Disease control in patients with non-small cell lung cancer using pemetrexed: Investigating the best treatment strategy.

BACKGROUND: Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. METHODS: A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. RESULTS: Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor-1 (TTF-1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001). CONCLUSIONS: Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF-1 positivity, could enhance disease control rates and extend survival.

Prognostic value of the serum creatinine/cystatin C ratio in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sarcopenia, characterized by skeletal muscle atrophy and physical inactivity, is a manifestation of chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. The serum creatinine (Cr)/cystatin C (CysC) ratio has been proposed as a marker of sarcopenia, given its correlation with total skeletal muscle mass, and as a prognostic indicator in COPD. This study aimed to evaluate the usefulness of the serum Cr/CysC ratio as a prognostic determinant in these patients. METHODS: A total of 124 outpatients with COPD were enrolled in this study. Their serum Cr and CysC levels were measured. Survival time analyses were conducted to compare mortality rates between the low and high serum Cr/CysC ratio groups. Multivariate analysis was performed to investigate the association between various factors. RESULTS: Using a serum Cr/CysC cut-off value of 0.885, the mortality rate (per 1000 person-years) for overall mortality was significantly higher in the low serum Cr/CysC ratio group (69.2 versus 28.6; hazard ratio, 2.47; 95% confidence interval, 1.06-5.79; p < 0.05). Similarly, the mortality rate due to respiratory disease was also higher (37.8 versus 8.2; hazard ratio, 4.68; 95% confidence interval, 1.05-20.9; p < 0.05). Multivariate Cox proportional hazards analysis revealed that serum Cr/CysC was an independent risk factor for respiratory disease mortality, regardless of age and airflow limitations. CONCLUSIONS: The serum Cr/CysC ratio could be a valuable clinical parameter for identifying sarcopenia and severe airflow obstruction. The study findings highlight the utility of this ratio as a prognostic predictor in patients with COPD.

Investigation of response of patients with non-small cell lung cancer to docetaxel (plus ramucirumab) therapy in second-line treatment.

BACKGROUND: Several options for second-line therapy are available for patients with advanced non-small cell lung cancer (NSCLC); however, the optimal therapy remains unclear. Docetaxel (DTX) monotherapy and DTX plus ramucirumab (RAM) are the recommended second-line treatment options. However, the efficacy of these treatments remains unsatisfactory. The aim of this study was to identify the clinical characteristics of patients with NSCLC who respond to DTX or DTX + RAM and factors that predict response. METHODS: Patients with NSCLC treated with DTX or DTX + RAM after second-line therapy were retrospectively analyzed. Patients were compared with those who responded or did not respond to the post-treatment efficacy assessment. RESULTS: Of 53 patients, 12 (22.6%) had lung cancer that responded to DTX or DTX + RAM therapy (response group). Multivariate analysis identified the absence of immune checkpoint inhibitors (ICIs) in the immediate prior therapy and a reduced dose of DTX after the second cycle as significant independent risk factors predicting nonresponse to DTX and DTX + RAM therapy in patients with NSCLC. The overall survival was significantly longer in the response group compared to the nonresponse group (p = 0.016). CONCLUSIONS: Our results suggest that DTX and DTX + RAM therapies immediately after treatment with ICI-containing regimens as well as continuation of DTX without dose reduction after the second cycle may increase the response rate and prolong survival in patients with NSCLC.

