Effectiveness of remdesivir-based therapy for moderate COVID-19: comparison of Omicron and other variant phases.

Remdesivir is an antiviral drug for the treatment of coronavirus disease 2019 (COVID-19), and the sustained antiviral activity against Omicron variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported. In this single-center retrospective study, we first compared the clinical effectiveness of remdesivir-based therapy between Omicron and other variant phases of moderate COVID-19 in a real-world setting. Between Dec 2020 and July 2022, a total of 406 patients with COVID-19 pneumonia were treated with remdesivir-based therapy on admission. The oxygen deterioration rate after initiation of treatment significantly decreased in the Omicron variant phase compared to the alpha and delta variant phases. In an adjusted multivariate Cox proportional hazards model, Omicron variant phase was significantly associated with delayed oxygen deterioration and early recovery from hypoxia. These favorable outcomes during the Omicron variant phase, compared to previous variant phases, might be due to the attenuation and the popularization of vaccination.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

＜Editors' Choice＞ Effects of high-flow nasal cannula oxygen therapy on oral intake of do-not-intubate patients with respiratory diseases.

High-flow nasal cannula (HFNC) oxygen therapy is used widely for hypoxemic respiratory failure. However, it is unknown whether the use of HFNC is compatible with retaining the ability to eat and drink of patients with end-stage respiratory diseases as a part of palliative care. A retrospective study was conducted on subjects with hypoxic respiratory failure due to end-stage respiratory diseases, including interstitial pneumonia and malignant respiratory diseases, who were treated with HFNC or reservoir mask oxygen therapy and died with do-not-resuscitate (DNR) and do-not-intubate (DNI) status. We compared the duration of eating solids and drinking liquids and clinical variables in the HFNC group with those in the reservoir mask group. The data from a total 43 subjects including 20 with HFNC and 23 with a reservoir mask were analyzed. Fitting HFNC to subjects temporarily improved oxygenation. Durations of survival, eating solids, and drinking liquids in the HFNC group were significantly longer than those in the reservoir mask group. No significant adverse effects were observed in either group. In conclusion, the use of HFNC led to prolonged survival while preserving the ability of oral intake in patients with DNR and DNI status.

Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a devastating lung disease caused by abnormal surfactant homeostasis, with a prevalence of 6-7 cases per million population worldwide. While mutations causing hereditary PAP have been reported, the genetic basis contributing to autoimmune PAP (aPAP) has not been thoroughly investigated. Here, we conducted a genome-wide association study of aPAP in 198 patients and 395 control participants of Japanese ancestry. The common genetic variant, rs138024423 at 6p21, in the major-histocompatibility-complex (MHC) region was significantly associated with disease risk (Odds ratio [OR] = 5.2; P = 2.4 × 10-12). HLA fine-mapping revealed that the common HLA class II allele, HLA-DRB1*08:03, strongly drove this signal (OR = 4.8; P = 4.8 × 10-12), followed by an additional independent risk allele at HLA-DPß1 amino acid position 8 (OR = 0.28; P = 3.4 × 10-7). HLA-DRB1*08:03 was also associated with an increased level of anti-GM-CSF antibody, a key driver of the disease (ß = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.

Prognostic impact of serum procalcitonin in non-small cell lung cancer.

INTRODUCTION: Increased serum procalcitonin (PCT), a well-known biomarker for sepsis, has been reported in several cancer types. We aimed to investigate the prognostic impact of PCT in non-small cell lung cancer (NSCLC). METHODS: Medical records of 51 consecutive patients with NSCLC (Aichi Medical University Hospital) admitted between July 2017 and July 2018 were retrospectively reviewed. The patients were divided into PCT-low (PCT < 0.1 ng/mL) and PCT-high (PCT ⩾ 0.1 ng/mL) groups, and their clinical characteristics and survival were compared. RESULTS: In contrast to the PCT-low group (n = 24), the PCT-high group (n = 27) showed significantly worse Performance Status (PS) and overall survival (OS) (PS 0-2/3-4, 16/8 versus 12/15, p = 0.034; median OS, not reached versus 127 days, p < 0.001), irrespective of the presence of infection (p = 0.785). Multivariate analysis showed that the disease stage (IV versus I-III) and high PCT level (⩾0.1 versus <0.1 ng/mL) were significantly worse prognostic factors with hazard ratios of 3.706 (p = 0.023) and 3.951 (p = 0.010), respectively. CONCLUSION: The results suggest that serum PCT in NSCLC was elevated regardless of the presence of infection. Higher PCT levels are associated with poor PS and shorter OS in NSCLC.

Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 µg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS: In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

Validation of a new serum granulocyte-macrophage colony-stimulating factor autoantibody testing kit.

Very recently, a modest but significant efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported. As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use. As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL-1 in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP. The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases.

Inhaled GM-CSF for Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).

CCR4 Expression in Tumor-Infiltrating Regulatory T Cells in Patients with Squamous Cell Carcinoma of the Lung: A Prognostic Factor for Relapse and Survival.

To clarify the prognostic impact of tumor-infiltrating effector regulatory T cells (eTregs) in non-small cell lung cancer (NSCLC), eTregs were evaluated by immunohistochemical detection of CCR4 and Foxp3 in 108 consecutive surgical NSCLC tumors. Multivariate analysis showed that a high ratio of CCR4+ eTregs to total Tregs (≥40%) was the only independent risk factor for relapse-free survival (odds ratio [OR]: 6.54, 95% confidence interval: 1.67-25.7, p = .007) and overall survival (OR: 3.76, p = .037) in lung squamous cell carcinoma (SqCC). These results highlight the prognostic importance of the balance of tumor-infiltrating Tregs in resected lung SqCC.

Small cell lung cancer and interstitial pneumonia associated with anti-transcriptional intermediary factor-1γ-positive dermatomyositis.

Antibodies to transcriptional intermediary factor-1γ (TIF-1γ) are strongly associated with malignancy in patients with dermatomyositis but a relatively low risk for interstitial lung disease. We report the case of a 68-year-old female with small cell lung cancer (SCLC) and interstitial pneumonia who was diagnosed first with dermatomyositis positive for serum anti-TIF-1γ antibodies. Because interstitial pneumonia co-existed, she was treated with carboplatin and etoposide without radiotherapy. A significant improvement in skin disease and SCLC was seen in response to chemotherapy. The levels of anti-TIF-1γ antibodies were also decreased by chemotherapy. Her interstitial pneumonia was mild with normal pulmonary function and did not change during the observation period. This is the first report of dermatomyositis associated with anti-TIF-1γ antibodies co-existing with interstitial pneumonia and SCLC. Because cases with interstitial pneumonia in cancer-associated dermatomyositis positive for anti-TIF-1γ antibodies are few in number, further studies are necessary to elucidate the clinical features.

Cost-utility analysis of aprepitant for patients who truly need it in Japan.

PURPOSE: Neurokinin-1 receptor antagonist (NK1RA) is recommended to prevent chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly or moderately emetogenic chemotherapy (HEC or MEC, respectively). We previously reported that aprepitant, an NK1RA, was needed to control CINV in 43% and 12% of patients who received HEC and MEC, respectively (Support Care Cancer 23:905-912, 2015). To elucidate the cost-effectiveness of aprepitant in these patients, a cost-utility analysis according to the necessity of aprepitant was performed. METHODS: A decision-analytic model was developed according to the necessity of aprepitant and CINV responses in both acute and delayed phases of chemotherapy. Probabilities of health states and medical costs were derived from the results of the abovementioned trial. RESULT: In patients who received HEC and needed aprepitant, the incremental cost-effectiveness ratio (ICER) with aprepitant, relative to the regimen with no aprepitant, was 7912 US dollars (USD) per quality-adjusted life year (QALY) gained, which was far below the commonly accepted threshold of 50,000 USD/QALY. The ICER was 27,457 USD/QALY in patients who received MEC and needed aprepitant. In contrast, in patients who received HEC or MEC but did not need aprepitant, the ICER was 175,959 or 478,844 USD/QALY, respectively. CONCLUSION: Regardless of whether a patient received HEC or MEC, aprepitant use was highly cost-effective for patients who truly needed it. These results warrant further research to predict the necessity of NK1RA treatment before initiating emetogenic chemotherapies.

Bicytopenia in Primary Lung Melanoma Treated with Nivolumab.

