Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease.

BACKGROUND: We aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy. METHODS: We retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS: The median follow-up duration was 15 months (range: 3-47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09-347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group. CONCLUSIONS: This study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.

Clinical Outcomes of Stereotactic Ablative Radiotherapy for All Stages of Non-Small Cell Lung Cancer; Definitive versus Consolidative.

Background and Objectives: Stereotactic ablative radiotherapy (SABR) is not confined to early stage non-small cell lung cancer (NSCLC) and has a potential role in stage IV disease. We aimed to evaluate the effect of SABR on local control rates and survival outcomes in patients with all stages of NSCLC according to the treatment aim. Materials and Methods: We retrospectively reviewed the medical records of 88 patients with NSCLC who received SABR at the Korea University Guro Hospital between January 2015 and March 2021. Among these, 64 patients with stage I-II NSCLC ineligible for surgery were treated with a definitive aim. Twenty-four patients with stage IV limited metastatic NSCLC showing a favorable response to prior systemic therapy were treated with a consolidative aim. Results: The median follow-up time was 34 (range: 5-88) months. Thirty-one patients developed recurrence (35.2%), with distant metastasis being the most common (25/31, 80.6%). In-field local recurrence occurred in four patients (4/88 patients, 4.5%). For patients treated with definitive SABR, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 91.8% and 58.6%, respectively. In patients treated with consolidative SABR, the 3-year OS and DFS rates were 86.7% and 53.8%, respectively. With respect to treatment-related pulmonary toxicity, grade 3 radiation pneumonitis incidence requiring hospitalization was 2.3% (2/88). Conclusions: Definitive SABR is appropriate for medically inoperable or high surgical risk patients with early stage NSCLC with acceptable treatment-related toxicities. Consolidative SABR improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC.

NAA10 as a New Prognostic Marker for Cancer Progression.

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.

Preliminary Results of Developing Imaging Complexity Biomarkers for the Incidence of Severe Radiation Pneumonitis Following Radiotherapy in Non-Small Cell Lung Cancer Patients with Underlying Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) has the potential to cause fatal pulmonary toxicity after radiotherapy and can increase the morbidity and mortality of non-small-cell lung cancer (NSCLC) patients. In this context, we aimed to develop imaging complexity biomarkers to predict the incidence of severe pulmonary toxicity in patients with NSCLC who have underlying IPF and are treated with radiotherapy. Methods: We retrospectively reviewed the medical records of 19 patients with NSCLC who had underlying IPF and were treated with radiotherapy at the Korea University Guro Hospital between March 2018 and December 2022. To quantify the morphometric complexity of the lung parenchyma, box-counting fractal dimensions and lacunarity analyses were performed on pre-radiotherapy simulation chest computed tomography scans. Results: Of the 19 patients, the incidence of grade 3 or higher radiation pneumonitis was observed in 8 (42.1%). After adjusting for age, sex, smoking status, histology, and diffusing capacity of the lung for carbon monoxide, eight patients with a lower fractal dimension showed a significantly higher hazard ratio of 7.755 (1.168-51.51) for grade 3 or higher pneumonitis than those with a higher fractal dimension. Patients with lower lacunarity exhibited significantly lower hazards in all models, both with and without adjustments. The lower-than-median lacunarity group also showed significantly lower incidence curves for all models built in this study. Conclusions: We devised a technique for quantifying morphometric complexity in NSCLC patients with IPF on radiotherapy and discovered lacunarity as a potential imaging biomarker for grade 3 or higher pneumonitis.

Clinical experience of consolidative radiotherapy for localized metastatic non-small cell lung cancer who showed favorable tumor response after systemic treatment.

BACKGROUND: Our study has aimed to assess the effects of consolidative high-dose radiotherapy on clinical outcomes in patients with localized metastatic non-small cell lung cancer (NSCLC) who showed favorable tumor response after systemic treatment. METHODS: We retrospectively reviewed the medical records of 83 patients with localized metastatic NSCLC, who received systemic therapy followed by consolidative local radiotherapy at the Korea University Guro Hospital between March 2017 and June 2022. In the current study, we defined localized metastatic disease as the presence of one to three metastatic sites at the time of diagnosis. And patients who showed favorable tumor response after systemic treatment, including oligo-progressive disease at the thoracic site which was amenable to curative high-dose local radiotherapy, were included. The planned total dose and fraction size mainly depended on the location of lesions. RESULTS: The median follow-up time after consolidative radiotherapy was 16 months (range: 5-52 months). The overall 2-year progression-free survival rates were 81.4%. Of 83 patients, only four (4.3%), treated with intensity-modulated radiation therapy, showed an in-field local recurrence. Interestingly, only one patient experienced a local failure among the 20 patients who showed an oligo-progressive disease at the thoracic site on the tumor response evaluation after systemic treatment. Regarding treatment-related pulmonary toxicity, three patients with grade-3 and one patient with grade-4 radiation pneumonitis were presented. CONCLUSIONS: If the disease is sufficiently controlled and localized by systemic therapy, local consolidative radiotherapy is thought to improves local control rates with acceptable treatment-related toxicities in patients with localized metastatic NSCLC, especially those with oligo-progressive disease.

Consolidative high-dose thoracic radiotherapy for limited metastatic nonsmall cell lung cancer: Focusing on oligo-progressive disease.

