Cancer Incidence in Pulmonary Vasculitis

Abstract

Pulmonary vasculitis is a potentially lethal autoimmune disease characterized by granulomatous inflammation of respiratory tract, necrotizing vasculitis affecting small-to medium-size vessels and antineutrophil cytoplasmic antibodies elevation. Typical therapy involves high-dose glucocorticosteroids combined with cyclophosphamide in a dose 1-2 mg/kg/per day. A high relapse rate in pulmonary vasculitis means prolonged courses of cyclophosphamide in some patients. Carcinogenic effects of cyclophosphamide, especially its toxic metabolite acrolein that is excreted into the urine, are responsible for the development of acute myeloid leukemia (AML) and bladder cancer. These and other malignancies are cyclophosphamide dose-depended. The aim of the present study was to assess the incidence of cancer in patients with pulmonary vasculitis in comparison with the incidence of cancer in the general population. Analyses were done according to the cumulative dose of cyclophosphamide, subdivided into low (≤35 g) and high (>35 g). During the observation period 15 cancers occurred. A significantly increased standardized incidence ratio (SIR) was observed for non-melanoma skin cancers (SIR 5.2; 95 % Cl 2.3-8.7), AML (SIR 4.3; 95 % Cl 2.1-11.2), and bladder cancer (SIR 3.4; 95 % Cl 1.6-5.2). Induction remission treatment and relapse treatment with cyclophosphamide involves a substantial risk of late appearing malignances in patients with pulmonary vasculitis. Monitoring and prophylactic management in pulmonary vasculitis after cessation of cyclophosphamide therapy is crucial.

Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

“…For example, in the Westman et al’s study[ 8 ], no case of skin cancer was observed during the first year of follow-up, however, the risk for NMSC was significantly associated with azathioprine therapy for more than 12 mouths (16-fold increase) and with glucocorticoids for more than 48 mouths (20-fold increase). Alternatively, subsequent studies in AASV were consistent with observations in the Westman et al’s study[ 10 , 12 ]. Furthermore, one study found that azathioprine might hasten the induction of NMSC by sensitising the skin cell genome to ultraviolet A radiation[ 24 ].…”

“…As shown in Fig 1 , our initial search rendered 2,762 potentially relevant articles, from which six cohort studies were included[ 8 – 12 , 14 ]. Three studies were monocentric cohorts[ 8 , 12 , 14 ], two study nationwide registry linkage[ 9 , 10 ], and one was a multinational study[ 11 ]. Among these studies, two were carried out in Sweden, one in Germany, one in Poland, one in Denmark and one in Europe and Mexico.…”

“…What’s more, different AASV types and sex ratio might contribute to the heterogeneity in our study. About 65% of the samples were patients with the GPA[ 9 , 10 , 14 ], 24% were with mixed GPA/MPA[ 8 , 11 ], and others with Pulmonary vasculitis[ 12 ]. The reported SIRs for cancers at all sites were 1.92(95%CI = 1.31–2.71) and 1.20(95%CI = 0.71–1.89) for GPA and MPA, respectively[ 11 ].…”

“…Much effort has been devoted to this field which demonstrated the SIRs for overall cancer has increased to more than 1.6 associated with AASV[ 6 , 8 – 13 ], but the risk of overall cancer appeared to be somewhat reduced in one study (SIR = 0.8, 95%CI = 0.5–1.4)[ 14 ]. Moreover, cancer type-specific analyses demonstrated an significantly increased risk of non-melanoma skin cancer (NMSC)[ 8 – 12 ], leukemia[ 9 – 12 ], and bladder cancer[ 6 , 9 – 12 , 15 ] in some studies. However, the reported risk is different.…”

Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer

“…Lung cancer is globally responsible for 1.4 million deaths annually and is the leading cause of cancer-related deaths in both women and men [1]. Approximately 80 % of the lung cancer patients have non-small cell lung cancer (NSCLC).…”