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1.
Cancer Med ; 12(13): 14327-14336, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37211905

RESUMO

BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51-0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Avaliação Nutricional , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Imunoterapia , Estudos Retrospectivos
2.
Thorac Cancer ; 13(19): 2829-2833, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36063818

RESUMO

BACKGROUND: Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is an innovative treatment for non-small cell lung cancer (NSCLC). Recently, the specific composition of the gut microbiome before initiation of cancer immunotherapy has been highlighted as a predictive biomarker in patients undergoing cancer immunotherapy, mainly in the US or Europe. However, the fact gut microbiome status is completely different in races or countries has been revealed. In addition, how the microbiome composition and diversity chronologically change during cancer immunotherapy is still unclear. METHODS: This multicenter, prospective observational study will analyze the association between the gut microbiome and therapeutic response in NSCLC patients who received atezolizumab-based immunotherapy. The aim of the present study is to clarify not only how the specific composition of the gut microbiome influences clinical response in NSCLC patients but the chronological changes of gut microbiota during atezolizumab-based immunotherapy. The gut microbiota will be analyzed using 16S rRNA gene sequencing. The main inclusion criteria are as follows: (1) Pathologically- or cytologically-confirmed stage IV or postoperative recurrent NSCLC. (2) Patients ≥20 years old at the time of informed consent. (3) Planned to treat with atezolizumab-based immunotherapy combined with platinum-based chemotherapy (cohort 1) and monotherapy (cohort 2) as a first immunotherapy. (4) Patients to provide fecal samples. A total of 60 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2024. DISCUSSION: This trial will provide more evidence of how gut microbiota composition and diversity chronologically change during cancer immunotherapy and contribute to the development of biomarkers to predict ICI response as well as biotic therapies which enhance the ICI response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Adulto , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Observacionais como Assunto , RNA Ribossômico 16S , Adulto Jovem
3.
Thorac Cancer ; 13(11): 1719-1721, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35437934

RESUMO

Intercostal cavernous hemangioma is extremely rare among benign vascular tumors. Achieving a definitive diagnosis preoperatively by radiographic examination alone is difficult; surgical resection is usually needed. Occasional cases are found as giant tumors, and some grow substantially during observation without treatment. Such tumors require extended surgical resection; however, small tumors can be completely resected by tumor extirpation alone. Thus, immediate surgical resection while the tumor is small might help to avoid invasive surgery. We herein describe cases of intercostal cavernous hemangioma with no invasion to the surrounding tissues, successfully treated by complete tumor resection using robot-assisted thoracic surgery.


Assuntos
Hemangioma Cavernoso , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Torácica , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Humanos
4.
Thorac Cancer ; 13(11): 1722-1725, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35437953

RESUMO

Castleman disease is a rare disease borne of a B cell lymphoproliferative disorder of uncertain cause. Standard therapy for the unicentric type of Castleman disease localized as a single mass or single lymph-node station is surgical extirpation. Nevertheless, in the thoracic cavity, unresectable cases or cases of incomplete extirpation of the tumor without lung scarring owing to tumor size/location have been noted. In such cases, lung resection (e.g., lobectomy, pneumonectomy) or additional therapy (immunotherapy, chemotherapy, radiotherapy) after resection is required. However, few instances of patients receiving induction immunotherapy or chemotherapy followed by surgery have been reported. Here, we describe a 21-year-old woman with unicentric Castleman disease originating from the left hilum. The tumor seemed to involve/be in contact with the pulmonary vein and bronchus. Tumor location indicated that initial resection was necessary to sacrifice upper and lower pulmonary lobes. To avoid these pulmonary resections, induction therapy followed by surgery was selected. Induction therapy using rituximab was very efficacious. Resection after induction therapy was completed only by tumor extirpation, and resulted in preservation of pulmonary function. Thoracic surgeons might consider induction therapy followed by resection if the tumor is resectable UCAD, but initial resection is needed and sacrifices a large amount of pulmonary function.


Assuntos
Hiperplasia do Linfonodo Gigante , Adulto , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/cirurgia , Feminino , Humanos , Imunoterapia , Pulmão/patologia , Pneumonectomia , Rituximab , Adulto Jovem
5.
Ann Thorac Cardiovasc Surg ; 28(3): 232-235, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-33071244

RESUMO

We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.


Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasias Pulmonares , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Cirurgia Torácica Vídeoassistida , Resultado do Tratamento
6.
Asian J Surg ; 45(1): 143-147, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33941441

RESUMO

OBJECTIVE: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL). METHODS: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy. RESULTS: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis. CONCLUSIONS: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Mediastino/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
7.
JMA J ; 4(4): 387-396, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34796293

RESUMO

INTRODUCTION: Several immunonutritional supplements have recently been developed. However, improvements in preoperative immunonutritional conditions using these supplements have not been analyzed in patients undergoing thoracic surgery. METHODS: This prospective, single-arm, single-institution pilot study involved patients planning to undergo thoracic surgery. Forty adults with a poor preoperative immunonutritional status were enrolled. The patients freely selected one of three oral immunonutritional supplements (IMPACTⓇ, MEINⓇ, or AboundⓇ) and started taking it on an outpatient basis from 7 to 14 days before thoracic surgery. The primary endpoint was the rate of improvement in three immunonutritional parameters on the hospitalization day: body mass index (BMI), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI). These improvement rates were compared with those of a matched historical control group. RESULTS: The PNI and GNRI improvement rates were significantly higher in the immunonutritional support group than in the control group (PNI: 103.1% ± 0.6% vs. 98.9% ± 1.3%, p = 0.0391; GNRI: 101.7% ± 0.8% vs. 99.3% ± 0.8%, p = 0.0266), although there was no significant difference in the BMI improvement rate (101.0% ± 0.6% vs. 100.2% ± 0.7%, p = 0.3626). The PNI and GNRI improvement rates were significantly higher in the IMPACTⓇ support group than in the control group (PNI: 104.5% ± 2.4% vs. 98.9% ± 1.3%, p = 0.0212; GNRI: 101.6% ± 1.1% vs. 99.3% ± 0.8%, p = 0.0415). CONCLUSIONS: The present study revealed that short-term preoperative immunonutritional support can actually improve immunonutritional parameters immediately before surgery. In particular, preoperative immunonutritional support using IMPACTⓇ supplementation might be the most promising agent in patients with a poor immunonutritional condition undergoing elective thoracic surgery. TRIAL REGISTRATION: University Hospital Medical Information Network 000035851.

8.
J Thorac Dis ; 13(9): 5487-5495, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34659815

RESUMO

BACKGROUND: Robot-assisted thoracic surgery (RATS) lobectomy for lung cancer is now performed all around the world. The camera and robotic devices are generally inserted from a low position via the thorax. We previously reported our original anterior approach (AA) for performing RATS lobectomy with a camera and robotic devices inserted via the anterior chest wall. However, whether AA is comparable or superior to the conventional approach (CA) remains unclear. METHODS: A total of 108 patients who underwent RATS lobectomy were included in the current study. We compared the AA with the CA for performing RATS lobectomy in terms of the operative and postoperative features, such as total operation/console time, blood loss and postoperative complications. RESULTS: Eighty-seven and 21 patients underwent the AA and CA in RATS lobectomy, respectively. The console and total operation time were significantly shorter in the AA group than in the CA group for RATS lobectomy (median console time: AA vs. CA, 112 vs. 148 min, P=0.0001; median total operation time: AA vs. CA, 193 vs. 243 min, P=0.0002), especially left upper lobectomy. Intraoperative blood loss and the frequency of postoperative complications were significantly reduced in the AA group compared with the CA group (median intraoperative blood loss: AA vs. CA, 20 vs. 105 mL, P<0.0001; postoperative complications: AA vs. CA, 8.0% vs. 28.6%, P=0.0088). CONCLUSIONS: These results suggest that our AA of RATS lobectomy can be very easily and safely performed.

9.
Thorac Cancer ; 12(15): 2217-2220, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34151529

RESUMO

Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non-small-cell lung carcinoma and are under investigation as an induction therapy. However, the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resectable non-small-cell lung carcinoma still remains unclear. Here, we report a case of stage IIIB non-small-cell lung carcinoma that underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab-paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in <1% of the total tumorous lesion suggesting near pathological complete response. This case suggests that this regimen might be a good option as induction therapy for non-small-cell lung carcinoma.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Terapia de Salvação/métodos , Antineoplásicos Imunológicos/administração & dosagem , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia
10.
Thorac Cancer ; 12(15): 2198-2204, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34173724

