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BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Estudios de Cohortes , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Mutación , Estudios Prospectivos , Proteínas Tirosina Quinasas Receptoras/genética , Análisis de SupervivenciaRESUMEN
Objective@#To investigate the clinical pathological feature of primary pulmonary sarcomatold carcinoma and to make a further understandine of the disease.@*Methods@#Data including clinical manifesation, pathological findings, molecular detection and immunophenotyping with pathologically confirmed primary pulmonary sarcomatold carcinoma was retrospectively analyzed.@*Results@#15 patients with PPSC were identified(13 men and 2 women, age ranged 56-76 years, median age 66 years). The tumor were located in the left lobus superior(8 cases), lobus inferior(6 cases), and the right lobus medius(1 case). The main clinical symptoms was cough, sputum, bloody sputum, chest pain. Among the 13 males, 10 had smoking history of more than 30 years, and 2 females had no smoking history. All cases presented with a spheroid solid lung mass. All tumor showed mild enhancement similar to that of the surrounding musculature after contrast enhancement, and inhomogeneous central low-attenuation areas were seen in 15 patients. Pathological pattern: 6 cases spindle cell carcinoma, 4 cases pleomorphic carcinoma, 2 cases giant cells carcinoma, 2 cases carcinosarcoma, 1 case pulmonary blastoma. The tumors were composed of both carcinomatous and sarcomatous elements. Immunohistochemistry showed that CK was all positive, EMA was positive in 7, VIM was positive in 10 of 15 cases.10 patients were tested for common related genes of lung cancer, 4 patients had MET14 jump mutation, EGFR L858R gene mutation occurred in 3 cases, KARS G13D gene mutation in 2 cases, and BRAF V600E mutation in 1 case. All 15 patients underwent lobectomy, 13 underwent adjuvant chemotherapy, and 6 underwent local radiotherapy. Postoperative follow-up was 8 to 50 months, 3 cases were lost, and 4 cases were survival 3 years after the surgery.@*Conclusion@#Pulmonary sarcomatold carcinoma is a rare histologic subtype of non-small cell lung cancer. Compared with other NSCLC, there is no special clinical and imageing characteristics. Its definite diagnosis relies on postoperative pathological analysis and immunohistochemical staining, and PSC needs to be diatinguished from a variely of disease. PPSC is more aggressive and poor prognosis.
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Objective To investigate the clinical pathological feature of primary pulmonary sarcomatold carcinoma and to make a further understandine of the disease.Methods Data including clinical manifesation,pathological findings,molecular detection and immunophenotyping with pathologically confirmed primary pulmonary sarcomatold carcinoma was retrospectively analyzed.Results 15 patients with PPSC were identified (13 men and 2 women,age ranged 56-76 years,median age 66 years).The tumor were located in the left lobus superior(8 cases),lobus inferior (6 cases),and the right lobus medius (1 case).The main clinical symptoms was cough,sputum,bloody sputum,chest pain.Among the 13 males,10 had smoking history of more than 30 years,and 2 females had no smoking history.All cases presented with a spheroid solid lung mass.All tumor showed mild enhancement similar to that of the surrounding musculature after contrast enhancement,and inhomogeneous central low-attenuation areas were seen in 15 patients.Pathological pattern:6 cases spindle cell carcinoma,4 cases pleomorphic carcinoma,2 cases giant cells carcinoma,2 cases carcinosarcoma,1 case pulmonary blastoma.The tumors were composed of both carcinomatous and sarcomatous elements.Immunohistochemistry showed that CK was all positive,EMA was positive in 7,VIM was positive in 10 of 15 cases.10 patients were tested for common related genes of lung cancer,4 patients had MET14 jump mutation,EGFR L858R gene mutation occurred in 3 cases,KARS G13D gene mutation in 2 cases,and BRAF V600E mutation in 1 case.All 15 patients underwent lobectomy,13 underwent adjuvant chemotherapy,and 6 underwent local radiotherapy.Postoperative follow-up was 8 to 50 months,3 cases were lost,and 4 cases were survival 3 years after the surgery.Conclusion Pulmonary sarcomatold carcinoma is a rare histologic subtype of non-small cell lung cancer.Compared with other NSCLC,there is no special clinical and imageing characteristics.Its definite diagnosis relies on postoperative pathological analysis and immunohistochemical staining,and PSC needs to be diatinguished from a variely of disease.PPSC is more aggressive and poor prognosis.
