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Background: Video-assisted thoracoscopic surgery is a widely recommended treatment for empyema in advanced stages. However, only a few studies have evaluated prognostic factors among patients with empyema who underwent video-assisted thoracoscopic surgery. Furthermore, no studies have evaluated predictors of direct discharge home. Patients and Methods: This multicenter retrospective cohort study included 161 patients with empyema who underwent video-assisted thoracoscopic surgery in five acute-care hospitals. The primary outcome was the probability of direct discharge home. The secondary outcome was the length of hospital stay after surgery. We broadly assessed pre-operative factors and performed univariable logistic regression for the direct discharge home and univariable gamma regression for the length of hospital stay after surgery. Results: Of the 161 included patients, 74.5% were directly discharged home. Age (>70 years; -24.3%); altered mental status (-33.4%); blood urea nitrogen (>22.4 mg/dL; -19.4%); and pleural pH (<7.2; -17.6%) were associated with high probabilities of not being directly discharged home. Fever (15.2%) and albumin (> 2.7 g/dL; 20.2%) were associated with high probabilities of being directly discharged home. The median length of stay after surgery was 19 days. Age (>70 years; 6.2 days); altered mental status (5.6 days); purulence (2.7 days); pleural thickness (>2 cm; 5.1 days); bronchial fistula (14.6 days); albumin (>2.7 g/dL; 3.1 days); and C-reactive protein (>20 mg/dL; 3.6 days) were associated with a longer post-operation hospital stay. Conclusions: Physicians should consider using these prognostic factors to predict non-direct discharge to the home for patients with empyema.
Subject(s)
Empyema, Pleural , Patient Discharge , Humans , Aged , Empyema, Pleural/surgery , Prognosis , Retrospective Studies , Treatment Outcome , Thoracic Surgery, Video-Assisted/adverse effects , AlbuminsABSTRACT
Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.
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The effectiveness of systemic steroid therapy on mortality in patients with pneumonic chronic obstructive pulmonary disease (COPD) exacerbation is unclear. We evaluated the association between systemic steroid therapy and 30-day mortality after adjusting for known confounders, using data from the Health, Clinic, and Education Information Evaluation Institute in Japan, which longitudinally followed up patients in the same hospital. We selected patients aged ≥40 years admitted for pneumonic COPD exacerbation. The exclusion criteria were censoring within 24 h, comorbidity with other respiratory diseases, and daily steroid use. Systemic steroid therapy was defined as oral/parenteral steroid therapy initiated within two days of admission. The primary outcome was the 30-day mortality rate. To account for known confounders, each patient was assigned an inverse probability of treatment weighting. The outcome was evaluated using logistic regression. Among 3,662 patients showing pneumonic COPD exacerbation, 30-day mortality in the steroid therapy and non-steroid therapy groups was 27.6% (169/612) and 21.9% (668/3,050), respectively. Systemic steroid therapy indicated a slightly higher estimated probability of 30-day mortality (difference in the estimated probabilities, 2.65%; 95% confidence interval, -1.23 to 6.54%, p-value = 0.181). Systemic steroid therapy within two days of admission was associated with higher 30-day mortality rates in pneumonic COPD exacerbation. Further validation studies based on chart reviews will be needed to cope with residual confounders.
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BACKGROUND: Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. OBJECTIVE: This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. METHODS: This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. RESULTS: Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], -10.7 to 13.0%) and -0.08% (95% CI, -10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were -3.22 (95% CI, -6.19 to -0.25 days) and -5.04 days (95% CI, -8.19 to -1.90 days), respectively. CONCLUSIONS: Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted.
