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Objectives: Objectives: In this study, we define a medical service type that combines Western medicine, Korean medicine, and complementary and alternative medicine (CAM) as an integrated medical service. This study, as part of tertiary hospital-based integrated medical service model and clinical field application, aims to collect status and opinions on integrated medical service for medical staff in the field.Methods: This is a survey study, and was conducted on doctors from Kyung Hee University Hospital and Korean medicine doctors from Kyung Hee University Korean Medicine Hospital. Respondents were recruited on a first-come, first-served basis until the number of respondents reached 120. The investigation was conducted for a total of 16 days from October 4, 2021 to October 19, 2021 by e-mail.Results: Recognition of integrated medical services was confirmed to be 45.8%, and 49.2% responded positively to the necessity of it. As a group of diseases that require the establishment of integrated medical services in the future, 'disorders of musculoskeletal systems and connective tissues' was the highest. The most expected advantages of providing integrated medical services were 'increased satisfaction of patients and guardians' and 'increased treatment effects.’Conclusions: In this study, we investigated the perception of doctors and Korean medicine doctors on integrated medical services that combine Western medicine, Korean medicine, and CAM. It has been confirmed that medical staff generally have a positive perception of integrated medical services, and if the scientific basis for the effect of integrated medical services is supported, the rate of positive perception is expected to increase.

Purpose Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.Materials and Methods Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.Results A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Purpose: To analyze the clinical manifestations of thyroid-associated ophthalmopathy accompanied by thyroid cancer.Methods: We performed a retrospective chart review of 33 patients diagnosed at our ophthalmology department with both thyroid- associated ophthalmopathy and thyroid cancer. We performed thyroid function tests at the first visit and at diagnosis of the thyroid cancer, and recorded the type of thyroid cancer, thyroidectomy history, clinical activity score (CAS), exophthalmometry, margin reflex distance (MRD) 1, diplopia, follow-up duration of ophthalmopathy, and ocular treatments. We divided patients into two groups according to the time of diagnosis of thyroid ophthalmopathy and thyroid cancer.Results: The average age of the 33 patients was 45.55 years, and eight and 25 were males and females, respectively. The average CAS score, exophthalmometry measurement, and MRD1 were 2.00 ± 1.67, 19.28 ± 3.24 mm, and 4.52 ± 1.58 mm, respectively. Patients whose ocular symptoms preceded the diagnosis of thyroid cancer tended to have a higher thyroid hormone level, CAS score, and exophthalmometry measurement, and required more ocular treatments, compared to the other patients. The average thyroid auto-antibody levels were increased in both groups. In patients whose ophthalmopathy preceded the thyroid cancer, exophthalmometry measurements were significantly decreased after thyroidectomy.Conclusions: It is crucial to identify ophthalmopathy in association with thyroid cancer. Patients whose ocular symptoms started before the diagnosis of thyroid cancer may present with hyperthyroidism and severe ocular symptoms, and may need ocular treatments. Patients should be informed that thyroid-associated ophthalmopathy may develop after thyroidectomy or radioiodine therapy, and their ocular symptoms should be closely monitored.

Satoru Miura,1 Hyun Ae Jung,2 Shin Yup Lee,3 Seung Hyeun Lee,4 Min Ki Lee,5 Yong Chul Lee,6 Maximilian J Hochmair,7 Cheng-Ta Yang,8 Angela Märten,9 James Chih-Hsin Yang,10 Sanjay Popat11,12 1Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea; 5Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea; 6Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea; 7Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 10Department of Medical Oncology, National Taiwan University Cancer Center and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 11Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 12The Institute of Cancer Research, London, United KingdomCorrespondence: Sanjay Popat, Lung Unit, Royal Marsden National Health Service Foundation Trust, 203 Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom, Tel +44-20-7808-2132, Email sanjay.popat@rmh.nhs.ukObjective: Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies.Materials and Methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in “real-world” practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective.Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35– 88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥ 2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥ 2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5– 32.5) and 45.2 months (95% CI: 41.7– 71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥ 2 was 26.4 and 33.1 months, respectively.Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across “real-world” patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.Graphical Abstract: Keywords: EGFR, afatinib, osimertinib, sequential, T790M

