[Retracted] Predictors of efficacy of anamorelin in patients with non­small cell lung cancer and cachexia: A retrospective study.

[This retracts the article DOI: 10.3892/ol.2023.14154.].

Predictors of efficacy of anamorelin in patients with non­small cell lung cancer and cachexia: A retrospective study.

Anamorelin, a ghrelin receptor agonist, is approved in Japan for the treatment of cachexia in patients with lung and gastrointestinal cancer. However, there is limited research on the usefulness of anamorelin in clinical settings, therefore, the present study evaluated its efficacy using patient characteristics. A total of 40 patients with non-small cell lung cancer and cachexia who were prescribed anamorelin in the Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine (Aomori, Japan) between July 2021 and November 2022, were retrospectively assessed. Anamorelin was prescribed at a dose of 100 mg once daily to patients who had lost >5% of their body weight within 6 months. All patients were weighed before treatment and those who continued anamorelin treatment for 12 weeks were also weighed at 12 weeks. A logistic regression analysis was used to analyze the association between background characteristics and early discontinuation of treatment with anamorelin (within 4 weeks). The median age was 67 years (range, 36-88), and 65% of the patients were male. There were 24 patients (60.0%) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score 1, 11 patients (27.5%) with an ECOG-PS score 2 and five patients (12.5%) with an ECOG-PS score 3. The early discontinuation group included 11 patients (27.5%). An ECOG-PS score ≥2 (odds ratio, 7.85; 95% confidence interval, 1.43-43.21; P=0.018) was associated with early discontinuation. A total of 18/40 patients (45.0%) were able to continue anamorelin treatment for 12 weeks, and the mean change in body weight was +2.31 kg, which was a significant change from the weight recorded at baseline (P=0.027). The mean changes in lean body mass and soft lean mass between baseline and 12 weeks were +1.97 kg (P=0.14) and +1.26 kg (P=0.15), respectively. The results from the present study indicate that anamorelin is unlikely to be useful for patients with a poor general condition (ECOG-PS score ≥2).

Role of G-protein-coupled estrogen receptor in the pathogenesis of chronic asthma.

BACKGROUND AND AIM: G protein-coupled estrogen receptor (GPER) is an estrogen receptor located on the plasma membrane. We previously reported that the administration of G-1, a GPER-specific agonist, suppressed development of acute ovalbumin (OVA)-induced asthma in a mouse model. Herein, we evaluate the involvement of GPER in a mouse model of chronic OVA asthma. METHODS: G-1 or saline was administered subcutaneously to BALB/c mice with chronic OVA asthma, and pathological and immunological evaluation was performed. In addition, Foxp3-expressing CD4-positive T-cells in the spleen and ILC2 in the lungs were measured using flow cytometry. RESULTS: We observed a significant decrease in the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) in the G-1 treated group. In the airways, inflammatory cell accumulation, Th2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and epithelial cytokine TSLP were suppressed, while in the BALF, anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. Furthermore, in splenic mononuclear cells, Foxp3-expressing CD4-positive T-cells were increased in the G-1 group, whereas treatment with G-1 did not change the percentage of ILC2 in the lungs. CONCLUSION: G-1 administration suppressed allergic airway inflammation in mice with chronic OVA asthma. GPER may be a potential therapeutic target for chronic allergic asthma.

Criterion validity of the health assessment questionnaire for the national screening program for older adults in Japan: The SONIC study.

AIM: In our previous study, we proposed that the total score of the 12 frailty-related items in the health assessment questionnaire for the national screening program for older adults could be used as an indicator of frailty. We aim to examine the criterion validity of the 12 frailty-related items for frailty. METHODS: The data used in this study were from older Japanese individuals aged 78-81 years (n = 461) who participated in the in-venue (2019) and mailed questionnaire (2020) surveys of the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. A receiver operator characteristic (ROC) curve analysis was used to evaluate the criterion validity of the 12 frailty-related items for frailty defined based on the Japanese version of the Cardiovascular Health Study criteria. A multivariable logistic regression model was used to examine the independent association of the 12 frailty-related items with frailty. RESULTS: The area under the ROC curve of the scores of the 12 frailty-related items for frailty was 0.79 (95% confidence interval [CI] = 0.73-0.85, P < 0.001). The cut-off value for frailty was 3 and 4 points, and the sensitivity and specificity were 55.9% and 85.8%, respectively. The multivariable logistic regression model showed that four or more scores of the 12 frailty-related items were significantly associated with frailty (adjusted odds ratio = 7.75, 95% CI = 4.10-14.65, P < 0.001). CONCLUSIONS: The results of this study suggest that the 12 frailty-related items in the health assessment questionnaire for older adults may be useful for assessing frailty in community-dwelling older adults in a simplified manner. Geriatr Gerontol Int 2023; 23: 437-443.

