Novel prospective umbrella-type lung cancer registry study for clarifying clinical practice patterns: CS-Lung-003 study protocol

Introduction Conventional cancer registries are suitable for simple surveillance of cancer patients, including disease frequency and distribution, demographics, and prognosis; however, the collected data are inadequate to clarify comprehensively diverse clinical questions in daily practice. Methods We constructed an umbrella‐type lung cancer patient registry (CS‐Lung‐003) integrating multiple related prospective observational studies (linked studies) that reflect clinical questions about lung cancer treatment. The primary endpoint of this registry is to clarify daily clinical practice patterns in lung cancer treatment; a key inclusion criterion is pathologically diagnosed lung cancer. Under this registry, indispensable clinical items are detected in advance across all active linked studies and gathered prospectively and systematically to avoid excessive or insufficient data collection. Researchers are to input information mutually, irrespective of the relevance to each researcher's own study. Linked studies under the umbrella of the CS‐Lung‐003 registry will be updated annually with newly raised clinical questions; some linked studies will be newly created, while others will be deleted after the completion of the analysis. Enrollment began in July 2017. Discussion We successfully launched the umbrella‐type CS‐Lung‐003 registry. Under this single registry, researchers collaborate on patient registration and data provision for their own and other studies. Thus, the registry will produce results for multiple domains of study, providing answers to questions about lung cancer treatment raised by other researchers. Through such analysis of each linked study, this registry will contribute to the comprehensive elucidation of actual daily practice patterns in lung cancer treatment. Key points CS‐Lung‐003 registry directly integrates multiple linked studies created under the umbrella of this cancer registry to solve various clinical questions regarding daily practice patterns of lung cancer treatment

Endobronchial Ultrasonography with a Guide-Sheath and Virtual Bronchoscopy Navigation Aids Management of Peripheral Pulmonary Nodules

Occasionally, we have difficulty in diagnosing small peripheral pulmonary nodules. However, efforts have been made to resolve this problem. For instance, computed-tomography (CT), positron emission tomography (PET), flexible bronchoscopy examination (BF), and videoassisted thoracic surgery (VATS) have been performed to investigate such nodules. We have used endobronchial ultrasonography with a guide-sheath (EBUS-GS) for BF examination, and recently applied the virtual reality technique "virtual bronchoscopy (VB)". Here, we present a case in which a combined technique with VB and EBUS-GS was useful. The patient was a 54-year-old man with a persistent cough and chest pain. Small nodules were seen in the bilateral lungs on the chest CT taken at the local hospital. A slight increase in the CEA level (6.1 ng/ml; normal level< 5.0 ng/ml) was shown as well as an uptake in the latter term on PET. As a result, he was referred to our hospital for a detailed work-up. We applied VB to confirm the location of the tumor, which allowed us to approach the lesion easily. Furthermore, we precisely localized the lesion using EBUS-GS. Then a biopsy was performed, which demonstrated bronchiolitis obliterans organizing pneumonia (BOOP). As seen in this case, combining VB and EBUS-GS seems beneficial for diagnosing peripheral pulmonary nodules

Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model

AuthorA series of oxicam non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be neuroprotective against 1-methyl-4-phenyl pyridinium in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway independent of cyclooxygenase (COX) inhibition. The present study endeavored to establish this novel effect of meloxicam (MLX), an oxicam NSAID, in a mouse Parkinson's disease (PD) model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice, which received MPTP (30 mg/kg/day; s.c.) for 5 consecutive days (chronic model) with 10-day follow-up saline administrations, showed significant motor dysfunction in the pole test due to reduced tyrosine hydroxylase (TH) protein levels in the brain on day 16 after MPTP/saline treatment. Daily coadministrations of MLX (10mg/kg/day; i.p.) and MPTP for the first 5 days and follow-up 10 days with MLX administrations alone (MPTP/MLX treatment) significantly ameliorated MPTP-induced behavioral abnormalities in mice. Concomitant decreases of TH protein levels in the striatum and midbrain of MPTP/MLX-treated mice were not only significantly (p<0.01 and p<0.05, respectively) ameliorated but phosphorylated Akt (pAkt473) expression in the midbrain was also significantly (p<0.01) increased in the midbrain when compared with MPTP/saline-treated mice. These results suggest that MLX, an oxicam NSAID, attenuated dopaminergic neuronal death in the experimental MPTP-PD model by maintenance of the Akt-signaling. Oxicam NSAIDs may serve as potential drugs for PD treatment via a novel mechanism of action

Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study

Abstract Background We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. Methods Chemotherapy-naïve patient with stage IIIB–IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. Results Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0–12.6), and overall survival was 48.0 (95% CI, 32.9–63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4–16.3) and 7.9 (95% CI, 1.1–14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. Conclusions In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status. Trial registration UMIN Clinical Trial Registry: UMIN000005569. Registered date: May 8, 2011

Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study

[BACKGROUND]:We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. [METHODS]:Chemotherapy-naïve patient with stage IIIB-IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. [RESULTS]:Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0-12.6), and overall survival was 48.0 (95% CI, 32.9-63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4-16.3) and 7.9 (95% CI, 1.1-14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. [CONCLUSIONS]:In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status.This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial

The main treatment goals for chronic obstructive pulmonary disease (COPD) are the reduction of its symptoms and future risks. The addition of the traditional herbal medicine Hochuekkito (TJ-41) treatment to pulmonary rehabilitation (PR) has been reported to improve dyspnea and health-related quality of life (HRQOL) in patients with COPD. However, the reason for this improvement is not sufficiently understood. The purpose of the present study was to investigate whether the addition of TJ-41 treatment to PR improves symptoms of apathy, dyspnea, and HRQOL and increases physical activity among apathetic patients with COPD. Apathetic patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. A total of 29.9% of COPD patients had apathetic symptoms without severe depression. After the 12-week treatment, Apathy Scale, Patient Health Questionnaire-9, visual analog scale for dyspnea, and COPD assessment test energy scores decreased significantly in the TJ-41 group (p &lt; 0.05), but not in the control group. Additionally, the total number of steps taken was significantly higher in the TJ-41 group than in the control group. TJ-41 combined with PR may benefit apathetic patients with COPD with respect to apathy, dyspnea, HRQOL, and physical activity, but larger randomized placebo-controlled trials are required to validate the findings because of the small sample size and lack of placebo controls in this study

Pre-Existing Interstitial Lung Abnormalities Are Independent Risk Factors for Interstitial Lung Disease during Durvalumab Treatment after Chemoradiotherapy in Patients with Locally Advanced Non-Small-Cell Lung Cancer

Introduction/Background: Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments; however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients and Methods: Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. Results: A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70; 95% confidence interval, 1.69–7.72; p < 0.001). Conclusions: We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs