ABSTRACT
Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed in 1325 of 3170 patients (42%), of whom 72 (5%) later developed BOS. Eighty-four patients developed BOS without detection of pre-BOS by routine screening. Among patients with pre-BOS, after adjusting for other significant variables, airflow obstruction (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1 to 3.7; P = .02), percent-predicted FEV1 on decline (HR, .98; 95% CI, .97 to 1.0; P = .02), active cGVHD (HR, 7.7; 95% CI, 3.1 to 19.3; P < .001), peripheral blood stem cell source (HR, 3.8; 95% CI, 1.7 to 8.6; P = .001), and myeloablative conditioning (HR, 2.0; 95% CI, 1.1 to 3.5; P = .02) were associated with subsequent BOS. The absence of airflow obstruction and cGVHD had a negative predictive value of 100% at 6 months for subsequent BOS, but the positive predictive value of both factors was low (cGVHD, 3%; any obstruction, 4%; combined, 6%). Several clinical factors at the time of pre-BOS, particularly active cGVHD and airflow obstruction, increase the risk for subsequent BOS. These factors merit consideration to be included in screening practices to improve the detection of BOS, with the caveat that the predictive utility of these factors is limited by the overall low incidence of BOS among patients with pre-BOS.
Subject(s)
Bronchiolitis Obliterans Syndrome , Bronchiolitis Obliterans , Hematopoietic Stem Cell Transplantation , Pulmonary Disease, Chronic Obstructive , Humans , Bronchiolitis Obliterans/diagnosis , Bronchiolitis Obliterans/epidemiology , Bronchiolitis Obliterans/etiology , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors , Pulmonary Disease, Chronic Obstructive/complicationsABSTRACT
BACKGROUND: The tyrosine kinase inhibitor pazopanib is used for treatment of sarcoma. Recent studies have suggested that the use of pazopanib may lead to the development of pneumothorax, an unexpected adverse effect in patients with sarcoma metastatic to the chest. METHODS: We conducted a retrospective case control study of patients with sarcoma with metastases to the chest with pneumothorax (cases) and without pneumothorax (controls). The control population was selected from tumor registry in a 1:4 (cases to controls) ratio. The primary outcome of interest was the association between pazopanib and pneumothorax risk in patients with sarcoma metastatic to the chest. Secondary objective was to evaluate risk factors for pneumothorax. RESULTS: We identified 41 cases and 164 controls. Using purposeful selection method the odds of developing pneumothorax while being on pazopanib was not significant in univariate (p = .06) and multivariable analysis (p = .342). On univariate analysis risk factors of pneumothorax in patients with sarcoma were age, male sex, African American race, the presence of cavitary lung nodules/masses, and the presence of pleural-based nodules/masses. On multivariate analysis, only the presence of cavitary lung nodules/masses (P < .001) and the presence of pleural-based nodules/masses (P < .001) remained as risk factors for developing pneumothorax. CONCLUSION: Pazopanib does not increase the risk of pneumothorax in patients with sarcoma and evidence of metastatic disease to the chest. Presence of cavitary lung nodules/masses and the presence of pleural-based nodules/masses were found to be risk factors for pneumothorax.
Subject(s)
Pneumothorax/chemically induced , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/adverse effects , Sarcoma/drug therapy , Sulfonamides/adverse effects , Adult , Aged , Case-Control Studies , Female , Humans , Indazoles , Logistic Models , Lung Neoplasms/secondary , Male , Middle Aged , Pyrimidines/therapeutic use , Retrospective Studies , Risk Factors , Sulfonamides/therapeutic useABSTRACT
Transdifferentiation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) has been reported mostly in adenocarcinomas and has been described as a cause of acquired tyrosine kinase inhibitor (TKI) resistance. However, transdifferentiation has also been described in patients with different histologic characteristics and patients not exposed to TKIs and with no epidermal growth factor receptor (EGFR) mutation (the target of TKIs). To this date transdifferentiation remains poorly understood. We conducted a retrospective case series of patients who had biopsy-proven SCLC within 2 years after a diagnosis of NSCLC or in the same location as the known primary NSCLC. We found that 0.2% of lung cancer patients at our institution experienced transdifferentiation. Among these, 30 had adenocarcinoma and 16 had squamous cell carcinoma. In 27 of the 30 patients with adenocarcinoma (90%), SCLC was found in the same location as the known primary. In 14 of the 30 patients (47%), SCLC occurred within 2 years after the NSCLC diagnosis. In 12 of the 16 patients with squamous cell carcinoma (75%), SCLC was found in the same location as the known primary. In 8 of these 16 patients (50%), SCLC occurred within 2 years after the NSCLC diagnosis. Few patients with adenocarcinoma and none with squamous cell carcinoma were treated with TKIs or had an EGFR mutation. In conclusion the findings in the current study suggest that the discovery of SCLC histology after treatment of NSCLC may be more common than thought suggesting that further study is warranted to evaluate the phenomenon of transdifferentiation.