Objectives: Currently, Korea’s medical services are divided into Western medicine and Korean medicine, and people who are not satisfied with the existing treatments are looking for complementary and alternative medicine(CAM). Therefore, this study attempted to confirm patients' perception of the ongoing collaborative treatment and integrated medical service that added CAM to collaborative treatment based on tertiary hospital users. So that we can confirm the expected advantage and disadvantage of integrated medical service system and the necessity of supporting medical expenses for it.Methods: The survey was conducted on 100 people who experienced tertiary hospital treatment and other 100 people who experienced both tertiary hospital treatment and Korean medicine treatment at the same period. The survey was conducted until the number of respondents in both group reached 100. The survey was conducted through e-mail and was conducted from September 27, 2021 to October 8, 2021.Results: For the advantages of collaborative treatment ‘increased in psychological stability,’ and for disadvantages ‘longer time spent for treatment’ were the most common. If integrated medical services are implemented in the future, expected advantages include ‘consideration of various treatments.’ and expected disadvantages include ‘increased medical cost.’ The needs to expand support for health insurance for integrated medical services were 75.5% among responders.Conclusions: We were able to find out the (expected) advantages and disadvantages of the collaborative medical care and the integrated medical system that medical users experienced or expected, also confirmed positive answers to the expansion of health insurance support for the integrated medical system.

Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance. Methods In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naive patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR). Results At the start of afatinib treatment, median age (range) was 62 years (34–88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0–30.2) and median OS was 36.5 months (95% CI: 32.9–41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups. Conclusion Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.

Purpose The purpose of this study is to analyze bilateral changes of matrix metalloproteinase-9 (MMP-9) expression in the tear film in patients with unilateral neurotrophic keratitis. Methods We included 24 eyes from 24 subjects with normal corneal sensitivity according to Cochet-Bonnet corneal esthesiometry in the control group and 25 subjects with the unilateral neurotrophic keratitis in the unilateral decrease of corneal sensitivity (UDCS) group. The expression of MMP-9 in tears was assessed using point-of-care immunoassay. The clinical parameters including meibomian gland plugging, quality of the secreted meibum, tear secretion using Schirmer I without anesthesia, and corneal erosions were evaluated among the control, affected, and contralateral unaffected eyes in the UDCS group. Results Tear MMP-9 grades in affected (2.5 ± 1.0) and contralateral eyes (2.6 ± 0.9) in the UDCS group were higher than those in control eyes (1.5 ± 0.7, P = 0.0003 and P = 0.0006, respectively). The lacrimal secretion decreased in the affected eyes but preserved in the contralateral eyes. There was no difference in corneal erosion scores between control eyes and contralateral eyes in the UDCS group. Tear MMP-9 grades in the contralateral eyes were significantly correlated with the meibum quality grades in the contralateral eyes (r = 0.525 and P = 0.025). Conclusions Patients with the unilateral neurotrophic keratitis demonstrated a significant bilateral increase of the MMP-9 expression in the tear film as compared with controls. Despite the tearing reflex and corneal surface barrier being preserved in the unaffected contralateral eyes, it is necessary to pay attention to the possible attenuation of meibomian gland function in the opposite eyes as well.

Plasma cell-free DNA (cfDNA) sequencing data have been widely studied for early diagnosis and treatment response or recurrence monitoring of cancers because of the non-invasive benefits. In cancer studies, whole exome sequencing (WES) is mostly used for discovering single nucleotide variants (SNVs), but it also has the potential to detect copy number alterations (CNAs) that are mostly discovered by whole genome sequencing or microarray. In clinical settings where the quantity of the acquired blood from the patients is limited and where various sequencing experiments are not possible, providing various types of mutation information such as CNAs and SNVs using only WES will be helpful in the treatment decision. Here, we questioned whether the plasma cfDNA WES data for patients with advanced non-small cell lung cancer (NSCLC) could be exploited for CNA detection. When the read count (RC) signals of the WES data were investigated, a similar fluctuation pattern was observed among the signals of different samples, and it can be a major challenge hindering CNA detection. When these RC patterns among cfDNA were suppressed by the method we proposed, the cancerous CNAs were more distinguishable in some samples with higher cfDNA quantity. Although the potential to detect CNAs using the plasma cfDNA WES data for NSCLC patients was studied here, further studies with other cancer types, with more samples, and with more sophisticated techniques for bias correction are required to confirm our observation. In conclusion, the detection performance for cancerous CNAs can be improved by controlling RC bias, but it depends on the quantity of cfDNA in plasma.

