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).

Imaging the early response to chemotherapy in advanced lung cancer with diffusion-weighted magnetic resonance imaging compared to fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography.

PURPOSE: To evaluate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) for assessment of the early response to chemotherapy and outcome in patients with advanced lung cancer through comparison with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT). MATERIALS AND METHODS: Twenty-eight lung cancer patients underwent DW-MRI, FDG-PET, and CT before and after one course of chemotherapy. Changes in the apparent diffusion coefficient (ΔADC), the mean standardized uptake value (ΔSUV), and the maximum diameter (ΔMD) were measured and compared. According to the response evaluation criteria, patients were divided into two groups, responders and nonresponders, and progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: The relationship between ΔADC and ΔSUV had the highest correlation coefficient. A cutoff value of ΔADC between responders and nonresponders was estimated as 21.5%. PFS and OS between responders and nonresponders were significantly different on DW-MRI (PFS, P = 0.012; OS, P = 0.006) and on FDG-PET (PFS, P = 0.017; OS, P = 0.036), but not on CT (PFS, P = 0.105; OS, P = 0.051). CONCLUSION: DW-MRI can be used to predict prognosis in patients with advanced lung cancer.

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.

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.

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.

Prognostic value of dual-time-point 18F-fluorodeoxyglucose positron emission tomography in patients with pulmonary sarcoidosis.

BACKGROUND AND OBJECTIVE: The value of dual-time- point (18) F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis. METHODS: Twenty-one patients with pulmonary sarcoidosis underwent (18) F-FDG PET examinations at two time points: an early scan at 60min and a delayed scan at 180min after injection of (18) F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1year after (18) F-FDG PET. Using these results, the accuracy of (18) F-FDG PET parameters and (67) Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. RESULTS: RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3±9.6%) than in patients with improved pulmonary lesions (improved group; -9.2±28.6%, P=0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or (67) Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV. CONCLUSIONS: RI-SUV showed better diagnostic accuracy compared with early SUV or (67) Ga uptake, in patients with persistent lung involvement at 1year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.

Differentiation of histological subtypes in lung cancer with 18F-FDG-PET 3-point imaging and kinetic analysis.

The purpose of this study was to evaluate differences in histological subtypes of lung cancer using (18)F-FDG-PET 3-point imaging and kinetic analysis. Subjects comprised 44 patients with histologically proven lung cancer (squamous cell carcinoma (SCC), n=18; well-differentiated adenocarcinoma (WDA), n=9; poorly/moderately differentiated adenocarcinoma (non-WDA), n=17) who underwent (18)F-FDG-PET/CT examinations at 1, 2 h and 3 h after injection of 185 MBq of (18)F-FDG, approximately. Mean standardized uptake value (SUV) in each lesion was measured at each time point and the increase rate of SUV (IR_SUV) was calculated. SUV and IR_SUV were compared among the 3 groups. In addition, to estimate differences in kinetic parameters for each group, kinetic analysis based on a 3-compartment model was performed. Our results showed SUV differed significantly at every time point among the 3 groups. IR_SUV between 2 and 3 h post-injection (IR_SUV (2-3)) differed significantly among the 3 groups, while both IR_SUV(1-3) and IR_SUV(1-2) were significantly higher in SCC than in WDA. In kinetic analyses, both K1 and k3 showed significant differences among the 3 groups, with highest values in SCC and lowest in WDA. In conclusion, (18)F-FDG-PET 3-point imaging and kinetic analysis enabled the differentiation of histological subtypes in lung cancer, arising from differences in glucose transporter density and enzymatic activity of hexokinase.

[Endobronchial ultrasonic-guided transbronchial needle aspiration (EBUS-TBNA) for lung cancer diagnosis].

BACKGROUND: Although bronchoscopy has an important role in the diagnosis of lung cancer, more invasive procedures, such as CT-guided biopsy or surgery, are needed when transbronchial approaches fail. OBJECTIVE: We investigated the usefulness of endobronchial ultrasonic-transbronchial needle aspiration (EBUS-TBNA) for lung cancer diagnosis. SUBJECTS AND METHODS: We retrospectively evaluated 122 cases who were finally diagnosed to have lung cancer from among 388 cases who underwent bronchoscopy because of abnormal shadows on their chest X-ray or CT. When bronchoscopic approaches were possible, conventional transbronchial lung biopsy or cytology (conventional approaches) were done. EBUS-TBNA was added whenever mediastinal or hilar lymph nodes enlarged to more than 1 cm in diameter, or if there were lesions attached to the lower respiratory tract. The diagnostic accuracy of conventional approaches and EBUS-TBNA were assessed. RESULTS: The number of cases diagnosed as lung cancer by conventional approaches was 79 cases (64.8%) among the 122 cases examined. Of the 43 cases undiagnosed by these procedures, 27 cases were diagnosed as lung cancer by EBUS-TBNA. Thus, 106 cases (86.9%) were diagnosed as lung cancer using conventional approaches plus EBUS-TBNA. No severe complications were observed in all the subjects. CONCLUSION: EBUS-TBNA is a safe and useful approach for the diagnosis of lung cancer together with staging.

[The current status of nausea, vomiting and food intake in outpatients with cancer chemotherapy].

