{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:34:24Z","timestamp":1787924064663,"version":"build-2784847793"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Pract.","Clinics and Practice"],"abstract":"<jats:p>Background\/Objectives: Osteosarcoma is a rare malignancy and the most common primary malignant bone tumor. Metastases commonly affect the lungs and are associated with reduced life expectancy. Calcifications can be present within a metastatic nodule at baseline or can appear during follow-up. We aimed to assess the clinical significance of calcifications in lung metastases, particularly in relation to radiological pattern, histopathological subtype, and treatment response. Methods: A retrospective cohort of patients with osteosarcoma and lung metastases at diagnosis was evaluated for the period 2000\u20132018. The presence of calcifications inside pulmonary lesions on baseline lung CT and\/or follow-up was assessed and recorded. Radiological data were then checked against histopathological data (i.e., osteosarcoma subtypes and chemotherapy response with necrosis percentage) and the radiological pattern of the primary tumor (i.e., osteolytic, sclerotic, or mixed pattern). Results: Of a cohort of 92 patients, 14 were excluded due to having no baseline or follow-up chest CT. Of the 78 patients with an osteosarcoma diagnosis, lung metastases at diagnosis, and chest CT who were enrolled (42 men and 36 women; mean age: 23.8 years [range, 6\u201373 years]), 70 (89.7%) had a baseline imaging study of the primary tumor (osteosarcoma). The presence of calcifications in lung metastases at both baseline and follow-up was significantly associated with the radiological pattern of the primary lesion (p &lt; 0.0001). Calcifications were not present in the lung metastases of any of the 18 patients (0%) with a lytic radiological pattern at any stage, whereas all 32 patients (100%) with a purely sclerotic pattern had calcifications within lung metastases at baseline or during follow-up; of the 20 patients with a mixed radiological pattern, 11 (55%) had no calcifications and 9 (45.0%) had detectable calcifications. No statistically significant association was found between histopathological subtype and calcification. Osteoblastic osteosarcoma was more frequently associated with calcification (66.0%). During induction chemotherapy, five poor responders and three good responders (necrosis &gt; 90%) developed calcifications (p = 0.72; OR = 0.67; 95% CI, 0.10\u20133.86). Conclusions: In patients with osteosarcoma, calcifications within pulmonary metastases are strongly associated with the radiological pattern of the primary tumor, and this association is greatest for a pure sclerotic pattern, followed by the mixed one. We found no statistically significant association between the occurrence of calcifications during follow-up and chemotherapy response measured by necrosis percentage of the surgical specimen in our limited cohort; further research is needed.<\/jats:p>","DOI":"10.3390\/clinpract16090161","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:27:46Z","timestamp":1787920066000},"page":"161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Relevance of Calcifications in Osteosarcoma Lung Metastases: Correlations Among Radiological Patterns, Histological Subtypes, and Chemotherapy Responses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-3215","authenticated-orcid":false,"given":"Paolo","family":"Spinnato","sequence":"first","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Mario","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Maria","family":"Carpenzano","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Gabriele","family":"Bilancia","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6440-3090","authenticated-orcid":false,"given":"Nicola","family":"Marrone","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Annamaria","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Maddalena Di","family":"Carlo","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-6705","authenticated-orcid":false,"given":"Emanuela","family":"Palmerini","sequence":"additional","affiliation":[{"name":"Osteoncology, Soft Tissue and Bone Sarcomas, Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33124, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-1034","authenticated-orcid":false,"given":"Luca","family":"Cevolani","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-2807","authenticated-orcid":false,"given":"Marco","family":"Colangeli","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8080-4484","authenticated-orcid":false,"given":"Marco","family":"Gambarotti","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40316 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1074-0155","authenticated-orcid":false,"given":"Alberto","family":"Righi","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40316 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-3777","authenticated-orcid":false,"given":"Alessandra","family":"Longhi","sequence":"additional","affiliation":[{"name":"Osteoncology, Soft Tissue and Bone Sarcomas, Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.4103\/0019-5413.132491","article-title":"Classification, imaging, biopsy and staging of osteosarcoma","volume":"48","author":"Kundu","year":"2014","journal-title":"Indian J. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1148\/rg.210171","article-title":"Pediatric Osteosarcoma: Correlation of Imaging Findings with Histopathologic Features, Treatment, and Outcome","volume":"42","author":"Nguyen","year":"2022","journal-title":"Radiographics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/MOP.0000000000001535","article-title":"Management of pediatric bone sarcomas","volume":"38","author":"Elliott","year":"2026","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S1470-2045(26)00141-5","article-title":"European guideline for imaging of primary paediatric and adult osteosarcoma and Ewing sarcoma: Systematic review and joint statement by the FOSTER consortium, Euro Ewing Consortium, European Society of Paediatric Radiology, and the European Association of Nuclear Medicine","volume":"27","author":"Adriaansen","year":"2026","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Duczkowski, M., Duczkowska, A., Olwert, A., Michalak, E., Bilska, K., Klepacka, T., Rych\u0142owska-Pruszy\u0144ska, M., Raciborska, A., and Bekiesi\u0144ska-Figatowska, M. (2024). Predictors of pulmonary metastases on chest