Approximately half of lung cancer patients (LCP) receiving chemotherapy are experiencing cancer-related fatigue (CRF). In East Asia, herbal medicines (HMs) have been used as tonics due to their anti-fatigue effect. This systematic review evaluated the effectiveness and safety of HMs for CRF in LCP. We comprehensively searched 12 electronic medical databases to search randomized controlled trials (RCTs) and quasi-RCTs investigating HMs for CRF in LCP, published up to September 2019. The primary outcome was the fatigue severity. Secondary outcomes included patients' quality of life (QOL), activities of daily life (ADL), and incidence of adverse events. Cochrane's risk of bias tool assessed the methodological quality of included RCTs. The risk ratio or mean difference was estimated with 95% confidence intervals by performing a meta-analysis. Twelve RCTs with 861 participants were included. Compared to conventional medicine alone, HM combined with conventional medicine significantly improved fatigue level, QOL, and ADL. As monotherapy, HM significantly improved ADL compared with megestrol. No serious HM-related adverse events were reported. Limited evidence suggests that HM could be effective and safe for CRF in LCP. However, further high-quality RCTs are needed to confirm these findings owing to the small number and low methodological quality of the included studies.

Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS-mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.

Purpose Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). Methods We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group. Results Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1-49%, and

Purpose The clinical implications of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in epidermal growth factor receptor (EGFR)-mutated lung cancer are not fully understood. The aim of this study was to evaluate the diagnostic and prognostic utility of the parameters in EGFR-mutated lung cancer patients. Patients and Methods We retrospectively enrolled 134 patients with advanced lung adenocarcinoma (72 EGFR-negative and 62 EGFR-positive). We evaluated the correlation between EGFR mutational status and the maximum standardized uptake value (SUVmax), as well as the associations between treatment outcomes in EGFR-mutated patients and various metabolic parameters of primary tumors. For the best predictive parameters, we calculated the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) using two SUV cutoffs: 1.5 (MTV1.5, TLG1.5) and 2.5 (MTV2.5, TLG2.5). Results Mean SUVmax was lower for EGFR-mutated tumors compared with EGFR wild-type (6.11 vs 10.41, p < 0.001) tumors. Low SUVmax was significantly associated with positive EGFR mutation (odds ratio = 1.74). Multivariate analysis for survival demonstrated that high MTV1.5, TLG1.5, MTV2.5, and TLG2.5 were independently associated with shorter progression-free survival (PFS) and overall survival (OS), and the highest hazard ratios were found in TLG1.5 (3.26 for PFS and 4.62 for OS). Conclusion SUVmax may be predictive for EGFR mutational status, and MTV and TLG of primary tumors may be promising prognostic parameters; 18F-FDG PET/CT has potential utility for the risk stratification of EGFR-mutated patients treated with targeted therapy.

To evaluate the changes in choriocapillaris vessel density (VD) in eyes with pachychoroid pigment epitheliopathy (PPE) using swept-source optical coherence tomography (OCT) angiography (OCTA).This study included 83 eyes with PPE and 42 control eyes. We collected OCT and OCTA parameters, including central point thickness, subfoveal choroidal thickness (SFChT), and choriocapillaris VD of the fovea (CC fovea) and parafovea. The parafoveal area was divided into superior, nasal, inferior, and temporal choriocapillaris areas. Maximum (CC max) and minimum (CC min) choriocapillaris VD were defined as the highest and lowest values among the four parafoveal subfield VDs, respectively. We analyzed the average choriocapillaris VD, CC max, CC min, CC fovea, and the difference between CC max and CC min (CC delta) individually and compared all the parameters between PPE and control eyes.CC max (56.0% ± 1.7%) was significantly higher and CC min (50.9% ± 2.0%) significantly lower in eyes with PPE than in control eyes (CC max, 55.3% ± 1.0%, P = 0.006; CC min, 51.5% ± 1.3%, P = 0.046). The CC delta value (5.0% ± 2.1%) and SFChT (389.9 ± 129.9 μm) were also significantly higher in eyes with PPE than in the control group (3.7% ± 1.5%, P 0.001; 268.2 ± 102.2 μm, P 0.001; respectively).Choriocapillaris VD showed higher variability (hyperperfusion and hypoperfusion) in eyes with PPE than in control eyes. Choriocapillaris hypoperfusion may precede the development of PPE; however, choriocapillaris hyperperfusion is associated with projection artifacts.

