Interstitial lung disorders following postoperative radiotherapy with concurrent or sequential hormonal therapy for breast cancer: a nationwide database study in Japan.

BACKGROUND: Hormonal therapy and radiotherapy are conducted concurrently or sequentially after breast cancer surgery. It remains unclear whether concurrent or sequential treatment is safer in terms of lung complications. Using a Japanese nationwide database, this study aimed to compare the occurrence of severe lung complications between concurrent and sequential treatments. METHODS: We identified patients who underwent partial mastectomy for stage 0-III breast cancer from July 2010 to March 2020 and received adjuvant hormonal therapy and radiotherapy concurrently (n = 1851) or sequentially (n = 18,429). Two propensity score analyses (1:4 matching and overlap weighting) were conducted to compare hospitalization for radiation pneumonitis and pneumonia within 1 year after surgery, and intensive care unit admission and mortality during the hospitalization. We conducted additional analyses stratified by hormonal drugs (aromatase inhibitors and tamoxifen). RESULTS: The propensity score-matched analysis showed no significant differences in occurrence of hospitalization for radiation pneumonitis (0.27 vs. 0.58%, p = 0.10) and pneumonia (0.16 vs. 0.58%, p = 0.05) between the concurrent and sequential treatments. The overlap propensity score-weighted analysis also showed no significant differences (0.25 vs. 0.56%, p = 0.08 and 0.15 vs. 0.44%, p = 0.06, respectively). Intensive care unit admission and in-hospital mortality did not differ significantly between the two treatments. The stratified analysis showed similar results. CONCLUSION: Our propensity score analyses revealed no significant differences in severe lung complications between concurrent and sequential hormonal therapy with radiotherapy following breast cancer surgery, regardless of the type of hormonal drugs. Clinicians can provide concurrent or sequential treatment with equivalent attention to early lung complications.

Therapeutic effects of bone marrow-derived mesenchymal stem cells on radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a fatal condition featured by interstitial pneumonitis and fibrosis. Mesenchymal stem cells (MSCs) have been widely used for treating RILI in rodent models. In the present study, we aimed to investigate whether the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on RILI were in a dose-dependent manner. A total of 100 mice were randomly divided into: a control group (n=25), subject to lung irradiation and injection of phosphate-buffered solution (PBS) via the tail vein; and the hBM-MSC group, subject to lung irradiation followed by injection of a low dose (1x103 hBM-MSCs/g), medium dose (5x103 hBM-MSCs/g) and high dose (1x104 hBM-MSCs/g) of hBM-MSCs in PBS through the tail vein, respectively. After sacrifice, the pulmonary tissues were subject to hematoxylin and eosin (H&E) staining, Masson's trichrome staining and immunohistochemical staining to investigate the pathological changes. Immunofluorescent staining was performed to evaluate the differentiation capacity of hBM-MSCs in vivo by analyzing the expression of SPC and PECAM. hBM-MSCs improved the survival rate and histopathological features in the irradiated mice, especially in the low-dose group. Marked decrease in collagen deposition was noted in the irradiated mice treated using a low dose of hBM-MSCs. In addition, hBM-MSCs attenuated secretion and expression of IL-10 and increased the expression of TNF-α. Furthermore, hBM-MSCs had the potential to differentiate into functional cells upon lung injury. Low-dose hBM-MSCs contributed to functional recovery in mice with RILI.

Impact of Interstitial Changes on Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Lung Cancer.

AIM: The aim of the present study was to evaluate the impact of interstitial changes (IC) on radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer. PATIENTS AND METHODS: We analyzed 260 consecutive patients with primary lung cancer treated with SBRT. According to the presence or absence of IC on the pre-treatment computed tomography, patients were divided into two groups: an IC group (n=18) and a non-IC group (n=242). RESULTS: RP of grade 2 or more was observed in 9 (50.0%) and 14 (6.7%) patients in the IC and non-IC group, respectively. All three patients with grade 5 RP were in the IC group. As indicated by multivariate analysis, the presence of IC was the only significant predictive factor of RP of grade 2 or more. CONCLUSION: The presence of IC was a significant indicator of grade 2 or more RP after SBRT for patients with lung cancer.

