Predictive value of 18F-FDG PET/CT for acute exacerbation of interstitial lung disease in patients with lung cancer and interstitial lung disease treated with chemotherapy.

BACKGROUND: We examined whether fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed before chemotherapy could predict the onset of acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer and ILD treated with chemotherapy. METHODS: Thirty-three patients with lung cancer and ILD who underwent 18F-FDG PET/CT and were treated with chemotherapy at Kumamoto University Hospital between April 2006 and March 2018 were retrospectively analyzed. The maximum standardized uptake value (SUVmax) of interstitial lesions was measured to quantify the background ILD activity. A prediction model of AE-ILD was developed using logistic regression analyses for the SUVmax, and receiver operating characteristic (ROC) curve analyses were conducted. RESULTS: Among the 33 patients, 7 experienced AE-ILD. The SUVmax of contralateral interstitial lesions was significantly higher in patients with vs. without AE-ILD (median SUVmax: 2.220 vs. 1.795, P = 0.025). Univariable logistic regression analyses showed that the SUVmax of contralateral interstitial lesions trended towards being significantly associated with the onset of AE-ILD [odds ratio: 8.683, 95% confidence interval (CI) 0.88-85.83, P = 0.064]. The area under the ROC curve of the SUVmax for predicting AE-ILD was 0.780 (95% CI 0.579-0.982, P = 0.025). The optimal cut-off value for SUVmax was 2.005, with sensitivity and specificity values of 0.857 and 0.769, respectively. CONCLUSIONS: The SUVmax of contralateral interstitial lesions in 18F-FDG PET/CT images might be useful for predicting the onset of AE-ILD in patients with lung cancer and ILD treated with chemotherapy.

Differential predictive factors for cardiovascular events in patients with or without cancer history.

Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.

Small Cell Lung Cancer Derived from Adenocarcinoma with Mutant Epidermal Growth Factor Receptor Provides a Signature of Transcriptional Alteration in Tumor Cells.

Small cell lung cancer (SCLC) transformation of epidermal growth factor receptor (EGFR) mutant adenocarcinoma (ADC) during EGFR tyrosine kinase inhibitor (TKI) treatment is an example of a rare subset of acquired drug resistance. We herein report the case of a 75-year-old man treated with afatinib who was then diagnosed with SCLC transformation. After two years of successful treatment with afatinib, the tumor relapsed, and a re-biopsy revealed SCLC harboring EGFR exon 19 deletion. We encountered a case of transcriptional alteration, potentially important for SCLC transformation of EGFR mutant lung ADC, that was recognized via the expression of NOTCH, ASCL1 and RB1 on immunohistochemical staining.

Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. The role of vascular endothelial growth factor (VEGF) in pathogenesis of AE-ILD is conflicting. The influence of bevacizumab (Bev), a monoclonal antibody against VEGF, on lung cancer patients with pre-existing ILD remains unclear. We examined the effect of Bev on reducing AE-ILD risk in non-squamous non-small cell lung cancer (NSCLC) patients receiving chemotherapy. METHODS: We analysed incidence of AE-ILD and outcomes of 48 patients with advanced non-squamous NSCLC with ILD who received first-line chemotherapy with (Bev group, n = 17) and without (non-Bev group, n = 31) Bev between July 2011 and July 2016. Gray's test, which was competing risk analysis during the study period, was performed for both groups. RESULTS: The most common regimen used for first-line chemotherapy was the combination of carboplatin plus pemetrexed (PEM) in both groups. The incidences of chemotherapy-related AE-ILD 120 days after first-line chemotherapy initiation were significantly lower in the Bev than in the non-Bev groups (0% vs. 22.6%, p = 0.037, Gray's test). However, there were no differences in development of progressive disease of lung cancer and other events as the competing risk factors of AE-ILD between the two groups. Only patients receiving PEM-containing regimens also showed a significant difference in the incidence of AE-ILD between the two groups (p = 0.044). The overall-cumulative incidence of AE-ILD during the first-line and subsequent chemotherapy was 29.2% (14 of the 48). The median progression-free survival was significantly longer in the Bev than in the non-Bev groups (8.0 vs. 4.3 months, p = 0.026). CONCLUSIONS: The addition of Bev to chemotherapy regimens may reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer.