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). They cause immune-related adverse events (irAEs), but the underlying mechanisms and predictors remain to be fully elucidated. In this retrospective study, we investigated the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and the occurrence of irAEs. METHODS: The study involved 115 patients with NSCLC who started ICI-only treatment in our hospital between January 2016 and April 2020. RESULTS: Forty-five patients (39.1%) had irAEs, and pretreatment NLR was significantly lower in the irAEs group than in the non-irAEs group (2.8 vs. 4.1; p = 0.036). The cutoff value of the NLR was 2.86 (area under curve, 0.62; sensitivity, 0.56; specificity, 0.71), and the incidence rate of irAEs was significantly higher in the NLR < 2.86 group than in the NLR ≥2.86 group (p = 0.004; odds ratio [OR]: 3.12; 95% confidence interval [CI]: 1.43-6.84). The multivariate analysis showed that the NLR was significantly associated with the occurrence of irAEs (p = 0.016; OR: 2.69; 95% CI: 1.21-6.01). CONCLUSIONS: Low pretreatment NLR may be a predictive factor for the occurrence of irAEs. By focusing on the potential risk of irAEs in patients with a low pretreatment NLR, irAEs can be appropriately managed from an early period.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Estudos Retrospectivos
11.
Expert Rev Anticancer Ther ; 21(9): 975-988, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34110954

RESUMO

INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are widely known to contribute to the long-term survival of ALK-rearranged non-small cell lung cancer (NSCLC) patients. Based on clinical trial data, treatment with second- or third-generation ALK inhibitors can be initiated after crizotinib therapy without analyzing resistance mechanisms, and some randomized trials have recently shown the superiority of second- or third-generation ALK inhibitors over crizotinib as the initial treatment; however, the optimal treatment for patients who relapse while on second- or third-generation ALK inhibitors is not well-defined. AREAS COVERED: This review provides an overview of the mechanisms of resistance to second- or third-generation ALK inhibitors that have been identified in both clinical and pre-clinical settings, and introduces strategies for overcoming resistance and discusses ongoing clinical trials. EXPERT OPINION: The comprehensive elucidation of both ALK-dependent and ALK-independent resistance mechanisms is necessary to improve the prognosis of patients with ALK-rearranged NSCLC. Liquid biopsy to clarify these mechanisms of resistance might play an important role in the near future.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/efeitos adversos
12.
Thorac Cancer ; 12(11): 1761-1764, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33939293

RESUMO

The incidence of central nervous system (CNS) metastases in patients with anaplastic lymphoma kinase (ALK) fusion gene-positive (ALK+) non-small cell lung cancer (NSCLC) is high, ranging from approximately 20%-70%. Although ALK inhibitors (ALKis) are generally effective for CNS metastases in patients with ALK+ NSCLC, relapse with CNS metastases is frequently observed. A 37-year-old woman with a high level of carcinoembryonic antigen was diagnosed with right lung adenocarcinoma (pathological stage IIIA) and underwent right lower lobectomy. Despite the administration of postoperative chemotherapy, her carcinoembryonic antigen (CEA) level remained elevated. Although crizotinib was administered due to the positivity for ALK fusion, brain metastases appeared at 19.0 months after the start of treatment. Treatment with alectinib following crizotinib resulted in the complete disappearance of brain metastases. However, brain metastases relapsed, and meningeal dissemination appeared at 38.3 months after the start of treatment with alectinib. Although ceritinib, brigatinib, and alectinib rechallenge were attempted, the CNS lesions worsened. Lorlatinib was then administered, resulting in the normalization of the CEA level (4.5 ng/ml) 4.1 months after the start of lorlatinib. The brain metastases and meningeal dissemination almost disappeared. The overall time from the start of crizotinib to lorlatinib is 89.5 months at present, and the patient continues to be treated with lorlatinib without relapse. Lorlatinib was effective in this case with brain metastases and meningeal dissemination after resistance to first- and second-generation ALKis. Appropriate sequential treatment with first-, second- and third-generation ALKis can lead to a long-term survival in ALK+ patients with brain metastases and meningeal dissemination.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Metástase Neoplásica , Inibidores de Proteínas Quinases/farmacologia , Análise de Sobrevida , Fatores de Tempo
13.
Sci Rep ; 11(1): 8110, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854137

RESUMO

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets-one TBLB and three surgical, with combined total of 2407 WSIs-demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Aprendizado Profundo , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adenocarcinoma/classificação , Área Sob a Curva , Carcinoma de Células Escamosas/classificação , Bases de Dados Factuais , Humanos , Pulmão/patologia , Neoplasias Pulmonares/classificação , Curva ROC , Carcinoma de Pequenas Células do Pulmão/classificação
14.
Sci Rep ; 10(1): 9297, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518413