Investigation of response factors for monotherapy with immune checkpoint inhibitors in non-small cell lung cancer patients with PD-L1 expression <50.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with programmed death ligand-1 (PD-L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD-L1 expression <50% has not yet been fully elucidated. The aim of this study was to identify the clinical characteristics of NSCLC patients with PD-L1 expression <50% who respond to single-agent ICIs and factors that predict response. METHODS: Patients with advanced or recurrent NSCLC with a PD-L1 tumor proportion score (TPS) of 50% or less who received new monotherapy with an ICI between July 2012 and December 2022 were retrospectively analyzed. Patients with response were compared with those without response in the post-treatment response assessment. RESULTS: Among the 37 patients, six (16.2%) NSCLC patients in the response group responded to ICI monotherapy and had a significantly lower body mass index (BMI) (p = 0.003). Significantly more patients in the response group developed immune-related adverse events (irAEs) than in the nonresponse group (p < 0.001). Multivariate analysis identified high BMI as a significant independent risk factor predicting nonresponse to ICI monotherapy in NSCLC patients with PD-L1 < 50%. CONCLUSIONS: Among NSCLC patients with PD-L1 < 50%, those with a higher BMI were more likely to be nonresponders to ICI monotherapy. In addition, the group that responded to ICI monotherapy may have been at higher risk of developing irAEs, suggesting that careful follow-up is warranted.

A case of severe pneumonia caused by Legionella longbeachae with positive results by a Legionella urinary antigen detection kit.

Legionella longbeachae is a Legionella bacteria often detected in soil, and is known as a rare cause of Legionella infections in Japan. In addition, detection of this Legionella species is often overlooked due to negative results from Legionella urinary antigen tests, which could lead to errors in the therapeutic approach. An 80-year-old woman was admitted to our hospital because of fever and dyspnea. Her blood tests showed elevated white blood cells, increased C-reactive protein and transaminases, and hyponatremia. Chest computed tomography showed dense consolidation in the right lung. We diagnosed Legionella pneumonia because the Legionella urinary antigen test was positive on the day after her admission. The patient was intubated and mechanically ventilated on the third day of hospitalization, because of respiratory failure. However, her condition did not improve and she died on the 10th day after admission. After her death, L. longbeachae was detected from sputum culture from her tracheal tube, and was diagnosed as the causative organism of her pneumonia. L. longbeachae infection reportedly rarely produces positive urinary antigen test results. Our experience suggests that the urinary antigen test using Ribotest Legionella might be able to detect Legionella spp. other than L. pneumophila.

Influencing factors of efficacy and long-term use of amrubicin in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. METHODS: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). RESULTS: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). CONCLUSIONS: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series.

BACKGROUND: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. CASES: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment. CONCLUSION: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Early recurrence factors in patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND: The clinical characteristics and risk factors for cancer recurrence have not been well evaluated regarding early recurrence in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) who receive concurrent chemoradiotherapy (CRT). The aim of this study was to determine the clinical characteristics and risk factors of patients with stage III unresectable LA-NSCLC treated with CRT who developed early recurrence. METHODS: We retrospectively reviewed the clinical records of 46 patients diagnosed with stage III unresectable LA-NSCLC treated with CRT at our center between July 2012 and July 2021. A tumor proportion score (TPS) < 50% was defined as "low expression" and a TPS > 50% was defined as "high expression." RESULTS: A total of 17 (37.0%) patients had a confirmed recurrence within 1 year of treatment. More patients had a lower body mass index in the early recurrence group than in the later recurrence group (p = 0.038). A higher number of patients in the late recurrence group underwent surgery after CRT (p = 0.036). Patients with a higher TPS were more likely to experience late recurrence than early recurrence (p = 0.001), whereas more patients with stage N3 disease were in the early recurrence group (p = 0.011). Multivariate analysis identified lower TPS expression as an independent risk factor for early recurrence after CRT. Overall survival was prolonged in the late recurrence group (p < 0.001). CONCLUSIONS: A lower TPS may be a predictor of early recurrence after CRT in patients with LA-NSCLC. These patients should be closely monitored for post-treatment recurrence.

Serum Derivatives of Reactive Oxygen Metabolites are Associated with Severity of Chronic Obstructive Pulmonary Disease and Affected by a p53 Gene Polymorphism.

