Effective Timing of Introducing an Inpatient Smoking Cessation Program to Cancer Patients

Purpose@#We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center. @*Materials and Methods@#The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation. @*Results@#A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success (p<0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02–2.70; p=0.040). @*Conclusion@#Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers.

Awareness and Use of Complementary and Alternative Medicine in Korean Lung Cancer Patients / 결핵및호흡기질환

Background@#Complementary and alternative medicine (CAM) has been used frequently, and its use continues to increase in lung cancer patients, despite insufficient scientific of its efficacy. To investigate this situation, we analyzed the current awareness and use of CAM in Korean lung-cancer patients. Methods: This prospective survey–based study was performed at seven medical centers in South Korea between August and October 2019. The survey assessed general patient characteristics and the awareness and use of CAM. We analyzed differences in the clinical parameters of patients aware and not aware of CAM and of CAM non-users and users. @*Results@#Of the 434 patients included in this study, 68.8% responded that they were aware of CAM and 30.9% said they had experienced it. In univariate analysis, the patients aware of CAM were younger with poor performance status, had advanced-stage lung cancer, received more systemic therapy, and received concurrent chemoradiation therapy (CCRT). By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were identified as independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters of CAM non-users and users. @*Conclusion@#Specific clinical parameters were associated with patients’ awareness of CAM, although there were no significantly different characteristics between CAM users and non-users.

A Phase II Trial of Osimertinib as the First-Line Treatment of Non–Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non–small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA. @*Materials and Methods@#Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety. @*Results@#Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis. @*Conclusion@#Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

The Tumor Control According to Radiation Dose of Gamma Knife Radiosurgery for Small and Medium-Sized Brain Metastases from Non-Small Cell Lung Cancer

Objective@#: The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). @*Methods@#: We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1–3 and 3–5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. @*Results@#: After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0–17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150–0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5–11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. @*Conclusion@#: The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Baseline Serum Interleukin-6 Levels Predict the Response of Patients with Advanced Non-small Cell Lung Cancer to PD-1/PD-L1 Inhibitors

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9–8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6–2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8–10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

Clinical Characteristics of Korean Patients with Lung Cancer Who Have Programmed Death-Ligand 1 Expression / 결핵및호흡기질환

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 ??%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA: LiquidLung-O-Cohort 2 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Administering the best treatment after failure of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy requires knowledge of resistance status. In this trial, treatment efficacy of osimertinib was assessed in patients with non-small cell lung carcinoma (NSCLC) harboring the T790M resistance mutation, detected from circulating tumor DNA (ctDNA) with unknown tumor mutation status. MATERIALS AND METHODS: To extract ctDNA from plasma, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas ver. 2 and PANA Mutyper were used for ctDNA genotyping. Patients with T790M, detected from ctDNA, were enrolled and they received a once-daily administration of osimertinib 80 mg. The primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety. RESULTS: Eighty patients with acquired resistance to prior EGFR-TKI therapies were screened. ctDNA of 21 patients showed T790M positivity, and 19 patients were enrolled. In the response-evaluable population (n=15), ORR was 66.7% (10/15). Median PFS was 8.3 months (95% confidence interval [CI], 7.9 to 8.7) and median DoR was 6.8 months (95% CI, 5.3 to 8.3) in the intent-to-treat population (n=19). No subject experienced drug-related adverse event of grades ≥ 3 or required dose reduction. The sensitivity of the ctDNA tests was 56.8% using both methods and 45.9% with either method from the estimated T790M-positive cases. CONCLUSION: Osimertinib has favorable efficacy in patients with NSCLC harboring T790M, detected from ctDNA with unknown tumor mutation status, in whom disease had progressed during prior EGFR-TKI therapy.

Clinical Characteristics of Korean Patients with Lung Cancer Who Have Programmed Death-Ligand 1 Expression / 결핵

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 ??%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

Collaborative Care to Relieve Psychological Distress in Patients with Medically Inoperable Lung Cancer: Design and Rationale for a Clinical Trial

Psychological distress is common in lung cancer patients with a poor prognosis. The present study aims to investigate the efficacy of collaborative care for patients with newly diagnosed inoperable lung cancer in South Korea. The study is a three-arm parallel-groups non-randomized clinical trial with an active arm that includes distressed patients who receive collaborative care, one comparison arm that includes distressed patients who receive enhanced usual care, and another comparison arm that includes non-distressed patients. In total, 267 consecutive patients newly diagnosed with medically inoperative lung cancer will be recruited. The primary outcomes are the changes in Hospital Anxiety and Depression Scale-depression and the Distress Thermometer at 12 and 32 weeks after enrollment. Sub-analyses of patients in the active arm of the study will include a comparison of the efficacy of a combination of oral antidepressant (escitalopram) treatment and collaborative care versus that of collaborative care alone.

