hodgkin lymphoma, immunosuppression, lung, pediatric

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