A 73-year-old man who was a current smoker complained of weakness in his limbs and slow movement and was diagnosed with primary lung melanoma with brain metastases. Following stereotactic brain radiotherapy, nivolumab was administrated. After the first cycle of nivolumab, his blood neutrophil count and hemoglobin levels started to decline. Excluding other possible causes, nivolumab was considered the most probable cause of bicytopenia. Nivolumab was not restarted, and the bicytopenia gradually recovered with no corticosteroid administration for this event. While serious hematological adverse events regarding immune checkpoint inhibitors have been assumed to be rare, severe neutropenia and anemia should be considered in patients receiving immune checkpoint therapy.

Cathepsin S, a new serum biomarker of sarcoidosis discovered by transcriptome analysis of alveolar macrophages.

BACKGROUND: Development of reliable new biomarkers remains crucial to improve diagnosis and assessing disease activity in sarcoidosis. The objective of this study was to seek such markers from the gene expression signature of alveolar macrophages by transcriptome analysis. METHODS: Pooled RNA extracted from alveolar macrophages from patients with active sarcoidosis and control patients was subjected to transcriptome analysis using microarrays. Expressed gene intensity in sarcoidosis relative to that in control was calculated. We measured serum cathepsin S (CTSS) concentrations in 89 healthy volunteers, 107 patients with sarcoidosis, 26 with interstitial pneumonia, 150 with pneumoconiosis, and 76 with pulmonary mycobacteriosis by the enzyme-linked immunosorbent assay. RESULTS: Among 12 genes with ratios higher than that of a housekeeping gene, we selected CTSS for scrutinizing protein expression in serum because of the feasibility of the protein assay. CTSS concentrations were significantly increased in sarcoidosis compared with not only controls but also all the other lung diseases. Receiver operating characteristics curve for sarcoidosis and parenchymal lung diseases revealed an area under the curve of 0.800 (95% confidence interval, 0.751-0.850; p=1.4 x 10-18) with 70% sensitivity and 78% specificity at a CTSS concentration of 15.5 ng/ml. A significant trend was identified between CTSS concentrations and the number of affected organs. Serum CTSS concentrations varied in parallel with clinical courses both spontaneously and in response to corticosteroid therapy. Epithelioid cells in granulomas were positive for immunohistochemical staining with CTSS. CONCLUSIONS: CTSS has the potential to be a useful biomarker in sarcoidosis.

Cost-effectiveness of aprepitant in Japanese patients treated with cisplatin-containing highly emetogenic chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse event in cancer chemotherapy. Although aprepitant is effective in preventing CINV, an increment in financial burden for uniform use of aprepitant is a concern. The aim of the present study was to define the cost-effectiveness of aprepitant from the perspective of the Japanese National Health Insurance system. Based on the results of a randomized phase II trial comparing an aprepitant-containing regimen versus a nonaprepitant regimen in Japanese patients who received cisplatin-containing highly emetogenic chemotherapy, a decision analytic model was developed. The incremental cost-effectiveness ratio (ICER) was calculated both in the outpatient care setting (OCS) and in the inpatient care setting (ICS). The use of the aprepitant-containing regimen was associated with improved quality of life compared with the nonaprepitant regimen, with an increment in quality-adjusted life years (QALY) of 0.0016. The incremental total medical costs associated with the use of the aprepitant regimen were lower in the OCS than in the ICS, 6192 JPY (56.92 USD) and 9820 JPY (90.27 USD), respectively. The ICER was calculated as 3 906 698 JPY (35 910 USD) per QALY gained in the OCS and 6 195 781 JPY (56 952 USD) per QALY gained in the ICS. Cost-effectiveness of the aprepitant-containing antiemetic therapy was limited to the OCS, considering the threshold of willingness-to-pay commonly accepted (5 million JPY [45 960 USD] in Japan and 50 000 USD in the USA). The efficacy of aprepitant offsets the costs for revisiting clinics or rehospitalization added with rescue medications in the OCS.

Clinical significance of serum anti-GM-CSF autoantibody levels in autoimmune pulmonary alveolar proteinosis.