Subject(s)
Empyema, Pleural , Thoracic Surgery, Video-Assisted , Humans , Thoracic Surgery, Video-Assisted/adverse effects , Empyema, Pleural/surgery , Retrospective Studies , Length of Stay , HospitalsABSTRACT
Rationale: Chest computed tomography is performed in patients with empyema for various reasons. However, its predictive ability for patient outcomes in empyema has not been evaluated. Objectives: To evaluate the predictive ability of computed tomography findings (pleural thickness, loculation, interlobar pleural effusion, lung abscess, and bronchopleural fistula) for 90-day mortality in empyema. Methods: This multicenter retrospective cohort study was conducted across six acute care hospitals in Japan. We included patients with confirmed empyema diagnoses who underwent chest computed tomography within 7 days of diagnosis. Imaging findings were defined as pleural thickness, loculation, interlobar pleural effusion, lung abscess, or bronchopleural fistula. One radiologist interpreted the computed tomography scans without patient information. The primary outcome was 90-day mortality. We calculated the differences in 90-day mortality between the presence and absence of each computed tomography finding using logistic regression with or without adjustment for early thoracic surgery. Results: A total of 711 patients were included in our study. Thoracic surgery was performed in 27% of patients, and the 90-day mortality rate was 10%. The differences (95% confidence intervals) in 90-day mortality without and with adjustment for early thoracic surgery were as follows: pleural thickness, 3.09% (-1.35% to 7.54%) and 2.70% (-1.80% to 7.20%); loculation, -4.01% (-8.61% to 0.60%) and -3.80% (-8.41% to 0.81%); interlobar pleural effusion, -9.15% (-14.58% to -3.72%) and -8.96% (-14.39% to -3.53%); lung abscess, 7.04% (-1.16% to 15.2%) and 6.86% (-1.34% to 15.05%); and bronchopleural fistula, 13.80% (7.66% to 19.94%) and 13.63% (7.50% to 19.77%), respectively. Conclusions: Although interlobar pleural effusion predicted lower 90-day mortality regardless of early thoracic surgery, the presence of bronchopleural fistula predicted higher 90-day mortality with empyema. Our results warrant further validation.
Subject(s)
Bronchial Fistula , Empyema, Pleural , Lung Abscess , Pleural Diseases , Pleural Effusion , Humans , Empyema, Pleural/diagnostic imaging , Prognosis , Retrospective Studies , Pleural Effusion/diagnostic imaging , Tomography, X-Ray Computed/methodsABSTRACT
Purpose: Whether the empirical use of anti-pseudomonal antibiotics actually improves patient outcomes is unclear. Hence, we aimed to determine whether empirical anti-pseudomonal antibiotics are better than anti-pseudomonal antibiotics in treating patients with recurrent lower respiratory tract infections (LRTIs). Patients and Methods: We extracted data from the Japanese nationwide database of the Real World Data Co., Ltd. Our target population was patients with LRTIs, defined as chronic obstructive pulmonary disease exacerbation and pneumonia. We included patients aged ≥40 years who were admitted for lower respiratory tract infections ≥2 times within 90 days. We excluded patients who had an event (death or transfer) within 24 h after admission. We ran a frailty model adjusted for the following confounding factors: number of recurrences, age, body mass index, activities of daily living, Hugh-Johns classification, altered mental status, oxygen use on admission, blood urea nitrogen, and systemic steroid use. Results: We included 893 patients with 1362 observations of recurrent LRTIs. There were 897 (66%) observations in the non-anti-pseudomonal antibiotic group and 465 (34%) in the anti-pseudomonal group; the numbers of in-hospital deaths were 86/897 (10%) and 63/465 (14%), respectively. Our frailty model yielded an adjusted hazard ratio (HR) (anti-pseudomonal group/non-anti-pseudomonal group) of 1.49 (95% confidence interval, 1.03-2.14). Conclusion: The empirical use of anti-pseudomonal antibiotics was associated with a higher HR of in-hospital mortality than the use of non-anti-pseudomonal antibiotics. Physicians might need to consider limiting the prescription of anti-pseudomonal antibiotics based on background factors such as the patient's baseline function and disease severity. Further studies are needed to evaluate the causal relationship between empirical anti-pseudomonal antibiotics and mortality, and identify specific patient population who benefit from empirical anti-pseudomonal antibiotics.