Purpose: Oxidative stress is known to activate tumor suppressor p53, which inhibits cell cycle progression and induces apoptosis. Levels of p53 in lung tissues from patients with chronic obstructive pulmonary disease (COPD) are increased compared with levels in nonsmokers or smokers without emphysema. A polymorphism in p53 codon 72 (rs1042522) is associated with emphysematous changes in patients with COPD. However, whether oxidative stress in the serum is associated with the p53 polymorphism and disease severity in COPD patients is unclear. Patients and Methods: A total of 251 patients with a history of smoking more than 10 pack-years were enrolled in this study, and serum levels of derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and d-ROMs/BAP ratio (oxidative stress index; OSI) were measured. The percent low-attenuation area (LAA%) and cross-sectional area of the erector spinae muscles (ESMCSA) at the Th12 level were calculated from chest high-resolution computed tomography images. p53 codon 72 C/G genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: In patients carrying the p53 GG genotype, LAA% was significantly higher than in those carrying the CC genotype. d-ROM levels and OSI were associated with COPD severity and correlated with airflow limitation and markers of muscle atrophy (ESMCSA and creatinine/cystatin C ratio). Associations between markers of oxidative stress and COPD severity were observed primarily in patients carrying the p53 codon 72 GG genotype. Conclusion: Susceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism.

Lung cancer with post-fracture healing changes causing difficulty in staging.

In cases wherein metastatic disease diagnosis in lung cancer is difficult with imaging, tissue biopsy should be performed. A 77-year-old woman presented with a complaint of cough. Positron emission tomography-computed tomography showed a left lung tumor with fluorodeoxyglucose accumulation, multiple lymphadenopathies, and right-rib sclerotic lesion. Although the diagnosis was lung adenocarcinoma, the bone lesion required differentiation from traumatic changes. A costal biopsy showed bone lesions as post-fracture healing changes, leading to variation in the therapeutic strategy to curative. In patients with lung cancer, history of trauma, and bone lesions with fluorodeoxyglucose accumulation, aggressive tissue biopsy is recommended for accurate staging.

Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. METHODS: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021. RESULTS: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). CONCLUSIONS: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control.

Acquired pulmonary arteriovenous malformation associated with bronchiectasis: a case report.

BACKGROUND: Pulmonary arteriovenous malformations are mostly caused by congenitally abnormal shunts between pulmonary arteries and pulmonary veins. CASE PRESENTATION: A 74-year-old Japanese woman with a history of bronchiectasis was admitted to our hospital because of dyspnea on exertion. Pulmonary angiography and reconstructed three-dimensional contrast-enhanced computed tomography images showed shunts between pulmonary arteries and pulmonary veins, indicating a diagnosis of pulmonary arteriovenous malformations. Coil embolization of the shunts was successful. CONCLUSIONS: Our findings imply that bronchiectasis can cause pulmonary arteriovenous malformations, and thus patients who present with hypoxemia with bronchiectasis should be carefully evaluated.

First case of lung cancer with pneumoconiosis and endobronchial leiomyoma complicating the diagnosis.

BACKGROUND: In the treatment of lung cancer, the presence or absence of mediastinal lymph node involvement has a significant bearing on the indication for surgery. In addition, if a tumor is found in the trachea during preoperative scrutiny of lung cancer, the possibility of intratracheal metastasis should be considered, since this kind of metastasis is a contraindication for surgery. In the present study, we experienced a case of lung cancer associated with pneumoconiosis and a rare intratracheal leiomyoma. In this case, preoperative staging was difficult, but endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and intratracheal tumor biopsy were helpful in determining the treatment strategy. CASE PRESENTATION: A 65-year-old man was referred to our hospital for evaluation of abnormal chest X-ray shadows. Sputum cytology indicated squamous cell carcinoma. PET-CT scan showed fluorodeoxyglucose uptake in a right upper lobe mass and the hilar, mediastinal and right supraclavicular lymph nodes, and bronchoscopy revealed a protuberant lesion in the left bronchus. Hence, EBUS-TBNA for the mediastinal lymph nodes and simultaneous evaluation of the protuberant lesion in the left bronchus were performed. The bronchial tumor was histopathologically diagnosed as leiomyoma. Since mediastinal lymph node biopsy showed no malignant cells, a right upper lobectomy and a right S6 segmentectomy were performed. Postoperative pathological evaluation of the dissected lymph nodes revealed pneumoconiosis but no metastasis. He was, thus, diagnosed with squamous cell lung carcinoma (pT2bN0M0, pStage IIA). CONCLUSIONS: We report a patient with lung cancer and coexistence of a rare endobronchial leiomyoma and pneumoconiosis, who underwent surgery after preoperative evaluation using EBUS-TBNA.

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows.

BACKGROUND: The risk of cancer treatment-related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. METHODS: We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. RESULTS: Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment-related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non-AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment-related AEs. CONCLUSIONS: Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment-related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

Relationship between clinical features and gene mutations in non-small cell lung cancer with osteoblastic bone metastasis.

OBJECTIVE: Lung cancer patients presenting with osteoblastic bone metastases at the first visit is rare. We investigated the clinical characteristics and gene mutation rate of non-small cell lung cancer patients with osteoblastic bone metastases at the time of the initial diagnosis. MATERIALS AND METHODS: We retrospectively screened newly diagnosed non-small cell lung cancer patients with osteoblastic bone metastases who presented from June 2015 to March 2021, and analyzed their clinical characteristics and status of EGFR gene mutations, EML4-ALK translocation and ROS1 rearrangements. For comparison, we collected data from patients with non-small cell lung cancer who had osteolytic bone metastases at their first visit between June 2015 and March 2021. RESULTS: Fifty patients had bone metastases at the initial diagnosis. Among them, eight patients (8/50 = 16%) had osteoblastic bone metastases, and the lung tumors in all of them were histopathologically adenocarcinomas. Among the eight cases, two were EGFR mutation-positive, none were EML4-ALK translocation-positive, two were ROS1 rearrangement-positive, and the remaining four cases were negative for all three gene mutations/rearrangements. Compared with the osteolytic bone metastasis group, the percentage of non-smokers was higher (p = 0.020) and the ROS1 rearrangement positivity rate was higher (p = 0.05) in the osteoblastic bone metastasis group. CONCLUSION: Our results indicate that osteoblastic bone metastases in NSCLC are suggestive of adenocarcinoma, and that a high proportion of these patients might be positive for ROS1 rearrangements, and hence, indicated for more aggressive diagnostic biopsies.

Serum Creatinine/Cystatin C Ratio Associated with Cross-Sectional Area of Erector Spinae Muscles and Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: Muscle atrophy is a major clinical feature of chronic obstructive pulmonary disease (COPD) and is considered a predictor of mortality in COPD patients. Recently, the cross-sectional area (CSA) of the erector spinae muscles measured by chest computed tomography (CT) scans (ESMCSA) has been reported as a clinical parameter reflecting disease severity and future prognosis in patients with COPD. In addition, the serum creatinine (Cr)/cystatin C (CysC) ratio has been considered a quantitative marker of residual muscle mass, because serum Cr levels are affected by muscle mass, and correction by CysC counteracts the effect of renal function on serum Cr levels. The purpose of this study was to assess whether the serum Cr level corrected by serum CysC can be used as a predictive marker of pulmonary function and disease severity in patients with COPD. PATIENTS AND METHODS: A total of 99 patients without COPD and 201 patients with COPD, with a smoking history of more than 10 pack-years were enrolled in this study, and serum Cr and CysC levels were measured. On chest high-resolution CT images, %low attenuation area (LAA%) (≤960 Hounsfield units (HU)) and ESMCSA at the Th12 level were identified. RESULTS: There was a significant correlation between the ESMCSA and the Cr/CysC ratio. The Cr/CysC ratio was significantly associated with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) values, especially in former smokers. CONCLUSION: The serum Cr/CysC ratio could be a convenient substitute for the measurement of muscle atrophy and pulmonary function testing in patients with COPD.

