Long­term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli: A case report.

Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.

Octogenarians With Anaplastic Lymphoma Kinase-rearranged Non-small-cell Lung Cancer: A Case Series.

BACKGROUND/AIM: Anaplastic lymphoma kinase (ALK) rearrangements define a distinct group of patients with non-small-cell lung cancer (NSCLC), mainly represented by never-smoking young individuals. However, we also encounter elderly patients with ALK-rearranged NSCLC over the age of 80 years. We report herein three cases of these patients that we have experienced. CASE REPORT: Three patients with ALK-rearranged NSCLC aged 80 years or older received therapy with the ALK-tyrosine kinase, alectinib. Of them, one was male and two had a history of smoking. Comorbidities, especially heart diseases, were prominent. Long-term survival was achieved with alectinib treatment in two patients. CONCLUSION: ALK-rearranged mutations should be evaluated even in octogenarians with NSCLC, regardless of sex and smoking history. Even if they have comorbid diseases, long-term control might be achieved with alectinib therapy in cooperation with physicians other than chest physicians and medical oncologists.

Five-year Disease Control With Alectinib in a Patient With Metastatic ALK-rearranged Lung Adenocarcinoma.

BACKGROUND/AIM: Therapy with alectinib could achieve prolonged progression-free and overall survival in patients with anaplastic lymphoma kinase gene (ALK)-rearranged non-small-cell lung cancer (NSCLC). However, a large proportion of the patients discontinue alectinib treatment due to recurrence. CASE REPORT: A 41-year-old male patient presented with cellulitis of the right upper extremity that had developed in the past 3 weeks. Chest radiograph at the time of admission incidentally revealed a nodule in the right lung. At diagnosis, the patient had spinal bone metastases and thrombosis in the common jugular vein subclavian veins. Therefore, in addition to warfarin therapy and irradiation to the bone metastases, chemotherapy was started. After identifying the presence of the ALK rearranged gene, alectinib therapy was initiated. Since then, alectinib treatment has been continued for more than 5 years. CONCLUSION: Although very rare, there are patients who might be able to maintain a long-term response to alectinib. It is important for chest physicians to manage such patients so that the effects of alectinib can be maintained for a long time.

Discontinuation of Immune Checkpoint Inhibitor and Survival in Patients With Non-small-cell Lung Cancer Without a Driver Gene Mutation.

BACKGROUND/AIM: Patients with non-small-cell lung cancer treated with immune checkpoint inhibitors (ICI) might be forced to discontinue treatment for various reasons. We conducted a retrospective study to evaluate the impact of discontinuation of ICI treatment on patient prognosis. PATIENTS AND METHODS: We performed a retrospective study that reviewed the medical charts of 86 patients treated with ICI monotherapy and 34 patients treated with a combination of ICI and chemotherapy during the period from February 2016 to February 2022 at our two hospitals. 'Discontinuation' was defined as a cessation of ICI treatment for more than two cycles for any reason. RESULTS: The two most common reasons for discontinuation were immune-related adverse events and at the request of the patient. Nineteen patients who had discontinued ICI, resumed ICI or another therapy. Discontinuation of ICI treatment was a favorable factor in overall survival in 84 patients with ICI monotherapy as well as in 34 patients treated with chemotherapy combined with ICI. CONCLUSION: This analysis found discontinuation of ICI treatment did not adversely affect prognosis. This suggests that when treating patients with non-small-cell lung cancer with ICI, chest physicians should respond flexibly, and, with careful monitoring, consider discontinuation of ICI.

Significance of Polar Charged Amino Acids in Compound Mutations in EGFR-mutated Patients Treated With First-line Afatinib.

BACKGROUND/AIM: Next-generation sequencing (NGS) has recently made it possible to investigate polar charged amino acids in compound mutations in the epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Several preclinical studies have suggested the involvement of polar charged amino acids in the treatment of EGFR mutations and EGFR-tyrosine kinase inhibitors (TKIs). With this background, a retrospective study was conducted aiming to clarify the prognostic significance of these amino acids in complex mutations in NSCLC patients with common EGFR mutations. PATIENTS AND METHODS: EGFR gene mutations were investigated using nonoverlapping integrated read sequencing system (NOIR-SS) in pathological specimens of 20 EGFR-mutated NSCLC patients. For clinical information, the medical records were retrospectively investigated. We investigated prognostic significance of these amino acids in compound mutations in progression free survival (PFS) and overall survival (OS) in patients treated with first-line afatinib. RESULTS: Among the 20 patients examined, 5 patients had polar charged amino acids in compound mutations and 15 had not. There were no statistically significant differences in the clinical background factors examined in these two groups of patients. In uni- and multivariate analysis, 'poor performance status' and 'polar charged amino acids in compound mutations' were significant favorable factors in OS. CONCLUSION: Patients with 'polar charged amino acids in compound mutations' might have favorable prognosis than those without them. Detailed examination of EGFR gene information might contribute to the understanding of TKI response duration.