Subject(s)
Cystic Fibrosis , Frailty , Pseudomonas Infections , Pulmonary Disease, Chronic Obstructive , Respiratory Tract Infections , Humans , Anti-Bacterial Agents/adverse effects , Pseudomonas Infections/drug therapy , Retrospective Studies , Activities of Daily Living , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/chemically induced , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/complicationsABSTRACT
BACKGROUND: Renal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel. PATIENTS AND METHODS: Previously treated NSCLC patients were randomly allocated (1:1) to receive docetaxel (60 mg/m²) on day 1 or nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function. RESULTS: Among the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mL/min, n = 49 for docetaxel and n = 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of >50 to ≤80 mL/min, n = 133 for docetaxel and n = 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population. CONCLUSION: Nab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/etiology , Creatinine/therapeutic use , Docetaxel/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/etiologyABSTRACT
Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies. Thus, we aimed to examine whether these factors could also be prognostic markers for chemoimmunotherapy. We retrospectively examined 237 patients with advanced NSCLC treated with chemoimmunotherapy. In the total group, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 8.6 months. Multivariate analysis of OS and PFS revealed significant differences based on PNI and LIPI. Programmed cell death ligand 1 (PD-L1) was also significantly associated with OS and PFS. PNI and a PD-L1 tumor proportion score (TPS) of <50% and poor LIPI (regardless of PD-L1 TPS) were associated with poor prognosis. PNI and LIPI predicted survival outcomes in patients with advanced NSCLC treated with chemoimmunotherapy, especially in patients with PD-L1 TPS <50%. For patients in this poor category, chemoimmunotherapy may result in a worse prognosis than expected.
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PURPOSE: We aimed to investigate whether induction chemotherapy with less than four courses is as effective as induction chemotherapy with more than four courses in non-small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy. METHODS: We retrospectively enrolled 249 patients with NSCLC who received chemoimmunotherapy at 12 centers in Japan between January and December 2019. The patient group that completed less than four courses owing to adverse events (AEs), and received subsequent maintenance therapy was compared to the group that received at least four courses of induction chemotherapy followed by maintenance therapy. RESULTS: On univariate and multivariate analyses, the patient group that transitioned to maintenance therapy after completing less than four courses of induction chemotherapy had significantly shorter progression-free survival (PFS) than those who completed at least four courses (hazard ratio [HR] 2.15, 95% confidence interval: 1.38-3.37, p < 0.001 and HR 2.32, 95% confidence interval: 1.40-3.84, p = 0.001, respectively). There was no obvious difference in PFS between the group in which induction chemotherapy ended in two or three courses leading to partial or complete response, and the group that continued at least four courses of induction chemotherapy (log-rank test p = 0.53). CONCLUSION: Treatment efficacy may be maintained if induction chemotherapy is completed in less than four courses owing to development of AEs, and is administered for more than two courses with partial or complete response; efficacy is maintained even on transitioning to maintenance therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Induction Chemotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/etiology , Retrospective StudiesABSTRACT
OBJECTIVES: Combination therapy of immune checkpoint inhibitors and chemotherapy is considered to be one of the standard treatment options for patients with advanced non-small-cell lung cancer (NSCLC). However, the clinical significance of immune checkpoint inhibitors combined with chemotherapy in elderly patients with NSCLC has not yet been fully understood. Therefore, this study aimed to evaluate how aging affects the therapeutic impact of chemotherapy combine with immune checkpoint inhibitors in elderly patients. MATERIALS AND METHODS: We retrospectively analyzed 203 patients with advanced NSCLC who were treated with the combination therapy of pembrolizumab and chemotherapy between January 2019 and December 2019 at 12 institutions in Japan. We analyzed the clinical impacts of age on the following two groups: those who received pembrolizumab with