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OBJECTIVE: To investigate the biodistribution and single-photon emission computed tomography (SPECT) imaging of (99m)Tc-labeled arginine-glutamic acid-threonine (RET) and arginine-glutamic acid-glycine (REG) in nude mice bearing human lung cancer xenografts. MATERIALS AND METHODS: RET and REG were labeled directly with (99m)Tc and their binding efficiency to tumor cells was measured in human nonsmall cell lung cancer H1299 cells. After intravenously injecting (99m)Tc-RET and (99m)Tc-REG into normal mice and nude mice bearing human lung cancer xenografts, their biodistribution was measured at different postinjection times, and percentages of injected dose per gram tissue (% ID/g) of organs of interest were calculated. The mice bearing H1299 lung cancer xenografts were scanned by SPECT at different times following the (99m)Tc-RET or (99m)Tc-REG injection. RESULTS: The radiochemical purity of (99m)Tc-RET and (99m)Tc-REG was 93.15%±2.02% and 92.90%±2.86%, respectively. The binding rate of (99m)Tc-RET and (99m)Tc-REG to H1299 cells was 3.56%±0.37% and 2.32%±0.31%, respectively. The uptake of (99m)Tc-RET and (99m)Tc-REG in tumor was 4.96±1.05% ID/g at 4 hours postinjection and 1.95±0.73% ID/g at 2 hours postinjection, respectively. Tumors in nude mice could be best imaged at 4.5-6 hours postinjection of (99m)Tc-RET. CONCLUSION: (99m)Tc-RET has a higher binding rate to H1299 cells than (99m)Tc-REG and might be used as a potential lung cancer imaging agent.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Oligopéptidos/farmacocinética , Compuestos de Organotecnecio/farmacocinética , Radiofármacos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único/métodos , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Tisular , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: We aimed to identify the factors determining long-term survival after surgical management for bronchial typical carcinoid (TC) and atypical carcinoids (AC) and to compare the clinical outcome of the different surgical strategies used in the two periods of 1980-1994 and 1995-2005. METHODS: Records of 82 patients with an initial pathological diagnosis of bronchial carcinoid tumor who underwent surgical management from January 1980 to December 2009 were reviewed. Tumors were classified as TC or AC using the 2004 World Health Organization criteria. RESULTS: There were 60 TC and 22 AC. Surgical procedures included lobectomies, sleeve or bronchoplastic resections, pneumonectomies, wedge resections, and segmental resections. Significantly fewer pneumonectomies and more sleeve and bronchoplastic resections were performed after 1994. The prognosis was more favorable for TC than AC. Comparing lymph node status N0 with N1 + N2, 5- and 10-year survival was 92% and 85% vs. 61% and 41%. No patient with lymph node involvement survived more than 15 years. CONCLUSIONS: Tumor subtype and lymph node status have the greatest impact on long-term survival following surgery. AC and/or regional lymph node metastases have the worst prognosis. Formal anatomic and tissue-saving lung resection plus systematic radical mediastinal lymphadenectomy for TC and AC should be standard.
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Objective To probe into the indication, operative skill of intrapericardial pneumonectomy, the prevention and cure in postoperative complication of intrapericardial pneumonectomy for locally advanced lung canc-er. Methods The clinical data of 43 cases of locally advanced lung cancer undergoing intrapericardial pneumonec-tomy from February 1998 to November 2007 were retrospectively analyzed. Results No surgical death occurred. The main postoperative complication was arrhythmia, acute pulmonary edema and pneumonia, with incidence as 41. 86%. The 1-,3- and 5-year postoperative survival rate was 79.1% ,30.2% and 11.6%. Conclusions The intrap-ericardial pneumonectomy skill not only can improve resection rate, reduce exploration rate, but also offer more oppor-tunity of further therapy in a part of locally advanced lung cancer.
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Background and purpose:The skeleton is the most common site of tumor metastasis in lung cancer.Skeletal complications from bone metastasis,such as severe bone pain,functional impairment,may substantially reduce quality of life,in some situations,may result in death.We explored the efficacy of ibandronate combined with chemotherapy in treatment of lung cancer with bone metastasis.Methods:Sixty-four lung cancer patients with bone metastasis were randomized into two groups:38 patients in study group received normal chemotherapy combined with ibandronate,and 26 patients in control group received normal chemotherapy only.Results:The response rate of pain relief in the study group and control group was 71.1% and 42.3%,respectively(P=0.006).In study group,serum alkaline phosphatise and serum calcium was decreased after treatment by ibandronate combined with chemotherapy(P0.05).Conclusion:Ibandronate is safe and well tolerated. Ibandronate combined with chemotherapy is effective in relief of the pain caused by bone metastases and may inhibit bone metastasis.