Lung cancer and combined pulmonary fibrosis and emphysema with anti-ARS antibody.

A 59-year-old man who had smoked for 23 pack-years was admitted to our hospital because of two-month history of back pain. The chest computed tomography scan demonstrated combined pulmonary fibrosis and emphysema (CPFE) and an irregular shaped nodule in the left lower lobe of the lung. A biopsy obtained from samples from subcarinal lymph nodes revealed non-small cell lung cancer. Anti-aminoacyl-tRNA synthetase (ARS) antibody was elevated up to 166 U/mL, although he had no symptoms suggestive connective tissue diseases. It is well known that most of CPFE patients are current or former heavy smokers, and some researchers described the relationship between CPFE and connective tissue diseases. To our best knowledge, this was the first report of lung cancer in patient with anti-ARS antibody-positive CPFE. In some anti-ARS antibody-positive patients, smoking might have a relationship with development of CPFE and lung cancer.

Body Weight Change in Non-small Cell Lung Cancer Patients Treated With EGFR-TKI.

BACKGROUND/AIM: Body weight (BW) changes in epidermal growth factor inhibitor-tyrosine kinase (EGFR-TKI) treated non-small cell lung cancer patients has yet to be fully investigated. For the purpose of clarifying changes in body weight in patients who received EGFR-TKI treatment in clinical practice, we performed a retrospective study. In this study, comparison between pretreatment BW and those at 12, 24 weeks, and 12 months in these patients was performed. PATIENTS AND METHODS: We included all the patients diagnosed with EGFR mutated NSCLC in two tertiary hospitals between April 2009 and March 2021. BW records in the medical chart of each patient who was treated with EGFR-TKI for more than 12 weeks were surveyed. In each patient, BW at 12, 24 weeks, and 12 months from the initiation of EGFR-TKI treatment were compared with pretreatment BW. RESULTS: Sixty-three patients obtained TKI treatment for more than 12 weeks and had comparable body weight records. Compared with the pretreatment BW, decreased BW was observed at 12, 24 weeks, and 12 months from the initiation of TKI treatment. CONCLUSION: Even in patients treated with EGFR-TKI, which is evaluated as less toxic and a more effective therapy, there might be patients who lose weight during the treatment period. Chest physicians will be required to provide medical care even for EGFR mutated patients, taking into consideration changes in BW.

Eosinophilic Pneumonia with Marked Peripheral Eosinophilia during the Course of Sarcoidosis.

Patients with sarcoidosis are known to have peripheral blood eosinophilia (PBE). However, most of them had PBE slightly above the upper limit of the normal range. Few patients had increased eosinophils in the bronchoalveolar lavage fluid (BALF), and eosinophilia in BALF enough to be diagnosed as eosinophilic pneumonia (EP) was extremely rare. We present herein a sarcoidosis case with PBE. There were fluctuations in peripheral eosinophils consistent with sarcoidosis disease activity, and peripheral blood eosinophils increased up to 50%, 12500/mm3, although the patient was affected by cough variant asthma and multimodal therapies for breast cancer. Some case reports showed EP in patients with sarcoidosis. To our best knowledge, however, no sarcoidosis patient presented with such a high level of PBE. In this report, we would like to emphasize that there might be patients with sarcoidosis who have a marked increase in peripheral blood eosinophils.

Pulmonary co-infection with Actinomyces odontolyticus and Mycobacterium kansashii.

Dear Editor, We read with interest the article by Balis et al. on pulmonary tuberculosis and actinomyces co-infection as a lung mass....

Nintedanib-mediated improvement in CT imaging in pulmonary fibrosis associated with systemic scleroderma.

Nintedanib is an antifibrotic drug that has an inhibitory effect on growth factor tyrosine kinases. In patients with idiopathic pulmonary fibrosis and systemic scleroderma-associated interstitial pneumonia (SSc-IP), nintedanib has been effective in suppressing the decline in forced vital capacity over time and the onset of acute exacerbation of interstitial pneumonia. Here, we report a SSc-IP patient who showed an improvement on CT images following nintedanib treatment. To our knowledge, this is the first report of such a case. Although SSc-IP patients are very rare, additional clinical experience and understanding will be required to prove the therapeutic benefit of nintedanib in these cases in relation to improved chest images.

Yellow nail syndrome with massive chylothorax after esophagectomy: A case report.