platinum and pemetrexed (pemetrexed regimen) and those who received pembrolizumab with carboplatin and nab-paclitaxel/paclitaxel (paclitaxel regimen). Progression-free and overall survival were assessed via the Kaplan-Meier method. RESULTS: Multivariate analysis demonstrated that progression-free and overall survival were significantly shorter in elderly patients (aged ≥75 years) with NSCLC than in non-elderly patients (aged <75 years) with NSCLC in the pemetrexed regimen group. In contrast, there were no significant differences in progression-free and overall survival between elderly patients and non-elderly patients with NSCLC in the paclitaxel regimen group. In elderly patients with NSCLC, a programmed death-ligand 1 tumor proportion score of ≥50% was significantly associated with progression-free survival, and performance status of ≥2 was significantly associated with overall survival. Low albumin level (<3.5 g/dL) was significantly associated with both progression-free and overall survival. CONCLUSION: The results of this retrospective study show that the pemetrexed regimen, but not the paclitaxel regimen, was related to poor clinical outcomes in elderly patients with NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Middle Aged , Pemetrexed/therapeutic use , Retrospective StudiesABSTRACT
Although previous studies suggest that cancer cachexia is a poor prognostic factor for immune checkpoint inhibitor monotherapy, the impact of cancer cachexia on chemoimmunotherapy is unclear. We investigated the impact of cancer cachexia on the therapeutic outcomes of chemoimmunotherapy for non-small cell lung cancer (NSCLC). We retrospectively analyzed patients' medical records with NSCLC who received chemoimmunotherapy in 12 institutions in Japan between January and November 2019. We defined cancer cachexia as weight loss exceeding 5% of the total body weight or a body mass index of < 20 kg/m2 and weight loss of more than 2% of the total body weight within 6 months before chemoimmunotherapy initiation, with laboratory results exceeding reference values. This study enrolled 235 patients with NSCLC, among whom 196 were eligible for analysis, and 50 (25.5%) met the criteria for cachexia diagnosis. Patients with cancer cachexia had a significantly higher frequency of a programmed death-ligand 1 (PD-L1) expression of ≥ 50% (48%, p = .01) and shorter progression-free survival (PFS; log-rank test: p = .04) than patients without cachexia. There was no significant difference in overall survival (OS) between the cachexia and no-cachexia groups (log-rank test: p = .14). In the PD-L1 ≥ 50% population, there was no significant difference in PFS and OS (log-rank test: p = .19 and p = .79, respectively) between patients with NSCLC in the cachexia or no-cachexia groups. Cancer cachexia might be a poor prognostic factor in patients with NSCLC receiving chemoimmunotherapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Cachexia/etiology , Carcinoma, Non-Small-Cell Lung/complications , Humans , Japan/epidemiology , Lung Neoplasms/complications , Progression-Free Survival , Retrospective StudiesABSTRACT
The usage of lung ultrasound as a preoperative examination for thoracic surgeries remains controversial. Our systematic review and meta-analysis aimed to evaluate preoperative lung ultrasound diagnostic accuracy for detecting pleural adhesions. We searched articles published in MEDLINE, Embase, CENTRAL, and the International Clinical Trials Registry Platform until October 2020. Inclusion criteria were observational studies, case-control studies, and case series assessing preoperative lung ultrasound diagnostic accuracy. The study quality of included articles was evaluated using the modified quality assessment of diagnostic accuracy studies-2 tool. The pooled sensitivity and specificity were calculated using the bivariate random-effects model. The overall quality of evidence was summarized using the grading of recommendations, assessment, development, and evaluation approach. Eleven articles were included in our systematic review. A high risk of bias was noted regarding undefined pleural adhesions and non-predefined pathological diagnosis. Based on the ten articles included for meta-analysis, the pooled sensitivity and specificity were 71% [95% confidence interval (CI), 56%-82%], and 96% (95% CI, 89%-99%), respectively. The overall quality of evidence was moderate. Our systematic review revealed that lung ultrasound had high specificity. It may serve as a rule-in test for detecting pleural adhesions before thoracic surgeries, which may assist surgeons in preparation for a prolonged surgery or increased risk of complications that occurred by trocar insertion such as bleeding and persistent air leak.
