Scleroderma-related interstitial lung disease is a major contributor to morbidity and mortality in severe systemic sclerosis (SSc). A new study found that myeloablative therapy followed by hematopoietic stem cell transplant (HSCT) in SSc improves quantitative lung computed tomography (CT) measures. Moreover, lung imaging improvements after myeloablative HSCT continue for up to 5 years.
Keith M. Sullivan, MD, from the Duke Cancer Institute and Duke School of Medicine in Durham, NC, presented these findings at the 2018 American College of Rheumatology and Association of Rheumatology Health Professionals Annual Meeting, held October 19 to 24 in Chicago, IL. Jonathan G. Goldin, MD, of the David Geffen School of Medicine in Santa Monica, CA, is the lead author of the study.
The study adds to findings from the Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial that demonstrated improved long-term survival of individuals with SSc treated with myeloablative HSCT compared to conventional treatment with intravenous cyclophosphamide. Goldin and colleagues wanted to further assess changes in scleroderma-related interstitial lung disease (SLD) in the SCOT trial.
Serial high-resolution CT scans were performed at least yearly in participants for up to 5 years; a total of 292 scans were performed. Sullivan emphasized that the CT scan process was tightly controlled to ensure high-quality scans even though SCOT was a multicenter trial. The same CT scan machines at each center were used for all time points, and all CT machines were standardized; standardized protocols were followed for thin-section thoracic imaging, as well. Independent radiographers judged the quality of the scans, determining that two-thirds of the obtained CT scans were “excellent” in quality and nearly one-third were considered “acceptable.”
“There is a specific process to provide quantitative scoring of sclerodermal lung disease on these high-resolution CTs,” Sullivan told attendees. “The first steps are making sure you have excellent image quality, then you segment the lung, then you de-noise the image, and what you’re left with is an algorithm and software that can look at pixels in the display and separate out normal pixels and those associated with fibrosis, honeycomb, or ground glass [patterns],” associated with SLD.
The sum of the percentages of those individual patterns—quantitative ground glass (QGG), quantitative lung fibrosis (QLF), and quantitative honeycomb (QHC)—adds up to the quantitative interstitial lung disease (QILD) score. This methodology has been recently validated in the radiologic community, Sullivan commented.
At baseline, there were no statistically significant differences in the quantitative imaging scores of either whole lung or most severely affected lobe between participants treated with cyclophosphamide and those who had undergone HSCT. The ground glass pattern was the most prominent pattern in SSc in combination with associated fibrosis, and minimal honeycomb patterning. Two-thirds of participants had more than 10% fibrosis in the most severely affected lung lobe.
The analysis of whole-lung results from all 75 participants demonstrated that QILD in the HSCT group markedly decreased to -3% by year 1 and continued to decrease to about -7% by year 5. In the same group, QLF remained stable over the 5 years with a slight negative direction. The cyclophosphamide-treated group showed an initial decrease in QILD at 6 months, but QILD stabilized or slightly increased over 5 years. Moreover, QLF increased by year 2 by approximately 4% in the cyclophosphamide group and remained at this level to year 5. A similar trend was seen in the quantitative analysis of the most severely affected lobe.
“These data are from all patients starting the study,” Sullivan commented. “But the [SCOT TRIAL] cyclophosphamide group had more failures and more early deaths…these are meaningful associations, especially since the worst-affected patients in one treatment group didn’t make it to the month 54 endpoint.”
Researchers also wanted to see if changes in QILD correlated directly with pulmonary function. “Pulmonary function should have gotten better in patients whose quantitative lung scores improved,” Sullivan said. Indeed, researchers found that improvements in forced vital capacity, forced expiratory capacity, and diffusing capacity for carbon monoxide correlated with improvement in QILD scores in participants who underwent HSCT. As expected, pulmonary function did not improve over time in the cyclophosphamide treatment group.
“Changes in quantitative lung CT scoring of scleroderma lung disease provide an objective radiologic validation of the long-term benefits of transplant compared to cyclophosphamide in individuals with severe scleroderma and lung involvement,” Sullivan concluded. “Improvement in imaging after transplant continues for up to 54 months after randomization, giving radiologic confirmation of a durable treatment benefit.”
Source: Goldin J, Keyes-Elstein L, Crofford L, et al. Changes in quantitative scleroderma lung CT measures in patients treated with cyclophosphamide or transplantation. Presented at: 2018 ACR/ARHP Annual Meeting; October 19-24; Chicago, IL. Abstract 901.