AIM: Precise clinical significance of antigranulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar proteinosis (aPAP) has not been well studied. METHODS: We obtained sera from 50 healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP patients was assessed by scoring computed tomography images in 19 patients. RESULTS: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and other diffuse lung diseases was 2.8 µg/ml with 100% sensitivity and 98% specificity. Antibody levels at baseline were significantly lower in the improved group than in the unimproved group (p = 0.008). CONCLUSION: Our results indicate the existence of threshold levels of serum anti-GM-CSF IgG for the development and persistence of aPAP.

Interstitial Lung Disease after Pleurodesis for Malignant Pleural Effusion.

Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.

A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis.

RATIONALE: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. OBJECTIVES: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. METHODS: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. RESULTS: CT grade score and CT extent score had significant correlation with diffusing capacity of the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre- and post-treatment examinations (ΔCT grade) correlated better with difference of PaO2 between pre- and post-treatment examinations (ΔPaO2) than ΔCT extent (difference of CT extent score between pre- and post-treatment examinations). In univariate analysis, ΔCT grade, ΔCT extent, ΔKL-6, Δ%DlCO, Δ%VC, and change in surfactant protein D correlated significantly with ΔPaO2. In multivariate analysis, ΔCT grade and ΔKL-6 correlated more closely with ΔPaO2. CONCLUSIONS: Although a number of CT variables were collected, the currently proposed grading system that correlates well with PaO2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort.

The ATS/ERS/JRS/ALAT statement "IPF by HRCT" could predict acute exacerbation of interstitial lung disease in non-small cell lung cancer.

INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are at high risk of acute exacerbation of ILD (AE-ILD) when treated with systemic chemotherapy. Standard treatment for NSCLC complicated by ILD has not been established. PURPOSE AND METHODS: To examine whether the type of ILD categorized by the official ATS/ERS/JRS/ALAT statement as "idiopathic pulmonary fibrosis (IPF) by high-resolution computed tomography (HRCT)" could predict chemotherapy-induced AE-ILD in NSCLC patients with ILD, we retrospectively reviewed all patients with NSCLC complicated by ILD who had received chemotherapy at our institute from January 2007 until December 2013. Patients' characteristics, pathology and clinical staging of lung cancer, chemotherapy, type of ILD and AE-ILD during chemotherapy were evaluated. ILD was classified according to the statement as follows: usual interstitial pneumonia (UIP), possible UIP, and inconsistent with a UIP pattern. RESULTS: A total of 46 patients had pre-existing ILD and received chemotherapy. The mean age was 73 years (range 46-83 years). Fifteen (32.6%) of 46 patients with ILD developed chemotherapy-induced AE-ILD, which was seen more frequently in patients with ILD with a UIP pattern or possible UIP pattern than in patients with a pattern inconsistent with UIP (80% versus 9.7%, p<0.001). Multivariate analyses including age, sex, performance status and radiographic patterns of ILD showed that the presence of a UIP or possible UIP pattern was an independent risk factor for chemotherapy-induced AE-ILD. CONCLUSIONS: ILD with a UIP pattern or possible UIP pattern by the classification could be a risk factor for AE-ILD in NSCLC patients with ILD.

Adenoid Cystic Carcinoma of the Lung with an EGFR Mutation.

An 80-year-old woman was referred to our hospital due to the presence of a mass that was identified on a chest X-ray. A further investigation demonstrated advanced adenoid cystic carcinoma of the lungs. Anti-cancer chemotherapy with docetaxel was carried out and the lesion remained as stable disease. Subsequently, pleural effusion was detected, and an investigation of the pleural effusion revealed the existence of malignant cells with an epidermal growth factor (EGFR) mutation. Gefitinib was administered and the pleural effusion resolved. This is the first case of a positive EGFR mutation of adenoid cystic carcinoma of the lung with a favorable response to an EGFR-tyrosine kinase inhibitor.

Successful treatment of non-small cell lung cancer with gefitinib after erlotinib-induced severe eyelid erosion: Two case reports.

Gefitinib and erlotinib are first-generation, small, molecular inhibitors of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Even as these drugs have led to a paradigm shift in the treatment of advanced non-small cell lung cancer (NSCLC), drug-induced adverse effects are commonly seen. We experienced two cases of NSCLC patients who developed erlotinib-induced eyelid erosion and were then successfully treated with gefitinib, without recurrence of toxicity or disease progression. As far as we had investigated, this is the first report documenting the successful cases treated with gefitinib after erlotinib-related severe eyelid erosion.