Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape oflung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensiveevidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatmentmodalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approacheswith other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas ofactive investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosinekinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancermanagement and keeps expanding its clinical implication. This review will discuss the current position and future role ofchemotherapy, and specific consideration for its clinical application in the era of precision medicine.
Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting β-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as “persistent controller users,” should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-toregular treatment combining low-dose ICS/rapid-onset long-acting β-agonists instead of using a SABA alone or with lowdose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.
Background: Tuberculosis (TB) is a major infectious disease in South Korea causing substantial disease burden, particularly in the elderly. This study aimed to identify the case detection rate of mobile TB screening for the elderly conducted in the Jeollanam-do region and to analyze risk factors of active TB. Methods: We screened the elderly population (≥65 years old) in Jeollanam-do from August to December 2017. Chest radiography was performed for all participants. Participants with TB presumptive signs were asked to submit sputum specimen(s). Sputum smear, culture, and polymerase chain reaction analyses were performed. Cascade analysis, chisquared tests, and Fisher exact tests were used to evaluate screening performance. Results: In total, 12,402 participants were screened, and 211 (1.7%) were suspected to have active TB; 181 of the suspected patients (85.8%) underwent sputum smear test, and 16 (8.8%) patients were confirmed to have TB. The TB prevalence among the elderly was bacteriologically confirmed to be 129 per 100,000 individuals, which was similar to national TB notification data for the same age groups. The proportion of active TB cases increased with age, and differed based on sex and past TB history. However, TB-related symptoms, comorbidity status, and TB screening history within 12 months were not predictive of active TB. Conclusion: This study identified that the prevalence rate was similar to national TB notification data from the same age groups. Periodic, community-based, systematic TB screening among the elderly population is recommended.
Background: Radial probe endobronchial ultrasound (R-EBUS) is widely used for diagnosing peripheral pulmonary lesions. However, the utility of R-EBUS–guided transbronchial lung biopsy (TBLB) for diffuse lung lesions (DLLs) remains unknown. We designed this study to evaluate the utility of R-EBUS–guided TBLB in DLLs. Methods: This retrospective study enrolled patients admitted from January 2016 to November 2017 who underwent TBLB for DLLs. The R-EBUS–guided TBLB and blind TBLB groups were compared. DLL was defined as any lung disorder that involved more than one segment of the lung. In both the groups, fluoroscopy and guided sheath were not used during TBLB. Results: A total of 127 patients underwent TBLB for DLLs (67 patients in the R-EBUS–guided TBLB group and 60 in the blind TBLB group). There were no differences in age, sex, and comorbid illnesses between the two groups. Furthermore, there was no difference in the TBLB diagnostic yield of the two groups (p=0.660) although more samples were collected from the R-EBUS–guided TBLB group (p=0.003). Procedure time was significantly longer in the R-EBUS–guided TBLB group than in the blind TBLB group (p<0.001). Thus, incidence of pneumothorax was significantly lower in the R-EBUS– guided TBLB group than in the blind TBLB group (p=0.032). Conclusion: Diagnostic yield in DLLs did not differ between the R-EBUS–guided TBLB and blind TBLB groups. Findings show that R-EBUS–guided TBLB in DLLs may reduce risk of pneumothorax.
Background: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m2 on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intentto- treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.
Background: Depression is a recognized complication of lung cancer underreported in developing countries such as Malaysia. Treating and identifying depression in cancer patients increases survival and quality of life. Our objectives are to study prevalence of depressive symptoms in newly diagnosed lung carcinoma, and examine the relationship of depressive symptoms with other influencing risk factors. Methods: A 2-year, cross sectional study February 2015–February 2017, was conducted at Hospital Tengku Ampuan Afzan, and Penang General Hospital. One hundred and three patients with newly diagnosed, biopsy confirmed primary lung carcinoma were recruited. Self-rated patient’s identification sheet, validated Center for Epidemiologic Studies Depression (CES-D), and Dukes University Religion Index score from three different main languages were used. Results: Prevalence of current depressive symptoms (CES-D total score ≥16) is 37.9%. The result suggests prevalence of those at high risk of moderate to major depression, may need treatment. Multivariate analysis reveals those with good Eastern Cooperation Oncology Group factor (η2=0.24, p<0.001) married (η2=0.14, p<0.001) with intrinsic religiosity (IR) (η2=0.07, p<0.02) are more resistant to depression. Conclusion: One in three of lung carcinoma patients, are at increased risk for depression. Clinicians should be aware that risk is highest in those with poor performance status, single, and with poor IR. We suggest routine screening of depression symptoms as it is feasible, to be performed during a regular clinic visit with immediate referral to psychiatrist when indicated.
Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD- 1) receptor, and anti–PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736–0.916). Conclusion: PD-L1 expression, defined as TPS ≥1%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.
Background: The utility of computed tomography (CT) in the differential diagnosis of patients with chronic obstructive pulmonary disease (COPD) exacerbation remains uncertain. However, due to the low cost associated with CT scan along with the impact of Koreas’ health insurance system, there has been a rise in the number of CT scans in the patients with initial diagnosis of COPD exacerbations. Therefore, the utility of CT in the differential diagnosis was investigated to determine whether performing CT scans affect the clinical outcomes of the patients with an initial diagnosis of COPD exacerbation. Methods: This study involved 202 COPD patients hospitalized with an initial diagnosis of COPD exacerbation. We evaluated the change in diagnosis or treatment after performing a CT scan, and compared the clinical outcomes of patient groups with vs. without performing CT (non-CT group vs. CT group). Results: After performing CT, the diagnosis was changed for two (3.0%) while additional diagnoses were made for 27 of the 64 patients (42.1%). However, the treatment changed for only one (1.5%), and six patients (9.3%) received supplementary medication. There were no difference in the median length of hospital stay (8 [6–13] days vs. 8 [6–12] days, p=0.786) and intensive care unit care (14 [10.1%] vs. 11 [16.7%], p=0.236) between the CT and non-CT groups, respectively. These findings remained consistent even after the propensity score matching. Conclusion: Utility of CT in patients with acute COPD exacerbation might not be helpful; therefore, we do not recommend chest CT scan as a routine initial diagnostic tool.
Background: Data on noninvasive ventilation (NIV) use in intensive care units (ICUs) are very limited in South Korea. Methods: A prospective observational study was performed in 20 ICUs of university-affiliated hospitals from June 2017to February 2018. Adult patients (age>18 years) who were admitted to the ICU and received NIV treatment for acuterespiratory failure were included. Results: A total of 156 patients treated with NIV were enrolled (mean age, 71.9±11.6 years). The most commonindications for NIV were acute hypercapnic respiratory failure (AHRF, n=89) and post-extubation respiratory failure(n=44). The main device for NIV was an invasive mechanical ventilator with an NIV module (61.5%), and the majorityof patients (87.2%) used an oronasal mask. After the exclusion of 32 do-not-resuscitate patients, NIV success rate was68.5% (85/124); ICU and hospital mortality rates were 8.9% and 15.3%, respectively. However, the success rate was lowerin patients with de novo respiratory failure (27.3%) compared to that of patients with AHRF (72.8%) or post-extubationrespiratory failure (75.0%). In multivariate analysis, immunocompromised state, de novo respiratory failure, post-NIV(2 hours) respiratory rate, NIV mode (i.e., non‒pressure support ventilation mode), and the change of NIV device weresignificantly associated with a lower success rate of NIV. Conclusion: AHRF and post-extubation respiratory failure were the most common indications for NIV in Korean ICUs. Overall NIV success was achieved in 68.5% of patients, with the lowest rate in patients with de novo respiratory failure. Keywords: Intensive Care Units; Noninvasive Ventilation; Masks
Background: Beyond its current function as a rescue therapy in acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) may be applied in ARDS patients with less severe hypoxemia to facilitate lung protective ventilation. The purpose of this study was to evaluate the efficacy of extended ECMO use in ARDS patients. Methods: This study reviewed 223 adult patients who had been admitted to the intensive care units of 11 hospitals in Korea and subsequently treated using ECMO. Among them, the 62 who required ECMO for ARDS were analyzed. The patients were divided into two groups according to pre-ECMO arterial blood gas: an extended group (n=14) and a conventional group (n=48). Results: Baseline characteristics were not different between the groups. The median arterial carbon dioxide tension/ fraction of inspired oxygen (FiO2) ratio was higher (97 vs. 61, p<0.001) while the median FiO2 was lower (0.8 vs. 1.0, p<0.001) in the extended compared to the conventional group. The 60-day mortality was 21% in the extended group and 54% in the conventional group (p=0.03). Multivariate analysis indicated that the extended use of ECMO was independently associated with reduced 60-day mortality (odds ratio, 0.10; 95% confidence interval, 0.02–0.64; p=0.02). Lower median peak inspiratory pressure and median dynamic driving pressure were observed in the extended group 24 hours after ECMO support. Conclusion: Extended indications of ECMO implementation coupled with protective ventilator settings may improve the clinical outcome of patients with ARDS.
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