Purpose: To evaluate the effect of the intense pulsed light (IPL) and meibomian gland (MG) expression (MGX) combination therapy according to the total numbers of sessions in the meibomian gland dysfunction (MGD).Methods: Ninety patients with MGD were included. Patients had maximal five sessions of IPL (Aqua Cel, Jeisys Medical) and MGX combination therapy at 2-week intervals. The ocular surface disease index (OSDI) questionnaire score, MG profile grades, tear matrix metalloproteinase-9 (MMP-9), tear break-up time (BUT), tear osmolarity, tear secretion, and corneal erosions were evaluated.Results: The number of patients who had a total of one to five sessions (1S to 5S) was 10, 25, 17, 20, and 18, respectively. The time-serial decrease of OSDI scores was significant in patients who had three or more sessions (3S, p = 0.002; 4S, p < 0.001; 5S, p < 0.001). The MG expressibility grade decreased with two or more sessions (2S–5S, p < 0.001), but the meibum quality significantly improved with all sessions (1S, p = 0.012; 2S, p = 0.024; 3S, p = 0.015; 4S, p < 0.001; 5S, p < 0.001). Although tear BUT increased even in patients with one session (1S, p = 0.040; 3S, p = 0.005; 4S, p = 0.006; 5S, p = 0.021), tear MMP-9, osmolarity, Schirmer I, and corneal erosions were not improved in every number of sessions. The female sex was the sole contributor to the final symptomatic improvement (p = 0.042), and the MGD stages were not related to the final OSDI decrease.Conclusions: The OSDI score, MGD grades, and BUT were improved after the IPL and MGX combination therapy in MGD patients. Unlike MGD grades and tear film instability might be improved just after a few sessions, the overall subjective relief was accomplished in three or more sessions.

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is a major treatment option for several types of cancer, including non-small cell lung cancer (NSCLC). The proposed study aims to investigate the safety and efficacy of Bojungikki-tang (BJIKT) therapy (an herbal medicine) in patients with advanced NSCLC treated with ICIs. This multicenter, randomized, placebo-controlled pilot study will be performed at three academic hospitals. Thirty patients with advanced NSCLC, undergoing atezolizumab monotherapy as second- and subsequent-line treatment, will be recruited and randomly assigned to either BJIKT treatment (atezolizumab + BJIKT) or placebo (atezolizumab + placebo). The primary and secondary outcomes are the incidence of adverse events (AEs), including immune- related AEs (irAEs) and non-immune-related AEs (non-irAEs); and early termination rate, withdrawal period, symptom improvement of fatigue, and skeletal muscle loss, respectively. The exploratory outcomes are patient objective response rate and immune profile. This is an ongoing trial. Recruitment started on 25 March 2022 and is expected to be completed by 30 June 2023. This study will provide basic evidence for the safety profiles, including irAEs, of herbal medicine in patients with advanced NSCLC treated with ICIs.

Moonkyoo Kong,1 Ji-Youn Sung,2 Seung Hyeun Lee3 1Division of Lung & Head and Neck Oncology, Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 2Department of Pathology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of KoreaCorrespondence: Seung Hyeun LeeDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Kyungheedae-ro 23, Dongdaemun-gu, Seoul 02447, Republic of KoreaTel +82 2 958 8511Fax +82 2 968 1848Email v3mann@naver.comPurpose: Reactive oxygen species modulator 1 (ROMO1) is a novel protein regulating intracellular reactive oxygen species production. Although increased ROMO1 expression has been associated with poor clinical outcomes in several human malignancies, the clinical implication of this protein in a radiotherapy setting has never been explored. The aim of this study was to investigate whether ROMO1 expression is associated with survival in lung cancer patients who received radiotherapy.Methods: ROMO1 protein expression was evaluated immunohistochemically using histologic score (H-score) in 49 tumor tissues from stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We performed survival analyses according to various clinicopathological parameters including ROMO1 expression.Results: ROMO1 expression was not associated with any clinicopathological parameter of age, sex, smoking status, stage, or histological subtype. Multivariate analyses showed that high ROMO1 expression was independently associated with worse progression-free survival (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.02–4.23) and with worse overall survival (HR = 2.79, 95% CI:1.13–6.87). In addition, high ROMO1 expression was independently associated with shorter time to loco-regional recurrence (HR=2.71, 95% CI:1.04–6.28) but was not associated with time to distant metastasis.Conclusion: ROMO1 overexpression was associated with early loco-regional recurrence and poor survival outcomes in stage III NSCLC treated with definitive radiotherapy. Our exploratory results provide a basis for further large-scale studies to validate whether ROMO1 could be a prognostic marker in this setting.Keywords: lung cancer, radiotherapy, reactive oxygen species, ROMO1, survival, biomarker