A survey on chemotherapy-induced nausea, vomiting and food intake was conducted on 126 outpatients receiving chemotherapy during a days from February 1 to February 12, 2010 in our hospital. Responses were obtained from 66 outpatients. In the acute phase, 11%of the patients developed nausea. In the late phase, 35%patients developed nausea. The development of nausea was significantly increased in the late phase, compared to the acute phase(p=0. 0008). Though nobody developed vomiting in the acute phase, 3% of the patients developed vomiting in the late phase. For food intake, in the acute phase, nobody showed a"reduced amount of diet", and 12% showed"not eating". In the late phase, 26% of the patients showed"reduced amount of food", and 8%"not eating". Food intake was significantly decreased in the late phase, compared in acute phase(p=0. 0001). Currently, in our hospital, steroids and/or 5-HT3 antagonists are given for antiemetic therapy, but the effect is not enough. We should add other antiemetics, which act in the late phase.

Long-Term Survival With Pembrolizumab Re-administration After Pseudo-Progression With Immune-Related Interstitial Lung Disease in a Patient With Non-small Cell Lung Cancer.

Immune checkpoint inhibitors may cause specific immune-related reactions, such as pseudo-progression. In particular, malignant pleural effusion tends to worsen due to this phenomenon. However, the appropriate management in such cases is unclear. We report a 73-year-old man with advanced lung adenocarcinoma and malignant pleural effusion who developed pseudo-progression with immune-related interstitial lung disease (irILD) induced by pembrolizumab (Merck & Co., Kenilworth, NJ, USA). After managing them with steroid treatments and chemotherapy, pembrolizumab was re-administered. At the time of writing, 30 months have passed since the re-administration of pembrolizumab without disease progression. This clinical course conveys an appropriate management strategy for patients with pseudo-progression and irILD.

Successful Re-administration of Atezolizumab for a Non-small-cell Lung Cancer Patient after Cardiac Tamponade Development as a Manifestation of Pseudo-progression Induced by Combination Treatment with Atezolizumab and Cytotoxic Chemotherapy.

Pseudo-progression is a phenomenon induced by treatment with immune checkpoint inhibitors and is characterized by an increase in tumor size or the appearance of new lesions, followed by tumor regression. However, life-threatening conditions, such as cardiac tamponade, can develop in such patients. We herein report on a 69-year-old man with lung adenocarcinoma who developed cardiac tamponade as a manifestation of pseudo-progression induced by treatment with atezolizumab combined with cytotoxic chemotherapy. After managing the cardiac tamponade, atezolizumab was successfully re-administered along with cytotoxic chemotherapy without disease progression.

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.

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.

The effectiveness of 18F-FDG PET/CT combined with STIR MRI for diagnosing nodal involvement in the thorax.

UNLABELLED: The purpose of this study was to compare the efficacy of short-tau inversion-recovery (STIR) MRI and 18F-FDG PET/CT for the detection of metastasis in mediastinal and hilar lymph nodes in patients with lung cancer. METHODS: Ninety-three patients with known or suspected lung cancer with mediastinal and hilar lymph node swelling underwent STIR MRI and 18F-FDG PET/CT examinations. STIR MRI scans were obtained with a 2% copper sulfate phantom placed along the back of each patient, with the lymph node-to-phantom ratio calculated for quantitative analysis. For qualitative analysis, the results of all STIR MRI scans were evaluated using a 5-point visual scoring system. To evaluate the diagnostic capabilities of STIR MRI and 18F-FDG PET/CT, we used receiver-operating-characteristic curve analysis to determine the optimal thresholds for the lymph node-to-phantom ratio, visual score, and maximal standardized uptake value. Further, the capability of each to determine N-stage was compared in each patient using the McNemar test. RESULTS: A total of 137 lymph nodes (82 malignant lesions, 55 benign lesions) were analyzed. When optimal threshold values were adopted, the quantitative and qualitative sensitivity, specificity, and accuracy of STIR MRI were not significantly different from those of 18F-FDG PET/CT. However, 18F-FDG PET/CT in combination with qualitative STIR MRI analysis had a significantly higher capability to detect nodal involvement on an individual-patient basis (96.9% specificity, 90.3% accuracy) than did 18F-FDG PET/CT alone (65.6% specificity, 81.7% accuracy). CONCLUSION: We found that the diagnostic capability of STIR MRI was not significantly different from that of 18F-FDG PET/CT. However, when those methods were combined, the diagnostic capability for N-staging was significantly improved.

Usefulness of 18F-fluorodeoxyglucose positron emission tomography for diagnosing disease activity and monitoring therapeutic response in patients with pulmonary mycobacteriosis.

PURPOSE: To evaluate the usefulness of (18)F-FDG PET in the imaging of pulmonary lesions related to disease activity and in monitoring responses to treatment in patients with pulmonary mycobacteriosis (PM). MATERIALS AND METHODS: We used high-resolution computed tomography (HRCT) and (18)F-FDG PET to evaluate 47 consecutive untreated patients with PM, 25 with tuberculosis (TB) and 22 with Mycobacterium avium-intracellulare complex (MAC), who presented with small peripheral pulmonary nodules