Granulomatosis with Polyangiitis following COVID-19 in an Adolescent.

Granulomatosis with polyangiitis (GPA) is a systemic disease that causes vasculitis in various organs. Although the mechanism of pathogenesis remains unclear, infection has been reported to be a causative factor. We herein report a case of GPA that developed following coronavirus disease 2019 (COVID-19) in an adolescent girl. One month after contracting mild COVID-19, the patient had facial allodynia, a fever, and weight loss and was admitted for multiple nodular shadows on a chest roentgenogram. GPA was diagnosed based on pathological findings of the lung and nasal mucosal biopsies. She received methylprednisolone and rituximab, and her symptoms and radiological findings improved.

Early- to late-life environmental factors and late-life global cognition in septuagenarian and octogenarians: The SONIC study.

This study aimed to evaluate cognitively stimulating environments throughout life and to examine direct and indirect associations between these environments and late-life cognition. Early-life education, three domains of work complexity (data, people, and things) based on the longest-held occupation, and engagement in late-life leisure activities (LAs) were assessed. A structural equation model was developed using cross-sectional data of 1721 Japanese older adults in 70 ± 1 and 80 ± 1 years. The model confirmed significant direct effects of work complexity with data and late-life LAs on late-life cognitive performance. The associations of education and work complexity with late-life cognition were mediated through the subsequent environment(s). However, the total effects of work complexity with people and things on late-life cognition were insignificant. The findings suggest that cognitively stimulating activities in adulthood and beyond may lead to individual differences in late-life global cognition. In addition, antecedent complex environments might make subsequent life environments more cognitively stimulating. The results are discussed from the perspectives of cognitive plasticity and environmental complexity.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Acute Exacerbation of Interstitial Lung Disease After SARS-CoV-2 Vaccination: A Case Series.

CASE PRESENTATION: An acute exacerbation of interstitial lung disease (ILD) is an acute deterioration that can occur at any time and is associated with significant morbidity and mortality rates. We herein report three patients with ILD who experienced acute respiratory failure after SARS-CoV-2 messenger RNA vaccination. All the patients were male; the mean age was 77 years. They had a smoking history that ranged from 10 to 30 pack-years. Duration from the vaccination to the onset of respiratory failure was 1 day in two patients and 9 days in one patient. In an autopsied case, lung pathologic evidence indicated diffuse alveolar damage superimposed on usual interstitial pneumonia. In the other two cases, CT scans showed diffuse ground-glass opacities and subpleural reticulation, which suggests acute exacerbation of ILD. Two patients were treated successfully with high-dose methylprednisolone. Although benefits of vaccination outweigh the risks associated with uncommon adverse events, patients with chronic lung diseases should be observed carefully after SARS-CoV-2 vaccination.

Associations between salivary testosterone levels and cognitive function among 70-year-old Japanese elderly: A cross-sectional analysis of the SONIC study.

AIM: This cross-sectional study aimed to investigate the associations between salivary testosterone concentrations and cognitive function in 70-year-old Japanese elderly people without dementia and stroke. METHODS: Participants were 197 Japanese community-dwelling people aged 69-71 years. Their salivary samples were collected, and their cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Participants were also administered a 10-item recall and a 24-item recognition test. The data for 179 (106 men and 73 women) individuals were analyzed, excluding individuals with a past history of stroke and dementia. Multivariate logistic regression analyses were performed after adjusting for lifestyle factors and analyzing data separately for men and women. RESULTS: MoCA-J scores showed that men with low testosterone concentrations had a significantly greater risk of low cognitive performance than those with high testosterone concentrations (adjusted odds ratio: 4.72, 95% confidence interval: 1.06-21.00), while no significant association was found in women. The 10-item recall test scores showed that higher testosterone concentrations were significantly associated with greater recall in the second trial in women (standardized beta = 0.24, P = 0.040), whereas no significant association was found in men. Salivary testosterone concentrations were positively associated with better cognitive performance in older men and women. CONCLUSIONS: The associations between salivary testosterone concentrations and cognitive function were shown by different tasks for men and women. Geriatr Gerontol Int 2022; 22: 1040-1046.

