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1.
Commun Biol ; 7(1): 338, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499610

RESUMO

Whether organ-specific regeneration is induced by organ-specific endothelial cells (ECs) remains unelucidated. The formation of white matter lesions due to chronic cerebral hypoperfusion causes cognitive decline, depression, motor dysfunction, and even acute ischemic stroke. Vascular ECs are an important target for treating chronic cerebral hypoperfusion. Brain-derived ECs transplanted into a mouse chronic cerebral hypoperfusion model showed excellent angiogenic potential. They were also associated with reducing both white matter lesions and brain dysfunction possibly due to the high expression of neuroprotective humoral factors. The in vitro coculture of brain cells with ECs from several diverse organs suggested the function of brain-derived endothelium is affected within a brain environment due to netrin-1 and Unc 5B systems. We found brain CD157-positive ECs were more proliferative and beneficial in a mouse model of chronic cerebral hypoperfusion than CD157-negative ECs upon inoculation. We propose novel methods to improve the symptoms of chronic cerebral hypoperfusion using CD157-positive ECs.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Camundongos , Animais , Células Endoteliais/metabolismo , AVC Isquêmico/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Endotélio/metabolismo
2.
Cancer Immunol Immunother ; 73(1): 4, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175294

RESUMO

INTRODUCTION: Nivolumab plus ipilimumab with chemotherapy (NICT) and pembrolizumab with chemotherapy (PCT) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). Compared with immune checkpoint inhibitor (ICI) monotherapy, ICI combination therapy can increase immune-related toxicity instead of prolonging survival. This study aimed to compare the efficacy and safety of NICT and PCT to decide on the favorable treatment. METHODS: We conducted a multi-center retrospective cohort study on patients who underwent NICT or PCT between December 2018 and May 2022. Propensity score matching (PSM) was performed with the variables age, sex, smoking status, performance status, stage, histology, and programmed cell death ligand-1 (PD-L1). The Kaplan-Meier method was used to compare survival for the matched patients. RESULTS: Six hundred consecutive patients were included. After PSM, 81 and 162 patients were enrolled in the NICT and PCT groups, respectively. The baseline characteristics were well-balanced. The median progression-free survival was equivalent (11.6 vs. 7.4 months; P = 0.582); however, the median overall survival (OS) was significantly longer in the NICT group than in the PCT group (26.0 vs. 16.8 months; P = 0.005). Furthermore, OS was better in PD-L1-negative patients who underwent NICT than in those who underwent PCT (26.0 vs. 16.8 months; P = 0.045). Safety profiles did not differ significantly in terms of severe adverse event and treatment-related death rates (P = 0.560, and 0.722, respectively). CONCLUSIONS: Real-world data suggests that NICT could be a favorable treatment option compared with PCT for patients with advanced NSCLC. Further follow-up is needed to determine the long-term prognostic benefit.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Antígeno B7-H1 , Neoplasias Pulmonares/tratamento farmacológico , Platina
3.
Eur J Clin Pharmacol ; 79(4): 503-511, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36773042

RESUMO

OBJECTIVES: Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy for advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to elucidate sequencing strategies of RAM and DOC following prior treatments, including immune checkpoint inhibitor (ICI), cytotoxic agent (CTx) alone, bevacizumab (BEV), and tyrosine kinase inhibitor (TKI). METHODS: We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx alone, BEV, and TKI, respectively. By tumor response to such treatments, the patients were further classified into "complete response (CR) + partial response (PR)," "stable disease," and "progressive disease" groups, respectively. We compared RAM and DOC efficacy among these groups. RESULTS: In total, 237 patients were registered. In the group with prior ICI, the objective response rate and disease control rate were significantly higher than those without prior ICI (p = 0.012 and 0.028, respectively), and the median progression-free survival (PFS) was also significantly longer (p = 0.027). There were no significant differences in PFS between the groups with and without CTx alone, BEV, and TKI. Multivariate analysis revealed that prior ICI was an independent factor associated with better PFS. Furthermore, the prior ICI group with CR + PR significantly prolonged PFS compared to the group without prior ICI (p = 0.013). CONCLUSION: RAM and DOC may be preferably administered after ICI, rather than after CTx alone, BEV, or TKI, and, furthermore, enhanced if the prior ICI has a favorable tumor response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Docetaxel/uso terapêutico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Ramucirumab
4.
Clin Case Rep ; 11(1): e6844, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36694652

RESUMO

This report described a rare case of subcutaneous anaerobic bacterial abscess due to Peptoniphilus olsenii and Gleimia europaea after COVID-19. The patient received incision and drainage of the abscess and antibiotics, thereby achieving recovery. Immunodeficiency related to COVID-19 and its treatment might contribute to secondary skin and subcutaneous bacterial infections.

