Efficacy of Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) Monotherapy Can Be Improved after Treatment with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer: Long-Term Follow-Up and Updated Analysis of Two Previous Prospective Clinical Studies.

INTRODUCTION: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

Safety and utility of Endoscopic Ultrasound with Bronchoscope-guided Fine Needle Aspiration (EUS-B-FNA) in suspected lung cancer patients with poor respiratory or general conditions: a prospective three-center observational study.

BACKGROUND: Although transbronchial diagnostic procedures are sometimes difficult to perform because of the patient's respiratory or general conditions, endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a known transesophageal diagnostic procedure, might be useful for such cases. We conducted this prospective three-center observational study to evaluate the safety and efficacy of EUS-B-FNA in suspected lung cancer patients with poor respiratory or general conditions. METHODS: Patients with suspected lung cancer with respiratory failure, Eastern Cooperative Oncology Group performance status of 2 or higher, or severe respiratory symptoms, were enrolled. The primary endpoints were the diagnostic yield of lung cancer and its safety, and the secondary endpoints were the success rate of molecular and programmed death ligand 1 (PD-L1) analyses, and the 6-month survival rate in patients with lung cancer. RESULTS: We enrolled 30 patients, of which 29 were included in the analysis. Among them, 26 were eventually diagnosed with lung cancer. The diagnostic yield for lung cancer was 100% (26/26). There were no adverse events associated with EUS-B-FNA requiring procedure discontinuation. The success rates of molecular analysis for EGFR, ALK, ROS-1, and BRAF were 100% (14/14), 100% (11/11), 100% (9/9), and 75% (6/8), respectively. The success rate of the PD-L1 analysis was 100% (15/15). The 6-month survival rate in patients with lung cancer was 53.8% (95% confidence interval [CI]: 33.4-76.4), and the median overall survival (OS) was 196 days (95% CI: 142-446). CONCLUSIONS: EUS-B-FNA is a safe and effective diagnostic method, even in patients with suspected lung cancer with poor respiratory or general conditions. TRIAL REGISTRATION: This clinical trial was registered at https://www.umin.ac.jp/ctr/index.htm (UMIN000041235, approved on 28/07/2020).

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial.

BACKGROUND: Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure. METHODS: Nab-paclitaxel (100 mg/m2 ) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). CONCLUSIONS: Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.

Palliative surgery for malignant superior vena cava obstruction resistant to immunotherapy: a case report.

BACKGROUND: A disease progression pattern in a limited number of sites, called oligoprogression, is relatively common in patients with lung cancer during immunotherapy. It is controversial how to manage clinically problematic oligoprogressive lesions, such as superior vena cava (SVC) obstruction resistant to immunotherapy. CASE DESCRIPTION: We present a case of a 43-year-old man who presented with facial swelling and pain in the right shoulder. Contrast-enhanced computed tomography (CT) revealed a tumor at the apex of the right lung, pulmonary and pleural nodules, and swollen mediastinal lymph nodes. A swollen mediastinal lymph node directly invaded into the SVC. Pathological diagnosis of the lymph node revealed adenocarcinoma. On the basis of these findings, the patient was diagnosed with lung adenocarcinoma with SVC obstruction (cT3N2M1c; stage IVB). First-line chemotherapy with carboplatin, pemetrexed, and pembrolizumab reduced the size of the primary tumor, pulmonary and pleural metastases, and most mediastinal lymph node metastases after four cycles of treatment, but one lesion invading the SVC increased. Therefore, surgical resection of the lesion and vascular replacement were performed. At present, 22 months have passed since the surgery, and maintenance therapy with pemetrexed and pembrolizumab is ongoing, without disease progression nor any adverse events. CONCLUSIONS: The clinical course of the case presented here suggests that palliative surgery may be an effective management option for a clinically problematic lesion, such as SVC obstruction, which increases during immunotherapy.

Immune Checkpoint Inhibitor-Induced Limbic Encephalitis during Treatment with Atezolizumab in a Patient with Small-Cell Lung Cancer: A Case Report and Review of the Literature.

Paraneoplastic neurological syndrome (PNS) is associated with malignancies, including small-cell lung cancer. Recently, PNS cases among patients with small-cell lung cancer (SCLC) induced by immune checkpoint inhibitors have increased. We herein report a 66-year-old man with SCLC who developed disorientation, dysphagia, and gait disturbance after three courses of treatment with atezolizumab. Brain magnetic resonance imaging revealed a high-intensity area in the bilateral temporal lobes. Blood test results were positive for anti-Hu and anti-Zic4 antibodies, which led to the diagnosis of limbic encephalitis as PNS. Some symptoms improved with intravenous administration of steroids and immunoglobulins.