Construct Validity of a New Health Assessment Questionnaire for the National Screening Program of Older Adults in Japan: The SONIC Study.

The Japanese government has implemented a new screening program to promote measures to avoid worsening lifestyle-related diseases and frailty among the older population. In this effort, the government formulated a new health assessment questionnaire for the screening program of old-old adults aged ≥75 years. The questionnaire comprises 15 items, of which 12 address frailty, two address general health status, and one addresses smoking habits. This study examined the construct validity of this questionnaire, using the explanatory factor analysis (EFA) and confirmatory factor analysis (CFA). The data used in this study were drawn from a mail-in survey conducted in 2020 as part of the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. A total of 1576 respondents (range, 78-99 years of age) were included in the study. Although the EFA did not show an interpretable factor structure of the questionnaire with 15 items, the CFA using only 12 frailty-related items showed the goodness of fit for a higher-order factor "frailty", and the five frailty-related sub-factors model was acceptable. These results suggest that the total score of the 12 frailty-related items in the questionnaire can be used as an indicator of the degree of "frailty".

Older Adults' Resilience Against Impact of Lifestyle Changes During the COVID-19 Pandemic.

Background: Older adults were expected to experience a decline in physical activities and an increase in social isolation during the COVID-19 pandemic. Methods: We investigated the changes in living conditions of 508 older adults (79.70 years ± 0.88) before (from July to December 2019) and during (in August 2020) the pandemic. We compared the mean score for the same individual instrumental activities of daily living (IADL), frequency of going out, exercise, and social interaction at two-time points. We also examined the influence of living arrangement (living alone or not) on the frequency of exercise and social interaction. Results: The frequency of going out decreased during the pandemic (in 2020); however, there was no significant change in IADL. The frequency of exercise and social interaction increased irrespective of the living arrangement. The frequency of exercise increased more in those living alone. Conclusions: Although older adults refrained from going out, they compensated for the risks of inactivity in daily life by increasing or maintaining their frequency of exercise and social interactions. The view that "older adults have a poor ability to accommodate the lifestyle changes during the COVID-19 pandemic" may be a stereotypical assumption.

Morphological features of bronchiectasis in patients with non-tuberculous mycobacteriosis and interstitial pneumonia.

OBJECTIVE: To compare the morphological features of bronchiectasis between patients with different underlying diseases, we performed quantitative analysis of high-resolution computed tomography (HRCT) images of 14 patients with non-tuberculous mycobacteriosis (NTM) and 13 with idiopathic pulmonary fibrosis (IPF). A 3D image of the bronchial structure was made from HRCT data. Bronchiectasis was defined as abnormal dilatation of the bronchi with the diameter greater than that of the accompanying pulmonary artery. We measured the inner and outer diameters, wall area as %total airway cross sectional area (WA%), and wall thickness to airway diameter ratio (T/D) of the 4-8th generations of bronchi. RESULTS: In patients with IPF, the inner and outer diameters linearly decreased toward the distal bronchi. In contrast, the inner and outer diameters of NTM fluctuated. The coefficient of variation of the outer diameters of the 6-7th generations of bronchi was larger in the NTM patients than in those with IPF, whereas no significant difference was observed in the coefficient of variation of the inner diameters between the groups. In IPF patients, WA% and T/D varied between the generation of bronchi, but the coefficient of variation of WA% and T/D was relatively small in those with NTM.

Association of Personality with Cognitive Failure among Japanese Middle-Aged and Older Adults.