5.
Transl Lung Cancer Res ; 11(9): 1835-1846, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36248332

RESUMO

Background: There is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD. Methods: We systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3-5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity. Results: In total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24-36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53-3.69; I2=0.0%). The pooled grade 3-5 ICIP rate was 12% (95% CI: 9-15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32-4.38; I2=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24-48%; I2=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86-1.32; I2=0.0%). Conclusions: Overall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

6.
Int J Chron Obstruct Pulmon Dis ; 17: 1495-1506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35801120

RESUMO

Purpose: Pulmonary fibrosis and emphysema result in relatively maintained ventilation and reduced diffusing capacity. This pulmonary functional impairment complicates the evaluation of pulmonary function in patients with combined pulmonary fibrosis and emphysema (CPFE). Therefore, a single and easy-to-use pulmonary function index to evaluate patients with CPFE warrants further studies. Respiratory impedance can easily be provided by oscillometry and might be a candidate index to evaluate pulmonary function in patients with CPFE. As a preliminary study to assess the utility of respiratory impedance, we investigated the associations of physiological indices, including respiratory impedance, in patients with idiopathic pulmonary fibrosis (IPF) with and without emphysema. Patients and Methods: This retrospective study evaluated patients with IPF who did and did not satisfy the diagnostic criteria of CPFE. All patients underwent oscillometry, spirometry, and diffusing capacity for carbon monoxide (DLCO). Correlations of the obtained physiological indices were analyzed. Results: In total, 47 patients were included (18 and 29 patients with CPFE and IPF, respectively). Respiratory reactance (Xrs) at 5 Hz (X5) in the inspiratory phase was associated with forced vital capacity (FVC) % predicted in patients with CPFE (rS=0.576, P=0.012) and IPF (rS=0.539, P=0.003). Inspiratory X5 positively correlated with DLCO % predicted only in patients CPFE (rS=0.637, P=0.004). Conclusion: Emphysema might associate Xrs with ventilation and diffusing capacity in patients with IPF and emphysema. Given the multiple correlations of Xrs with FVC and DLCO, this study warrants further studies to verify the utility of oscillometry in a large-scale study for patients with CPFE.


Assuntos
Enfisema , Fibrose Pulmonar Idiopática , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Impedância Elétrica , Enfisema/complicações , Fibrose , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos
8.
Respir Med Case Rep ; 36: 101619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251929

RESUMO

Pure red cell aplasia (PRCA), Good's syndrome (GS), and thymoma-associated multiorgan autoimmunity (TAMA) are associated with thymoma. Herein, we describe the case of a 56-year-old woman with PRCA, GS, and TAMA simultaneously. She was treated with cyclosporine, immunoglobulin supplementation, and prednisolone; however, she died of uncontrolled sepsis due to extreme immunosuppression. The combination of these three diseases is likely to lead to fatal infections, and to avoid such infections, it may be necessary to reduce or discontinue immunosuppressants and steroids as soon as possible if the diseases are controlled, as well as regular immunoglobulin supplementation.