Successful treatment with lorlatinib in a patient with meningeal carcinomatosis of ALK-positive non-small cell lung cancer resistant to alectinib and brigatinib: A case report.

RATIONALE: Although anaplastic lymphoma kinase (ALK) inhibitors are effective treatment options for ALK-positive non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis, achieving long-term survival in patients with NSCLC with meningeal carcinomatosis resistant to ALK inhibitors is difficult. Lorlatinib, a third-generation ALK inhibitor, was designed for selective CNS penetration, and exerts potent antitumor activity against tumors resistant to first- and/or second-generation ALK inhibitors. However, there is limited information about the activity of lorlatinib in ALK inhibitor-resistant meningeal carcinomatosis. Here, we report a case of ALK-positive lung adenocarcinoma with meningeal carcinomatosis in which lorlatinib was used after resistance to alectinib and brigatinib. PATIENTS CONCERNS: A 55-year-old woman with no history of smoking presented to our hospital with a swelling on the left neck. Clinical imaging and histopathological examination revealed a tumor of adenocarcinoma histology in the left upper lung with no CNS metastasis. DIAGNOSES: The patient was diagnosed with ALK-positive lung adenocarcinoma (cT3N3M1b: stage IVA). INTERVENTIONS: She received the second-generation ALK inhibitors, alectinib and brigatinib, in the first and second-line settings, respectively. However, she developed meningeal carcinomatosis. Hence, treatment with lorlatinib was initiated in the third-line setting. OUTCOMES: The symptoms associated with meningeal carcinomatosis, such as disturbance of consciousness and diplopia, improved dramatically. At 8 months from the initiation of lorlatinib, the patient remained well without disease progression. LESSONS: Lorlatinib is an effective treatment option for patient with ALK-positive NSCLC who develop meningeal carcinomatosis resistant to second-generation ALK inhibitors. Therefore, lorlatinib should be considered in such cases, even when patients exhibit serious symptoms associated with meningeal carcinomatosis.

An air-locking port and high-flow nasal cannula in non-intubated uniportal video-assisted thoracic surgery for pneumothorax with pulmonary dysfunction: a case report.

BACKGROUND: Non-intubated video-assisted thoracic surgery is a therapeutic option for intractable secondary spontaneous pneumothorax in patients who are poor candidates for surgery with endotracheal intubation under general anesthesia. However, intraoperative respiratory management in this surgery is often challenging because of hypoxia caused by surgical pneumothorax. CASE PRESENTATION: A 75-year-old man with idiopathic pulmonary fibrosis who had been on home oxygen therapy underwent non-intubated uniportal video-assisted thoracic surgery for intractable spontaneous pneumothorax. During the operation, oxygen was administered using a high-flow nasal cannula at a high flow rate. An air-locking port for single-incision surgery was used to minimize the inflow of air into the pleural cavity. The intrapleural air was continuously suctioned through the chest tube. The air-leak point was easily identified and closed using ligation. Oxygenation was satisfactory throughout the operation. CONCLUSIONS: Non-intubated uniportal video-assisted thoracic surgery for secondary spontaneous pneumothorax with an air-locking port, continuous pleural suction, and high-flow nasal cannula may achieve satisfactory intraoperative oxygenation in patients with respiratory dysfunction. The intrapleural space can be feasible for surgical manipulation without surgical pneumothorax in non-intubated video-assisted thoracic surgery even when supplied with oxygen at a high flow rate using a high-flow nasal cannula.

The Association between Malignant Pleural Mesothelioma and Thoracic Radiation Therapy for Hodgkin's Lymphoma: The First Case Report in Japan.

Malignant pleural mesothelioma (MPM) is mostly observed in patients with a history of asbestos exposure. Although other causes are rare, there are several reports of MPM induced by therapeutic radiation, mainly in Europe and North America. However, no such case has been reported in Japan. We herein report a 50-year-old Japanese woman who developed MPM 25 years after thoracic radiation therapy for Hodgkin's lymphoma. The patient had no history of exposure to asbestos; therefore, her history of radiation therapy was considered to be the cause of MPM. Clinicians should consider secondary MPM in patients with a history of thoracic radiation therapy.

Utility of Endoscopic Ultrasound with Bronchoscope-guided Fine-needle Aspiration for Detecting Driver Oncogenes in Non-small-cell Lung Cancer during Emergency Situations: Case Series.