This study explored the associations between personality traits and cognitive failure (including minor lapses and prospective and retrospective memory failure) among middle-aged and older adults living in Japan. The participants were 373 adults, aged 40-84 (167 men and 206 women). The 15-item Japanese version of the Short Inventory of Minor Lapses was used to evaluate minor lapses, and the 16-item Japanese version of the Prospective and Retrospective Memory Questionnaire was used to assess prospective and retrospective memory failure. The participants' variables evaluated for their association with cognitive failure were gender, age, education, paid work, social network, chronic disease, sleep quality, and the Big Five personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and conscientiousness). Multivariable regression analyses demonstrated that sleep quality (ß = -0.232), neuroticism (ß = 0.163), and conscientiousness (ß = -0.295) were related to minor lapses; age (ß = 0.152), sleep quality (ß = -0.168), and conscientiousness (ß = -0.290) were associated with prospective memory failure; and age (ß = 0.268), sleep quality (ß = -0.146), and conscientiousness (ß = -0.221) were associated with retrospective memory failure. These findings may facilitate the development of efficient strategies for the prevention of cognitive dysfunction and its adverse consequences for personal health.

The efficacy of nintedanib in 158 patients with idiopathic pulmonary fibrosis in real-world settings: A multicenter retrospective study.

BACKGROUND: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. METHOD: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. RESULT: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (-253 ± 163 vs -125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (-353 ± 250 vs -112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. CONCLUSION: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.

Leisure activity moderates the relationship between living alone and mental health among Japanese older adults.

AIM: As living alone is associated with poor mental health, seeking a moderating factor in this relationship may help enhance quality of life of older people living alone. Therefore, this study examined the moderating effect of leisure activity on the relationship between living alone and mental health in older people. METHODS: This study employed a cross-sectional analysis of questionnaire data. Research was conducted in a metropolitan Tokyo ward from September to October 2017. Participants were 314 community-dwelling Japanese individuals (158 women, 156 men) aged 70-84 years (mean ± SD, 77.7 ± 4.4). We analyzed mental health using the Japanese version of the World Health Organization-Five Well-Being Index as the outcome variable, and the 11 items of the Leisure Activity Scale and living arrangements as explanatory variables. Multivariate analyses were used to examine effects of leisure activity on living arrangements and mental health. RESULTS: The proportion of people living alone was 22.9% (N = 72), and the mental health score was mean ± SD, 14.2 ± 7.2. Multiple regression analysis showed that subjective economic status (ß = -0.177), instrumental activities of daily living (ß = 0.167), living arrangements (ß = -0.142) and leisure activity (ß = 0.481) were associated with mental health. The interaction effect between living arrangements and leisure activity on mental health was significant (ß = 0.112). CONCLUSIONS: Our findings show that leisure activity moderates poor mental health in older adults living alone. Accordingly, interventions should encourage older adults living alone to engage in leisure activity to improve their mental health. Geriatr Gerontol Int 2021; 21: 421-425.

Procalcitonin expression in patients with large cell neuroendocrine carcinoma of the lung.

OBJECTIVE: Procalcitonin (PCT) has received much attention as a serum marker for bacterial infection. Elevated serum PCT is occasionally seen in severe trauma, heatstroke, and neoplastic diseases, including lung cancer with neuroendocrine component. RESULTS: In the present study, we evaluated PCT expression in the specimen of pulmonary neuroendocrine tumors, comparing large cell neuroendocrine carcinoma (LCNEC), carcinoid, and small cell lung carcinoma (SCLC). Pathological specimens of 10 LCNEC, 4 carcinoid, and 7 SCLC cases were evaluated with immunochemical staining of PCT. Clinical characteristics and serum levels of PCT and C-reactive protein were also evaluated. We observed positive PCT expression in 5 (50%) LCNEC and 2 (50%) carcinoid specimens that were surgically resected. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease progression. In patients with SCLC, PCT was not detected in the tumor or serum. This is the first immunohistochemical study of the PCT expression in the lung tumor specimens. We concluded that, in patients with LCNEC, high serum PCT levels may be indicative of disease activity and serve as a biomarker.