10.
Invest New Drugs ; 40(3): 634-642, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35024985

RESUMO

OBJECTIVE: Ramucirumab plus docetaxel (RAM/DOC) therapy is currently the standard for previously treated advanced non-small cell lung cancer (NSCLC), irrespective of histology. However, in the clinical trial, only the first-line platinum-based chemotherapy refractory patients were enrolled and the eligible criteria was strict to avoid hemoptysis, especially in squamous cell NSCLC (Sq). Thus, the efficacy and safety data on ramucirumab for Sq in real-world settings after immune checkpoint inhibitors monotherapy or combination therapy approved as novel first-line therapy is lacking. METHODS: We retrospectively analyzed previously treated patients with advanced NSCLC who underwent RAM/DOC therapy at four institutions. Clinical data on the initiation of RAM/DOC were collected from medical records. Treatment outcomes were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Incidence of pulmonary hemorrhage was assessed according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Overall, 237 patients with NSCLC were included and 38 (16%) had squamous cell carcinoma. There were no significant differences in median progression-free survival and overall survival between Sq and non-Sq patients (5.8 months vs. 4.3 months, P = 0.0937; 15.2 months vs. 13.4 months, P = 0.714, respectively). Of all patients, 13 (5%) developed pulmonary hemorrhage. According to histological analysis, there was no significant difference in pulmonary hemorrhage proportion between Sq and non-Sq cohorts (2/38 vs. 11/199, respectively, P = 0.947). CONCLUSIONS: For previously treated patients with Sq, the efficacy and safety of RAM/DOC therapy were confirmed in a real-world setting and were similar to non-Sq.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Docetaxel , Células Epiteliais/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Resultado do Tratamento , Ramucirumab
11.
Medicine (Baltimore) ; 101(1): e28476, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029896

RESUMO

RATIONALE: Thymic carcinoma (TC) is a malignant mediastinal tumor, and there are no established treatments for pre-treated patients with advanced TC. Recently, lenvatinib was approved for such patients in Japan, ahead of other countries. Higher dose lenvatinib may be more efficacious than conventional treatments, although many patients experience grade 3 hypertension. Therefore, lenvatinib dose reduction remains controversial in terms of efficacy and tolerability. PATIENT CONCERNS: Case 1 involves a 72-year-old woman who underwent complete resection of TC and was taking cilnidipine and azilsartan for hypertension. Six years later, multiple lung metastases were observed, and lenvatinib was started. Case 2 involves a 60-year-old man with TC, and was taking amlodipine for hypertension. A chest computed tomography showed progression in primary and metastatic lesions, and the patient started lenvatinib. DIAGNOSES: In both patients, grade 3 hypertension was observed after the administration of lenvatinib. INTERVENTIONS: In Case 1, lenvatinib dose was reduced 3 times because lenvatinib was not interrupted despite grade 3 hypertension. In contrast, in Case 2, lenvatinib was interrupted when grade 3 hypertension occurred and was resumed after a decrease in blood pressure to baseline. OUTCOMES: In Case 2, higher tumor regression may have been achieved because of the maintenance of a high dose of lenvatinib compared with that in Case 1. LESSONS: Lenvatinib is a promising agent for advanced TC; however, hypertension should be addressed cautiously, especially at the outset of administration. Lenvatinib may have to be appropriately interrupted and resumed as soon as the blood pressure is controlled to maximize efficacy and minimize toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Idoso , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Timoma/patologia , Neoplasias do Timo/patologia
12.
Int J Infect Dis ; 116: 255-257, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35065256

RESUMO

Messenger RNA (mRNA) vaccines that protect against COVID-19 are widely used in many countries owing to their high efficacy and safety profiles. Recently, few severe adverse events, such as anaphylaxis and myocarditis, were reported in healthy individuals. The safety of mRNA COVID-19 vaccines has not been adequately studied in patients with interstitial lung disease. We report 2 cases of acute exacerbation of preexisting interstitial pneumonia associated with mRNA COVID-19 vaccination. In both cases, lung disease was stable before the vaccination. Initial responses to steroid therapy were unfavorable, and intravenous cyclophosphamide was administered in both cases. Both patients were diagnosed with vaccine-related exacerbation of interstitial pneumonia based on laboratory results, radiologic features, and the observed clinical course, which lacked other causative events. We suggest that clinicians should note the possibility of acute exacerbation of pneumonia after mRNA COVID-19 vaccination and carefully monitor patients with interstitial lung disease.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , RNA Mensageiro/genética , SARS-CoV-2 , Vacinação/efeitos adversos
13.
J Geriatr Oncol ; 13(2): 207-213, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602370