Upfront Cranial Radiotherapy Followed by Erlotinib Positively Affects Clinical Outcomes of Epidermal Growth Factor Receptor-mutant Non-small Cell Lung Cancer With Brain Metastases.

BACKGROUND/AIM: The optimal treatment strategy for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) has not yet been fully determined. The aim of this study was to investigate the optimal management of EGFR-mutant NSCLC patients with BM. PATIENTS AND METHODS: A multicenter retrospective study was performed on the clinical outcomes of 81 advanced/recurrent EGFR-mutant NSCLC patients with BM treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) (gefitinib n=52 or erlotinib n=29). RESULTS: Among the 81 patients, 30 patients received upfront cranial radiotherapy (CRT) and 51 did not. The multivariate cox analyses revealed that the use of erlotinib and upfront CRT were independent predictive factors for overall survival (OS) (erlotinib: HR 0.21; 95% CI, 0.10-0.48; p<0.001; upfront CRT: HR 0.42; 95% CI, 0.20-0.88; p=0.022). CONCLUSION: Erlotinib and upfront CRT were associated with a favorable prognosis among EGFR-mutant NSCLC patients with BM. Upfront CRT followed by erlotinib may be an appropriate initial management approach for EGFR-mutant NSCLC patients with BM.

Acute Exacerbation of Idiopathic Interstitial Pneumonia in a Patient with Hepatocellular Carcinoma after Transcatheter Arterial Therapy Using Miriplatin.

A 76-year-old Japanese woman with recurrent hepatocellular carcinoma presented with acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) after transcatheter arterial therapy using miriplatin. She had a history of preexisting IIP five years before presenting at our hospital. On day 4 after transcatheter arterial therapy, she complained of shortness of breath. Subsequently, she developed acute respiratory failure on day 11 after transcatheter arterial therapy. Chest computed tomography revealed extensive ground-glass opacity and traction bronchiectasis in bilateral lung fields; subsequently, she was diagnosed with AE-IIP triggered by transcatheter arterial therapy using miriplatin. Despite systemic administration of high-dose corticosteroid and cyclophosphamide, she died of respiratory failure on day 36.

A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti-PD-1 immune checkpoint antibody in a lung cancer patient.

INTRODUCTION: The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death-ligand 2 (PD-L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo-responsive Th2 cells via the PD-1/PD-L2 inhibitory pathway in lung could be reawaken by PD-1 blockade therapy. METHODS: We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2-associated pulmonary disease, triggered by nivolumab, an anti-PD-1 antibody, in an advanced non-small cell lung cancer patient. Based on the current case report and literature, the present study proposes a potential mechanism of the onset of AEP as an immune-related adverse event (irAE). RESULTS: A 62-year-old man was diagnosed with lung adenocarcinoma and nivolumab was selected as the third-line regimen. After three cycles of nivolumab treatment, chest computed tomography revealed pulmonary infiltrates in both lungs. The patient was diagnosed with AEP based on the diagnostic criteria for AEP. Nivolumab was suspended and the patient was started on oral prednisolone. His symptoms and radiological findings had rapidly improved. CONCLUSIONS: Given the increasing frequency of the use of anti-PD-1 antibodies, clinicians should be aware of the risk of AEP as a potential irAE. This study may improve our understanding of the pathophysiology underlying Th2-associated irAEs and AEP.

Negative Impact of Coexisting Interstitial Lung Disease on Clinical Outcomes in Small-cell Lung Cancer Patients.

BACKGROUND/AIM: The impact of interstitial lung disease (ILD) on the clinical outcome of patients with small-cell lung cancer (SCLC) is not fully understood. The aim of this study was to investigate the impact of ILD on treatment and survival outcomes of SCLC patients. PATIENTS AND METHODS: A retrospective analysis was performed on the clinical outcomes of SCLC patients, treated with chemotherapy, with or without ILD ([ILD group (n=16) and non-ILD group (n=51)]. RESULTS: Median PFS and OS were significantly shorter in the ILD group than in the non-ILD group (median PFS, 184 vs. 290 days, p=0.008; median OS, 236 vs. 691 days, p<0.001). Multivariate analysis revealed that coexisting ILD was an independent predictive factor of PFS (hazard ratio [HR]=2.06; 95% confidence interval [CI]=1.01-4.18; p=0.046) and OS (HR=3.29; 95%CI=1.53-7.08; p=0.002). CONCLUSION: Coexisting ILD might be a negative predictive factor of PFS and OS of SCLC patients treated with chemotherapy.