A Phase I/II Study of Biweekly Carboplatin and Nab-paclitaxel With Concurrent Radiotherapy for Patients With Locally Advanced Unresectable Stage III Non-small-cell Lung Cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small-cell lung cell cancer (LA-NSCLC). We conducted a phase I/II study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with radiotherapy (RT). MATERIALS AND METHODS: In the phase I part, patients with inoperable stage IIIA/IIIB NSCLC were treated with carboplatin (area under the time-concentration curve, 4) and nab-PTX (60-100 mg/m2) on days 1, 15, and 29. Thoracic RT was administered from day 1 to a total dose of 60 Gy in 30 fractions. In the phase II part, patients were administered carboplatin and nab-PTX on days 1, 15, and 29 at the recommended dose (RD). The primary endpoint of the phase I part was to determine the maximum tolerated dose and the RD. In the phase II part, the primary endpoint was 2-year overall survival (OS) rate, and secondary endpoints were the objective response rate, progression-free survival, OS, and safety profile. RESULTS: In the phase I part, although maximum tolerated dose was not obtained, the RD was carboplatin (area under the time-concentration curve, 4) and nab-PTX (100 mg/m2). Of the evaluable 28 patients, the rate of 2-year OS was 67.8% (95% confidence interval, 49.3%-82.1%). The objective response rate was 96.4%, and the median follow-up time was 33.2 months. The median progression-free survival was 18.2 months (95% confidence interval, 13.1 months to not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.2%), and pneumonitis (3.6%). CONCLUSIONS: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT was well-tolerated and exerted promising antitumor activity.

Destroyed lung due to sustained inflammation after chemoradiotherapy followed by durvalumab.

A 68-year-old male patient with squamous cell carcinoma (cT4N2M0) of the left upper lobe received chemoradiotherapy followed by durvalumab, an immune checkpoint inhibitor. The tumour responded well to the therapy, but an infiltrative shadow appeared in the left upper lobe, which was outside the radiation field. Despite treatment with corticosteroid and antibiotics, the development of a cavitary lesion was noted. As Aspergillus fumigatus was isolated from the bronchoscopy specimen, antifungal agents were also administered, but the cavitary lesion further developed. Because his general condition worsened and the entire left lung was destroyed, the patient underwent a left pneumonectomy and recovered without recurrence. The pathology of the removed lung revealed a scarred nodule with granulation tissue around and a cavernous lesion having a necrotic substance inside. We considered that durvalumab might further accelerate the inflammatory response, which had been introduced by fungal infection, leading to uncontrollable inflammation of the lung.

A pilot study of adjuvant chemotherapy with carboplatin and oral S-1 for patients with completely resected stage II to IIIA non-small cell lung cancer.

BACKGROUND: Adjuvant chemotherapy with platinum-based regimens for completely resected early-stage non-small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials. OBJECTIVES: We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S-1 for patients with completely resected stage II to IIIA NSCLC. METHODS: Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S-1 at 80-120 mg/bodyweight per day for two weeks, followed by one-week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two-year survival rate. RESULTS: A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1-4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6-91.4%). Two-year disease-free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied. CONCLUSIONS: Carboplatin and oral S-1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients. KEY POINTS: Carboplatin and oral S-1 had modest survival benefit but this regimen was not tolerable. Fatal pulmonary embolism occurred in this regimen.

Effect of nintedanib on non-small cell lung cancer in a patient with idiopathic pulmonary fibrosis: A case report and literature review.

Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In addition, in EU countries, nintedanib plus docetaxel is used for patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. Here, we report a case of advanced NSCLC in a patient with IPF successfully treated with nintedanib monotherapy. A 69-year-old man was diagnosed with NSCLC complicated by IPF. After three lines of chemotherapy, he still had progressive disease. Because his IPF had also progressed, requiring supplemental oxygen, we decided to start best supportive care and introduced nintedanib to treat his IPF. One month later, we observed a partial remission of the primary tumor and pleural disseminations without severe adverse events. Nintedanib monotherapy might therefore be an effective therapeutic choice for NSCLC in patients with IPF who are unable to tolerate cytotoxic chemotherapy. KEY POINTS: Efficacy of nintedanib administered in a NSCLC patient with IPF. Nintedanib monotherapy might be a therapeutic option for NSCLC patients with IPF who are unable to tolerate chemotherapy.