Since it is difficult to obtain tumor tissue via airway observation for lung cancer patients with a poor respiratory condition, endoscopic ultrasound with bronchoscope-guided fine-needle-aspiration (EUS-B-FNA), a transesophageal procedure, is effective for such patients. We herein report three patients with driver oncogenes taken to the emergency department because of lung cancer-related symptoms. EUS-B-FNA was performed because of the patients' poor respiratory conditions to detect driver oncogenes. The general conditions improved, and the patients achieved a long-term survival with tyrosine kinase inhibitors. Our findings suggest that EUS-B-FNA should be considered to detect driver oncogenes in lung cancer patients despite poor respiratory conditions in emergency departments.

Infliximab Was Found to Be Effective for Treating Immunosuppressive Drug-resistant Hepatitis due to Durvalumab.

A 69-year-old man with stage III lung squamous cell carcinoma developed immune-related hepatitis following treatment with durvalumab, and was given high-dose corticosteroids and immunosuppressive drugs (mycophenolate mofetil, azathioprine, tacrolimus) but without demonstrating any improvement. Two cycles of infliximab (5 mg/kg) were then administered and thereafter the hepatitis improved. At the time of writing (9 months after the initiation of first course of durvalumab), the patient is alive without either any hepatitis symptoms nor any lung cancer progression. Infliximab may be effective for treating non-small cell lung cancer (NSCLC) patients who develop immunosuppressive drug-resistant immune-related hepatitis caused by durvalumab.

Whole-brain Radiation and Pembrolizumab Treatment for a Non-small-cell Lung Cancer Patient with Meningeal Carcinomatosis Lacking Driver Oncogenes Led to a Long-term Survival.

We herein report a 66-year-old woman with advanced lung adenocarcinoma [programmed cell death and its ligand 1 (PD-L1) tumor proportion score 60%] lacking driver oncogenes in whom meningeal carcinomatosis, along with sudden onset dizziness, deafness, and consciousness disturbance, appeared after second-line chemotherapy. Whole-brain radiation therapy (WBRT) and Pembrolizumab were subsequently administered, and third-line chemotherapy with Pembrolizumab is now ongoing. At the time of writing, the patient has achieved a 23-month survival without disease progression. Our findings suggest that the combination of WBRT and an immune checkpoint inhibitor is effective for non-small-cell lung cancer patients lacking driver oncogenes who develop meningeal carcinomatosis.

[Hypersensitivity pneumonitis-like disease caused by exposure to Mycobacterium avium complex in bathtub water at home: a case report].

We report here a case of hypersensitivity pneumonitis-like disease in an adult, likely due to exposure to Mycobacterium avium complex (MAC) in his bathtub water at home. A 63-year-old man was referred to our hospital with exertional dyspnea. Chest computed tomography showed bilateral, diffuse, centrilobular ground-glass nodules. Bronchoalveolar lavage showed marked lymphocytosis. Transbronchial biopsy showed epithelioid cell granulomas and lymphocyte alveolitis. Cultures of the patient's sputum and bathtub water yielded MAC. Variable-number tandem repeat analysis of the MAC strains in the sputum and bathtub water samples showed that the strains were genetically identical. The clinical condition of the patient improved at home under chemotherapy by avoiding the use of the bathtub.

A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer.

PURPOSE: To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks. RESULTS: Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1-21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7-53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur. CONCLUSION: S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.

Excessive ventilatory response during exercise in patients with non-hypoxic pulmonary hypertension.

The slope of the regression line between carbon dioxide output (VCO2) and minute ventilation (VE) (SLOPE) is useful for evaluating ventilation-perfusion inequality during exercise. A cardiopulmonary exercise test was carried out in 8 pulmonary hypertension (PH) patients without hypoxemia (group PH), 38 male patients with old myocardial infarction (group OMI), and 20 healthy men (group Ctrl). The average SLOPE for each group was 36.3+/-3.3, 28.7+/-0.9 and 25.6+/-0.5, respectively. There were significant differences among them. Group OMI was divided into 3 groups: OMI class 0: peak oxygen consumption (VO2) > or =21 ml x kg(-1) min(-1); OMI class I: 14 ml x kg(-1) x min(-1) < or =peak VO2<21 ml x kg(-1) min(-1); OMI class II: peak VO2< 14ml x kg(-1) x min(-1). There were no significant differences in peak VO2 between the groups PH and OMI class I, but the SLOPE in the group PH was greater than the SLOPE in OMI class I (p=0.0019). Compared with OMI class II, group PH had a greater peak VO2 (p=0.0215), although their SLOPE was equivalent to that of OMI class II. These results suggest that PH patients have severe ventilation-perfusion inequality despite good exercise capacity. When performing a cardiopulmonary exercise test on PH patients, it is necessary to observe not only VO2 or VCO2, but also VCO2/VE, in order to prevent aggravation of the ventilation-perfusion inequality, which leads to exercise-induced hypoxemia.