RESUMO

OBJECTIVE: Ramucirumab (RAM) plus Docetaxel (DOC) is one of the standard treatments after first-line treatment failure in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the efficacy and safety of RAM plus DOC in older patients. We aimed to clarify these and elucidate the prognostic factors. MATERIALS AND METHODS: In this multicenter retrospective study, conducted at four medical facilities in Japan, we evaluated the efficacy and safety data for two groups (<65 and ≥ 65 years). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to reveal the prognostic factors for better PFS and OS. Patient characteristics and adverse events (AEs) in both groups were compared using the Mann-Whitney's U and Fisher's exact tests for categorical variables. RESULTS: A total of 237 patients were included, of whom 43% (n = 103), and 57% (n = 134) were aged <65, and ≥ 65 years. Median OS was 12.2 (95% CI: 9.4-15.0), and 14.8 months (95% CI: 10.8-18.8), respectively, and there were no significant differences between the groups (p = 0.534). Multivariate analysis identified DOC dose reduction (none vs performed, HR: 2.66, 95% CI: 1.62-4.35, p < 0.001) as an independent prognostic factor for OS in older patients, and a similar result was shown for the PFS. Grade ≥ 3 all AEs were identified in 42.7% and 56.7% of younger and older patients, respectively, and there was a significant difference between the groups (p = 0.033); however, the difference between the groups disappeared with primary DOC dose reduction (p = 0.526). CONCLUSION: The efficacy of RAM plus DOC administration in older, pretreated patients with advanced NSCLC was comparable to those of younger patients, whereas RAM plus DOC should be cautiously administered to older patients because of severe toxicity. Moreover, appropriate DOC dose reduction may be recommended for increased survival benefit and safety in such patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ramucirumab
14.
J Med Virol ; 94(3): 1067-1073, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34708883

RESUMO

Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID-19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID-19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID-19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV-deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti-CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection-related mortality. The cumulative incidences of CMV infection and anti-CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%-39.0%) and 12.3% (95% CI, 4.8%-23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13-16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV-DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID-19 should be limited.


Assuntos
Tratamento Farmacológico da COVID-19 , Coinfecção , Infecções por Citomegalovirus , Corticosteroides/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Humanos , Unidades de Terapia Intensiva
15.
Angiogenesis ; 25(2): 147-149, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34591203

RESUMO

We report a unique case of advanced non-small cell lung cancer that exhibited the opposite response to its unilateral choroidal metastases upon ramucirumab plus docetaxel treatment. A combination of cisplatin, pemetrexed, and pembrolizumab was administered as first-line treatment, resulting in shrinkage of all the lesions. However, although the patient was continued on a course of pembrolizumab, all the lesions had recurred approximately two months later. Ramucirumab plus docetaxel, administered as sequential treatment, resulted in maintained shrinkage of the choroidal lesions, yet all the other lesions progressed. Ramucirumab may be a suitable therapy for choroidal metastases, especially if administered immediately after immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Resultado do Tratamento , Ramucirumab
16.
Lung Cancer ; 162: 175-184, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34823108

RESUMO

OBJECTIVE: Several studies have demonstrated that anti-angiogenic agents (AAs) have the ability to regulate immune-related cells in the tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). Therefore, we investigated the drug interaction between ICI and AA for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We systematically searched PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science before August 23, 2021. ICI and AA therapy included the concomitant and sequential use of ICIs and AAs. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients who received ICI and AA therapy were evaluated and compared to those of patients who received either monotherapy. Subgroup analyses were performed to clarify the cause of heterogeneity; the timing and sequence of ICI and AA administration were predefined as the subgroups. RESULTS: Thirteen studies involving 2414 patients were included in the meta-analysis. ICI and AA therapy had significantly higher ORR than either monotherapy (OR [95% CI]: 0.61 [0.50-0.74]; p < 0.001; I2 = 29%). PFS and OS were favorable benefits in ICI and AA therapy; however, significant heterogeneity was identified in these analyses (I2 = 80% and 59%, respectively). According to the administration timing and sequence, ICI immediately after AA showed no PFS and OS benefits compared to ICI monotherapy (HR [95 % CI]: 1.54 [1.14-2.08] and 1.50 [1.04-2.15], respectively), whereas favorable PFS and OS were demonstrated when AA was concomitantly administered with ICI (HR [95 % CI]: 0.57 [0.43-0.76] and 0.80 [0.61-1.05], respectively) or when AA was administered immediately after ICI (HR [95 % CI]: 0.58 [0.34-1.00] and 0.56 [0.40-0.80], respectively). CONCLUSION: ICI and AA therapy can provide favorable clinical effects compared to either monotherapy; however, ICI administered immediately after AA may not show survival benefits.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão , Microambiente Tumoral
17.
Transl Lung Cancer Res ; 10(4): 1642-1652, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012781

