{"doi":"10.1016/j.chest.2021.11.033","title":"Early Radiographic Progression of Scleroderma","abstract":"BackgroundRadiographic end points commonly are included in therapeutic trials for systemic sclerosis (SSc)-interstitial lung disease (ILD); however, the relationship between these outcomes and long-term mortality is unclear.Research QuestionDo short-term changes in radiographic measures of ILD predict long-term survival in patients with SSc?Study Design and MethodsThe Scleroderma Lung Study (SLS) I and II evaluated the safety and efficacy of cyclophosphamide (in SLS I and II) and mycophenolate mofetil (in SLS II) for the treatment of SSc-ILD. Changes in the extent of ILD over time were assessed on high-resolution CT scans of the chest by quantitative image analysis, an approach that applies a computer-based algorithm to assess changes in the radiographic extent of ILD objectively. Participants subsequently were followed for up to 12 years (SLS I) and 8 years (SLS II). Cox proportional hazards models determined whether the change in the quantitative radiographic extent of ILD predicted survival, adjusting for other known predictors of survival.ResultsAmong SLS I and II participants, 82 and 90 had follow-up imaging scans, respectively, and were included in the analysis. Participants in both trials who showed an increase in the total quantitative radiographic extent of ILD scores of ≥ 2% at 12 months (SLS I) or 24 months (SLS II) experienced significantly worse long-term survival than those with change scores of < 2% (P ≤ .01, log-rank test). In the multivariate Cox models, radiographic progression remained associated with worse long-term survival in SLS I (P = .089) and SLS II (P = .014).InterpretationData from two independent clinical trial cohorts with extensive long-term follow-up demonstrated that radiographic progression of ILD over 12 to 24 months, in both treatment and placebo arms, can predict increased risk for long-term mortality in patients with SSc. These findings suggest that radiographic end points may serve as surrogates for mortality in SSc-ILD. Radiographic end points commonly are included in therapeutic trials for systemic sclerosis (SSc)-interstitial lung disease (ILD); however, the relationship between these outcomes and long-term mortality is unclear. Do short-term changes in radiographic measures of ILD predict long-term survival in patients with SSc? The Scleroderma Lung Study (SLS) I and II evaluated the safety and efficacy of cyclophosphamide (in SLS I and II) and mycophenolate mofetil (in SLS II) for the treatment of SSc-ILD. Changes in the extent of ILD over time were assessed on high-resolution CT scans of the chest by quantitative image analysis, an approach that applies a computer-based algorithm to assess changes in the radiographic extent of ILD objectively. Participants subsequently were followed for up to 12 years (SLS I) and 8 years (SLS II). Cox proportional hazards models determined whether the change in the quantitative radiographic extent of ILD predicted survival, adjusting for other known predictors of survival. Among SLS I and II participants, 82 and 90 had follow-up imaging scans, respectively, and were included in the analysis. Participants in both trials who showed an increase in the total quantitative radiographic extent of ILD scores of ≥ 2% at 12 months (SLS I) or 24 months (SLS II) experienced significantly worse long-term survival than those with change scores of < 2% (P ≤ .01, log-rank test). In the multivariate Cox models, radiographic progression remained associated with worse long-term survival in SLS I (P = .089) and SLS II (P = .014). Data from two independent clinical trial cohorts with extensive long-term follow-up demonstrated that radiographic progression of ILD over 12 to 24 months, in both treatment and placebo arms, can predict increased risk for long-term mortality in patients with SSc. These findings suggest that radiographic end points may serve as surrogates for mortality in SSc-ILD. Take-home PointsStudy Question: Do short-term changes in radiographic measures o","journal":"CHEST Journal","year":2021,"id":165141,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":216170,"name":"Donald P Tashkin","orcid":"0000-0002-5607-4872","position":1,"is_corresponding":false},{"id":348233,"name":"Michael D. Roth","orcid":"0000-0003-2194-6578","position":2,"is_corresponding":false},{"id":348235,"name":"Jonathan Goldin","orcid":"0000-0003-3007-9947","position":3,"is_corresponding":false},{"id":688709,"name":"Grace H.J. Kim","orcid":null,"position":4,"is_corresponding":false},{"id":348232,"name":"Elizabeth R. Volkmann","orcid":"0000-0003-3750-6569","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:45:36.425208Z","pmid":"34896093","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}