Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study

Abstract

BackgroundInterstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA.MethodsBetween April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA.ResultsThirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA.ConclusionsThis is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to determine the risk factors for ILD-AA in advanced lung cancer patients. ΔSP-D might be a serum prognostic biomarker of ILD-AA. Clinicians should evaluate serum SP-D during chemotherapy and should carefully monitor the clinical course in patients with high ΔSP-D.

Drug-Induced Interstitial Lung Disease: A Systematic Review

“…A prospective study of 42 patients with DIILD undergoing transbronchial lung biopsy (TBLB) or bronchoalveolar lavage (BAL) reported an overall diagnostic agreement of 67% [ 15 ], while a retrospective analysis of patients with DIILD undergoing TBLB ( n = 4) or open biopsy ( n = 16) at a single centre reported a lower diagnostic agreement (45%) [ 119 ]. In contrast, CT features of diffuse alveolar damage (DAD) are highly congruous with histopathological features of DAD [ 1 ] and confer high mortality [ 33 , 39 , 80 , 90 , 94 , 95 , 121 , 122 ]. In general, the correlation imaging pattern of CT and pathology is suboptimal [ 119 ].…”

“…Other: For BAL, the presence of desquamated type II pneumocytes is associated with mortality [ 16 ]. Others have also found that circulating and/or BAL KL-6 and heat shock protein 47 are associated with higher mortality [ 12 , 119 , 121 , 122 ]. Their association with a more severe clinical presentation and with DAD, however, means that their incremental value as prognostic markers remains unclear.…”

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma

“…Inversely, SFTPB and SFTPC are hydrophobic proteins with the capacity of mitigating surface tension in the lung [12]. Strikingly, it has been proposed that SFTPD expression was associated with tumour progression and survival of patients with lung cancer [13][14][15]. Furthermore, recent evidence also showed that SFTPD could suppress the progression of pancreatic cancer by inducing epithelial-mesenchymal-transition (EMT) and apoptosis of pancreatic cancer cells [16,17].…”

Fibrotic lung toxicity induced by cytotoxic drugs, radiation and immunotherapy in patients treated for lung cancer

“…Recently, a similar predictive role of Surfactant Protein D (SP-D) for onset of ILD induced by anticancer agents was compared with KL 6 in an interesting case control study [18]. Nakamura et al also reported that SP-D was associated with worse prognosis and development of diffuse alveolar damage [18].…”

“…KL 6 is typically elevated in patients with idiopathic interstitial pneumonia and in certain cases of cancer, and may therefore be useful for evaluating disease activity and clinical outcome in patients with ILD-IPF: it could predict the likelihood of radiation pneumonitis or lung toxicity induced by chemotherapy [15][16][17][18][19][20]. Recently, a similar predictive role of Surfactant Protein D (SP-D) for onset of ILD induced by anticancer agents was compared with KL 6 in an interesting case control study [18]. Nakamura et al also reported that SP-D was associated with worse prognosis and development of diffuse alveolar damage [18].…”