Experimental treatment of radiation pneumonitis with human umbilical cord mesenchymal stem cells.

OBJECTIVE: To evaluate of the curative effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on rat acute radiation pneumonitis. METHODS: Fourty rats were randomly divided into control group, radiation group, stem cell prevention group, stem cell treatment group and prednisone treatment group. All rats except those in the control group were radiated with X ray to establish the acute radiation pneumonitis damage model. The hUC-MSCs cultured in vitro was administrated to the rats of the prevention group via tail vein (1×10(6) cells/kg BW) 24 h before the radiation, while the same administration was performed in the rats of the treatment group 24 h after the radiation. After 24 h post the radiation, the rats in the radiation group were given 0.4 mL physiological saline, and those in the prednisone group were given 1 mg/kg prednisone. All rats were observed and executed 72 h after the radiation to detect lung histological changes. RESULTS: After the administration of hUC-MSCs, the survival status of the rats in the prevention group and treatment group was obviously better than that in the control group. As shown by the histological staining, the morphology, proliferation activity and bronchial state of lung tissues were better in the prevention group and treatment group than in the control group. CONCLUSIONS: The hUC-MSCs have definite therapeutic effects on acute radiation pneumonitis in rats.

Fibrotic changes after postmastectomy radiotherapy and reconstructive surgery in breast cancer. A retrospective analysis in 109 patients.

PURPOSE: The purpose of this study was to analyze the probability and time course of fibrotic changes in breast reconstruction before or after postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Between 1995 and 2004, 109 patients were treated with PMRT at Tübingen University and underwent heterologous (HL) or autologous (AL) breast reconstruction prior or subsequent to radiation therapy. Fibrosis of the reconstructed breast after radiotherapy was assessed using the Baker score for HL reconstructions and the Common Terminology Criteria for Adverse Events (CTCAE) for all patients. Actuarial rates of fibrosis were calculated for the maximum degree acquired during follow- up and at the last follow-up visit documented. RESULTS: Median time to follow-up was 34 months (3-227 months). Radiotherapy was applied with a median total dose of 50.4 Gy. A total of 44 patients (40.4%) received a boost treatment with a median dose of 10 Gy. Breast reconstruction was performed with AL, HL, or combined techniques in 20, 82, and 7 patients, respectively. The 3-year incidence of ≥ grade III maximum fibrosis was 20% and 43% for Baker and CTCAE scores, respectively. The corresponding figures for fibrosis at last follow-up visit were 18% and 2%. The 3-year rate of surgical correction of the contralateral breast was 30%. Initially unplanned surgery of the reconstructed breast was performed in 39 patients (35.8%). Boost treatment and type of cosmetic surgery (HL vs. AL) were not significantly associated with the incidence of fibrosis. CONCLUSIONS: We found severe fibrosis to be a frequent complication after PMRT radiotherapy and breast reconstruction. However, surgical intervention can ameliorate the majority of high grade fibrotic events leading to acceptable long-term results. No treatment parameters associated with the rate of fibrosis could be identified.

Possibilities for the use of autologous mesenchymal stem cells in the therapy of radiation-induced lung injuries.

Possible therapeutic effect of systemic (intravenous) transplantation of autologous mesenchymal stem cells was studied in experiments (C57Bl/6 mice) and pilot clinical trial. Clinical trial was performed on 11 patients with radiation-induced lung injuries developed after combined chemotherapy and radiation therapy for lymphogranulomatosis or breast cancer. The patients were subjected to single transplantation of mesenchymal stem cells and course of standard pharmacotherapy. The method for isolation of autologous mesenchymal stem cells was licensed. The transplantation of mesenchymal stem cells was followed by a decrease in the mortality rate of mice with radiation-induced lung injury. Clinical trial showed that cell therapy with autologous mesenchymal stem cells does not induce progression of the underlying oncological disease. Parameters of spirography, immune status, lung scintigraphy, and markers for inflammation and tissue hypoxia in the patients remained practically unchanged 1 year after the treatment. These clinical signs reflect stabilization of the radiation process.