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BACKGROUND/AIM: Although surgical thoracoscopy is recommended in the diagnosis of malignant pleural mesothelioma (MPM), the invasiveness of this procedure is of strong concern. Our review aimed to evaluate the accuracies of medical thoracoscopy (MT), computed tomography (CT)-guided biopsy, and ultrasound (US)-guided biopsy in the diagnosis of MPM among patients with pleural effusion. MATERIALS AND METHODS: We searched the MEDLINE, Embase, Central, and International Clinical Trials Registry Platform databases for studies evaluating the diagnostic accuracy of at least one of the biopsy procedures among patients with pleural effusion of unknown aetiology who had undergone thoracentesis and/or blind biopsy. A hierarchical summary receiver operating curve was created for MT. RESULTS: Following full-text screening, 15 studies were included. MT studies had a high risk of bias and low applicability concern; however, hierarchical summary receiver operating curve revealed that MT had a high sensitivity. CONCLUSION: MT might be a useful rule-in test for guiding the use of more invasive diagnostic procedures.
Subject(s)
Biopsy/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Mesothelioma, Malignant/pathology , Pleural Neoplasms/pathology , Thoracoscopy/methods , Tomography, X-Ray Computed/methods , Diagnosis, Differential , Humans , Mesothelioma, Malignant/diagnosis , Pleural Neoplasms/diagnosis , ROC Curve , Reproducibility of ResultsABSTRACT
INTRODUCTION: We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC. METHODS: In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m2) on day 1 or nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis. RESULTS: Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment. Median OS was 16.2 months (95% confidence interval [CI]: 14.4-19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9-16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68-1.07). Median progression-free survival was 4.2 months (95% CI: 3.9-5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9-4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63-0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0-36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9-20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nab-paclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively). CONCLUSIONS: Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC.
Subject(s)
Lung Neoplasms , Nanoparticles , Albumin-Bound Paclitaxel/therapeutic use , Albumins , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/therapeutic use , Humans , Lung Neoplasms/drug therapy , Paclitaxel/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Legionella spp. can cause severe pneumonia and most Legionella pneumonia (LP) cases are diagnosed using the urine antigen test (UAT). However, diagnosis of LP with negative UAT results (LPNUAT) is challenging. We investigated the clinical and radiological features of LPNUAT. METHODS: We retrospectively collected LP cases with positive UAT (LPPUAT) and cases of suspected LP with negative UAT that were examined by Legionella culture between July 2014 and March 2020. We investigated the clinical and CT findings for LP that showed negative UAT results and was diagnosed by culture and compared these findings with those for other pneumonias suspicious for LP with negative results in UAT and Legionella culture (OPSLP). RESULTS: Eight LPNUAT, 20 LPPUAT, and 19 OPSLP cases were included in this study. There were no significant differences in the clinical and CT findings between LPPUAT and LPNUAT when examined by UAT. In LPNUAT, dyspnea, renal dysfunction, liver dysfunction, and bilateral lesions were more commonly observed and inflammatory changes and the number of affected lobes were significantly higher when examined by culture than when examined by UAT. Comparison to OPSLP, LPNUAT did not show such differences, but rather showed disturbances in consciousness, hyponatremia and rhabdomyolysis. Furthermore, lobar consolidation was observed more frequently and bronchial wall thickening and centrilobular nodules were observed less frequently in LPNUAT. CONCLUSIONS: LP characteristics such as disturbance of consciousness, hyponatremia, rhabdomyolysis, lobar consolidation, and less bronchial wall thickening and centrilobular nodule contribute to the diagnosis of LP in patients with negative UAT results.
