BackgroundIdiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF.MethodsAn IPF-cohort (treated with pamrevlumab for 48 weeks) was retrospectively studied using FRI. Serial CT’s were compared from 66 subjects. Post-hoc analysis was performed using FRI, FVC and mixed effects models.ResultsLung volumes, determined by FRI, correlated with FVC (lower lung volumes with lower FVC) (R2 = 0.61, p < 0.001). A negative correlation was observed between specific image based airway radius (siRADaw) at total lung capacity (TLC) and FVC (R2 = 0.18, p < 0.001). Changes in FVC correlated significantly with changes in lung volumes (R2 = 0.18, p < 0.001) and siRADaw (R2 = 0.15, p = 0.002) at week 24 and 48, with siRADaw being more sensitive to change than FVC. Loss in lobe volumes (R2 = 0.33, p < 0.001), increasing fibrotic tissue (R2 = 0.33, p < 0.001) and airway radius (R2 = 0.28, p < 0.001) at TLC correlated with changes in FVC but these changes already occur in the lower lobes when FVC is still considered normal.ConclusionThis study indicates that FRI is a superior tool than FVC in capturing of early and clinically relevant, disease progression in a regional manner.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0918-5) contains supplementary material, which is available to authorized users.
PurposePancreatic ductal adenocarcinomas exhibit a high degree of desmoplasia due to extensive extracellular matrix deposition. Encasement of mesenteric vessels by stroma in locally advanced pancreatic cancer (LAPC) prevents surgical resection. This study sought to determine if the addition of a monoclonal antibody to connective tissue growth factor, pamrevlumab, to neoadjuvant chemotherapy would be safe and lead to improved resectability in this surgically adverse patient population.MethodsIn this phase I/II trial, 37 patients with LAPC were randomised 2:1 to gemcitabine/nab-paclitaxel plus (Arm A, n=24) or minus (Arm B, n=13) pamrevlumab. Those who completed six cycles of treatment were assessed for surgical eligibility by protocol-defined criteria. Resection rates, progression-free and overall survival were evaluated.ResultsEighteen (75%) patients in Arm A and seven (54%) in Arm B completed six cycles of therapy with similar toxicity patterns. In Arms A and B, carbohydrate antigen 19–9 response, as defined by ≥50% decline from baseline, occurred in 13 (65%) and 5 (42%), respectively. Sixteen (16%) per cent of patients were radiographically downstaged by National Comprehensive Cancer Network criteria (5 in Arm A (21%) and 1 (8%) in Arm B). Positron emission tomography normalised in 9 (38%) vs 3 (23%) of patients in Arm A vs Arm B, respectively, and correlated with surgical exploration. Eligibility for surgical exploration was 17 (71%) vs 2 (15%) (p=0.0019) and resection was achieved in 8 (33%) vs 1 (8%) of patients in Arm A vs Arm B (p=0.1193), respectively. Postoperative complication rates were not different between arms.ConclusionsNeoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.