computed tomography in children and adolescents with osteosarcoma-tips for qualifying patients for thoracotomy. BMC Pediatr., 24.","DOI":"10.1186\/s12887-024-04858-0"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cromb\u00e9, A., Simonetti, M., Longhi, A., Hauger, O., Fadli, D., and Spinnato, P. (2024). Imaging of Osteosarcoma: Presenting Findings, Metastatic Patterns, and Features Related to Prognosis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13195710"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1016\/j.ejrad.2015.09.022","article-title":"The many faces of pulmonary metastases of osteosarcoma: Retrospective study on 283 lesions submitted to surgery","volume":"84","author":"Ciccarese","year":"2015","journal-title":"Eur. J. Radiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e240703","DOI":"10.1148\/radiol.240703","article-title":"Calcified Osteosarcoma Lung Metastases","volume":"312","author":"Spinnato","year":"2024","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ejrad.2008.03.001","article-title":"\u201cBubble-like\u201d lung metastases in osteosarcoma patients","volume":"71","author":"Briccoli","year":"2009","journal-title":"Eur. J. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1007\/s11547-025-02008-9","article-title":"New insights into imaging of pulmonary metastases from extra-thoracic neoplasms","volume":"130","author":"Cicchetti","year":"2025","journal-title":"Radiol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chiesa, A.M., Spinnato, P., Miceli, M., and Facchini, G. (2021). Radiologic Assessment of Osteosarcoma Lung Metastases: State of the Art and Recent Advances. Cells, 10.","DOI":"10.3390\/cells10030553"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2967\/jnumed.117.190595","article-title":"18F-FDG Uptake During Early Adjuvant Chemotherapy Predicts Histologic Response in Pediatric and Young Adult Patients with Osteosarcoma","volume":"59","author":"Davis","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1148\/radiol.2017162758","article-title":"Prognostic Value of Metabolic and Volumetric Parameters of FDG PET in Pediatric Osteosarcoma: A Hypothesis-generating Study","volume":"287","author":"Im","year":"2018","journal-title":"Radiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.2967\/jnumed.109.062356","article-title":"18F-FDG PET SUVmax correlates with osteosarcoma histologic response to neoadjuvant chemotherapy: Preclinical evaluation in an orthotopic rat model","volume":"50","author":"Dutour","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/bjc.2017.453","article-title":"Indeterminate nodules in osteosarcoma: What\u2019s the follow-up?","volume":"118","author":"Ghosh","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.jpedsurg.2010.11.027","article-title":"Do characteristics of pulmonary nodules on computed tomography in children with known osteosarcoma help distinguish whether the nodules are malignant or benign?","volume":"46","author":"Brader","year":"2011","journal-title":"J. Pediatr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1016\/j.ejca.2005.03.036","article-title":"Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution","volume":"41","author":"Bacci","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1385\/MO:23:4:455","article-title":"Diffuse calcification of metastases after intensive multiagent chemotherapy in widespread osteosarcoma leading to death in a 18-year-old male: Report of a case and literature review","volume":"23","author":"Gassiamis","year":"2006","journal-title":"Med. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38","DOI":"10.21037\/aoj-20-70","article-title":"Osteosarcoma mineralization changes on radiographs have moderate correlation to chemotherapy response using bone subtraction methodology","volume":"5","author":"Henderson","year":"2020","journal-title":"Ann. Jt."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1148\/radiology.143.2.6978499","article-title":"Radiographic changes in primary osteogenic sarcoma following intensive chemotherapy. Radiological-pathological correlation in 63 patients","volume":"143","author":"Smith","year":"1982","journal-title":"Radiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1007\/s00247-025-06410-3","article-title":"Lung nodules in pediatric osteosarcoma: Calcification as the most reliable radiological indicator to confirm metastasis","volume":"55","author":"Benavent","year":"2025","journal-title":"Pediatr. Radiol."},{"key":"ref_22","first-page":"e20220433","article-title":"CT features of osteosarcoma lung metastasis: A retrospective study of 127 patients","volume":"49","author":"Silva","year":"2023","journal-title":"J. Bras. Pneumol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4103\/1817-1737.62469","article-title":"The calcified lung nodule: What does it mean?","volume":"5","author":"Khan","year":"2010","journal-title":"Ann. Thorac. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00247-007-0735-3","article-title":"Unusual thoracic CT manifestations of osteosarcoma: Review of 16 cases","volume":"38","author":"Rastogi","year":"2008","journal-title":"Pediatr. Radiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8417","DOI":"10.21037\/jtd-24-1015","article-title":"Association of CT characteristics of osteosarcoma lung metastases with spontaneous pneumothorax: A retrospective analysis","volume":"16","author":"Li","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/MPH.0000000000000753","article-title":"Pulmonary Nodule Size < 5 mm Still Warrants Investigation in Patients with Osteosarcoma and Ewing Sarcoma","volume":"39","author":"Kusma","year":"2017","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e23506","DOI":"10.1200\/JCO.2021.39.15_suppl.e23506","article-title":"Metastatic osteosarcoma at diagnosis: Analysis of 92 cases from a single institution","volume":"39","author":"Longhi","year":"2021","journal-title":"J. Clin. Oncol."}],"container-title":["Clinics and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-7283\/16\/9\/161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:10:33Z","timestamp":1787922633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-7283\/16\/9\/161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":27,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["clinpract16090161"],"URL":"https:\/\/doi.org\/10.3390\/clinpract16090161","relation":{},"ISSN":["2039-7283"],"issn-type":[{"value":"2039-7283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}