Subject(s)
Antigens, Bacterial/urine , Immunologic Tests/methods , Legionnaires' Disease/diagnostic imaging , Negative Results , Tomography, X-Ray Computed , Adult , Aged , Biomarkers/urine , Female , Humans , Legionella pneumophila/immunology , Legionella pneumophila/isolation & purification , Legionnaires' Disease/diagnosis , Legionnaires' Disease/microbiology , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Patients with activating epidermal growth factor receptor (EGFR) mutations are highly responsive to EGFR-tyrosine kinase inhibitors (TKIs). However, it has been reported that approximately 15-30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression, and patients with EGFR mutations exhibit a higher incidence of brain metastasis than those without such mutations. The efficacy of osimertinib for treating CNS metastasis has been reported, but its efficacy for CNS metastasis in radiotherapy-naïve patients is unclear. METHODS: In the present prospective two-cohort phase II trial, 65 patients (T790M cohort, 40 patients; first-line cohort, 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive non-small cell lung cancer (NSCLC) will be included. Patients will be treated once-daily with osimertinib 80 mg. The primary endpoint is the response rate of brain metastasis as assessed using the PAREXEL criteria. Key secondary endpoints are progression-free survival and the response rate of brain metastasis as assessed using the RECIST criteria. We will exploratorily analyze the relationships of the blood concentration of osimertinib with its efficacy against brain metastasis of NSCLC and the accumulation of osimertinib in cerebrospinal fluid and evaluate tumor-derived DNA from plasma specimens for mutations in EGFR and other genes. Recruitment, which in October 2016, is ongoing. DISCUSSION: Although previous reports revealed the efficacy of osimertinib for CNS metastasis, these reports only involved subgroup analysis, and the efficacy of osimertinib for patients with previously untreated CNS metastasis remains unclear. The OCEAN study is the only trial of osimertinib for patients with untreated brain metastasis of NSCLC. This study should provide novel data about osimertinib. If the results of the OCEAN study are positive, then avoidance of radiotherapy will be recommended to patients harboring EGFR mutations and brain metastasis. TRIAL REGISTRATION: UMIN identifier: UMIN000024218 (date of initial registration: 29 September 2016). jRCT identifier: jRCTs071180017 (date of initial registration: 13 February 2019).
Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/secondary , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Central Nervous System Neoplasms/genetics , ErbB Receptors/genetics , Female , Follow-Up Studies , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Prognosis , Survival Rate , Young AdultABSTRACT
LESSONS LEARNED: The usefulness of maintenance gemcitabine (GEM) after biweekly carboplatin + GEM in elderly patients with non-small cell lung cancer could not be proved. Superior overall survival was obtained in the group that did not receive maintenance therapy. BACKGROUND: The primary objective of this randomized phase II study was to assess progression-free survival (PFS) in elderly patients with advanced non-small cell lung cancer (NSCLC) treated with gemcitabine (GEM) maintenance therapy versus best supportive care following first-line GEM plus carboplatin (CBDCA). METHODS: Elderly chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned 1:1 to the control arm or the study arm. All patients received biweekly combination therapy with GEM and CBDCA (1,000 mg/m2 GEM and CBDCA at an area under the curve [AUC] of 3 on days 1 and 15, every 4 weeks). In the study arm, patients with objective response or stable disease following three or four cycles of initial chemotherapy received maintenance GEM. RESULTS: Eighty-four patients were enrolled. The objective response rates (ORRs) were 17.5% in the control arm and 14.0% in the study arm. The most common toxicity was neutropenia (control arm: 47.5% and study arm: 69.8%). The median progression-free survivals were 4.99 months (control arm) and 4.44 months (study arm), and the median overall survivals (OSs) were 21.7 months (control arm) and 8.2 months (study arm). CONCLUSION: Our data do not support maintenance GEM after biweekly CBDCA+GEM in elderly patients with NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Humans , Lung Neoplasms/drug therapy , Treatment Outcome , GemcitabineABSTRACT