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Objective To study the clinical value of serum cytokeratin 19 fragment (CYFRA21-1) as a biomarker in evaluating its prognosis,monitoring and follow-up of the postoperative patients with non- small cell lung cancer (NSCLC).Methods Serum CYFRA21-1 was determined by radioimmunoassay for 207 patients with NSCLC before and after surgical operation at Tongji Hospital,Shanghai.Relationship between serum CYFRA21-1 and the prognosis,recurrence and metastasis of lung cancer was analyzed retrospectively.Results The patients were followed-up for 37 months in average.Preoperative serum CYFRA21-1 was positive in 42.0% (87/207) of all the cases,48.8% (60/123) of squamous cell earcinama and 34.6% (27/78) of adenocarcinoma,with statistical significance (X~2=3.901,P
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Objective To analyze the special CT findings of lung metastatic tumor for the purpose of improving CT diagnostic ability. Methods Six cases with primary tumor and lung metastasis tumor proved by operations and pathology were reviewed. Results The special CT findings of lung metastasis can be divided into two types, cavernous metastasis was found in 4 cases and vacuolar metastasis in 2 cases. Conclusion Consulting to clinical expression and special CT findings, a precise diagnosis could be made in cases of lung metastatic tumor with special manifestations.
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Objective To determine the effects of pre-operative chemotherapy on p53 expression and apoptosis in lung cancer.Methods 42 patients with lung cancer were divided into pre-opreative chemotherapy group (n=14) and control group (n=28) without preoperative chemotherapy.Method of immunohistochemistry was used to detect the expression of p53 . Terminal deoxynucleotidyl transferase nick end labeling (TUNEL) was used to detect the apoptotic cells.Results The positive rate of p53 expression were as follows;53 5% for control group,64 3% for prechemotherapy group,64 3% for postchemotherapy group respectively;the apoptosis indexes were 6 3?1 9 for control group,7 3?1 6 for prechemotherapy group,14 5?4 6 for postchemotherapy group.Conclusions The preoperative chemotherapy can induce apoptosis in lung cancer ,but can not affect p53 expression .
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PURPOSE: To evaluate the CT findings of histopathologically proven pulmonary hamartoma MATERIALS AND METHODS: CT findings of 16 patients with pulmonary hamartoma, histopatologically proven between 1990 and 1996, wereretrospectively reviewed. Diagnosis was based on thoracotomy9n=11) or fine-needle aspiration biopsy(n=5). Weanalyzed the location, margin discreteness, shape, and size of the mass, and the presence of calcification or fatdensity, as seen on CT scan. RESULTS: All 16 tumors showed a discrete and smooth margin and there was nopredilection for any specific site. They were lobulated(11/16, 69%), round(4/16, 25%) or oval(1/16, 6%) and wereless than 1cm(2/16), 1~ < 2cm(4/16), 2~ < 3cm(5/16), 3~ < 4cm(3/16) or 4~5cm(2/16) in size. Nine of 16 cases(56%)showed calcification;this was either popcorn-type(n=3), stippled(n=3), eccentric(n=2), or diffuse(n=1). Five of 16cases(31%) showed fat attenuation. CONCLUSION: On CT, pulmonary hamartomas showed a discrete margin, werelobulated (rather than round or oval) and varied in size. calcification was more common than fat density. These CTfindings may be useful for the differential diagnosis of pulmonary hamartoma.
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Humanos , Biopsia con Aguja Fina , Diagnóstico , Diagnóstico Diferencial , Hamartoma , Tomografía Computarizada por Rayos XRESUMEN
Purpose:To detect the telomerase activity of lung cancer cells in peripheral blood by TRAP.Methods:The mononuclear cell fraction in peripheral blood was isolated by Ficoll Hypaque gradient centrifugation. Then the telomerase activity of cancer cells in peripheral blood of 49 pre chemotherapy patients was determined by PCR TRAP. Results:In the 49 cases, 65.3%(32/49) cases showed significantly increased telomerase activity, among these cases the telomerase activity was especially high in small cell lung cancer and advanced non small cell lung cancer patients, and telomerase activity in the primary chemotherapy patients was higher than in the recurrent chemotherapy patients. Conclusions:Telomerase activity may be a tumor marker of cancer cells in peripheral blood and can evaluate chemotherapy response in lung cancer.
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0.05). The pulmonary carcinoma incidence rate of the rats treated at the dosages of (6.88?0.31) mg/m3, (15.06?0.35) mg/m3 and (35.33?1.69) mg/m3 were 6.56%?8.96% and 12.70% respectively. Immunohistochemical staining showed that COF could induce abnormal expression of p53 and FHIT protein in lung tissue. Only in experimental group the positive expression of mutant p53 protein located in bronchi epithelial cell nucleus were found. The positive expression rate of p53 protein in lung tissue section of tumor cases was significantly higher than that of control group(P