AIM: Prior clinical data have shown a significant survival benefit of consolidative local radiotherapy for patients with limited metastatic non-small cell lung cancer (NSCLC). Therefore, this study aimed to evaluate the impact of consolidative high-dose thoracic radiotherapy on local control rates and survivals in patients with limited metastatic NSCLC, especially focusing on oligo-progressive disease. METHODS: We retrospectively reviewed the medical records of 45 patients with limited metastatic NSCLC who received consolidative high-dose thoracic radiotherapy at the Korea University Guro Hospital between March 2015 and December 2020. In the current study, we included patients who showed partial response, stable disease, or oligo-progressive disease on tumor response evaluation after systemic treatment. All patients underwent stereotactic body radiation therapy (23 patients) or intensity-modulated radiation therapy (IMRT, 22 patients). RESULTS: The median follow-up time was 42 months (range: 5-88 months). The overall 2-year disease-free survival (DFS) and overall survival (OS) rates were 80.7% and 88.4%, respectively. Among the 45 patients, only two patients treated with IMRT showed in-field local recurrence. There was no local failure among the patients who showed oligo-progressive disease after systemic treatment. In addition, the response to systemic treatment was not a significant factor for either DFS or OS rates (p = .471 and p = .414, respectively) in univariate analysis. CONCLUSIONS: Consolidative high-dose thoracic radiotherapy improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC. It is also effective and should be considered in patients with oligo-progressive disease after systemic treatment.

Clinical Characteristics and Treatment Outcome of Peginterferon Plus Ribavirin in Patients Infected with Genotype 6 Hepatitis C Virus in Korea: A Multicenter Study.

BACKGROUND/AIMS: Because of the limited geographic distribution, there have been insufficient data regarding hepatitis C virus (HCV) genotype 6 in Korea. This study aimed to investigate the clinical characteristics and available treatment outcomes of patients with genotype 6 HCV in Korea. METHODS: From 2004 to 2014, data were collected from Korean patients infected with genotype 6 HCV in eight hospitals. RESULTS: Thirty-two patients had genotype 6 HCV. The median age was 44 years, and 6c was the most common subtype. The baseline median alanine transaminase level was 88 (21 to 1,019) IU/mL, and the HCV RNA level was 1,405,000 (96,500 to 28,844,529) IU/mL. Twenty-five patients were treated with peginterferon (PEG-IFN) and ribavirin. Three follow-up losses occurred. Additionally, 13 patients attained a sustained virologic response (SVR), seven patients relapsed, and two patients exhibited a null response. The SVR rates were 40% and 75% for the 24- and more than 48-week treatments, respectively, and five of the six patients who achieved a rapid virologic response (RVR) attained a SVR. CONCLUSIONS: Korean patients infected with genotype 6 HCV are relatively young, and 6c is the most common subtype. When treated with PEG-IFN and ribavirin, the SVR rate was 52%. Similar to other genotypes, a longer duration of treatment and attainment of RVR are important for SVR.

Establishment and characterization of three immortal bovine muscular epithelial cell lines.

We have established three immortal bovine muscular epithelial (BME) cell lines, one spontaneously immortalized (BMES), the second SV40LT-mediated (BMEV) and the third hTERT-mediated (BMET). The morphology of the three immortal cell lines was similar to that of early passage primary BME cells. Each of the immortal cell lines made cytokeratin, a typical epithelial marker. BMET grew faster than the other immortal lines and the BME cells, in 10% FBS-DMEM medium, whereas neither the primary cells nor the three immortal cell lines grew in 0.5% FBS-DMEM. The primary BME cells and the immortal cell lines, with the exception of BMES, made increasing amounts of p53 protein when treated with doxorubicin, a DNA damaging agent. On the other hand, almost half of the cells in populations of the three immortal cell lines may lack p16(INK4a) regulatory function, compared to primary BME cells that were growth arrested by enforced expression of p16(INK4a). In soft-agar assays, the primary cells and immortal cell lines proved to be less transformed in phenotype than HeLa cells. The three immortal epithelial-type cell lines reported here are the first cell lines established from muscle tissue of bovine or other species.

Establishment of immortal swine kidney epithelial cells.

Using normal swine kidney epithelial (SKE) cells that were shown to be senescent at passages 12 to 14, we have established one lifespan-extended cell line and two lifespan-extended cell lines by exogenous introduction of the human catalytic subunit of telomerase (hTERT) and simian virus 40 large T-antigen (SV40LT), all of which maintain epithelial morphology and express cytokeratin, a marker of epithelial cells. SV40LT- and hTERT-transduced immortal cell lines appeared to be smaller and exhibited more uniform morphology relative to primary and spontaneously immortalized SKE cells. We determined the in vitro lifespan of primary SKE cells using a standard 3T6 protocol. There were two steps of the proliferation barrier at 12 and 20, in which a majority of primary SKE cells appeared enlarged, flattened, vacuolated, and ss-galactosidase-positive, all phenotypical characteristics of senescent cells. Lifespan-extended SKE cells were eventually established from most of the cellular foci, which is indicative of spontaneous cellular conversion at passage 23. Beyond passage 25, the rate of population doubling of the established cells gradually increased. At passage 30, immortal cell lines grew faster than primary counterpart cells in 10% FBS-DMEM culture conditions, and only SV40LT-transduced immortal cells grew faster than primary and other SKE immortal cells in 0.5% FBS-DMEM. These lifespan-extended SKE cell lines failed to grow in an anchorage-independent manner in soft-agar dishes. Hence, three immortalized swine kidney epithelial cells that are not transformed would be valuable biological tools for virus propagation and basic kidney epithelial cell research.