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.

Department of Internal Medicine University Hospital Halle Halle Saale Germany

Department of Medical Oncology and Radiotherapy Oslo University Hospital Oslo Norway

Department of Nuclear Medicine University of Leipzig Leipzig Germany

Department of Oncology St Jude Children's Research Hospital Memphis TN USA

Department of Paediatric Haematology and Oncology Royal Hospital for Children and Young People and University of Edinburgh Edinburgh UK

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

Department of Pediatric Hematology and Oncology University Children's Hospital Bratislava Slovakia

Department of Pediatric Hematology and Oncology University College London Hospitals London UK

Department of Pediatric Hematology and Oncology University Hospital Giessen Marburg Giessen Germany

Department of Pediatric Hematology and Oncology University Hospital Motol and 2nd Medical Faculty of Charles University Prague Czech Republic

Department of Pediatric Hematology and Oncology University Hospitals Leuven Louvain Belgium

Department of Pediatric Oncology and Hematology University Children's Hospital of Krakow Kraków Poland

Department of Radiation Oncology Medical Faculty of the Martin Luther University Halle Germany

Department of Radio Oncology Medical University Vienna Vienna Austria

Department of Radiology University Hospital Halle Ernst Grube Straße 40 06120 Halle Salle Germany

Diagnostic Imaging and Pediatrics Warren Alpert Medical School Brown University Providence RI USA

Hôpital Armand Trousseau Sorbonne Université Paris France

Institute of Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Karolinska University Hospital Astrid Lindgrens Children's Hospital Stockholm Sweden

Medical Faculty of the Martin Luther University of Halle Wittenberg Halle Saale Germany

Pediatric Radiology IROCRI Lincoln RI USA

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

Service d'Hématologie Et d'Immunologie Pédiatrique Hôpital Robert Debré Paris France

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