Respiratory evaluation of the risk for postoperative pulmonary complications in patients who preoperatively consulted pulmonologists: Studying both patients who underwent and who precluded planned surgery.

BACKGROUND: Due to advances in medicine, patients with pulmonary diseases have become candidates for surgery under general anesthesia. They often consult pulmonologists to assess their tolerability for surgery. The purpose of this study was to evaluate the significant characteristics responsible for postoperative pulmonary complications (PPCs) and the preclusion of the planned surgery. METHODS: The clinical data of 462 consecutive patients who consulted at the Department of Respiratory Medicine before surgery under general anesthesia were used in this study. The relationship between the patient׳s characteristics and their outcomes were analyzed. The patients who were scheduled for lung resection were excluded. RESULTS: Of the 386 patients who underwent planned surgery, 353 had no PPCs (Group A) and 33 developed PPCs (Group B). Planned surgery under general anesthesia was precluded in 31 patients due to respiratory problems (Group C). The significant predictors for PPCs consisted of a higher age, male gender, asthma, gastrointestinal surgery, cardiovascular surgery and a lower percentage of the predicted forced expiratory volume in 1 second (% predicted FEV1). The significant factors associated with the preclusion of planned surgery included interstitial pneumonia (IP), dermatologic surgery and a lower % predicted FEV1. The predicted probability of PPCs in Group C was significantly higher than that in Group A and lower than that in Group B (all p-values < 0.05). CONCLUSION: The common clinical finding for predicting PPCs and encouraging the preclusion of the planned surgery under general anesthesia was a lower % predicted FEV1.

Trousseau's syndrome triggered by an immune checkpoint blockade in a non-small cell lung cancer patient.

PD-1 blockade therapy activates T cells by blocking the interaction between PD-1 and PD-L1 and promotes IFN-γ and Th1 cytokine production. In turn, IFN-γ and Th1 cytokines produced by activated T cells promote TF synthesis in monocytes/macrophages, which results in hypercoagulability leading to thrombosis.

Successful treatment by pembrolizumab in a patient with end-stage renal disease with advanced non-small cell lung cancer and high PD-L1 expression.

We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation. Therefore, pembrolizumab can be administered for patients with ESRD and advanced NSCLC, who harbor high PD-L1 expression, during preparation for hemodialysis.

Lung abscess following bronchoscopy due to multidrug-resistant Capnocytophaga sputigena adjacent to lung cancer with high PD-L1 expression.

Lung abscess following flexible bronchoscopy is a rare and sometimes fatal iatrogenic complication. Here, we report the first case of a lung abscess caused by multidrug-resistant Capnocytophaga sputigena following bronchoscopy. A 67-year-old man underwent bronchoscopy to evaluate a lung mass. Seven days after transbronchial lung biopsy, he presented with an abscess formation in a lung mass. Empirical antibiotic therapy, including with garenoxacin, ampicillin/sulbactam, clindamycin and cefepime, was ineffective. Percutaneous needle aspiration of lung abscess yielded C. sputigena resistant to multiple antibiotics but remained susceptible to carbapenem. He was successfully treated by the combination therapy with surgery and with approximately 6 weeks of intravenous carbapenem. Finally he was diagnosed with a lung abscess with adenocarcinoma expressing high levels of programmed cell death ligand 1. The emergence of multidrug-resistant Capnocytophaga species is a serious concern for effective antimicrobial therapy. Clinicians should consider multidrug-resistant C. sputigena as a causative pathogen of lung abscess when it is refractory to antimicrobial treatment.

Reversible Restrictive Lung Disease in Pseudomesotheliomatous Carcinoma in a Lung Harboring a HER2-mutation.

Pseudomesotheliomatous carcinoma of the lung is very rare, and reversible restrictive lung disease with pseudomesotheliomatous carcinoma has not yet been previously reported. We herein report a patient with HER2-positive non-small-cell lung cancer (NSCLC) showing pseudomesotheliomatous carcinoma who was successfully treated with bevacizumab combination chemotherapy. A 56-year-old Japanese woman with advanced NSCLC presented with dyspnea. We administered chemotherapy with cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) plus bevacizumab (15 mg/kg), followed by pemetrexed plus bevacizumab. After eight cycles of maintenance chemotherapy, chest CT demonstrated a marked tumor reduction and an improvement of the right lung volume. The vital capacity was thereafter found to have significantly increased according to pulmonary function tests.