BACKGROUND: No study has investigated the capability of high-resolution computed tomography (HRCT) to detect a lateral bronchus abnormality, degree of air bronchogram, and distribution of affected lesions in the diagnosis of Mycoplasma pneumoniae pneumonia (MPP). METHODS: We prospectively enrolled patients with serologically-confirmed MPP or culture-confirmed other bacterial pneumonia (OBP). The distribution of affected areas, abnormalities in lateral bronchial lesions, the degree of air bronchogram, and previously reported findings on HRCT were evaluated for MPP and OBP. Predictive HRCT findings for MPP were determined by logistic regression analysis. We provisionally designed our HRCT criteria (negative, probable, or highly suspected) for diagnosing MPP and investigated the diagnostic yield of the HRCT criteria. RESULTS: Sixty-three MPP and 126 OBP patients were included in this study. Logistic regression analysis showed that the absence of peripheral predominance, bronchial wall thickening, lateral bronchial wall thickening, intralobular or lobular ground-glass opacities, intralobular ground-glass opacities connected to a lateral bronchus, and less air bronchogram in infiltrates were significant predictors of MPP. Our HRCT criteria showed that the sensitivity and specificity in negative, probable, and highly suspected MPP were 0.0 and 0.33, 1.0 and 0.69, and 0.5 and 0.98, respectively. CONCLUSIONS: HRCT had considerable ability to detect a lateral bronchial abnormality and to diagnose or rule out MPP based on the distribution of affected areas, abnormalities in lateral bronchial lesions, and the degree of air bronchogram in the infiltrates.
Subject(s)
Bronchi/diagnostic imaging , Pneumonia, Mycoplasma/diagnostic imaging , Radiographic Image Enhancement/methods , Tomography, X-Ray Computed/methods , Bronchography , Diagnosis, Differential , Humans , Pneumonia, Bacterial/diagnostic imagingABSTRACT
Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually acquire resistance to these drugs. The identification of various resistance mechanisms for determination of subsequent treatment for these patients will require a method for simultaneous detection of multiple genetic alterations with high sensitivity. We performed cancer personalized profiling by deep sequencing (CAPP-Seq) with circulating tumor DNA obtained from patients with NSCLC who acquired resistance to first- or second-generation EGFR-TKIs. Plasma samples from 27 patients were analyzed, and 24 samples underwent CAPP-Seq successfully. Original activating EGFR mutations were detected in 23 patients, with the remaining patient showing MET amplification. With regard to known mechanisms of EGFR-TKI resistance, the T790M mutation of EGFR was detected in 17 of the 24 patients, MET amplification in 9 patients (6 of whom also harbored T790M), ERBB2 amplification in 2 patients (1 of whom also harbored T790M), and EGFR amplification in 4 patients (all of whom harbored T790M). Our results thus show that CAPP-Seq is applicable to clinical samples for the identification of multiple somatic mutations in circulating tumor DNA obtained from patients with NSCLC at the time of disease progression during treatment with first- or second-generation EGFR-TKIs. Patients positive for the T790M mutation of EGFR were also found to constitute a molecularly heterogeneous population. KEY POINTS: CAPP-Seq is applicable to clinical samples for the identification of multiple somatic mutations.The T790M mutation of EGFR is associated with amplification of MET, ERBB2, or EGFR in NSCLC patients resistant to EGFR-TKIs.T790M-positive patients are molecularly heterogeneous, and genetic alterations coexisting with T790M may differ between patients treated with first-generation or second-generation EGFR-TKIs.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , DNA Mutational Analysis/methods , Drug Resistance, Neoplasm/genetics , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/genetics , Circulating Tumor DNA/genetics , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Feasibility Studies , Female , Gene Amplification , High-Throughput Nucleotide Sequencing , Humans , Lung Neoplasms/blood , Lung Neoplasms/genetics , Male , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-met/genetics , Receptor, ErbB-2/geneticsABSTRACT
BACKGROUND/AIM: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. MATERIALS AND METHODS: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. RESULTS: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.