Boksoon Chang,1 In Kyung Hwang,2 Seung Hyeun Lee1 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, South Korea; 2Department of Medicine, Graduate School, Kyung Hee University, Seoul, South KoreaCorrespondence: Seung Hyeun LeeDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University College of Medicine, Kyungheedae-ro 23, Dongdaemun-gu, Seoul, 02447, South KoreaTel +82 2 958 8511Fax +82 2 968 1848Email v3mann@naver.comPurpose: Reactive oxygen species modulator 1 (Romo1) is a key regulator of intracellular reactive oxygen species production. Previous studies have shown that Romo1 overexpression in tumor tissue is associated with poor clinical outcomes in various clinical settings for lung cancer treatment. The aim of the present study was to assess the predictive value of serum Romo1 in patients received curative resection for lung cancer.Methods: Serum samples were collected from patients with lung adenocarcinoma who underwent surgical resection. Baseline serum Romo1 and carcinoembryonic antigen (CEA) levels before surgery were measured. Univariate and multivariate analyses were performed to identify whether serum Romo1 was associated with disease-free survival (DFS).Results: A total of 77 samples were analyzed. Using the cut-off value of 866 pg/mL, the population was classified into low (n = 42, 54.4%) and high (n = 35, 45.4%) Romo1 groups. The median DFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (25.5 months vs not reached [NR], p = 0.0105). In addition, the median DFS of patients in the high CEA (> 2.9 ng/mL) group was significantly shorter than those in the low CEA group (26.8 months vs NR, p = 0.0092). Multivariate analyses showed that both high Romo1 and CEA levels were independently associated with poor DFS (hazard ratio [HR] = 2.19; 95% confidence interval [CI]: 1.14– 8.37, and HR = 2.95; 95% CI: 1.23– 9.21, respectively). Moreover, combination of these two biomarkers resulted in higher HR of 4.11 (95% CI, 1.53– 14.05) for DFS than those of Romo1 and CEA.Conclusion: Elevated serum Romo1 levels were significantly associated with early recurrence in patients with lung adenocarcinoma treated with surgical resection. Serum Romo1 may be a promising predictive biomarker for this patient population.Keywords: reactive oxygen species modulator 1, serum, biomarker, recurrence, surgery

Background Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. Methods A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. Results 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1–33.2%. Conclusion Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

We evaluated the reliability and validity of the 5-scale grading system to interpret the point-of-care immunoassay for tear matrix metalloproteinase (MMP)-9. Six observers graded red bands of photographs of the readout window in MMP-9 immunoassay kit (InflammaDry) two times with 2-week interval based on the 5-scale grading system (i.e. grade 0–4). Interobserver and intraobserver reliability were evaluated using intraclass correlation coefficients. The interobserver agreements were analyzed according to the severity of tear MMP-9 expression. To validate the system, a concentration calibration curve was made using MMP-9 solutions with reference concentrations, then the distribution of MMP-9 concentrations was analyzed according to the 5-scale grading system. Both intraobserver and interobserver reliability was excellent. The readout grades were significantly correlated with the quantified colorimetric densities. The interobserver variance of readout grades had no correlation with the severity of the measured densities. The band density continued to increase up to a maximal concentration (i.e. 5000 ng/mL) according to the calibration curve. The difference of grades reflected the change of MMP-9 concentrations sensitively, especially between grade 2 and 4. Together, our data indicate that the subjective 5-scale grading system in the point-of-care MMP-9 immunoassay is an easy and reliable method with acceptable accuracy.