Yellow nail syndrome (YNS) is a rare condition characterized by the triad of yellow nails, lymphedema, and respiratory manifestations. Diuretics and thoracic drainage are often not effective in YNS, and the most effective treatments are pleurodesis and decortication/pleurectomy. A 66-year-old man was admitted to our hospital for YNS after esophagectomy with gastric tube reconstruction for esophageal cancer. The patient presented with yellow nails and lymphedema. Chest X-rays and computed tomography showed massive pleural effusions and ascites that were both chylous. The patient was considered to have YNS that became apparent after surgery. He recovered with diuretics and a low-fat diet without pleurodesis and decortication/pleurectomy. Thoracic surgery can exacerbate the functional impairment of lymphatic drainage in patients with asymptomatic and undiagnosed YNS, and can lead to further development of YNS-related clinical symptoms. Despite relatively massive chylothorax following thoracic surgery, chylothorax related to YNS could be successfully controlled with conservative treatment without pleurodesis and decortication/pleurectomy.

Imaging characteristics of nontuberculous mycobacterial pulmonary nodules.

Introduction. Nontuberculous mycobacteriosis (NTM) of the lungs can develop nodules. In order to clarify some of the characteristics of lung NTM nodules, we examined volume doubling time (VDT) and maximum standardized uptake value (SUVmax) in positron emission tomography (PET) of pathologically diagnosed NTM nodules. Methods. From November 2012 to August 2018, clinical and radiological information were retrospectively investigated in eight patients who were surgically resected and diagnosed as NTM. These eight patients were followed up until November 2020 and were confirmed to have no appearance of lung cancer or reappearance of lung NTM nodules. The VDT was calculated using the Schwartz formula. Results. The median maximum diameter of the nodule at the time of the first CT scan was 16.0 (range: 9.9-20.0) mm. The median maximum diameter of the nodule on CT performed before the surgical biopsy was 18.8 (range: 10.4-32.8) mm. The median doubling time calculated from these results was 203 (range: 20-568) days. Caseous granulomas and acid-fast bacilli were histologically confirmed in all eight patients. Culture of excised nodules revealed Mycobacterium intracellulare in five patients and Mycobacterium avium in three patients. Six patients received PET, and median SUVmax was: 7.0 (range: 3.3-21.0). Median VDT was around 200 days. Some patients had irregular-shaped nodules. Conclusions. CT/PET-CT characteristics of lung nodules are not reliable in differentiating lung NTM nodules from malignant ones. To avoid unnecessary resection, it may be better to collect various information on imaging findings in the nodule itself and in opacities other than the nodule.

Association between peripheral eosinophils and clinical outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

INTRODUCTION: Programmed cell death ligand 1 is considered a predictor of the therapeutic effect of immune checkpoint inhibitors (ICPIs), but a more simple and useful predictor is needed. OBJECTIVES: The aim of this study was to identify the relationship between eosinophil counts and percentages and response to ICPI therapy. PATIENTS AND METHODS: In 190 patients with non-small cell lung cancer (NSCLC) treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of ICPI therapy initiation, the maximum counts and percentages of eosinophils during ICPI therapy, response to therapy, and time to treatment failure (TTF) were investigated. RESULTS: Both an increase in the peripheral eosinophil count and an elevation of eosinophil percentage following the initiation of ICPI therapy were observed, regardless of whether the patients had controlled or progressive disease. The median time to the maximum eosinophil percentage was 5 weeks in patients with controlled disease and 2 weeks in those with progressive disease. The cutoff value for the maximum eosinophil counts and percentage during ICPI therapy was set at 300/µl and 5%, respectively, to identify the presence or absence of a therapeutic effect. Time to treatment failure was longer in patients with maximum eosinophil counts exceeding 300/µl and a maximum eosinophil percentage above 5%. In a multivariable analysis, a maximum eosinophil percentage of 5% during ICPI therapy was a significant predictive factor for therapeutic efficacy. CONCLUSIONS: The measurement of peripheral eosinophils up to around 5 weeks following the initiation of treatment, especially the maximum eosinophils count and percentage, might provide useful information about the efficacy of ICPIs.

Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients.

Background/Aim: To clarify the clinical significance of the absolute increase in the number and proportion of peripheral eosinophils associated with immune checkpoint inhibitor (ICPI) treatment in non-small cell lung cancer (NSCLC) patients. Patients and Methods: We performed a retrospective study, by reviewing the medical charts of 191 patients who were treated with ICPI monotherapy and 80 patients treated with the combination of ICPI and chemotherapy during the period from February 2016 and April 2021. Results: In patients treated with ICPI monotherapy, there was a significant difference in time to treatment failure (TTF) between the two groups divided by eosinophils ≥ or <10%. Similarly, a significant difference was found in TTF between the two groups divided by eosinophils ≥ or <1,500/µl. Factors related to both an increase in the number and percentage of peripheral eosinophils were "immune-related adverse effects (irAE) that did not lead to discontinuation of administration". Conclusion: Some patients with irAE might have a 'favorable' absolute increase in peripheral eosinophils.