Severe interstitial pneumonia associated with anti-PD-1 immune checkpoint antibody after talc slurry pleurodesis.

A 70-year-old Japanese man with recurrent squamous cell carcinoma of the head and neck presented with severe interstitial pneumonia associated with nivolumab, after talc slurry pleurodesis. Following the development of malignant pleural effusion, he underwent chest drainage and was administered intrathoracic talc as a pleurodesis. Two weeks later, we administered nivolumab (3mg/kg) to be repeated every 2 weeks. However, on day 12, chest computed tomography scan demonstrated diffuse non-segmental ground-glass opacity and mild bronchiectasis. We diagnosed interstitial pneumonia associated with nivolumab. Although corticosteroid pulse therapy was initiated, the patient died of respiratory failure on day 14.

A Favorable Response to Levetiracetam in a Patient with Metastatic Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer, and there are no standard-of-care treatments for patients with metastatic ACC. We herein report a patient with lung metastasis of ACC who achieved a favorable response to levetiracetam. A 52-year-old Japanese man was admitted to our hospital because of multiple lung metastases of ACC. We performed first-line chemotherapy with cisplatin plus gemcitabine, and subsequently oral S-1 as second-line chemotherapy, which resulted in disease progression. The patient developed symptomatic epilepsy and received levetiracetam (250 mg twice daily). At five months after the initiation of levetiracetam, chest computed tomography showed regression of the metastatic lung lesions.

Long-term complete response to carboplatin plus paclitaxel combined with bevacizumab in a patient with metastatic spindle cell carcinoma.

We report the case of a 62-year-old Japanese male with metastatic spindle cell carcinoma (SpCC) who showed a long-term complete response (CR) to bevacizumab combination chemotherapy. We performed chemotherapy with carboplatin (AUC 6, day 1) plus paclitaxel (200mg/m2, day 1) plus bevacizumab (15mg/kg, day 1) for four cycles. After the chemotherapy, CT imaging demonstrated a CR. We subsequently administered bevacizumab (15mg/kg) repeated every 3 weeks as maintenance therapy for 12 cycles. The patient discontinued maintenance chemotherapy because of grade 3 proteinuria, but the anti-tumor effect of CR was maintained at 35 months after the discontinuation of chemotherapy.

Granulomatosis with polyangiitis can cause periaortitis and pericarditis.

Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous inflammation usually involving the upper and lower respiratory tracts and necrotizing vasculitis predominantly affecting small-sized vessels. Although categorized as a small vessel vasculitis, GPA can cause periaortitis and pericarditis. Physicians should recognize all categories of vasculitis can affect any size arteries.

Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with Spontaneous Regression after Computed Tomography-guided Needle Biopsy: A Case Report and Summary of 8 Reported Cases.

A 72-year-old woman was admitted to our hospital with a solitary right lung nodule. She had no symptoms and no abnormal physical findings except for bladder cancer. Tumor markers were mildly elevated but no other abnormal laboratory data were found. The nodule was diagnosed to be pulmonary mucosa-associated lymphoid tissue lymphoma on computed tomography-guided needle biopsy. Thereafter, she first underwent surgery for bladder cancer. The lung nodule was found to have slightly increased at three months and then disappeared at 15 months after the biopsy. The notable clinical course of this rare disease suggests the effectiveness of a non-interventional treatment strategy.

Cisplatin-induced eosinophilic pneumonia.

A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

FDG-PET and chemotherapy for successful diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.

Non-small cell lung cancer was metastasized at the septal side of right atrium in 59-year-old woman who had undergone surgery for lung cancer 11 years ago. The cardiac metastasis was found by whole-body 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), and cytologically confirmed by myocardial aspiration biopsy with right heart catheterization. The patient was treated with 4 cycles of carboplatin/pemetrexed followed by maintenance therapy with pemetrexed. The metastatic cardiac tumor shrank, and the atrioventricular (AV) block in ECG was improved. In this case, FDG-PET and chemotherapy were valuable for diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.