RESUMO

BACKGROUND: Docetaxel (DOC) plus ramucirumab (RAM) has been recommended as an optimal therapy for previously treated patients with non-small cell lung cancer (NSCLC). In a clinical setting, there are few reports about DOC plus RAM, therefore its effect on factors such as Eastern Cooperative Oncology Group (ECOG) performance status (PS) and metastatic sites is still unknown. METHODS: We recruited NSCLC patients who received DOC plus RAM in four medical facilities in Japan from June 2016 to March 2020. We retrospectively investigated the overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of DOC plus RAM and conducted univariate and multivariate analyses using PFS as a dependent factor. Patients were followed up until June 30, 2020. RESULTS: A total of 237 patients were consecutively enrolled. For all patients, the ORR, DCR, and median PFS were 25.2%, 63.9%, and 4.5 months, respectively. The ORR and DCR for malignant pleural effusion (MPE), lung metastasis, and liver metastasis were 7.7% and 53.8%, 30.3% and 77.5%, and 48.6% and 71.4%, respectively. In the multivariate analysis, MPE, lung metastasis, and liver metastasis were not prognostic factors for poor PFS. However, ECOG-PS 2 or more [hazard ratio (HR): 1.66, 95% confidence interval (CI): 1.14-2.40, P=0.008] and brain metastasis (HR: 1.71, 95% CI: 1.23-2.37, P=0.001) were significant and independent factors associated with shorter PFS. CONCLUSIONS: DOC plus RAM could be an optimal therapy for previous treated NSCLC patients with lung and liver metastasis, and furthermore, should be used carefully for patients with poor ECOG-PS or brain metastasis. KEYWORDS: Docetaxel and ramucirumab; non-small cell lung cancer (NSCLC); metastatic site; poor performance status.

18.
Thorac Cancer ; 12(7): 1137-1140, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33605078

RESUMO

Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion.


Assuntos
Derrame Pleural/diagnóstico , Sarcoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/patologia , Sarcoma/patologia
19.
Clin Transl Oncol ; 23(3): 582-590, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32661824

RESUMO

PURPOSE: This study evaluated the efficacy and safety of nivolumab treatment beyond progressive disease (PD) in non-small cell lung cancer (NSCLC). PATIENTS/METHODS: Medical records of consecutive patients with advanced NSCLC who received nivolumab between December 2015 and December 2018 were reviewed. Clinical outcomes of three groups of eligible patients who received nivolumab as a second-line treatment after PD were compared based on Response Evaluation Criteria in Solid Tumors v1.1. We conducted subgroup analyses in patients with and without new lesions at first PD. RESULTS: Twenty-eight patients continued nivolumab treatment beyond PD (TBP). Post PD, 46 patients switched to other anti-cancer treatment (OAT), and 21 received no further anti-cancer treatment (NAT). There were no significant differences in overall survival (OS) or survival post progression (SPP) between TBP and OAT groups (OS: 15.6 vs. 13.4 months, P = .40, SPP: 12.2 vs. 9.3 months, P = .42). Subgroup analyses indicated that among patients without new lesions at first PD, SPP was longer in the TBP than in the OAT groups (12.6 vs. 9.3 months, P = .22, HR: 0.64; 95% CI 0.31‒1.31). The frequency of immune-related adverse events leading to discontinuation during nivolumab beyond PD was equivalent to that for pre-PD (10.7 vs. 12.6%). CONCLUSIONS: No significant benefits were associated with continuation of nivolumab for advanced NSCLC patients. Continuation of nivolumab beyond PD could be a more useful option in patients without new lesions at first PD. Treatment-related toxicities require attention during nivolumab treatment not only before PD but also beyond PD.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Transversais , Progressão da Doença , Substituição de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Análise de Regressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos
20.
Respir Med Case Rep ; 31: 101313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33318921

RESUMO

A 60-year-old man was admitted for ground glass opacity in the lower lung field and mediastinal lymphadenopathy. Blood tests revealed elevated serum IgM levels, and the urine test detected Bence-Jones protein. Surgical biopsy from the mediastinal lymph node and lung showed small lymphocytes and plasma cells between follicles, and AL kappa amyloid deposition. Genetic examination detected MYD88 L265P mutation. Our diagnosis was lymphoplasmacytic lymphoma (LPL), involving the mediastinum and the lung, followed by amyloidosis. Mutation analysis, in addition to conventional histological evaluation, was useful for a precise diagnosis.

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