RESUMO

Lung cancer is one of the major causes of cancer-related deaths in many countries around the world, and its histopathological diagnosis is crucial for deciding on optimum treatment strategies. Recently, Artificial Intelligence (AI) deep learning models have been widely shown to be useful in various medical fields, particularly image and pathological diagnoses; however, AI models for the pathological diagnosis of pulmonary lesions that have been validated on large-scale test sets are yet to be seen. We trained a Convolution Neural Network (CNN) based on the EfficientNet-B3 architecture, using transfer learning and weakly-supervised learning, to predict carcinoma in Whole Slide Images (WSIs) using a training dataset of 3,554 WSIs. We obtained highly promising results for differentiating between lung carcinoma and non-neoplastic with high Receiver Operator Curve (ROC) area under the curves (AUCs) on four independent test sets (ROC AUCs of 0.975, 0.974, 0.988, and 0.981, respectively). Development and validation of algorithms such as ours are important initial steps in the development of software suites that could be adopted in routine pathological practices and potentially help reduce the burden on pathologists.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Aprendizado de Máquina Supervisionado , Algoritmos , Biologia Computacional/métodos , Diagnóstico por Computador/métodos , Humanos , Neoplasias Pulmonares/patologia , Redes Neurais de Computação
15.
Cancer Med ; 9(7): 2343-2351, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32022477

RESUMO

BACKGROUND: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). METHODS: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. RESULTS: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. CONCLUSION: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Epidemiologia Molecular/métodos , Mutação , Pneumonectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
16.
Ann Thorac Cardiovasc Surg ; 26(5): 248-255, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32074540

RESUMO

BACKGROUND: Complete blood cell count (CBC)-derived inflammatory biomarkers are widely used as prognostic parameters for various malignancies, but the best predictive biomarker for early-stage non-small-cell lung cancer (NSCLC) is unclear. We retrospectively analyzed early-stage NSCLC patients to investigate predictive effects of preoperative CBC-derived inflammatory biomarkers. PATIENTS AND METHODS: We selected 311 consecutive patients with pathological stage IA NSCLC surgically resected from April 2006 to December 2012. Univariate and multivariate Cox proportional analyses of recurrence-free survival (RFS) were used to test the preoperative systemic immune inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR). RESULTS: Preoperative high MLR levels were significantly associated with patient sex, smoking status, and postoperative recurrence (p <0.0001, p = 0.0307, and p = 0.0146, respectively), and preoperative high SII levels were significantly correlated with postoperative recurrence (p = 0.0458). Neither NLR nor PLR were associated with any related factors. Only preoperative MLR levels (p = 0.0269) were identified as an independent predictor of shorter RFS. The relative risk (RR) for preoperative high MLR level versus low level patients was 2.259 (95% confidence interval [CI]: 1.094-5.000). Five-year RFS rates in patients with preoperatively high MLR levels were significantly lower than in those with low MLR levels (82.21% vs. 92.05%, p = 0.0062). In subgroup analysis by tumor size and MLR level, the high MLR level subgroup with tumors >2 cm had significantly shorter RFS than other subgroups (p = 0.0289). CONCLUSIONS: The preoperative MLR level is the optimal predictor of recurrence in patients with pathological stage IA NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Inflamação/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos/imunologia , Monócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neutrófilos/imunologia , Contagem de Plaquetas , Pneumonectomia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Carga Tumoral
18.
Ann Thorac Cardiovasc Surg ; 26(5): 240-247, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31996508

