title: Bleomycin-Induced Pulmonary Changes on Restaging Computed Tomography Scans in Two Thirds of Testicular Cancer Patients Show No Correlation With Fibrosis Markers.
abstract: In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, bleomycin-induced pneumonitis is a well-known and potentially fatal side effect. We sought to determine the prevalence of lesions as signs of bleomycin-induced pulmonary changes on restaging computed tomography (CT) scans after treatment and to ascertain whether fibrosis markers were predictive of these changes.
  
  
  
  This prospective nonrandomized cohort study included metastatic testicular cancer patients, 18-50 years of age, treated with BEP chemotherapy. Restaging CT scans were examined for lesions as signs of bleomycin-induced pulmonary changes by two independent radiologists and graded as minor, moderate, or severe. Plasma samples were collected before, during, and after treatment and were quantified for transforming growth factor-β1 (TGF-β1), growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP).
  
  
  
  In total, 66 patients were included: forty-five (68%) showed signs of bleomycin-induced pulmonary changes on the restaging CT scan, 37 of which were classified as minor and 8 as moderate. No differences in TGF-β1, GDF-15, or hs-CRP plasma levels were found between these groups.
  
  
  
  Bleomycin-induced pulmonary changes are common on restaging CT scans after BEP chemotherapy for metastatic testicular cancer. Changes in TGF-β1, GDF-15, and hs-CRP plasma levels do not differ between patients with and without radiological lesions as signs of bleomycin-induced pulmonary changes and are therefore not helpful as predictive biomarkers.
  
  
  
  Bleomycin-induced pneumonitis (BIP) is a well-known and potentially fatal side effect in metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin chemotherapy. Currently, the decision to discontinue bleomycin administration is made during treatment and is based on clinical signs. An upfront or early marker or biomarker that identifies patients likely to develop BIP would be preferable. This study found that bleomycin-induced pulmonary changes are common on restaging computed tomography scans and mostly resolve. No correlation was seen between these changes and fibrosis or inflammation markers (transforming growth factor-β1, growth differentiation factor-15, and high-sensitivity C-reactive protein).
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martha W
authors.initials: MW
authors.lastname: den Hollander
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nico-Derk L
authors.initials: ND
authors.lastname: Westerink
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sjoukje
authors.initials: S
authors.lastname: Lubberts
authors.affiliation: Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Alfons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Department of Pulmonology, University of Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rienhart F E
authors.initials: RF
authors.lastname: Wolf
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Renska
authors.initials: R
authors.lastname: Altena
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Nuver
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anna M E
authors.initials: AM
authors.lastname: Walenkamp
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands j.a.gietema@umcg.nl.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D002097:C-Reactive Protein / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005355:Fibrosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology; D055436:Growth Differentiation Factor 15 / Q000235:genetics; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011014:Pneumonia / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000503:physiopathology; D013736:Testicular Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D005047:Etoposide; D002097:C-Reactive Protein; D002945:Cisplatin
keywords: Bleomycin; Growth differentiation factor-15; Testicular neoplasms; Tomography, spiral computed; Toxicity; Transforming growth factor β1