Clinical Validation of a Protein Biomarker Panel for Non-Small Cell Lung Cancer

We validated the diagnostic performance of a previously developed blood-based 7-protein biomarker panel, AptoDetect™-Lung (Aptamer Sciences Inc., Pohang, Korea) using modified aptamer-based proteomic technology for lung cancer detection. Non-small cell lung cancer (NSCLC), 200 patients and benign nodule controls, 200 participants were enrolled. In a high-risk population corresponding to ≥ 55 years of age and ≥ 30 pack-years, the diagnostic performance was improved, showing 73.3% sensitivity and 90.5% specificity with an area under the curve of 0.88. AptoDetect™-Lung (Aptamer Sciences Inc.) offers the best validated performance to discriminate NSCLC from benign nodule controls in a high-risk population and could play a complementary role in lung cancer screening.

What is Currently the Best for Adenocarcinoma without Driver Mutation? / 결핵및호흡기질환

No abstract available.

Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung Cancer Harboring HER2 Mutation: Case Report

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A > G), which has never been reported. The patient was treated with afatinib for more than four months. She showed rapid radiologic response within a month, and maintained stable state until the last dose of afatinib.

Review of Sarcoidosis in a Province of South Korea from 1996 to 2014 / 결핵및호흡기질환

BACKGROUND: Since the introduction of endobronchial ultrasound (EBUS)–guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. METHODS: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. RESULTS: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. CONCLUSION: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: searching the evidence to guide the decision

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label, Multi-Center, Non-Interventional Study

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: NCT 01273454).

Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Direct sequencing (DS) is the standard method for detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC); however, low detection sensitivity is a problem. The aim of this study is to demonstrate higher detection rate of EGFR gene mutation with peptide nucleic acid (PNA) clamping compared with DS. MATERIALS AND METHODS: This is a single arm, prospective study for patients with stage IIIB/IV or relapsed NSCLC. Using tumor DNA from 138 patients, both DS and PNA clamping for EGFR gene in exon 18, 19, 20, and 21 were performed. Discrepant results between the two methods were verified using Cobas and a mutant enrichment based next generation sequencing (NGS). Patients with activating mutations were treated with EGFR tyrosine kinase inhibitor (EGFR-TKI, gefitinib, or erlotinib) as first line treatment. RESULTS: Of 138 paired test sets, 24 (17.4%) and 45 (32.6%) cases with activating mutations were detected by DS and PNA clamping, respectively. The difference of detection rate between the two methods was 15.2% (95% confidence interval, 8.7% to 17.8%; p < 0.001). Between the two methods, 25 cases showed discrepant results (n=23, PNA+/DS-; n=2, PNA-/DS+). Mutations were confirmed by Cobas or NGS in 22 of 23 PNA+/DS- cases. The response rates to EGFR-TKI were 72.2% in the PNA+/DS+ group and 85.0% in the PNA+/DS- group. CONCLUSION: PNA clamping showed a significantly higher detection rate of EGFR gene mutation compared with DS. Higher sensitivity of PNA clamping was not compromised by the loss of predictive power of response to EGFR-TKI.

Usefulness of Rigid Bronchoscopic Intervention Using Argon Plasma Coagulation for Central Airway Tumors

OBJECTIVES: Argon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors. METHODS: Twenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal. RESULTS: The median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P<0.001). The median American Thoracic Society dyspnea grade (3 [IQR, 1 to 4] vs. 1 [IQR, 0 to 1], P<0.001) and forced expiratory volume in one second (1.03 L [IQR, 0.52 to 1.36 L] vs. 1.98 L [IQR, 1.57 to 2.64 L], P=0.004) were significantly improved after intervention. There were no procedure-related acute complications and deaths. CONCLUSION: Rigid bronchoscopy with APC is an effective and safe procedure to alleviate central airway obstruction caused by tumors.

Successful Treatment of Crizotinib-Associated Severe Hepatotoxicity in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

Crizotinib-associated severe hepatotoxicity has been rarely reported and experts recommended stopping crizotinib treatment in patients with grade 3/4 transaminase elevation. We experienced a case of anaplastic lymphoma kinase-positive non-small cell lung cancer occurring as a result of severe hepatotoxicity due to crizotinib-associated hepatitis, accompanied by the reactivation of chronic hepatitis B, which was reversed with dose reduction and anti-viral therapy. Our case highlights the possibility that crizotinib might induce hepatitis and this might be associated with the underlying presence of chronic hepatitis B. In addition, crizotinib could be continued with reduced unless there are any other therapeutic options.

Prevalence of Chronic Sputum and Associated Factors in Korean Adults

Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (> or =70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.

Repeated Favorable Responses to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in a Case of Advanced Lung Adenocarcinoma / 결핵및호흡기질환

The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.