Prospective Long-Term Follow-Up of Pulmonary Diffusion Capacity Reduction Caused by Dose-Dense Chemotherapy in Patients with Breast Cancer

Abstract

Background Our previous study of pulmonary function in 34 patients with early breast cancer without preexisting lung disease showed that anthracycline- and taxane-based adjuvant dose-dense chemotherapy (DDC) caused a significant 16.4% mean reduction in carbon monoxide diffusing capacity (DLCO). The present study reports the pulmonary and oncological outcomes of these patients on long-term follow-up. Patients and methods The primary endpoint was DLCO measured by the pulmonary function test (PFT) performed at a median of 27 months after DDC (range, 8–97) in 25 patients without disease recurrence. DLCO values were recorded as a percentage of predicted values according to age, height, and hemoglobin level and analyzed relative to baseline pre-DDC DLCO values. The secondary endpoints were symptoms, additional therapies, and cancer outcomes during a median of 11 years' follow-up (range, 4.4–11.4). Results A longitudinal general linear model showed significant effects of time on DLCO and its trend (F(1, 87) = 14.68, p < 0.001 and F(1, 87) = 10.26, p=0.002, respectively). Complementary descriptive analysis showed a significant recovery on the follow-up PFT (75.6% vs. 81.9%, p=0.002), but it was still significantly lower than the baseline DLCO (81.9% vs. 92.0%, p=0.003). Five patients (20%) still showed a >20% relative DLCO reduction from baseline. Patients with dyspnea or fatigue at later clinical follow-up had a significantly lower DLCO value on the follow-up PFT than nonsymptomatic patients (80.5% vs. 92.1%, p=0.02). DLCO recovery was inversely correlated with age (R = −0.39, p=0.05), but no significant correlation was found with the length of time until the follow-up PFT or additional therapies. There was no association of DDC-related DLCO reduction with cancer outcomes. Conclusions The significant reduction in DLCO seen after DDC in patients with potentially curable breast cancer is evident years afterwards, especially in older patients. While most patients partly recover, some will have a lasting symptomatic DLCO impairment.

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors

“…The latter was reduced, in particular, in subjects who had received intravenous high-dose courses of chemotherapy for malignant blood disorders prior to allo-HSCT. This finding is in line with reports from various other studies indicating that DL CO is the most sensitive test for detecting chemotherapy-induced lung injury [30][31][32][33][34][35]. In previous studies, we have found impaired gas diffusing capacity in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation [33] and in very long-term adult survivors of childhood acute lymphoblastic leukemia [34].…”

“…In previous studies, we have found impaired gas diffusing capacity in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation [33] and in very long-term adult survivors of childhood acute lymphoblastic leukemia [34]. Late adverse effects of chemotherapy on gas diffusing capacity have also been shown in patients treated for lung cancer [32] and breast cancer [35]. Although the underlying mechanisms of cytotoxic lung injury are multifactorial and remain unclear, it is thought that microvascular damage may be a common denominator and an important feature [30, 31].…”

Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer

“…Therefore, DLCO was thought to have the highest radiosensitivity; additionally, to the best of our knowledge, significant lung dose-volume relationships after SRT with ΔDLCO and ΔDLCO/VA have not been previously reported. Although there were conflicting results for DLCO after SRT, it may be difficult to measure ΔDLCO in a retrospective design because DLCO is a vulnerable parameter and can be affected by chemotherapy agents [31,32]. Stephans et al reported correlations of lung ΔFEV1% predicted with lung V5 Gy (cc) and V10 Gy (cc), but there was no correlation between ΔDLCO and lung dose-volume parameters in SRT [33].…”