title: Time and dose-related changes in radiological lung density after concurrent chemoradiotherapy for lung cancer.
abstract: Radiation pneumonitis is an important cause of morbidity after concurrent thoracic chemoradiotherapy (CCRT). However, asymptomatic changes in lung density on computed tomography (CT)-scans occur more commonly, and correspond to regions of inflammatory changes. Characterization of dose- and time-related changes in radiological lung density (RLD) may facilitate improved radiation planning, and allow for a more objective measure for assessing damage. We studied changes in RLD following CCRT with cisplatin-etoposide, using deformable registration to co-register follow-up scans. All CT-scans performed for up to 24 months post-treatment were evaluated in 25 patients treated with CCRT for stage III non-small-cell lung cancer. A total of 104 scans (median of 3 per patient) were co-registered with planning scans using a deformable registration tool (VelocityAI, Atlanta, USA). Last follow-up scan was at median 9.4 months (range 3.4-22.6 months). Seven patients developed clinical radiation pneumonitis. RLD changes (in Hounsfield units) were measured in regions receiving 3-66Gy. Linear mixed models were used to study dose-density changes over time. No significant changes in RLD were observed in the first 3 months post-treatment. Increases in RLD were observed at 3-6 months (p<0.0001) and 6-12 months (p=0.006), but stabilized at 1 year. Increases were most evident in regions receiving >30Gy, with only minor density changes at lower dose levels. Planning target volume size was significantly associated with RLD changes (p=0.03). Limiting lung doses to ≤30Gy during CCRT may limit sub-clinical damage, and the time-course of RLD changes may allow for early quantification of pulmonary damage when evaluating novel treatment strategies.
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands. E.Phernambucq@vumc.nl
authors.forename: Erik C J
authors.initials: EC
authors.lastname: Phernambucq
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.forename: Andrew
authors.initials: A
authors.lastname: Vincent
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Suresh
authors.initials: S
authors.lastname: Senan
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017564:Radiation Pneumonitis / Q000209:etiology; D011879:Radiotherapy Dosage; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D005047:Etoposide; D002945:Cisplatin