RESUMO

BACKGROUND: Elderly non-small-cell lung cancer (NSCLC) patients are increasing. In general, elderly patients often have more comorbidities and worse immune-nutritional condition. PATIENTS AND METHODS: In total, 122 NSCLC patients aged 75 years or older, underwent thoracic surgery between January 2007 and December 2010. In all, 99 of 122 patients (81.1%) who had preoperative comorbidities were retrospectively analyzed. We evaluated the preoperative immune-nutritional condition using the controlling nutritional status (CONUT) score. RESULTS: We decided the best cutoff value for CONUT score was 1; as a result, 42 of 99 patients (42.4%) had abnormal preoperative CONUT score. Univariate analyses showed sex (P = 0.0099), smoking status (P = 0.0176), pathological stage (P = 0.0095), and preoperative CONUT score (P = 0.0175) significantly affected overall survival (OS). In multivariate analysis, pathological stage (relative risk (RR): 2.12; 95% confidence interval (CI): 1.10-3.90; P = 0.0268) and preoperative CONUT score (RR: 2.10; 95% CI: 1.20-3.67; P = 0.0094) were shown to be independent prognostic factors. In Kaplan-Meier analysis of OS, the preoperative abnormal CONUT score group had significantly shorter OS than did the preoperative normal CONUT score group (P = 0.0152, log-rank test); however, there were no statistical differences both in disease-free survival (DFS) and cancer-specific survival (CSS; P = 0.9238 and P = 0.8661, log-rank test, respectively). In total, 22 patients (46.8%) were dead caused by other diseases such as pneumonia or other organs malignancies. CONCLUSION: Preoperative abnormal CONUT score is a poor prognostic factor for the elderly NSCLC patients with preoperative comorbidities and might predict poor postoperative outcome caused by not primary lung cancer but other diseases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Avaliação Geriátrica , Neoplasias Pulmonares/cirurgia , Desnutrição/diagnóstico , Avaliação Nutricional , Estado Nutricional , Pneumonectomia/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Desnutrição/imunologia , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Pneumonectomia/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Semin Thorac Cardiovasc Surg ; 32(4): 1036-1045, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31009697

RESUMO

Red blood cell distribution width (RDW) is a parameter measured in blood sample tests that reflects the variation in the volume of erythrocytes and used to differentiate an anemic state. The RDW has been used to predict a poor survival in various types of cancer; however, the prognostic impact of the RDW in resected pathologic stage I nonsmall cell lung cancer (NSCLC) patients remains to be elucidated. A total of 273 patients with resected pathologic stage I NSCLC were included in this study. The cut-off value of RDW was set at 14.5, which was the upper limit of the normal range of the RDW. The controlling nutritional status (CONUT) score, which was calculated by the albumin, cholesterol, and the lymphocyte count, was also investigated. Among 273 patients, 34 (12.5%) were RDW-high, while 239 (87.5%) were RDW-low. RDW-high was significantly associated with a lower body mass index (P < 0.01), a lower level of hemoglobin (P < 0.01), a higher level of C-reactive protein (P < 0.01), and a high CONUT score (P = 0.03) than RDW-low. Patients with RDW-high exhibited significantly shorter recurrence-free and overall survivals (RFS and OS, respectively) than those with RDW-low (P < 0.01 and P < 0.01, respectively). Multivariate analyses showed that the RDW was an independent prognostic factor for both the RFS and OS (RFS, hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.14-3.95, P = 0.02; OS, HR: 2.44, 95% CI: 1.28-4.49, P < 0.01). The RDW was shown to be associated with a worse long-term prognosis in resected pathologic stage I NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Eritrócitos , Humanos , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
20.
J Thorac Dis ; 12(12): 7127-7134, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33447401

RESUMO

BACKGROUND: Smoking cessation is a highly important preparation before thoracic surgery. We examined the effects of short-term smoking cessation intervention before pulmonary resection on postoperative pulmonary complications (PPCs). METHODS: A retrospective analysis of prospectively collected data was performed for 753 patients who underwent curative surgical resection for thoracic malignancy at 3 institutions. Patients with a smoking history were instructed to quit smoking. After confirming smoking cessation by at least four weeks before surgery, surgical resection was performed. Subjects were classified into three groups based on their smoking status: abstainers (anyone who had stopped smoking for at least 4 weeks but less than 2 months), former smokers (anyone who had abstained from smoking for more than two months prior to surgery), and never smokers (those who had never smoked). We examined the relationship between the preoperative smoking status and PPCs. RESULTS: Surgery was performed for 660 primary lung cancers and 93 metastatic lung tumors. The smoking statuses were classified as follows: abstainers (n=105, 14%), former smokers (n=361; 48%) and never smokers (n=287, 38%). The incidence of PPCs among abstainers, former smokers and never smokers was 15%, 8% and 6%, respectively (P=0.01). The mean duration of post-operative chest tube drainage among abstainers, former smokers and never smokers was 3.2, 2.2 and 2.2 days, respectively (P=0.04). The mean post-operative hospital stay among abstainers, former smokers and never smokers was 12.1, 10.6 and 10.2 days, respectively (P=0.07). There was no 30-day mortality in the cohort. CONCLUSIONS: Short-term smoking cessation intervention did not enough reduce the PPCs as much as in former or never smokers.

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