Clinical outcomes and survival following placement of self-expandable metallic stents for central airway stenosis and fistula.

BACKGROUND: Self-expandable metallic stent (SEMS) placement is an urgent procedure for patients with malignant central airway stenoses (CASs) and central airway fistulas (CAFs). The aim of this study was to determine the outcome and survival after SEMS placement in patients with malignant CASs and CAFs. METHODS: SEMSs were inserted into 20 patients with malignant CASs and four with malignant CAFs. Hospital records, the modified Medical Research Council dyspnea scale (mMRC) grade, performance status (PS), symptoms, procedure-related complications and survival after placement were retrospectively reviewed. RESULTS: Spiral Z stents were inserted in nine patients, covered Ultraflex stents in 14, and a bare Ultraflex in one patient. After SEMS placement, 20 patients (83.3%) showed improvement in mMRC grade, 19 (79.2%) showed improvement in PS, and 21 (87.5%) showed improvement in symptoms. There were three patients whose stents migrated out of place, but there were no patients with obstructive granulation, infection, or mucous plugs. Median survival days after stent insertion was 98 days for CAS and 103 days for CAF, and mean survival days was 383 ± 707 days for CAS and 93 ± 33 days for CAF. Two patients with CAS by malignant lymphoma and thymic cancer survived more than six years because they were also treated with efficient therapies. The five-year survival rate after stent insertion was 7.7%. CONCLUSIONS: SEMS placement for CAS and CAF is associated with improvement in mMRC grade, PS and symptoms in 87.5% of patients. Patients with a malignant CAS are usually terminal, but the possibility of increasing survival rate will become a reality with new efficient therapies. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Reasonable clinical outcomes and improved survival of patients following SEMS placement for thoracic malignancy with central airway stenosis and fistula. WHAT THIS STUDY ADDS: The possibility of increasing survival rate will become a reality with new efficient therapies.

Second SVC stent treatment for tumour ingrowth.

We herein report a case of lung cancer with recurrent superior vena cava (SVC) syndrome, which was treated with additional stent placement. Our report suggests the possibility that additional SVC stent placement is an option for treatment of tumour ingrowth, even in patients with poor performance status.

A case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis.

A 53-year-old woman was referred to our hospital for detailed examination of abnormal chest shadows recognized on CT imaging. Transbronchial lung biopsy of a right S6 nodular shadow led to a diagnosis of lung adenocarcinoma. FDG-PET-CT showed FDG accumulation in the Th11 and L2 vertebral bodies and osteoblastic bone lesions. Since osteoblastic bone metastasis in lung cancer is extremely rare, CT-guided bone biopsy was performed. The tumor was diagnosed as ROS1-rearranged lung adenocarcinoma, for which crizotinib was administered, which led to improvement of both the primary and metastatic lesions. We report here a rare case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis of lung cancer.

ADRB2 gene polymorphism and emphysema heterogeneity can modulate bronchodilator response in patients with emphysema.

BACKGROUND: Genetic variation in the ß2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to ß2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients. We hypothesized that differences in emphysema distribution and heterogeneity may have masked significant alterations of the bronchodilator response among ADRB2 genotypes in COPD patients in previous studies. METHODS: The BDR (induced by 20 µg of procaterol) was measured in 211 patients who had a smoking history of more than 10 pack/years and had undergone chest high resolution computed tomography examination. A low attenuations area (<960 Hounsfield Units) was identified and the emphysema heterogeneity index (EHI%) was calculated with a range in value from -100% to 100%. ADRB2 Arg16Gly genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The BDR was augmented in patients with homogenous emphysema compared with those with upper-dominant emphysema. In patients carrying the AA genotype of ADRB2, the BDR was significantly increased in patients with upper-dominant emphysema, but not in patients with lower-dominant emphysema. CONCLUSION: Combination analysis of ADRB2 Arg16Gly polymorphism and EHI% may predict the effectiveness of ß2-adrenergic receptor agonist treatment in patients with COPD and emphysema.